REVISTA ROMÂNĂ PSIHIATRIE - de

REVISTA ROMÂNĂ PSIHIATRIE - de

REVISTA ROMÂNĂ PSIHIATRIE - de

REVISTA ROMÂNĂ de PSIHIATRIE Vol XX Nr. 2 June 2018 QUARTERLY CNCSIS B+ p-ISSN: 1454-7848 e-ISSN: 2068-7176 ARPP ASOCIAŢIA ROMÂNĂ DE PSIHIATRIE ŞI PSIHOTERAPIE www.romjpsychiat.ro ROMANIAN JOURNAL OF PSYCHIATRY COMITET DE REDACŢIE Redactor şef: Dan PRELIPCEANU Redactor-şefi adjuncți: Dragoş MARINESCU Aurel NIREŞTEAN COLECTIV REDACŢIONAL Doina COZMAN Liana DEHELEAN Marieta GABOŞ GRECU Maria LADEA Cristinel ŞTEFĂNESCU Cătălina TUDOSE Secretar de redacţie: Valentin MATEI CONSILIU ŞTIINŢIFIC Vasile CHIRIŢĂ (membru de onoare al Academiei de Ştiinţe Medicale, Iaşi) Michael DAVIDSON (Professor, Sackler School of Medicine Tel Aviv Univ., Mount Sinai School of Medicine, New York) Virgil ENĂTESCU (membru al Academiei de Ştiinţe Medicale, Satu Mare) Ioana MICLUŢIA (UMF Cluj-Napoca) Şerban IONESCU (Universitatea Paris VIII, Universitatea Trois- Rivieres, Quebec) Mircea LĂZĂRESCU (membru de onoare al Academiei de Ştiinţe Medicale, Timisoara) Juan E. MEZZICH (Professor of Psychiatry and Director, Division of Psychiatric Epidemiology and International Center for Mental Health, Mount Sinai School of Medicine, New York University) Eliot SOREL (George Washington University, Washington DC) Maria GRIGOROIU-ŞERBĂNESCU (cercetător principal gr.I) Teodor T. POSTOLACHE, MD (Director, Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore)

REVISTA ROMÂNĂ PSIHIATRIE - de

CUPRINS ARTICOLE DE SINTEZĂ & 47 ARTICOLE SPECIALE & 52 & 55 & 57 ARTICOLE ORIGINALE & 59 & 63 & tratamentului de monitorizare al alcoolismului cu comorbiditate hepatică. Un studiu observațional 68 & 75 CAZ CLINIC & 83 INSTRUCŢIUNI PENTRU AUTORI 86 Modelul atașamentului la adult. Influența asupra abilităților parentale Carmen I. Truțescu, Iuliana Dobrescu Personalitatea și strategiile de adaptare în dinamica vârstelor Aurel Nireștean, Andra Oltean, Emese Lukacs Dimensiunea conștiinței și personalități patologice Emese Lukács, Aurel Nireștean, Andra Oltean Perspectiva dimensională a subvariantelor tulburării obsesiv-compulsive Emese Lukács, Aurel Nireștean, Tudor Nireștean, Andra Oltean Relația dintre depresie și factorii socio-economici Ioana A. Pacearcă, Floris P. Iliuță, Oana Manea, Mirela Manea Comorbidități ale consumului abuziv de alcool Maria Bonea, Mădălina C Neacșu, Ioana V Micluția Biomarker-ii Claudiu I. Vasile Monitorizarea pacienților alcoolici folosind Testul Audit Claudiu I. Vasile Diagnostic diferențial: tulburare delirantă - tipul somatic vs anorexia nervosa Ana-Anca Talașman, Alexandra Dolfi Revista Română de Psihiatrie este indexată de Consiliul Naţional al Cercetării Ştiinţifice din Învăţământul Superior la categoria B+. Apare trimestrial.

Colegiul Medicilor din România acordă abonaţilor la această publicaţie 5 credite EMC/an. Articolele ştiinţifice publicate în revistă sunt creditate cu 80 credite EMC/articol. Revista Română de Psihiatrie este editată de Asociaţia Română de Psihiatrie şi Psihoterapie şi Asociaţia Medicală Română

REVISTA ROMÂNĂ PSIHIATRIE - de

REVIEW ARTICLES ADULT ATTACHMENT PATTERN. INFLUENCE ON PARENTING SKILLS 1 2 Carmen I. Truțescu , Iuliana Dobrescu The assessment of adult functionality includes the global analysis of several perspectives. The role of parent, with clearly defined goals related to the growth and education of children, is fundamental. There are more and more debates in recent years about the more complex implications of the adult personality in the psycho- emotional development of the offspring, directly and indirectly, the psychological balance of the parent contributing to the maintenance of the mental health of the children.

The parenting style can be considered the result of the educational process to which the adult who became a parent had access. Personal beliefs and parental values ​​influence and delineate the set of rules, expectations of performance, and interventional patterns used in education ofchildren. Darling and Steinberg, in a 1993 paper, bring clarifications towards distinction between parenting practices and parenting styles; in the author's opinion, parenting practices are defined as specific behaviors that parents use to socialize their children while parenting style as the emotional climate in which parents grow up their children.(1) Depending on the child's responsiveness and the urgency of the requirements formulated for children, Diana Baumrind (2) defines three different types of parenting styles: democratic style, authoritarian style and permissivestyle.

Democratic style. The parent has a high receptivity; the requirements and limits set out are clear, allowing children to develop their autonomy, working maturely, independently, and developing appropriate child behaviors. Inappropriate behaviors are sanctioned by coherent, not arbitrary or violent measures. Often behaviors are not punished, but the consequences of the child's actions are explored and discussed, and the child can see that behavior is inappropriate and should not be repeated. (3) However, when a child is punished, the parent will explain the reason for the punishment adopted. Children respond to parental punishment because it is reasonable and fair. As a result, children with democratic education style parents are more likely to be successful, will be appreciated by those around them, generous and capableofself-determination.(2,4,5) Authoritarian style. The parent has a low response capacity and his requirements are absolutist; their children must follow the instructions formulated without any explanation. (3, 4) Body punishment is a common form of discipline. Some supporters of this parental style believe aggression from someone in the outside world will be less shocking for a child who is accustomedtotheseformsofrelationship.

Children raised using this type of parenting may have weaker social skills, tend to be conform, very obedient, quiet, but not very happy, with feelings of self- culpability and being at risk for depression, which may persist until maturity. Those who manage to develop self- confidence can present behavioral changes in teenagers, while under-developed teenagers with low self-efficacy mayresorttosubstanceabuseorsuicide.(4,5) Permissive style. Marked by high reactivity and low absolutist requirements. (3) Studies on pre-school children with permissive parents indicate that they tend to be immature, with poor or absent impulse control (5). In 1 MD, medic specialist psihiatrie pediatrică, Institutul Național pentru Sănătatea Mamei și Copilului – Alessandrescu-Rusescu, București 2 Prof. Univ., medic primar psihiatrie pediatrică, Spitalul Clinic de Psihiatrie “Alexandru Obregia”, UMF” Carol Davila” București, ReceivedFebruary26,2018, Revised February28,2018,AcceptedMarch17,2018 Abstract The role of parents in raising and educating children is fundamental, and, in recent years, there is an increase in mentioning their active participation in maintainingthementalhealthofchildren. Beyond the rational approach to problems in raising the children, different structural factors, personality traits, and personal life experiences, sometimes with traumatic effects, can interfere with adherence to the chosen parenting style. Adopting an inconsistent attitude in the application of self-imposed or recommended educational rules or principles, emotional instability or expression of fluctuating feelings, alternating between guilt and aggression may represent just a few examples of behaviors that launch the hypothesis of a fundamental relationship between the way of exercising the profession of parent and parental attachmentpattern.

Specialists in child psychology and psychiatry carefully evaluate the attachment of young individuals, being considered an important determinant of the pattern of subsequent social relationships. The adult attachment is however a controversial topic, many authors assimilating it with personality traits while other sustain its substantial impact on social relationships, especially on couple and familyrelationship. This paper aims to review the data on adult attachment and its relation to the individual's functionality as aparent.

Key words: adult attachment, parenting, personalitytraits 47

REVISTA ROMÂNĂ PSIHIATRIE - de

48 adolescence, they have a three times higher risk for pathological alcohol consumption compared to the same agepopulation(6). Parenting (parenting practices) is a specific behavior - taken over or acquired - that a parent chooses to use in the care, growth and education of his child. (2) Attachment and care systems are often activated simultaneously.(7) Apart from the parental attitudes mentioned above, special attention has been paid to Neglect; these parents have no expectations and do not react adequately to children's interactions, neglect the emotions and opinions of the child, most of the times their parents and children have contradictory behavior; the child will be full of resentment, and the parent will be indignant, lacking in authority. Children get retreated into social situations, withschoolabsenteeismordelinquency.(3,5) Literature data shows that there is a strong link between the parent's attachment style and the parenting style to which he / she will adhere, the parent with secure attachment, adopting an autocratic (democratic) educational style, gives the child the opportunity to make choices and to develop in a flexible, democratic, safe and assertive manner, while parents with anxious attachment style tend to develop permissive parenting techniques. (7) Similar results have also been reported by Millings et al., who also emphasized that there are no significant differences between mothers and fathers, the type of attachmentbeingapredictoroftheparentingstyle(8). Psychotherapy, particularly psychodynamic and systemic, recognize the importance of understanding the intrapsychic dynamics of the adult becoming a parent and addressing the family. Therefore, we start from recognizing that previous experiences of the individual make their presence felt in all inter-human relationships, including in the parent-child relationship, both at the level of educational principles and at the level of communicationandemotionalrelationship.(9,10) Personality traits, individual communication skills, developed and trained coping techniques, assertiveness level, or pre-clinical psycho-emotional conditions all can be considered variables that interfere withtheparentingstylepracticed(5).

From the perspective of attachment, adequate parenting skills require the congruent action of the areas of sensation and perception, reward, executive functions, motor skills and learning abilities. (10) The authors also talk about the role of working memory in allowing parents to plan their parental actions based on the information transmitted to the child, the context and previous experiences, and correlates them with the mother's ability to focus and keep attention in the tasks as well as her spatialmemory.(11) Personal experiences at the expense of an attachment relationship, such as childhood mistreatment or neglect, can reduce the feeling of safety among peers and may exacerbate reactions to later tensions or conflictual situations. (7, 10) Although it seems to influence the relationship with age equals, the state of insecurity may appear in relation to one's own children, of which, approaching a persistent attitude can be difficult. (12,13) In general terms, attachment can be understood as an emotional bond that an individual can establish with another person. Attachment relationship refers to the connection one has developed with the person who represents the primary attachment figure, mainly the person providing the care; toward this person the child reach or maintains the approach in a differentiated and usuallypreferredway.(14) There are two concepts of attachment development; on the one hand, the behaviorist, according to which attachment is learned, and the one detached from psychoanalysis, which considers that individuals are born withtheabilitytoformtheirattachment.

The behaviorist theory argues that attachment patterns are developed through classical or operative conditioningprocesses,asfollows: ·Classical conditioning, in which emphasis is placed on the importance of stimulus - response: children are born with hunger reflexes, and when fed, this reflex is diminished and a well-being, pleasure is established, which is then associated with the person providing the food, searching for that person perpetuating beyond the moments of hunger, which leads to the learning of the attachment.

·Operational conditioning: behavior which leads to rewards will be repeated, unlike the one that draws an unpleasant result that will not repeat itself. Feeding leads to positive feelings that will lead to the perpetuation of the generating behavior and will create a secure attachment. For example, the child will show desire for proximity with a smile, looking for the mother, as she responds with the same type of reaction, thus enhancing his behavior. (15, 16,17) Behaviorism therefore supports the idea that any rewarded behavior will be reproduced. (15) The hypothesis was taken up and supplemented by further research which considers that parents teach their children to love them throughthreemechanisms(TheoryofSocialLearning): ·Direct training, when asking the child to show his attachment,forexamplebytellingthemtoembracethem; ·Modeling by mimicking emotional behavior of parents, as when the parents caress the child, and he does the same gesture; ·Social encouragement which parents apply after observing children's behavior towards others, trying to modify behavioral errors by explaining why it is not good to act in a certain way. For example, when a child reacts violently when another takes his toy, parents explain that it isnotgoodtoscreamandhittheotherchild.(15,18) One of the limitations we can observe regarding behaviorist theory is that it is unable to explain why attachment relationships persist for long periods of time, even when persons to which an individual shows attachment are missing and they don't meet his needs. (9, 15) Psychoanalytic theory, explaining the mother- child relationship centered on the need for food, sees this feeding relationship as a means rather than as a goal. From the point of view of psychoanalysis, satisfying the basic need of the child gives him the opportunity to shift his attention from the primary needs, for which he knows he will always have support, to the environment, which he begins to discover, and in which gradually establishes its own position, thus achieving a strong affection towards the mother, based on safety and trust, which goes beyond Carmen I.Truțescu,IulianaDobrescu:AdultAttachmentPattern.InfluenceonParentingSkill s

REVISTA ROMÂNĂ PSIHIATRIE - de

49 the physiological dependence relationship. The early mother-child relationship is imperative for the harmonious development of the child's subsequent personality, the emotional safety that mother transmits to her child being responsible for the cognitive ability of the child and also for his social assessment skills. Supplements to psychoanalytic theory have argued that newborns, like animal babies, are born with a series of abilities which form a psychological system that facilitates the creation of an attachment behavioral system withrespecttotheprimarycaregiver.(14,19) Growing, the inner work pattern of the Ego and of others is gradually developed, especially of their caregivers, and children can differentiate behaviors and emotional feelings associated with them, simultaneously appropriating some of the observed behavioral reactions. (14,19) These behavior patterns end up being biologically rooted and activated throughout their later life by various environmental stimuli and conditions generated by different social circumstances, such as the need for protection and care. The attachment theory emphasizes learning through observation and reinforcement, which children take in their future interactions with their classroom mates, in the classrooms, and ultimately in their family relationships (17, 20), and the role that attachment playsitasabufferagainststress (12).

Moreover, the attachment theory represented other processes by which parents can lead to social competence, arguing that safe relationships with caregivers in early childhood predicted later competence in several areas (21, 22). Social competence is also associated with attachment security, attachment among infants being a good predictor for social competence during childhood and adolescence (20). Considering the fact that the individual's interpersonal relationships and experiences are unique, a multitude of variables that relate both to that person and to his / her relational, social and economic background, can influence the development of the attachment. (14, 19) Depending on the degree of deviation from normality, attachment is classified into two broad categories: secure andinsecure.

Secure attachment is the ideal attachment type in which all the information received by the individual has induced the idea of ​​security, self-confidence and freedom of knowledge. Children who have developed such an attachment are those who have always felt that someone is near to help them and that the family is a secure environment. As a form of manifestation, these children are those who get upset when the mother / parents leave, trying to resist, but after a few minutes they can be easily reconciled by someone else and continue their activities because they know that separation is a temporary one and thatparentswillalwayscomeback.

From a relational point of view, these children learn to express their needs and emotions directly, they feel able to create social relationships and enjoy it. The basis of this attachment is a healthy emotional process, which includes empathy, harmony, emotional resonance, all mediated by the brain and associated with a positive affectivestate(23,24). In turn, insecure attachment is divided into three types(12,16,19): 1.Anxious-preoccupied attachment - Children with this type of attachment have a dual, duplicate attitude towards their parents. They will develop a "sticky" and addictive behavior, but when they interact with their parents, they reject them. (16) They are unable to develop feelings of safety in relation to attachment figures, unable to move awayfromthemtoexploretheenvironment.

When a stressful situation occurs, they cannot be dissuaded and do not want to relate to their parents. This is caused by the inconsistency of parents in meeting their needs, these children not knowing when their requests will be heard and when they will be ignored. All these relationship traits between children and parents will gradually lead to the creation of a negative self-image of the child and to a series of exaggerated actions and manifestationstoachieveattention(12,25). 2.Avoiding attachment - In this psychological context, children lose their confidence in adults, do not feel that they can provide the help they need and then they start to avoid the significant person. Also, these children do not have the necessary safety to explore the environment in which they live, they are independent of the parents' presence, both physically and emotionally. (12) They do notseekcontactwithapersoninastressfulsituation. Parents of these children refuse to help when they ask for it, they are insensitive, and evade when facing more difficult tasks, most often their support is mossing in emotionalstresses situations(26).

Therefore, children with an avoidant attachment are considered unworthy and unacceptable by others becauseoftheparentalrejection.(12,25) 3.Anxious-avoiding attachment - This type of attachment is absolutely dysfunctional and installs in children who have been abused and who have been deprived of the presence of an attachment figure. The behavior of these children is unpredictable, it is lacking coherence and predictability towards others. It's named also a disorganized attachment type. Their reactions are generallydifficulttopredict.(12.26) By reviewing the above attachment types, attachment can be said to be an evolutionary mechanism, developed at the individual's psychological level, to overcome the stressful situations that they encounter throughout their lives. Among the protagonists of this process are the people who constitute the early universe of the individual, respectively the mother. (26) Their unavailability or abuse will result in an insecure attachment pattern, each defining some subsequent behaviorandrepresentingariskfactorforit(27). The attachment theory, as described by Bowlby in 1969, refers to the attachment of children to the primary attachment figure, (14) but it can be extended to personal relationshipsdevelopedinadulthood(13,28). The child, in the relationship he develops with the caregiver, develops working patterns and relationships with others, influencing the patterns of cognitive, emotional and behavioral response. These attachment models are characterized by two dimensions, called anxietyandavoidance(9,29).

When the comfort and safety needs are constantly met, the child develops a secure connection to the attachment figure (15) characterized by a positive image of the self. However, if the attachment figure does meet his needs, it develops a relationships pattern in which Romanian Journal of Psychiatry, vol. XX, No.2, 2018

REVISTA ROMÂNĂ PSIHIATRIE - de

50 individual fears are manifested, and the individual expects rejection from others. People with this type of attachment, named anxious-fearing, feel the anxiety at high level, mostly the anxious preoccupation for relations with others.(12,30). If the individual experience is a neglect one, which is repeated consistently enough, the individual can develop the belief that the relationship with others is untrustworthy, considering himself as autonomous and self-sufficient. These people can then avoid, during the development close relationships, fearing that the relationship with others will only bring them disappointment. People with this model of work are at risk for developing the evasive attachment, defined as a tendencytodismissoravoidintimaterelationships(30). Preoccupation for adult attachment relationships began in the early 1970s with studies on responses toward loses, initially death of partners (31) and marital separation (32). More recently, the interest in adult attachment has been extended to include marital relationships that have translated attachment models described by Ainsworth in models encountered at adults. Thus attachment patterns (security, avoidance or ambivalence) are recognized in terms of romantic relationships, patterns that can also be reported to the parent-childrelationship.(19,32) When discussing the adult's attachment, it is a matter of differentiating it from personality, making it difficult to establish the causal relationship between the two aspects and, above all, their correspondence, if we accept that they exist. (15) There are some individual personality traits that clearly do not come from attachment experiences. These features, called temperamental or constitutional, apparently result from genetic factors or otherbiologicalfactors.(22,33) The hypothesis of associating anxious attachment with more interpersonal problems has been the subject of many researches; it was highlighted that avoiding type people generally had problems with offspring care (cold, distant, introverted or competitive attitude) while anxious people had problems with emotionality (intense expression of emotions). (34) Other authors have pointed out that individuals with unreliable attachment were predisposed to loneliness and social isolation and / or couple relationships assessed as less satisfactory, marked by more frequent conflicts, divisions and frequent acts of violence(13,34,35).

Since attachment involves an internal model of social relations, we tend to look for the effect of attachment experiences on relationships rather than on, for example, memory or athletic mode (33). The insecure attachment influences the care and parenting skills when the individual becomes adult, being distant, cold and with the tendency to reject the child. Inhibition is, in these parents, a coping strategy driven by fear, anxiety, anger, sadness, shame,guilt.(10,12) The attachment style analysis was examined in many psychodynamic conditions but also with some the psychiatricdiagnosticentities.

We mention the proven relationship between avoided attachment and lack of social communication skills, favoring communication via virtual or online social networks (36, 37) and the development of post-traumatic stress disorder in adults with a history of exposure to childhoodviolence(10,38). Anxiety disorders are characterized by dysfunctions of the stress control system and response to fear that develop in the context of life experiences and persist throughout life, generating the idea of involving early attachment to the etiology of subsequent anxiety disorders. (10, 13, 15)Activation of the attachment system accompanies therefore anxiety and stress response. (27, 37) A comparative analysis of the relationship between communication skills and the parental relationship in parents of ADHD's children versus typical children's parents shows that exaggerating personal weaknesses and coercive behavior as well as promoting self-devaluation makes parents with anxious attachment to engage in non-constructive communication in relationship with the child with ADHD (39), while mothers with secure attachment more often have the ability to overcome stressful moments and adapt to parentalstatusrequirements(7,11,17). Knowing the association between individual psychological variables and the relational-educational style that an adult develops in parenting provides the possibility of early psycho-educational intervention (primary screening and prophylaxis of psychological disorders and even some of the psychiatric disorders of children and adolescents) as well the implementation of some complex psychotherapies programs that include not only the child's symptomatology but also the modification ofthepsycho-familialframework.

References: 1.Darling N, Steinberg L. Parenting style as context: An integrative model.PsychologicalBulletin,1993,113:487–496. 2.Baumrind D. Parenting styles and adolescent development. In J. Brooks-Gunn, R. Lerner, A.C. Peterson (Eds.), The encyclopedia of adolescence.NewYork:Garland,1991,746-758. 3.Santrock JW. A topical approach to life-span development, third Ed. NewYork:McGraw-Hill,2007. 4.Stassen Berger K. The Developing Person Through the Life Span. WorthPublishing,2011,273–274. 5.Dornbusch S, Ritter P, Leiderman P, Robert D, Fraleigh M. The Relation of Parenting Style toAdolescent School Performance. Wiley on behalfoftheSocietyfor ResearchinChildDevelopment,2014,1245. 6.VerzelloA. Teens and alcohol study: Parenting style can prevent binge drinking. News. BrighamYoung University,2014.

7.Nanu ED, Nijloveanu DM.Attachment and Parenting Styles. Procedia - SocialandBehavioralSciences,2015,203:199– 204. 8.Millings A, Walsh J, Hepper EG, O'Brien M. Good partner, good parent: Responsiveness mediates the link between romantic attachment and parenting style. Personality and Social Psychology Bulletin, 2013, 39:170-180. 9.Collins NL, Allard LM. Cognitive representations of attachment: The content and function of working models. In: Fletcher GJO, Clark MS (eds.) Blackwell handbook of social psychology: Interpersonal processes. MA: Blackwell,2004,60–85.

10.Hill EM, Young JP, Nord L. Childhood adversity, attachment, security, and adult relationships: A preliminary study. Special issue: Mental disorders in an evolutionary context. Ethnology and Socio- Biology, 1994, 15:323-338. 11.Barrett J, Fleming AS. All mothers are not created equal: Neural and psychobiological perspectives on mothering and the importance of individual differences. Journal of Child Psychology and Psychiatry. 2011,52, 368–397. 12.Mikulincer M, Shaver PR, Pereg D. Attachment theory and affect regulation: The dynamic development, and cognitive consequences of attachment-related strategies. Motivation and Emotion. 2003, 27: 77- 102.

13.Mikulincer, M., Shaver, P. R. (2007). Attachment in adulthood: Structure,dynamicsandchange. NY:TheGuildfordPress. 14.Bowlby J. Attachment and loss: Vol. 1.Attachment. NY: Basic Books. Carmen I.Truțescu,IulianaDobrescu:AdultAttachmentPattern.InfluenceonParentingSkill s

REVISTA ROMÂNĂ PSIHIATRIE - de

51 1969 15.Dollard J, Miller NE. Personality and psychotherapy. New York: McGraw-Hill,1950. 16.Bandura A, Walters HR. Social learning and personality development. NewYork:Holt,Rinehart&Winston,1963. 17.Bandura A. Self-efficacy: Toward a unifying theory of behavioral change.PsychologicalReview, 1977, 84:191-215. 18.Hay DF, Vespo JE. Social learning perspectives on the development of the mother-child relationship. In: Birns B, Hay D F (eds.). The differentfacesofmotherhood, PlenumPress, NewYork, 1988 19.Ainsworth MD, Bowlby J. An ethological approach to personality development.AmericanPsychologist, 1991, 46:331-341. 20.Shaffer A, Burt KB, Obradovic J, Herbers JE, Masten AS. Intergenerational continuity in parenting quality: The mediating role of social competence. Developmental Psychology, 2009, 45(5): 1227- 1240.

21.Berscheid E, Regan PC. The psychology of interpersonal relationships.Mahwah, NJ: Prentice-Hall,2005. 22.Sroufe LA, Egeland B, Carlson EA, Collins WA. The development of the person: The Minnesota study of risk and adaptation from birth to adulthood. NewYork:GuilfordPress, 2005. 23.SchoreAN. Effects of a secure attachment relationship on right brain development, affect regulation, and infant mental health. Infant Mental HealthJournal,2001,22(1–2):7–66; 24.Siegel DJ, Hartzell M. Parenting from the inside out: How a deeper self-understanding can help you raise children who thrive, Penguin, NewYork, 2003 25.Kobak RR, Cole HE, Ferenz-Gillies R, Fleming WS, Gamble W. Attachment and emotion regulation during mother-teen problem solving: A control theory analysis. Child Development, 1993, 64: 231- 245.

26.Stevenson-Hinde J, Verschuere K. Attachment in childhood, Oxford Press, 2002 27.Oshri A, Sutton TE, Clay-Warner J, Miller JD. Child maltreatment typesandrisk behaviors:Associationswithattachmentstyleandemotion regulation dimensions, Personality and Individual Differences, 2015, 73: 127–33 28.Hazan C, Shaver PR. Romantic love conceptualized as an attachment process. Journal of Personality and Social Psychology, 1987, 52: 511–524. 29.Brennan KA, Clark CL, Shaver PR. Self-report measurement of adult romantic attachment: An integrative overview. In: Jimpson JA, Rholes WS (eds.), Attachment theory and close relationships, NY: The GuildfordPress, 1998,pg.46–76.

30.Smith ER, Murphy J, Coats S. Attachment to groups: Theory and measurement. Journal of Personality and Social Psychology, 1999, 77(1):94–110. 31.Bowlby J, Parkes CM. Separation and loss within the family. In: Anthony EJ, Koupernik C (eds.), The child in his family, International Yearbook of Child Psychiatry and Allied Professions, New York: Wiley, 1970, pp.197-216 32.Weiss M, Hechtman L, Weiss G. ADHD in parents. Journal of the American Academy of Child and Adolescent Psychiatry, 2000, 39: 1059–1061.

33.Mercer J. Understanding attachment parenting, child care, and emotionaldevelopment.PraegerPublishers,London,2006 34.Bartholomew K, Horowitz LM. Attachment styles among young adults: a test of a four-category model. J Pers Soc Psychol; 1991, 61: 226- 44. 35.Corcoran K, Mallinckrodt B. Adult attachment, self-efficacy, perspective taking, and conflict resolution. Journal of Counselling & Development,2000, 78:473-483. 36.Buote V, Wood E, Pratt M. Exploring similarities and differences between online and offline friendships: The role of attachment style. Computers inHuman Behavior,2009,25:560–567. 37.Caplan SE. Relations among loneliness, social anxiety, and problematicInternetuse.CyberPsychology&Behavior,2007,234–242. 38.Salzinger S, Feldman R, Ng-Mak D. Adolescent outcome of physicallyabusedschoolchildren, 2008,15-65. 39.Fatahyah Y, Antigonos S. Adult attachment and constructive communication in parents of children with Attention Deficit Hyperactivity Disorder (ADHD). The 9th International Conference on CognitiveScience,availableonlineatwww.sciencedirect.com,2013. *** Romanian Journal of Psychiatry, vol. XX, No.2, 2018

REVISTA ROMÂNĂ PSIHIATRIE - de

SPECIAL ARTICLES PERSONALITY AND COPING STRATEGIES IN AGE DYNAMICS 1 1 1 Aurel Nireștean , Andra Oltean , Emese Lukacs Any attempt to describe personality necessarily implies looking at life roles and the temporal dimension of human existence. The latter is the foundation of personal destiny, and influences self-awareness and the ways in which one connects with others. A person's subjective wellbeing, in both its cognitive and affective components, is dependent upon the quality of human relationships, and favors coping capacities in the diversity of life roles throughoutallitsstages.

Considered to be a major existential aim, being “yourself” means self-knowledge and self-acceptance. Likewise, it implies a harmony between self-image and self-esteem, and gives a person the natural feeling of belonging to humanity. Human nature includes the individual dimension of personality as well as an important part of the personal and collective archetypes, confirming in a special way the concept of “unity in diversity”. Thus, being yourself favors and at the same time transcends inter-human differences. Genetics, society and culture simultaneously determine these differences andconfirmthediversityofthehumancondition. Throughout the various stages and in the diverse roles one plays in life, the personal attributes that should be developed are the ones that favor the most efficient coping mechanisms, while also taking into account the fact that agecanenhaceordiminishthem.

Man is not born an adult, and all childhood experiences - among which the relationship with family and people close to you play a major role – form the foundations of a person's emotional life, cognitive strategies, and major existential motivations for the following stages of life. Man also has one body – biological maturation precedes the psychological one, and decisively influences it. Together they shape one's self- image. But man is also a social being, one's internal world being a projection of the external one. The binoms activism/passivity, dominant/submissive, interpersonal closeness/detachment dominate the individual's life and shapethematurationprocess.

Mind theory says that human beings have the capacity to intuit and anticipate the psychic content of the people around them, which constitutes a major coping attribute. There is a complex inter-conditioning between the dimensions of the individual personality and the psyche. Thus, the psychic functions and the dominant personality structures mature and manifest themselves simultaneously,andsustainaperson's copingabilities(1). The relationship between the emotional life of the individual and the diversity and hierarchy of personal motivations plays a special role. Precocious affective experiences decisively influence ulterior biological and socio-cultural motivations, as well as the ways a person responds or reacts to external stimuli. The ability to cope and resonate emotionally, their depth and persistence are particularly involved in the representation of the self and of the outside world – inner working model. They determine self-knowledge and self-esteem as well as the coping ability and the ways in which one influences one's surroundings.

The process of individual maturation is also determined by the ability for self-determination – a personological character dimension whose value rises progressively – in normal people – throughout the various stages of maturation (2). This is confirmed also by the fact that self-determination is optimized by cognitive- behavioral therapies and the administration of anti- depressants. Whether we look at it as reality or myth, adulthood/maturity implies the passage/progression from an immature and dependent human condition/state, to an independent and socially inter-dependent one, in which an individual is free to make decisions and select interpersonal relationships and existential values and beliefs.

Individual self-determination – whose major aim is self-fulfillment – constitutes thus a tiered process that is partially conscious and partially unconscious. Such isthepassageofhumanbeingsfromoneagetoanother. 1 ReceivedFebruary26, 2018, Revised February28,2018,AcceptedMarch17,2018 PsychiatricClinicNo.II, UMFTg.Mures Abstract Any attempt to describe the human personality always implies looking a the roles and stages of life. In the various stages of life, the coping mechanisms that must be developed are the ones that prove to be the most efficient and valuable in the shaping of a personal destiny. In their great diversity, coping mechanisms express the level of individual maturity. Irregardless of age, they are conditioned by the personality dimensions and the quality of interpersonal relationships. They sustain the subjective wellbeing, and thus the self-esteem of the human person. From the dimensional perspective of the Big-Five model, agreeability and openness, along with self-determination underlie the most important coping mechanisms and give valuetothehuman person.

Key words: personality, coping mechanism, Big Five dimensionalmodel 52

REVISTA ROMÂNĂ PSIHIATRIE - de

53 Personhood is thus a temporary structure whose dimensions are conditioned both genetically and socio- culturally. Genetically they are stable throughout life, while environmental and interpersonal relationship factors shape the dimensional facets which are dominantly thrownintothedynamicsofexistence(2). In the contemporary social and cultural context dominated by post-modern attributes, man is a duplicitous being who simultaneously cultivates narcissistic tendencies and pro-social abilities. It grabs selfishly what is “good” and tackles “evil” subjectively as being the exclusive attribute of others. In relating to others, morality is conjectural/relative, egocentric or altruistic. Virtues are displayed–oftenostensive–onlytoenhanceone's value. The destiny of an individual is in great measure influenced by one's coping abilities, which in turn are undergirded by the personality dimensions, the quality and complexity of interpersonal relationships, the quality of one's motivations, and last but not least, by the specific stagesoflife.

The coping mechanisms of the individual allow the anticipation and control of the negative and positive events of life. They consist of stable personality traits as well as the ability to consciously mobilize one's affective, cognitive,volitionalandmotivationalresources(3). Coping mechanisms are individual psychological attributes that play a major existential role manifested throughout a person's life, and which produce a great variety of strategies and behaviors. They are aimed at more or less specific aspects of one's life such as personal safety, interpersonal relationships, reproduction, parental attributes, professional options and involvement, socialstatus(4).

In the constant search for self-fulfillment – happiness– as a support for one's subjectivewellbeing,the contemporary human being feels the need to surpass oneself.That is why, in the spirit of competitiveness which has been promoted since the first stages of life, - the need to be “someone” in other people's eyes is born and becomes dominant. The attachments people form with othersarethusbasedonlyoncommoninterest. The most intense and complex implication of a person in life's roles takes place in adulthood, while relating in the most meaningful way to life's experiences and events happens in youth and with the elderly. The quality of the involvement in existential roles depends thus on the quality of the coping mechanisms which differs from person to person and from age to age, especiallyinthepresenceofstress factors. In youth, the processes of biological and psychological maturation harmonize, emotional life is intense, and self-knowledge is in its beginning stages. Special aptitudes and talents often become evident and professional options are being formulated. While self- searching, young people are curious, non-conformist, thirst for novelty, give importance to appearance, are pragmatic and idealistic, and often abuse drugs. Self- esteem is fragile and inter-personal relationships are many andmostlyshort-livedandshallow(5).

Adulthood is the age of maturity, in which self- knowledge and self-acceptance are reached. It is the age of stable, adaptable emotions, of introspection and reflection, and of elaborate cognitive strategies. The adult is intensely involved in a multitude of roles – the professional one being dominant – nowadays for females as well – and has complicated relationships with others. An enhanced sense of responsibility for one's opinions and actions is present, and self-esteem goes hand-in-hand with self-image.

The 3rd age is characterized usually by a certain devolution of the somatic state and of the ability to function in the various life roles. They are diminished, as are social contacts and relationships. The fear of dependency, of poverty, and of death can appear at this stage along with the various ways of dealing with impotence and of accepting it.The tendency to undervalue oneself, lower self-esteem, and social isolation are often evident at this stage. But this stage of life also means psychological maturity and spiritual growth, the acceptance of one's personal biography, the capacity to select what is valuable in life, and the promotion of its true sense. The wisdom which inspires and guides those who are younger can protect against age discrimination which is so present nowadays. The elderly can also pursue a symbolic “eternal life” through their children's accomplishmentsorthroughreligion(6).

The life coping abilities of the human person integrate the levels and ways of self-expression, their dominant existential motivations, and their age-specific traits. From the personological dimensional perspective of the Big Five model – neuroticism and extraversion are the most studied dimensions at any age. Together with conscientiousness, they condition and differentiate the states of subjective wellbeing (7). This subjective wellbeing is enhanced but fragile in youth, less strong in adults, and once again higher in the elderly, mostly in its affective/emotional component. The subjective wellbeing grows in time, provided that adulthood is lived at higher level of conscientiousness, agreeability and openness to experience(8).

The level of extraversion diminishes with age leading to a less active social life, except for people with high levels of openness. The heightened level of introversion can become an important coping mechanism when the environment is uncertain or dangerous. Enhanced extraversion spells success in finding a partner or a friend, but is also risky. When the environment is harmonious and safe, the heightened levels of extraversion are coping factors and favor exploring the environment, especially in youth. Together with agreeability, extraversion influences interpersonal relationshipsnomattertheage.

Neuroticism grows with age – especially in females – and it means affective instability, pessimism, low sense of wellbeing and self-esteem. Extreme neuroticism is expressed by hypervigilance toward danger in adults and the elderly, but at the same time it favors episodes of anxiety and depression. The depression and anxiety are aggravated when associated with low levels of conscientiousness. Dysfunctional relationships between youth and adults – especially parents – appear frequently when, in this context, the level of extraversion is also low. On the other side, high levels of both neuroticism and agreeability favor work efficiency in adults and enhance thecognitivecomponentoftheirsubjectivewellbeing(9). Besides, low neuroticism associated with high levels of conscientiousness and extraversion enhance the diversity and quality of interpersonal relationships in youth and adults. Low neuroticism and low extraversion Romanian Journal of Psychiatry, vol. XX, No.2, 2018

REVISTA ROMÂNĂ PSIHIATRIE - de

54 favor the ability to climb in the social and professional hierarchy in adults, while high levels of extraversion are a supportive factor in the commercial and artistic professions,asisopennesstoexperience. Neuroticism ad extraversion are believed to be shaped at any age by material gain. In adults they are shaped also by the quality of personal relationships, and in the elderly, especially males, by their marital status. At these stages, if the levels of neuroticism and extraversion are also joined by an enhanced level of openness, an efficient coping mechanism appears which protects a person's state of subjective wellbeing and emotional balance(8).

T h e d i m e n s i o n s o f a g r e e a b i l i t y, conscientiousness and openness to experience are less the subject of study as they relate to age, but their levels must constantly be related to those of neuroticism and extraversion with which they correlate in complex ways. For example, high agreeability associated with high extraversion positively influence subjective wellbeing. The low values of agreeability and conscientiousness favordisinhibitedbehavioranddelinquency. High levels of conscientiousness have a multitude of adaptive effects. For example, they influence the professional orientation in youth, and ensure heightenedefficiencyin conventionalactivities.They also ensure stability in professional roles and the quality of marital status with the elderly. High quality academic performance is associated with high levels of openness to experience, especially in young people, while low levels of conscientiousness explain in great measure the behavioraldisordersinyouthandADHD inadults(8). The openness to experience is a special dimension which evens out the differences between individuals and often compensate for the maladaptive values of the other dimensions of personality. It implies originality, curiosity, artistic and aesthetic sense, as well as magical thinking, faith, a capacity for self-transcendence, and is, at any age, a major adaptive factor. Its heightened levels sustain artistic abilities, the ability for self- transcendence, and a heightened state of subjective wellbeing in both its affective and cognitive forms. These heightened levels can also explain the high intensity of certain depressive episodes, especially in women. Still, the correlation between age and openness to experience remains strictly individual, thus underlining the specificityoftheother.

The human person's coping mechanisms are shaped by structural dimensions of personality and psychological peculiarities of age. In this context, self- determination together with agreeability and openness to experience constitute the most relevant elements of adaptivesupport. REFERENCES: 1. Nirestean, A., Lukacs, E., Buicu, G., Bilca, M., Pokorny, V. The spiritual dimension of personality and its role in mental health. RomanianJournalofPsychiatry,1, pp.1-4,2016 2. Lazarescu, M., Nirestean, A. Tulburarile de personalitate, Iasi, Ed. Polirom,2007 3. Ionescu, S., Jacquet Marie-Madeleine, Lhote, C. Mecanismele de aparare,Iasi,Ed.Polirom,2007 4. Norbert, S. Dictionar de psihologie, Bucuresti, Ed.Univers Enciclopedic,1996 5. McCrae, R.R. & Costa, P.T., Jr.Age, personality, and spontaneous self- concept.JournalofGerontology:SocialSciences, 43,S77-S185, 1988 6. Laplanche, J., Pontalis, J.B. Vocabularul psihanalizei, Bucuresti, Ed.Humanitas,1994 7. McCrae, R.R., Costa, P.T., Jr. The Five Factor Theory Of Personality, in John, O.P., Robins, R.W., Pervin, L.A. (Eds) Handbook of Personality, TheGuilfordPress, pp.159-181,2008 8. Costa, P.T, Jr., Widiger, T.A. (Eds) Personality Disorders and the five- facto Model (2nd ed.), Washington DC: American Psychological Association,2002 9. McCrae, R.R. The maturation of personality psychology: Adult personality development and psychological well-being. Journal of ResearchinPersonality,36,307-317, 2002a *** Aurel Nireștean, Andra Oltean, Emese Lukacs: Personality and Coping Strategies in Age Dynamics

SPECIAL ARTICLES CONSCIENTIOUSNESS DIMENSION AND PATHOLOGICAL PERSONALITIES 1 1 1 Emese Lukács , Aurel Nireștean , Andra Oltean 3 The Conscientiousness dimension – a component of the Big Five model, also called Five Factor Model – is one of the basal dimensions of personality, easy to investigate by means of the current instruments of personological assessment. It may be correlated both to the Persistence dimension – temperament factor – and to Self-directedness – character factor – from Cloninger's 7 factors model. So, Conscientiousness – both genetically conditioned and shaped by interpersonal and educational experiences within the personogenesis – is a mouldable dimension (1)(5).

Its assessment, allows to estimate the self-control ability, a must in any personological characterization. Conscientiousness represents the foundation of Self- directedness on a medium and long-term basis of the human person and conditions – along with the agreeableness dimension – the person's ability to learn fromexperience(2). Its extreme variants in a positive or negative sense, may define pathological personality traits, which are easily recognized from a clinical point of view. However, they are also frequently encountered in the absence of a propercategoricaldiagnosis.

The Conscientiousness dimension characterizes best the manner in which the person relates to activity. It contains several facets such as trust in one's own abilities – that correlates best with self-esteem – to which is added caution, need of rigor and order, responsibility, persistence,efficiencyinactionandmoralintegrity. A person with high values of Conscientiousness – in an adaptive sense – is characterized by a high level of self- control and trust in his own abilities, high expectations and standards, being always eager to rise and progress. He is a neat and pedantic person, meticulous and tenacious in front of obstacles. Usually prefers an organized and well- structured style of activity, is cautious in his decisions, responsible, perseverant and completes all the assumed tasks. His emotional manifestations are controlled, slightly expansive and contagious, less flexible and spontaneous. Such a person is trustworthy, complies easily with norms and authorities and adopts very easily a balancedandhealthylifestyleregimen.

An excessive high Conscientiousness transforms these traits in their maladaptive variants. Thus, a person with very high values of this dimension has in perspective a higher and higher level of performance, and he self- imposes exaggerated and unrealistic standards. He prefers algorithmic actions, but rigid and monotone ones, has much difficulty in adapting to any change and to novelty in general. He is disadvantaged by indecision, meticulousness and difficulty in synthesizing. Due to his great effort, mostly wasted, his actions are less lucrative. His excessive and disturbing need of order is a compensatory one, that gives him the feeling of having everythingundercontrol(4).

A person with a high Conscientiousness in a maladaptive sense, is dominated by professional ambitions at the expense of the interpersonal relationships quality, which remain distant and formal. He always gives himself credit to know the best variant and action strategy and does not make any compromise. Despite the exaggerated perfectionism, he is not satisfied with the results of his involvement. He abides excessively by norms and regulations, and as a consequence of the lack of spontaneity and flexibility, he can never unwind, his relaxationabilitiesbeingalwayslimited. A person with a low Conscientiousness – adaptively – is less interested in a professional rising career. He is 1 PsychiatricClinicNo2 TârguMureș, UniversityofMedicineandPharmacyTârgu Mureș Received February 26, 2018, Revised February 28, 2018, Accepted March 17, 2018 Abstract Personality disorders must also be approached from a dimensional perspective always, as it allows more subtle assessments of the dominating temperament and character.

As it has both genetic conditionings and social-cultural ones, the Conscientiousness dimension – closely related to activism – centers the personality's structure and it may favoror disadvantagetheindividualdestiny. The adaptive variants of Conscientiousness favor personal self-directedness process, self-control and the subjective well-being. In return, the maladaptive variants – in terms of extremely high or low values, accompany most ofthepersonalitydisorders. Thus, the psychobehavioral manifestations of Obsessive- Compulsive Personality Disorder, Borderline Personality Disorder,Antisocial Personality Disorder and Narcissistic Personality Disorder, but also of Avoidant Personality Disorder and Histrionic Personality Disorder may be dimmed, exacerbated or nuanced by the values of Conscientiousness. These are also predictive factors for a diversity of episodes and mental illnesses, in the case of which the therapeutic compliance influences in a decisive manner.

Keywords: Conscientiousness, personality disorders, self- directedness 55

56 characterized by a high flexibility, spirit of adventure, prefers assuming risks and frequent changes. He has a high tolerance to unstructured tasks and adapts himself easily and quickly to new situations. He is a spontaneous, casual and nonconformist person who tends to resist any form of authority when he feels restrained from manifestinghimselffreelyandnaturally. Low Conscientiousness in a maladaptive sense, manifests itself by a very low self-control, lack of professional enthusiasm and a total lack of respect to social norms and regulations.Aperson with excessive low values of this dimension lacks discipline and perseverance, is unpredictable, and does not respect his promises and initial plans. He is very easy to distract, excessively relaxed as to the tasks received, disorganized and inefficient in actions. He is characterized by immaturity, deficiency in searching the meaning of life and irresponsibility. From a professional point of view, his achievements are usually below the level of his aptitudes. He is a stubborn person, hard to lead, who takes decisions impulsively ignoring the consequences and who oftencommitstoxicexcessesandimmoralacts(4). The high or low values of the Conscientiousness dimension, in an adaptive sense, substantiates specific personological attributes that can be commented and understood always in connection with the other dimensionsoftheperson(1).

Maladaptive Conscientiousness is sometimes a characteristic of pathological personalities. In its extreme variants is defining for the obsessive-compulsive personality, at its the opposite pole being the borderline and antisocial type personalities. They are the most representative correspondences of personological categorical diagnosis, uniting attributes that derive directly from the high or low values of the Conscientiousnessdimension. Thus, a very high Conscientiousness, in the case of obsessive-compulsive personality disorder, it manifests through the tendency of controlling his own behavior and that of the persons around him, in an exaggerated manner, in excessive devotion for work, perfectionism, rigidity, excessive preoccupation for organization, order and details, joining social norms and beliefs, incapacity to relax and enjoy himself. In borderline and antisocial type personality disorders, an excessively low Conscientiousness is manifested by total lack of self- control due to pathological impulsiveness and disconsideration for the other persons around him, affective and attitudinal instability, relational hypersensitivity and low tolerance to frustration. Severe behavior disorders are associated with the violation of legal and moral norms, irresponsibility, ignoring the hazard,incapacitytolearnfromexperience(2). The histrionic personality disorder is characterized by such low values of Conscientiousness that explain low self-control and recurrent impulsive conducts in case of thispersonality.

In the case of the other pathological personalities, the Conscientiousness dimension may be commented more from the quality point of view, according to its various facets, its values, overall, are not near to the extreme ones (3). The perfected self-control of the paranoid personality, decreases under the circumstances in which he loses control over the entourage that he usually selects and dominates. The schizoid is restrained and hypercontrolled apparently, in fact being indifferent and affectively detached. The schizoid is meticulous and perseverantonlyinhiseccentricandbizarrebehavior. The narcissistic personality controls his attitude selectively according to the “quality and value” of the entourage.

In the avoidant personality, reserved and retreated, the exaggerated self-control derives from the lack of trust in his own abilities, especially in the social and relational ones. The dependent personality, also with low self- esteem, is undecided, lacks initiative and spontaneity, he may be resistant and perseverant in routine activities, sometimes even in unpleasant tasks if the dependence relationimposesit. Knowledge and assessment of the Conscientiousness dimension allow the recognition of a specific individual vulnerability with a predictive and prophylactic role, particularly within the context of some of its extreme values, even in the absence of a categorical personological diagnosis.

It may condition the clinical and evolutional feature of the psychopathological pictures and the therapeutic compliance, that its high values may simultaneously favor ordisadvantage. The dysfunctionality corresponding to the extreme variants – may be potentiated, masked or compensated by theotherdimensions. As it is tightly connectable to activism, the Conscientiousness dimension is a measure of efficiency in roles of the human person and a permanent support of self- determination. References: 1.Lăzărescu, M., Nireștean, A. (2007) – Tulburările de personalitate. (PersonalityDisorders) PoliromPublishing,Iași 2.Lăzărescu, M., Bumbea, O. (2008) – Patologie obsesivă. (Obsessive Pathology)AcademieiRomânePublishing,Bucharest 3.Lukacs, E., Nireștean, A. (2012) – Primul episod psihotic între dimensiuni și categorii personologice. (First psychotic episode between dimensionsandpersonologicalcategories)PhDThesis,Târgu-Mureș 4.Lukacs, E., Nireștean, A. (2018) – Obsesionalitatea – între ego- sintonie și ego-distonie în Persoana umană – un model de diversitate antropologică (Obsessionality – between ego-syntonic and ego-dystonic in the Human Person – a model of anthropological diversity), University Press Publishing,TârguMureş 5.Sava, F. (2008) – Inventarul de personalitate DECAS. Manual de utilizare. (DECAS Personality Inventory. User Manual.) ArtPress, Timișoara *** Emese Lukács, Aurel Nireștean, Andra Oltean: Conscientiousness Dimension and Pathological Personalities

57 SPECIAL ARTICLES DIMENSIONAL PERSPECTIVE ON THE SUBVARIANTS OF OBSESSIVE-COMPULSIVE PERSONALITY DISORDER 1 1 1 1 Emese Lukács , Aurel Nireștean , Tudor Nireștean , Andra Oltean The topic of obsessionality incorporates basic aspects of the human existence, passing through history, cultures, and various fields of the individual's life and of the society. We always find it in the structured development of human practices, in the activity accomplished with responsibility and persistence. It is also expressed through discipline, virtue and order in life, by observing the order and social hierarchy in a traditional way, the ethical and moral norms andbymeansofthereligiousandsacredrituals(1)(7). The obsessionality integrated in adaptive experiences and behaviors, dominated by rigorousness, self-discipline, fairness, responsibility, persistence and efficiency, is always differentiated by the structural maladaptive obsessionality, best expressed by the Obsessive- CompulsivePersonalityDisorder(OCPD) (2). Current criteria for OCPD impose the presence of four or more of the eight ones defined, meaning that two persons with this categorical diagnosis may differ considerably from one another. On the other hand, they do not fully grasp the other variant – the psychasthenic one – of the obsessive-compulsive personality. The dimensional assessment comes to complete the categorical assessment, the “Conscientiousness” factor of the “Big-Five” model being specific for OCPD. It allows estimating with a greater accuracy the manner in which a person relates to theroles,challengesandexistentialvalues. The facets of the Conscientiousness dimension – competence, deliberateness, dutifulness, orderliness, persistence, desire of achievement – may vacillate between two poles and allow easily the recognition and differentiation between the “typical” obsessive and the “psychasthenic”one(4).

Thus, regarding the competence, its values are high for the “typical” obsessive who has a high but fragile self- esteem. He is a perfectionist, has always on the horizon a higher and higher level of performance. He is never satisfied with the results of his involvement and consequently he is always involving himself again, looking to reconfirm his abilities and own abilities. He cannot cope easily with challenges, his achievements being under the level of his aptitudes, and consequently he has neither the satisfaction ofthefulfilledaction.

As for deliberateness, a facet related to the person's tendency to reflect before acting, it is the sole facet of the Conscientiousness dimension of which value is high in bothstructuralvariants(6). The “typical” obsessive is excessively cautious, careful at details, drafts plans, projects, considers different eventualities, sometimes loses a lot of time, but finally he decides himself. His choices are usually well founded – sure, pragmatic and rewarding. The psychasthenic problematizes intensely, but remains undecided. He experiences the planning as a tormenting process, with intense ruminations on the variants of action.As he is unsure, avoids the responsibility related to decisionsandhisresolvesarealwayspostponed. Dutifulness, another facet of Conscientiousness, is high in the case of the typical” obsessive. He observes the norms and regulations – “that's how it is done”, “as appropriate”. He is formal and rigid, convinced that only he knows the best variant of action. He is intolerant, does not compromise, hence his multiple interpersonal conflicts. His activity is developed under the imperative of an obligation, of a “must”, and usually he cannot unwind. On the other hand, the psychasthenic has a low sense of duty. He is indecisive and inconsequent, ambivalentand ambitendent,always having difficulties in respecting his promises. He does not have or does not value. Unlike him, the psychasthenic has a low self-esteem, is hypobulic and distrustful in his 1 PsychiatricClinicNo2 TârguMureș, UniversityofMedicineandPharmacyTârgu Mureș Received February 26, 2018, Revised February 28, 2018, Accepted March 17, 2018 Abstract The obsessionality concept integrates the basic aspects of the human condition. In its adaptive variants obsessionality represents a major existential support. Its maladaptive variants are better expressed by the Obsessive-Compulsive Personality Disorder. This has two structural subvariants – typical obsessive, respectively ”psychastenic”, that can be differentiated by assessing the facets of Conscientiousness. They have high values in the case of the typical obsessive, and low values in the psychastenicone,exceptforthedeliberatenessfacet. While searching the harmony between self-esteem and self-image, the typical obsessive cultivates his dominant structural traits by self-control and moral self- devaluation, while the psychastenic, lacking dignity, indulges himself in a subsidiary and devaluing position appropriatetothedeficientself-esteem.

Keywords: Obsessive-compulsive personality disorder, structural variants,dimensionalperspective

58 impose his point of view, he compromises easily and tends towardsdependencerelationships. Orderliness, the need of structuring and organizing, manifests itself at opposite poles in the case of the two structural variants. Thus, the “typical” obsessive is hyper- orderly, meticulous, careful at details, pedantic, punctual and disciplined. He prefers rigid, algorithmic actions from which he does not deflect. His exaggerated need of physical orderliness gives him safety and the feeling of having everything under control. By contrast, the psychasthenic is always disorderly and scattered, negligentinhisappearance(3).

With regard to self-disciplined and persistence, the “typical” obsessive is resistant in doing routine work and motivated to complete an activity he started. He prefers tasks lacking improvisation, spontaneity and ingenuity. He does not deflect from his schedule, finding it very hard to reorient and readapt himself along the way. Finishing the activities he started is difficult, he never experiences the satisfaction of the accomplished act, but on the other hand, he succeeds where others would be brought down by fatigue and boredom. Instead the psychasthenic, is inconsequent and inefficient, starts several activities without finishing most of them. As he is ambivalent and ambitendent, he stops sometimes an activity that he has started,inordertostartanotheroppositevariant. The desire of achievementof the “typical”obsessive is high, as he is an ambitious person who works seriously, completely selflessly and with desire to rise, observing the professional norms. He is always disadvantaged by meticulousness, by his difficulty to synthesize, by self- imposed exaggerated standards and sometime unrealistic ones. His professional ambitious are detrimental to the quality of his interpersonal relationships. Unlike him, the psychasthenic has a low desire of achievement, is abulic, inconsequent and ambivalent, lacking professional enthusiasm.

The tendency to reflect excessively before acting and the intense ruminations on the variants of action, make both the “typical” obsessive and the psychasthenic one to belong to the same personality. Both structural variants – between rigor and ambiguity – relate always anxiously to the roles and values of life. The “typical” obsessive – orderly, persistent and more efficient – comes closer to the adaptive variants of obsessionality compared to the psychasthenic one, who perseveres only in his ambivalence and ambitendency, being completely inefficient.

Overall, the values of the Conscientiousness dimension are low in psychasthenic structures, only one facet – deliberateness – makes an exception. This fact puts the psychasthenic into a position similar to the pathological personalities dominated by psycho- behavioral instability, such as the antisocial and the borderline ones. Like these personalities, the psychasthenic may be sometimes incorrect and immoral in interpersonal relationships, lacking dignity and moral standing that the obsessive personality self-arrogates unconditionally.

The obsessive personalities always try to strengthen their high but fragile self-esteem in order to harmonize it with the self-image by self-control, by cultivating order and moral values (5). He does this in order to reach the harmony between self-esteem and self-harmony. Unlike him, the psychasthenic with a low self-esteem does not feel the need of an identity reshuffle and he indulges himselfinadevaluingposition. References: 1.Lăzărescu, M., Nireștean, A. (2007) – Tulburările de personalitate. (PersonalityDisorders) PoliromPublishing,Iași 2.Lăzărescu, M., Bumbea, O. (2008) – Patologie obsesivă. (Obsessive Pathology)AcademieiRomânePublishing,Bucharest 3.Lukacs, E., Nireștean, A. (2018) – Obsesionalitatea – între ego- sintonie și ego-distonie în Persoana umană – un model de diversitate antropologică (Obsessionality – between ego-syntonic and ego-dystonic in the Human Person – a model of anthropological diversity), University Press Publishing,TârguMureş 4.Sava, F. (2008) – Inventarul de personalitate DECAS. Manual de utilizare. (DECAS Personality Inventory. User Manual.) ArtPress, Timișoara 5.Lukacs. E., Nirestean,A., Szasz, T., Tirintica, R., Nirestean, T., (2014)- Valori existențiale la personalitatea obsesivă, în Personaltiate și valori existențialeVolI,UniversityPressTârgu Mureș 6.Lăzărescu, M., (2010) – Bazele psihopatologiei clinice, Editura AcademieiRomâne,București 7.Predescu,V., (1989)–PsihiatrieVolI,EdituraMedicală,București *** Emese Lukács, Aurel Nireștean, Tudor Nireștean, Andra Oltean: Dimensional Perspective on the Subvariants of Obsessive-Compulsive Personality Disorder

ORIGINAL ARTICLES THE RELATIONSHIP BETWEEN DEPRESSION AND SOCIOECONOMIC FACTORS Ioana A. Pacearcă, Floris P. Iliuță, Oana Manea, Mirela Manea INTRODUCTION Major depressive disorder is a serious, chronic, common, recurrent disorder linked to a decline in social functioning and quality of life, also it is one of the principal causes of morbidity, disability and disease burden worldwide –(13). It is expected that depression will become the second cause of disability worldwide by 2020 and it is ranked by the World Health Organization as the fourth leading cause of disability across nations(4,5). The lifetime prevalence rate for major depressive disorder is 5% to 17%, indicating that there is a variability in prevalence estimates in different countries –(68).Almost all studies found that women have a twofold greater prevalence of major depressive disorder compared with men and that the highest onset rate of depressionoccursbetween20and50years(6,9). The socioeconomic factors can influence the prevalence of depression, but the studies results are controversial because they vary across countries, preponderantly between high income countries and low income countries (3,10,11). Socioeconomic status indicators, like employment status, education and income or wealth can affect health outcomes, also having an impact on major 1 MD, Psychiatry Specialist, PhD candidate, Assistant Lecturer, Fundația Sfântul Spiridon Vechi, „Carol Davila” University of Medicine and Pharmacy, FacultyofDentalMedicine,Psychiatryand PsychologyDepartment,Bucharest,Romania;Correspondence:ioanaand10@yahoo.com; 2 MD, Psychiatry Resident, PhD student,Assistant Lecturer, „Prof. Dr.Al. Obregia” Clinical Hospital of Psychiatry, „Carol Davila” University of Medicine andPharmacy, FacultyofDentalMedicine,PsychiatryandPsychologyDepartment,Bucharest,Romania ; 3 MD, PsychiatrySpecialist,PhD student,C.F. 2 ClinicalHospital,Bucharest,Romania; 4 MD, Senior Psychiatrist, PhD, Professor of Psychiatry, „Prof. Dr. Al. Obregia” Clinical Hospital of Psychiatry, „Carol Davila” University of Medicine and Pharmacy, Faculty of Dental Medicine, Psychiatry and Psychology Department, Bucharest, Romania.

ReceivedNovember19,2017, Revised January11, 2018,AcceptedJanuary31,2018 ABSTRACT Introduction: Depression is a commonly occuring worldwide disorder linked to a decline in social functioning and quality of life. Socioeconomic factors can influence the prevalence and course of depression, but the studies results are controversial because they vary across countries. Objectives: The purpose of this research was to study associations between socioeconomic indicators present at patientswithdepressionandhospitalizationoutcomes. Methods: The study included a group of 410 patients, with ages between 18 and 65 years, diagnosed with depressive episode or recurrent depressive disorder that were hospitalized in the “Prof. Dr. Al. Obregia” Psychiatry Hospital of Bucharest, between June 1, 2016 and May 31, 2017.

Results: The mean age of the group was 54.23 years, 80% of the lot were female patients, 41.76% had graduated vocational school or not graduated high school and 79.99% were retired. The number of readmissions had a mean value of 5.65 and the mean value for the hospitalization days was 9.00. We found statistical significant differences regarding the length of hospitalization for the different categories of education andemploymentstatus. Conclusions: Depression is a high prevalence, impairing disorder associated with the individuals socioeconomic status and this study results demonstrate the importance of futureresearchinthisdomain.

Key words:major depressive disorder, education, employment status, income, hospitalization REZUMAT Introducere: Depresia este o tulburare frecvent întâlnită la nivel global, legată de scăderea funcționării sociale și a calității vieții. Factorii socio-economici pot influența prevalența și evoluția depresiei, însă rezultatele studiilor suntcontroversate,deoarecediferăîntrețări. Obiective: Scopul acestei cercetări a fost studierea asociațiilor dintre indicatorii socio-economici prezenți la paciențiicudepresieșiindicatoriispitalizării. Metode: Studiul a inclus un grup de 410 pacienți, cu vârste cuprinse între 18 și 65 de ani, diagnosticați cu episod depresiv sau tulburare depresivă recurentă, care au fost spitalizați în Spitalul Clinic de Psihiatrie "Prof. Dr. Al. Obregia"dinBucurești,între1iunie2016și31mai2017. Rezultate: Vârsta medie a grupului a fost de 54,23 ani, 80% din lot au fost pacienți de sex feminin, 41,76% au absolvit școala profesională sau nu au absolvit liceul și 79,99% erau pensionați. Numărul de reinternări a avut o valoare medie de 5,65, iar valoarea medie pentru zilele de spitalizare a fost de 9,00. Am constatat diferențe semnificative statistic în ceea ce privește durata spitalizării pentru diferitele categorii de educație și statut profesional.

Concluzii: Depresia este o tulburare cu o prevalență crescută și debilitantă asociată cu statutul socio-economic al indivizilor, iar rezultatele acestui studiu demonstrează importanțacercetărilorviitoareînacestdomeniu. Cuvinte cheie:tulburare depresivă majoră, educație, statut profesional, venituri, spitalizare 59

60 depressivedisorder(12). We hypothesis that there would be a statistically significant association between socioeconomic factors present at patients with depression and hospitalization outcomes (length of stay and number of previous admissions). We have formulated this hypothesis considering that the socioeconomic indicators can influence the severity of this disorder, which could be predictedalsobythehospitalizationoutcomes. METHODS A non-randomized observational retrospective study was conducted by reviewing the observation sheets of 410 patients, with ages between 18 and 65 years, diagnosed with depressive episode or recurrent depressive disorder, according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) criteria, and treated in one of the departments of “Prof. Dr. Al. Obregia” Psychiatry Hospital of Bucharest, between June 1, 2016 and May 31, 2017 Cases of patients diagnosed with depression associated with other mental disorders, patients who had psychotherapy for depression, patients with important somatic comorbidities, drug abuse and pregnancy were excluded from the study. The study complied with the ethical norms regarding clinical research and it was approved by the Local Ethics Committee.

The collected data was introduced in a OpenOffice Calc version 4.1.1 Copyright © 2014 The Apache Software Foundation database. The statistical analysis was performed with the following programs: 1) R version 3.4.0 Copyright (C) 2017The R Foundation for Statistical Computing Platform R Core Team, among the R standard packages, there were also used asbio and asympTest; 2) Python version 3.6.0 with scientific and graphic modules: scipy, numpy, statsmodels, statistics, matplotlib, seaborn, pandas in form of Anaconda (c) 2016 Continuum Analyticsdistribution.

For the categorical variables (gender, employment status, education) the relative frequency (the reported number to the total number) and the absolute frequency (number) were estimated. For the interval variables (age, length of stay, number of readmissions, monthly income) it was determined the central trend. Standard error mean (SEM) was calculated to determine (using the Student's t distribution) a 95% confidence interval for the arithmetic mean (CI95%).Also, it was used the Shapiro-Wilk test for normality. The main endpoints of the study were the number of readmissions and the current length of hospitalization. To analyze the endpoints on different categories there was used ANOVA, post-hoc ANOVA (protected against inherent type I errors in multiple tests with the Bonferroni correction) and the Spearman correlation coefficient. P-values of 0.05 or less with a confidence interval (CI) of 95% were considered statisticallysignificant RESULTS The mean age of the pacients was 54.23 (SEM: ±0.36) [CI95%: 53.51 to 54.95] years, mentioning that the distribution had an important negative skewness (-1.89), and the female patients (n = 328, 80%) outnumbered the male patients (n = 82, 20%). Education level was analyzed for a number of 340 patients because of insufficient data and it was shown that 16.76% (n = 57) had no studies or graduated gymnasium, 41.76% (n = 142) had graduated .

. vocational school or not graduated high school, 34.11% (n = 116) graduated high school and 7.35% (n = 25) had higher education. Employment status was analyzed for a number of 403 patients because of insufficient data and it was shown that 10.17% (n = 41) were unemployed, 79.99% (n = 322) were retired and 9.92% (n = 40) were employed. The mean value of the monthly income was 683.62 (SEM: ±18.17) [CI95%: 647.85 to 719.39] RON and the distribution had an important positive skewness (2.91). The number of readmissions had a mean value of 5.65 (SEM: ±0.26) [CI95%: 5.09 to 6.15] and the distribution had an important positive skewness (2.06). The mean value for the length of stay was 9.00 (SEM: ±0.21) [CI95%: 8.58 to 9.43] days and the distribution had animportantpositiveskewness (2.46).

Patients with higher education had 3 more days of hospitalization than patients from other education categories, the difference having statistical meaning, as shown in tables 1, 2 and 3. There were no statistical significant differences between the educational categories intermsofthenumberofreadmissions. Table 1 – Length of stay for education categories - ANOVA test indicatethattherearestatisticaldifferences. Table 2 – Length of stay (days) for education categories – mean (±SD) Table 3 – p values of length of stay for education categories after post-hocANOVA IoanaA. Pacearcă, Floris P. Iliuță, Oana Manea, Mirela Manea: The Relationship Between Depression and Socioeconomic Factors Length of Stay (Days) No Studies or Graduated Gymnasium Graduated Vocational School or Not Graduated High School Graduated High School Higher Education Mean (±SD) 8.54 (±3.72) 8.91 (±3.76) 8.87 (±4.08) 11.96 (±7.98) Comparison No Studies or Graduated Gymnasium Graduated Vocational School or Not Graduated High School Graduated High School Graduated Vocational School or Not Graduated High School 0.37 1.00 Graduated High School 0.33 1.00 -0.03 1.00 Higher Education 3.41 0.006 3.04 0.007 3.08 0.008 Variability Source Degrees of Freedom Square Sum Square mean F Statistic p Between Groups 3 232.17 77.39 4.18 0.006 4 Inside Groups 336 6224.39 18.52 - -

61 Patients who are retired have the shortest stay in the hospital, almost 2 days shorter than the unemployed patients (p < 0.05) and a bit over 3 days shorter than patient who are employed (p < 0.01), as shown in tables 4, 5 and 6. There were no statistical significant differences between the emloyment status categories in terms of the number of readmissions. Table 4 – Length of stay for employment status categories - ANOVAtestindicatethattherearestatisticaldifferences. Table 5 – Length of stay (days) for employment status categories –mean (±SD) Table 6 - p values of length of stay for education categories after post-hocANOVA The correlations between endpoints and age and monthlyincomehadthefollowingresults: - a weak, negative correlation, with statistic significance between monthly income and number of readmissions, as shown intable7; - a weak, negative correlation, with statistic significance betweenageandlenghtofstay,asshown intable8. Table 7 – Correlation between number of readmissions and age and monthly income - Spearman correlation coefficient and p- value.

Table 8 – Correlation between lenght of stay and age and monthly income - Spearman correlation coefficient and p- value. DISCUSSION In this study we found that being slightly over 50 years old, being of female gender, with fewer years of education, less professional activity and with a low income are important factors associated with depression, suggesting that major depressive disorder is more common in socially disadvantaged people, results that are similar with other research studies reported in the literature (10,13). Literature data regarding the relationship between depression and different socioeconomic indicators are still in debate, because the collected information from various countries is most likely influenced by the sociocultural setting–(10,1315).

Other studies point out that higher levels of education may prevent and may confer a better coping with depression, involving improved cognitive skills and behaviors regarding health-related issues(14,16).Also, employment status inserts individuals, on social positions that can be characterized by the power and prestige it has within society(17). The study results suggest that the distress caused by the major depressive disorder and reflected in the elevated length of stay is increased for the patients with higher education.

Retirees had the shortest length of stay in comparison with the groups of unemployed and employed patients. It is recognized that economic difficulties and environmental features of work (e.g. social contact, social identity, skill use and development, regular activity, physical security) can influence the mental health of the individual (18,19), which can explain the increased length of stay for the unemployedandemployedpatientsgroup. Although there were weak correlations, our study found that lower income is associated with higher hospital readmission rates for depression and younger age is associated with an increase in length of stay. These results could suggest that the economic burden influences the evolution and prognosis of major depressive disorder and that the impairment caused by depression is higher in the earlyyears.

Romanian Journal of Psychiatry, vol. XX, No.2, 2018 Variability Source Degrees of Freedom Square Sum Square mean F Statistic p Between Groups 2 467.40 233.70 15.04 < 0.00001 Inside Groups 400 6216.00 15.53 - - Length of Stay (Days) Unemployed Retired Employed Mean (±SD) 10.12 (±3.66) 8.39 (±3.52) 11.75 (±6.57) Comparison Unemployed Retired Retired -1.73 0.026 Employed 1.63 0.192 3.36 < 0.0001 Correlation Number of Readmissions Age ρ Spearman 0.01 p value 0.839 Monthly Income ρ Spearman -0.135 p value 0.038 Correlation Lenght of stay Age ρ Spearman -0.137 p value 0.005 Monthly Income ρ Spearman -0.073 p value 0.211

62 These results suggest that the length of stay for major depressive disorder is influenced by socioeconomic and demographic characteristics and that the severity of depression could be predicted through hospitalization outcomes. This study has several limitations, which need to be considered. One of them was the location of this study, the sample consisted of hospitalized patients who can differ from primary and secondary care. Another limitation that should be taken into account is that the nature of our data is cross-sectional. A further limitation was that we had no data on patients or family wealth, which is another socioeconomic indicator. If more larger scale studies are to be conducted in our country, there will be much more needed information on this disorder which continues to escalateintermsofprevalence.

CONCLUSIONS Depression is a high prevalence and impairing disorder whose worldwide importance has been manifold demonstrated. This study results highlight the association between depression and low socioeconomic status present at patients admitted with this disorder. Education, income and employment status have an intricate relationship with depression and hospitalization outcomes. Future research might help us to better understand this multifaceted relationship and to improve prevention, therapeutic outcomesandqualityoflife.

ACKNOWLEDGEMENT All the authors had an equal contribution and have similar rights. All the authors approved the final version of this article. Theauthorsreportnoconflictofinterestforthisarticle. LIST OF ABBREVIATIONS: CI–confidenceinterval n–numberofcases SEM –standarderrormean SD –standarddeviation REFERENCES 1.Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression , chronic diseases , and decrements in health : Lancet. 2007;851–8. 2.Ustün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. Global burden of depressive disorders in the year 2000. Br J Psychiatry. 2004;184:386–92.

3.Kessler RC, Bromet EJ. The Epidemiology of Depression Across Cultures.AnnuRevPublicHealth. 2013;34(1):119–38. 4.Murray CJL, Lopes AD. The Global Burden of Disease: a comprehensive assessment of mortality and disability disease, injuries, and risk factors in 1990 and projected to 2020. Global Burden of Disease andInjurySeries;v.1. 1996. p. 990. 5.Murray CJL, Lopez AD. Evidence-Based Health Policy--Lessons from the Global Burden of Disease Study. Science (80- ). 1996;274(5288):740–3. 6.Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. 11th edn. Wolters Kluwer;2015.

7.Simon GE, Goldberg DP, Von Korff M, Ustün TB. Understanding cross-national differences in depression prevalence. Psychol Med. 2002;32(4):585–94. 8.Demyttenaere K, Bruffaerts R, Posada-Villa J, Gasquet I, Kovess V, Lepine JP, et al. Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys. JAMA.2004;291(21):2581–90. 9.Van de Velde S, Bracke P, Levecque K. Gender differences in depression in 23 European countries. Cross-national variation in the gendergapindepression.SocSciMed. 2010;71(2):305–13. 10.Lorant V, Deliège D, Eaton W, Robert A, Philippot P, Ansseau M. Socioeconomic inequalities in depression: a meta-analysis. Am J Epidemiol.2003;157(2):98–112.

11.Andrade L, Caraveo-Anduaga JJ, Berglund P, Bijl R V., De Graaf R, Vollebergh W, et al. The epidemiology of major depressive episodes: Results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. IntJMethodsPsychiatrRes. 2003;12(1):3–21. 12.Duncan GJ, Daly MC, McDonough P, Williams DR. Optimal indicators of socioeconomic status for health research. Am J Public Health. 2002;92(7):1151–7. 13.Rai D, Zitko P, Jones K, Lynch J, Araya R. Country- and individual- level socioeconomic determinants of depression: Multilevel cross- nationalcomparison.BritishJournalofPsychiatry.2013.p.195–203. 14.Lahelma E, Laaksonen M, Martikainen P, Rahkonen O, Sarlio- Lähteenkorva S. Multiple measures of socioeconomic circumstances andcommonmentaldisorders. SocSciMed.2006;63(5):1383–99. 15.Araya R, Lewis G, Rojas G, Fritsch R. Education and income: Which is more important for mental health? J Epidemiol Community Health. 2003;57(7):501–5.

16.Patel V, Kleinman A. Poverty and common mental disorders in developing countries. Bulletin of the World Health Organization. 2003. p. 609–15. 17.Krieger N, Williams DR, Moss NE. Measuring Social Class in US Public Health Research: Concepts, Methodologies, and Guidelines. AnnuRevPublicHealth.1997;18(1):341–78. 18.Warr PB. Work, unemployment, and mental health. Oxford science publications.1987.xiv,361 p. 19.WHO. Mental health and work: Impact, issues and good practices. WorldHealthOrganization.2000. 1-77p.

*** IoanaA. Pacearcă, Floris P. Iliuță, Oana Manea, Mirela Manea: The Relationship Between Depression and Socioeconomic Factors

ORIGINAL ARTICLES COMORBIDITIES OF ALCOHOL USE DISORDER 1 2 3 Maria Bonea , Mădălina C Neacșu , Ioana V Micluția 1 Teaching Assistant, PhD student, Psychiatry Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj Napoca. Correspondence: Bonea Maria, Psychiatry Clinic, Victor Babeș Street no. 43, Cluj-Napoca, România. E-mail: Bonea.Maria@umfcluj.ro; Phone: 004 0727 187 292 2 nd Psychiatry Resident, 2 Psychiatry Clinic, Cluj County Emergency Hospital 3 Professor Doctor, Head of Psychiatry Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj Napoca Received December 3, 2017, Revised December 11, 2017, Accepted December 22, 2017 Abstract Introduction: Dual diagnosis is frequent among psychiatric patients. Alcohol use disorder (AUD) negatively affects the treatment and the progression of co- occurring disorders. The reverse could also be valid, other symptoms of other diseases and therapies may hinder the achievementandmaintenanceofabstinence.

Aim: The aim of the present study is to assess the frequency of psychiatric and medical comorbidities, of the prescribeddrugs andthehospitalcostsrelatedtoAUD. Methods: Using AtlasMed database, we searched the patients admitted to the Cluj County Emergency Hospital st Psychiatry Department between January the 1 and st December 31 2016, with a main or secondary diagnosis of alcohol dependence. The socio-demographic (age, gender, geographic area), the psychiatric and medical diagnosis and the prescribed psychotropic medications were recorded.

Results: 623 alcoholic patients were admitted to the Cluj County Emergency Hospital Psychiatry Department, during a one year span, mostly men, accounting for 23% of the total number of hospitalisations and 12.1% of the hospital costs. The most frequent psychiatric comorbidities were personality disorders, major depressive disorder (MDD), neurocognitive disorders, alcohol-related psychosis and suicide attempts. The most common medical conditions in alcoholics were alcoholic liver disease (ALD), cardiovascular disease, dyslipidemia, alcoholic polyneuropathy, alcoholic pancreatitis, type 2 diabetes and head injuries. The most commonly prescribed psychiatric medications were benzodiazepines,anticonvulsantsandtiapride. Conclusions: Alcohol dependence has become an increasingly stringent public health problem, from the point of view of prevalence, frequent admittances, relapses andcomorbidities.

Key words: alcoholism, dependence, dual diagnosis, therapy,hospitalcosts INTRODUCTION According to the International Classification of Diseases, 10th Revision (ICD-10), alcohol abuse was associated with over 200 medical conditions (1). The presence of alcohol dependence affects the prognosis and treatment of associated diseases, and in the long run increases hospital morbidity and mortality (2). The economic impact is significant, literature studies indicating a 50% increase in costs related to treatment and decreased productivity over abstinent patients (3), with substantially higher indirect costs(4).

Approximately half of alcoholics also have a diagnosis of personality disorder, involving frequent heavy drinking patterns, but not necessarily a worse prognosis if the patientsarecompliantlateron(5). Depression constitutes a frequent comorbidity, or it can be only part of the alcohol withdrawal syndrome, the later one resolving spontaneously in a few weeks. In addition to the common genetic interface, there is also a neuroimmune hypothesis, both being caused by central nervous system (CNS) inflammation, which provides another potential explanation for this recurrent dual diagnosis (6).Although the literature reports a high prevalence of anxiety disorder among alcoholics (up to 35%), it is difficult to discern if these symptoms are part of alcohol intoxication or withdrawal or make up for a separate diagnosis. An AUD in a psychotic patient increases the risk of relapse and mortality (7). Alcohol induced neuronal destruction generates a spectrum of neuropsychiatric conditions including mild cognitive impairment (MCI), Wernicke–Korsakoff syndrome (WKS) and dementia (8). Although moderate alcohol intake may decrease the risk of progression from MCI to dementia, heavy drinking has the oppositeeffect(9).

MATERIALAND METHODS Using the AtlasMed database, officially employed by the Cluj County Emergency Hospital Psychiatry Department, admissions between January 1st and December 31st 2016 of patients, with a main or secondary diagnosis of alcohol dependence, according to ICD-10 diagnostic criteria were analyzed. Socio-demographic data (age, gender, geographic area), the psychiatric and medical diagnosis and the prescribed psychotropic medications were prescribed. The Analysis ToolPak in Microsoft Office Excel 2010 was used for statistical data analysis and the assessment of relative risk (RR). The study procedures respect confidentiality and are in accordance to the norms of research and were approved by the Local Ethical Committee.

RESULTS st st Between January 1 and December 31 2016, 623 patients were admitted 817 times with a main or secondary diagnosis of alcohol dependence, accounting for 23.02% of the total 3549 hospital admissions. During that one year period, the number of admissions varied between 1 (75.76%) and 9 (one case). Men were over-represented 63

64 (87%), the mean age was 52.4 years, less for women (50.4 years). Both men and women came mainly from urban areas(64%). 2016 direct hospital costs for AUDs (intoxication, abuse, dependence, withdrawal) were 562794.3 Euro (12.1% of the total costs, placing this disorder on the 4th place on the yearly hospital costs hierarchy according to the main psychiatricdiagnosis)(Table1). The most common psychiatric comorbidities were personality disorders (53.1%), MDD (15.75%) and neurocognitive disorders (MCI, 9.72%; dementias, 4.02% and WKS, 1.94%) (Table 2). The most frequent personality disorders were emotionally unstable personality disorder, impulsive type, both in men and women,andantisocialpersonalitydisorder. 77.52% of the patients were hospitalized for alcohol withdrawal syndrome, the rest of 22.48% were abstinent and were admitted for other disorders. Most often, the subjects experimented an uncomplicated alcohol withdrawal (71.01%), the rest underwent complicated alcohol withdrawal, with seizures (14.07%), with delirium(10.97%)orboth(3.93%).

Table 3 shows the distribution of somatic comorbidities of AUD according to gender. 31.14% developed alcohol liver disease (ALD) (men slightly more frequent than women, 35.62% vs 32.14%). 29.37% had a history of cardiovascular disease (hypertension, coronary heart disease, arrhythmias or stroke) and 12.18% had dyslipidemia. The neurological comorbidities were represented by alcoholic polyneuropathy (10.46%), head injuries (5.15%) and epilepsy (3.72%). Type 2 Diabetes is present in 4.15% of patients in both male and female alike. 3.72% developed various stages of alcoholic pancreatitis. Although not a comorbidity per se, carbamazepine allergic reaction was a complication present in 0.86% of thesubjects.

The prescribing trends in psychotropic medications are shown in Figure 1. All the patients received benzodiazepines. Among them, the most prescribed were diazepam (73.19%), nitrazepam (16.05%) and lorazepam (9.31%). For the entire study, the most prescribed drug was carmbamazepine (73.84%). Other prescribed anticonvulsants were valproate (17.98%), gabapentine (5.46%)andphenobarbital(3.37%). The anticraving medications recommended for the treatment of alcoholism were seldom prescribed. Only 3.85% of the patients admitted in 2016 received opioid antagonists (nalmefene 1.93%, naltrexone 0.64%), aversion therapy with disulfiram (0.96%) or acamprosate (0.32%). It is worth mentioning the use of metronidazole asanantidipsotropicin1.44%ofthepatients. The most prescribed antidepressants for the treatment of the depressed alcoholic patients were tianeptine (41.03%), sertraline (18.8%) and mirtazapine (11.97%). Doxepin (5.13%), trazodone (4.27%), escitalopram (4.27%) and agomelatine (1.71%) were recommended lessoften.

Excluding tiapride, the third most prescribed drug in the present study (43.98%), typical antipsychotics were given in11.4%ofcasesandtheatypicalonesin16.37%. DISCUTIONS Despite the fact that in the Western countries the gender gap regarding alcohol use is progressively diminishing (10), the Transylvanian population does not follow the same trend. There is still a significant difference between men and women, probably due to the traditional social acceptabilityofalcoholintoxicationinmales. The direct hospital costs of AUD in 2016 places th nd alcoholism on 4 place (12.1%), close to 2 (acute rd psychotic disorder, 14.43%) and 3 place (MDD, 13.82%) th but very far from 5 place (bipolar affective disorder, one of the most severe psychiatric disorders, that involves more expensive drugs than the ones usually used for alcoholic patients) (Table 1). For technical reasons, to avoid overlapping reported expenses, these results do not include the costs of admissions with only a secondary diagnosis of AUD. Thus, the real total hospital costs for alcoholics are higher, transforming this addiction into an importantpublichealthproblem.

Women appeared to be more vulnerable to the complications of heavy drinking. They had a 2.5 times greater risk to develop an alcohol-related psychosis (p=0.044), a 1.62 times higher risk to have comorbid depression and were more predisposed to attempt suicide (3.57% of females vs 1.67% of males). In addition, women had a 3.52 times greater risk to experiment a complicated withdrawal (p=0.0001) and WKS and more female schizophrenic abused alcohol (5.95%) then males (1.11%). MCI and dementias were an exception, since they were almost two times more frequent in men.Anxiety disorders were unexpectedly rarely coded (0.67%), probably through overlapping symptoms of alcohol withdrawal. Patients with a personality disorder had a 1.61 times greater risk to be admitted more than 2 times in one year (p=0.001). Though the gender distribution of emotionally unstable personality disorder, impulsive type was similar, in our study, the borderline type was reported onlyinfemales.

As expected, approximately one third of the patients developed alcoholic liver disease, males (36.62%) slightly more than women (32.14%). A similar distribution was reported for cardiovascular diseases, with a mild masculine predominance (33.4% of male vs 29.76% of females). While dyslipidemia was recorded only in 12.18% of the subjects, the real prevalence is probably much higher. By virtue of our study design, dyslipidemia as well as important comorbidities, such as smoking and obesity, could not be assessed, since they are rarely coded as official diagnosis. Thus, a thorough evaluation of the patients' charts is needed. Alcoholic pancreatitis was less common (3.72%), women were twice as likely to develop significant elevations of serum lipase than men (7.14% of females vs 3.71% of males). Type 2 Diabetes was present in 4.15% of alcoholics, with an equal gender distribution and there were not any patients with type 1 diabetes. Apart from cognitive impairments, alcohol induced neurological complications were polyneuropathy (10.46% of individuals, with similar gender distribution) and head injuries, generally caused by falling during intoxications or during complicated withdrawal seizures (slightly more frequent in men, 4.82% than in women, 3.57%). 3.72% of alcohol dependent individuals had a diagnosis of epilepsy, twice as common in men. Of them, only 23% presented with a complicated withdrawal with seizures, since they were probably covered by their chronic anticonvulsant treatment. Actually a rare complication (only 7 cases or 0.87% of patients, exclusively male), carbamazepine Maria Bonea, Mădălina C Neacșu, Ioana V Micluția: Comorbidities of Alcohol Use Disorder

65 allergic reaction is of major importance since it is potentially lethal. Additionally, since carbamazepine was the most prescribed drug in our study, vigilance is required tocatchearlysigns ofanaphylaxis. Considering that most of the subjects in the present study were admitted for alcohol withdrawal, concurrently to international guidelines, the most prescribed drug classes were benzodiazepines and anticonvulsants. All the patients were treated most frequently with diazepam (73.19%), the main substitution medication for alcohol withdrawal, followed by nitrazepam (16.05%, with insomnia being one of the most distressing symptoms for psychiatric patients) and lorazepam (9.31%). The latter is the drug of choice for elderly and liver impaired patients (in our study, in subjects with alcohol liver disease, lorazepam prescription rose from 8.67% to 12.66%). In these particular situations, diazepam has a higher risk of excessive sedation and respiratory depression (11). Another widely used class was anticonvulsants. As stated earlier, carbamazepine was the most prescribed drug for alcoholic patients in 2016 in our clinic. It was recommended in the short term for preventing seizures (by increasing the convulsant threshold), although some systematic reviews declared it even more effective and with fewer side effects for treating alcohol withdrawal than benzodiazepines (12). In the long term, carbamazepine produces a decrease in drinks per drinking day and a delay in time to relapse (13). In addition to its antiepileptic and mood stabilizing effects on highly impulsive individuals, valproate has the benefits of diminishing heavy drinking days in bipolar patients with a dual diagnosis (14). Seldom prescribed, gabapentin seems to be as efficient as lorazepam in the treatment of mild withdrawal, in outpatients (15), and also, in the long run it prevents craving and relapse (16). Granting that barbiturates are not first-line therapy, in selected cases, phenobarbital proved beneficial for severe complicated withdrawal (in this study, 25.93% of patients with complicated withdrawal with seizures and 5.66% of the ones with delirium received phenobarbital, vs 2.92% of the cases with uncomplicated withdrawal) (17). In the present study, levetiracetam was a preexisting treatment of epileptic patients and was not prescribed for psychiatric purposes. Nevertheless, levetiracetam does not seem to be a suitable choice for alcoholic epileptic individuals, since it is the only anticonvulsant that does not prolong the duration of abstinence and does not decrease heavy drinking (18). In such a situation, considering that ethanol can increase the likelihood of seizures, a tight collaboration with a neurologist could improve the prognosis.

The anticraving medications were seldom prescribed, due to the prohibitive cost of opioid antagonists and acamprosate (which is no longer even available in Romania). The latter and naltrexone are only moderately effective, but significantly reduces the risk of relapse after abstinence is obtained, with minimal side effects (19, 20). Nalmefene, with the advantage of “as needed” administration, seems to be superior to naltrexone, according to some studies (21) (others suggest only a limited efficacy for certain patients (22). Although their effectiveness has yet to be established due to great variability of studies' design, their use could prove salutary in lack of other viable therapeutic alternatives. Disulfiram, the only pharmacotherapeutical option for alcoholism for decades, has become a second-line drug because of its potentially dangerous aversive reaction. Nonetheless, its administration under supervision can be useful when other options have failed (adjunct to cognitive-behavioural, educational and psychosocial interventions) (23). There is also the practice of using metronidazole for its alleged aversive properties (1.44% of the patients), yet the evidence of its disulfiram-like reaction in combination with ethanol is scarce (24). Furthermore, a treatment longer than 2 weeks with metronidazole dramatically pauperizes the variability of microbiota, with unforeseeable effects on the functioning oftheentirebody(25).

Tianeptine was the most widely prescribed antidepressant in the present study, with the advantagethat dose reduction is not necessary for liver impaired patients, with or without cirrhosis. Its effectiveness in depressed alcoholics, while delayed to 4 to 8 weeks, was established, however its influence on craving, maintaining abstinence and long term prognosis of alcohol dependence is not clear (26). Lately, tianeptine's μ opioid receptor agonist activity was proved (27), accountable, apart from the antidepressant and anxiolytic effects (28), for its addictive potential (especially for patients under 50 years, with a history of drug or alcohol abuse) (29). The use of selective serotonin reuptake inhibitors (SSRI) is controversial, since they could trigger heavy drinking, especially for type B alcoholism (earlier onset, more alcohol intake) (30). Furthermore, a series of 93 cases describes even the onset of alcohol dependence after therapy with SSRIs for MDD (31). Still, a safer alternative could be naltrexone in combination with sertraline (but not escitalopram), with positive effects on this dual diagnosis (32). Although doxepin has an indication for depression during alcohol abstinence, in the present study it was rarely used. Because of multiple side effects, it remains a second-line medication. Also, mirtazapine was seldom prescribed, although it is effective in the long term both as an antidepressant, as well as for lowering alcohol consumption (even if other studies suggest that it does not influence alcohol intake, mirtazapine is considered safe for this group of patients) (33, 34). Since it is insufficiently studied in depressed alcoholics, trazodone was prescribed particularly for persistent insomnia after achieving abstinence, notably because it does not appear to influence relapserates(35).

Antipsychotics were prescribed mostly for psychosis and aggressiveness.Ameta-analysis of 13 randomized double blind placebo controlled studies (3 papers on tiapride) did not show any benefit regarding abstinence, craving control or the reduction of the consumed amount of alcohol for neither antipsychotic (36). Tiapride (the third most prescribed drug in our study, 48.98%) is worth special mention. It was prescribed for short term control of agitation and aggressiveness. In the long term, its benefit is controversial, a randomized double blind placebo controlled study noticed earlier and higher rates of relapse forpatientsthatreceivedtiapride(37).

CONCLUSIONS Alcohol dependence represents a costly public health problem. On the Psychiatry ward in Cluj-Napoca, an alcoholic patient has the following profile, according to our study: an approximately 50 year old man, from an Romanian Journal of Psychiatry, vol. XX, No.2, 2018

66 urban area, with at least one psychiatric or somatic comorbidity, admitted for alcohol withdrawal syndrome. More often, men tend to develop a somatic complication and women a psychiatric comorbidity. Cluster B personality disorders were the most frequent in alcoholics. The most prescribed classes of drugs were benzodiazepines and anticonvulsants, while anticraving medicationwas rarelyrecommended. ABREVIATIONS ALD –Alcoholicliverdisease APD –Acutepsychoticdisorder ARP-Alcohol-relatedpsychosis AUD –Alcoholusedisorder BAD -Bipolaraffectivedisorder CNS -Centralnervoussystem ICD-10 - International Classification of Diseases, 10th Revision MCI –Mildcognitiveimpairment MDD –Majordepressivedisorder SSRI -Selectiveserotoninreuptakeinhibitors SUD –Substanceusedisorder(otherthanalcohol) WKS - Wernicke–Korsakoff syndrome TABELSAND FIGURES Table 1. Annual hospital costs according to the main psychiatric diagnosis Table 2. Gender distribution of psychiatric comorbidities of AUD Table3. Gender distributionofsomaticcomorbiditiesofAUD Figure1.Psychotropicmedicationused inAUD REFERENCES 1.Rehm J, Shield KD. Global alcohol-attributable deaths from cancer, livercirrhosis,andinjuryin2010.AlcoholRes. 2013;35(2):174-83. 2.Schoepf D, Heun R. Alcohol dependence and physical comorbidity: Increased prevalence but reduced relevance of individual comorbidities for hospital-based mortality during a 12.5-year observation period in general hospital admissions in urban North-West England. Eur. Psychiatry. 2015;30(4):459-68.

3.Manthey J, Laramee P, Parrott S, Rehm J. Economic burden associated with alcohol dependence in a German primary care sample: a bottom-up study.BMC publichealth.2016;16:906. 4.Laramee P, Kusel J, Leonard S, Aubin HJ, Francois C, Daeppen JB. The economic burden of alcohol dependence in Europe. Alcohol Alcohol..2013;48(3):259-69. 5.Newton-Howes GM, Foulds JA, Guy NH, Boden JM, Mulder RT. Personality disorder and alcohol treatment outcome: systematic review andmeta-analysis.Br J Psychiatry.2017;211(1):22-30. 6.Neupane SP. Neuroimmune Interface in the Comorbidity between Alcohol Use Disorder and Major Depression. Front Immunol. 2016;7:655.

7.EMCDDA. Comorbidity of Substance Use and Mental Disorders in Europe: A Review of the Data. EMCDDA Papers. Luxembourg: Maria Bonea, Mădălina C Neacșu, Ioana V Micluția: Comorbidities of Alcohol Use Disorder Diagnosis Cost (RON) Cost (Euro) % No. Schizophrenia 597635,98 1305266,98 28,07% 736 APD 3079184,8 671242,92 14,43% 143 MDD 2948860,7 642833 13,82% 426 AUD 2581699,76 562794,3 12,1% 586 BAD 959734,3 2092160,41 4,49% 138 Total costs 21328786,16 4649541,22 Psychiatric comorbidity Men Women Total No % No % No % Personality disorder 276 51.21% 42 50.00% 318 53.1 MDD 75 13.91% 19 22.62% 94 15.75 MCI 54 10.02% 4 4.76% 58 9.72 Dementia 23 4.27% 1 1.19% 24 4.02 ARP 15 2.78% 6 7.14% 21 3.52 SUD 16 2.97% 4 4.76% 20 3.35 Delusional disorder 13 2.41% 0 0.00% 13 2.18 Suicide attempt 9 1.67% 3 3.57% 12 2.01 WKS 9 1.67% 2 2.38% 11 1.84 Schizophrenia 6 1.11% 5 5.95% 11 1.84 BAD 5 0.93% 2 2.38% 7 1.17 Somatic comorbidity Men Women Total No. % No. % No. % ALD 192 35.62 27 32.14 219 31.38 Cardiovascular disease 180 33.4 25 29.76 205 29.37 Dyslipidemia 75 13.91 10 11.9 85 12.18 Polyneuropathy 64 11.87 9 10.71 73 10.46 Brain injury 26 4.82 3 3.57 29 4.15 Type 2 Diabetes 25 4.64 4 4.76 29 4.15 Epilepsy 25 4.64 1 1.19 26 3.72 Pancreatitis 20 3.71 6 7.14 26 3.72 Carbamazepine allergy 7 1.3 0 0 7 0.86

67 Publications Office of the European Union; (2015). Available from: http://www.emcdda.europa.eu/publications/insights/comorbidity- substance-use-mental-disorders-europe 8.Hayes V, Demirkol A, Ridley N, Withall A, Draper B. Alcohol-related cognitive impairment: current trends and future perspectives. NeurodegenerDis Manag.2016;6(6):509-23. 9.Xu G, Liu X,Yin Q, ZhuW, Zhang R, Fan X.Alcohol consumption and transition of mild cognitive impairment to dementia. Psychiatry Clin. Neurosci.2009;63(1):43-9. 10.Hasin DS, Grant BF. The National Epidemiologic Survey onAlcohol and Related Conditions (NESARC)Waves 1 and 2: review and summary offindings.Soc PsychiatryPsychiatrEpidemiol.2015;50(11):1609-40. 11.Soyka M, Kranzler HR, HesselbrockV, Kasper S, Mutschler J, Moller HJ. Guidelines for biological treatment of substance use and related disorders, part 1: Alcoholism, first revision. World J Biol Psychiatry. 2017;18(2):86-119.

12.Minozzi S,Amato L,Vecchi S, Davoli M.Anticonvulsants for alcohol withdrawal.CochraneDatabaseSyst Rev. 2010(3):Cd005064. 13.Malcolm R, Myrick H, Roberts J, Wang W, Anton RF, Ballenger JC. The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen InternMed. 2002;17(5):349-55. 14.Salloum IM, Cornelius JR, Daley DC, Kirisci L, Himmelhoch JM, Thase ME. Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism: a double-blind placebo-controlled study. Arch GenPsychiatry. 2005;62(1):37-45.

15.Leung JG, Hall-Flavin D, Nelson S, Schmidt KA, Schak KM.The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother.2015;49(8):897-906. 16.Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial.JAMAInternMed. 2014;174(1):70-7. 17.Mo Y, Thomas MC, Karras GE, Jr. Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials. J CritCare.2016;32:101-7. 18.Richter C, Effenberger S, Bschor T, Bonnet U, Haasen C, Preuss UW, et al. Efficacy and safety of levetiracetam for the prevention of alcohol relapse in recently detoxified alcohol-dependent patients: a randomized trial.J ClinPsychopharmacol.2012;32(4):558-62.

19.Rosner S, Hackl-HerrwerthA, Leucht S, Lehert P,Vecchi S, Soyka M. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010(9):Cd004332. 20.Donoghue K, Elzerbi C, Saunders R, Whittington C, Pilling S, Drummond C. The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta-analysis.Addiction.2015;110(6):920-30. 21.Soyka M, Friede M, Schnitker J. Comparing Nalmefene and Naltrexone in Alcohol Dependence: Are there any Differences? Results fromanIndirectMeta-Analysis.Pharmacopsychiatry.2016;49(2):66-75. 22.Palpacuer C, Laviolle B, Boussageon R, Reymann JM, Bellissant E, Naudet F. Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence: A Systematic Literature Review and Meta- Analysis of 11Published and Unpublished Double-Blind Randomized ControlledTrials.PLoS Med. 2015;12(12):e1001924. 23.Brewer C, Streel E, Skinner M. Supervised Disulfiram's Superior Effectiveness in Alcoholism Treatment: Ethical, Methodological, and PsychologicalAspects.AlcoholAlcohol..2017;52(2):213-9. 24.Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP. Lack of disulfiram-like reaction with metronidazole and ethanol. Ann Pharmacother. 2002;36(6):971-4.

25.Becker E, Schmidt TSB, Bengs S, Poveda L, Opitz L, Atrott K, et al. Effects of oral antibiotics and isotretinoin on the murine gut microbiota. Int.J.Antimicrob.Agents. 2017;50(3):342-51. 26.Favre JD, Guelfi-Sozzi C, Delalleau B, Loo H.Tianeptine and alcohol dependence.EurNeuropsychopharmacol.1997;7Suppl3:S347-51. 27.Gassaway MM, Rives ML, Kruegel AC, Javitch JA, Sames D. The atypical antidepressant and neurorestorative agent tianeptine is a mu- opioidreceptoragonist.TranslPsychiatry.2014;4:e411. 28.Samuels BA, Nautiyal KM, Kruegel AC, Levinstein MR, Magalong VM, Gassaway MM, et al. The Behavioral Effects of the Antidepressant T i a n e p t i n e R e q u i r e t h e M u - O p i o i d R e c e p t o r . Neuropsychopharmacology. 2017;42(10):2052-63.

29.Rouby F, Pradel V, Frauger E, Pauly V, Natali F, Reggio P, et al. Assessment of abuse of tianeptine from a reimbursement database using 'doctor-shopping' as an indicator. Fundam Clin Pharmacol. 2012;26(2):286-94 30.Atigari OV, Kelly AM, Jabeen Q, Healy D. New onset alcohol dependence linked to treatment with selective serotonin reuptake inhibitors.IntJ RiskSafMed.2013;25(2):105-9. 31.Brookwell L, Hogan C, Healy D, Mangin D. Ninety-three cases of alcohol dependence following SSRI treatment. Int J Risk Saf Med. 2014;26(2):99-107.

32.Pettinati HM, Oslin DW, Kampman KM, Dundon WD, Xie H, Gallis TL, et al. A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence.Am J Psychiatry. 2010;167(6):668-75. 33.Cornelius JR, Douaihy AB, Clark DB, Daley DC, Chung TA, Wesesky MA, et al. Mirtazapine in Comorbid Major Depression and Alcohol Use Disorder: A Long-Term Follow-Up Study. J Addict Behav TherRehabil.2013;3(1). 34.Cornelius JR, Chung T, DouaihyAB, Kirisci L, Glance J, Kmiec J, et al. Mirtazapine in comorbid major depression and an alcohol use disorder: A double-blind placebo-controlled pilot trial. Psychiatry Res. 2016;242:326-30.

35.Kolla BP, Schneekloth TD, Biernacka JM, Frye MA, Mansukhani MP, Hall-Flavin DK, et al.Trazodone and alcohol relapse: a retrospective studyfollowingresidentialtreatment.Am JAddict. 2011;20(6):525-9. 36.Kishi T, Sevy S, Chekuri R, Correll CU. Antipsychotics for primary alcohol dependence: a systematic review and meta-analysis of placebo- controlledtrials.J ClinPsychiatry.2013;74(7):e642-54. 37.Bender S, Scherbaum N, Soyka M, Ruther E, Mann K, Gastpar M. The efficacy of the dopamine D2/D3 antagonist tiapride in maintaining abstinence: a randomized, double-blind, placebo-controlled trial in 299 alcohol-dependent patients. Int J Neuropsychopharmacol. 2007;10(5):653-60.

*** Romanian Journal of Psychiatry, vol. XX, No.2, 2018

ORIGINAL ARTICLES BIOMARKERS IN FOLLOW-UP TREATMENT OF ALCOHOLISM WITH HEPATIC COMORBIDITY. AN OBSERVATIONAL STUDY 1 Claudiu I. Vasile 1 MD, Psychiatry Specialist at “Elisabeta Doamna” Psychiatry Hospital Galati,, PhD candidate at „Carol Davila” University of Medicine and Pharmacy, Psychiatry and Psychology Department, Bucharest, Romania;, Assistant Lecturer, at University Dunarea de Jos of Galati, Faculty of Medicine and Pharmacy Correspondence: vasilemclaudiu@yahoo.com; Received December 3, 2017, Revised December 11, 2017, Accepted December 22, 2017 Abstract The aim of this paper is the evolution of the biological markers and of alcoholism when the patient diagnosed with alcoholism is undergoing detox treatment. After detox, the biological markers of alcoholism undergo changes as the patient undergoes treatment. As a result of the successive visits for the detox treatment from alcohol, correlations were identified between GGT, GPT and GOT values in the group of patients diagnosed with alcoholism, as well as in the group of the patients with alcoholism and associatedhepatopathy.

The study aims to investigate a group of patients diagnosed with alcoholism that undergo the detox treatment and the manner in which the biological markers evolve in the case of the patients with alcoholism and associated hepatopathy. The results of the study will be capitalized in the form of a statistical and mathematical model so that clinicians can establish strategies for therapeutic approach for patients with relapses in alcoholismandhepatopathyassociated toalcoholism. Keywords: Alcoholism, biological markers, hepatopathy, liver comorbidity INTRODUCTION: Alcohol is the most widespread substance used for addictive purposes.According to WHO (1), worldwide consumption in 2010 was equal to 6.2 litres of pure alcohol per year consumed by people over 15 years of age, which translates to about 13.5 grams of pure alcohol per day (2,3). In Romania, the average consumption per capita in 2010 was 14.4 litres per year, while the European average was 10.9litrespercapita(1,2,4).

Monitoring abstinence and resumption of consumption at patients in a strict treatment program is of utmost importance. It has been noted that patients who undergo alcohol tests during these programs strictly follow therapy sessions, miss the sessions less and relapse less. A very appropriate test is the determination of carbohydrate- deficient transferrin (CDT). It highlights abstainers better than GGT or MCV due to better sensitivity and because its level is not that affected by hepatic suffering. On the other hand, relapse is well documented by the GGT level or the combination of GGT and transaminases (5). It is worth mentioning that the GGT level lacks accuracy as an independent marker but is considered to be useful in combination with CDV or MCV level according to Javros (6) GGT was much more sensitive than CDT (P

69 admissions for detox the impact of drug treatment and counselling at admission for detox treatment in order to reduce the effects of alcoholism quantifiable through biological markers (especially in patients with hepatopathyassociatedwithalcoholism). STUDYDESIGN. METHODOLOGY: The study focuses on the observational analysis of a group or batch of patients diagnosed with ethanolic dependence (331 patients (T.E.- witness batch ) out of which 202 patients were diagnosed with alcoholic hepatopathy (H.P. - experimental batch)), the patients are aged between 18-81 years old according to ICD 10 and DSM-IV.

Observational analysis was used as a method of study which was carried out over a two-years' time interval between 2014-2016, on a batch of patients who were hospitalized in Elisabeta Doamna Galati Psychiatric Hospital. Observational analysis has been used cumulatively with statistical dissemination of collected information, data series analysis and critical interpretation of observations using the mathematical and statistical model. The method implied criteria segmentation of information and obtaining the experimental batch from the witness batch, with the indication that it was segmented according to the criterion of determining significant alcoholic hepatopathy (identification of hepatic dysfunctions by elevated biological markers values GGT, GOT and GPT). The mathematical and statistical model proposes to highlight the link between the modification of GGT, GOT and GPT in a four-detox enrolment sequence in patients with hepatopathy associated with alcoholism. It also seeks to identify the influence of detox treatment at admission for detox on the behaviour in the outpatient periods considered by the model as being "Black Box" periods. The ethical and conduct norms regarding clinical research were complied with, patients' agreement (written consent) was obtained andconflictsofinterestwereavoidedforthisstudy. Fig.1 Identifying the clinical and outpatient flow of treating patientswithalcoholism Observational data were statistically synthesized by applying their qualitative transformation, the results being disseminated on relative values, regarding the evolution of symptoms associated with alcoholism, in four distinct observational sequences (visits) made by the author on the witness batch (T.E.) of 331 patients within the timeframe specifiedabove.

Thus, the updated Gretl version 3 program was used for this, regarding the econometric data library and time series with March 2018. At the same time, the Excel modules of the Office package, version 2013, were used. The transformations of the quantitative data into qualitative data were performed on the basis of relative weights and frequency ranges, averages, standard deviations for structural indicators (age, gender, urbanization, and admission period for detox) were calculated. Statistical tests were used (Breusch-Pagan heteroscedasticity analysis, t-Student test, forecasts for confidenceintervals95%).

Relative weightings have been highlighted for associated comorbidities such as hepatopathy, polyneuropathy, epilepsy, heart disease and other comorbiditiesassociatedwithalcoholism. The study aims to assess the impact of alcoholism on changes in biological markers in patients with associated hepatopathies. In order to achieve this goal, the author tookintoaccountthefollowingobjectives: 1. Delineation of the sub-sample of patients with alcoholic hepatopathyfromthetotalsample. 2. Calculationof differencesbetweenthe relativevalues of comorbidities risk in alcoholism as compared to the comorbidities risk in alcoholism and associated hepatopathy.

3. Assessing the results of the biomarkers GGT, TGP, GOT, in relation to the reference interval of biomarkers for determining the polarization of the sample on the critical area and highlighting the impact difference of polarization for alcoholic patients as compared to patients with associatedalcoholichepatopathy. 4. Building an econometric model on the data resulted, based on the smallest squares method for assessing the impact of alcoholism on changes in the biological markers (patients with hepatopathy associated with alcoholism vs. totalpatientswithalcoholism).

RESULTS: The average distribution of the phenomenon in the urban environment according to the witness batch of 331 patients is 60% at a standard error of 0.0002 with a t rationof25.92andp-value

70 Comorbidity analysis for patients with alcoholism was performed on the basis of observations from the observational study of the witness and experimental batch, resulting in a high incidence of hepatopathy in the witness batch and a significant incidence of polyneuropathy and epilepsy. Comorbidities were reported for heart disease and other conditions in statistically significant weights. During the next detox visits, visits 2-4, there was a reduction in comorbidities regarding neuropathy, epilepsy, heart disease and other comorbidities associated to alcoholism, while among hepatopathy in the witness batch level, the fluctuation increased up to the third visit for detox, then it returned to the distribution level from the first visit, characterized by 2 thetendencyliney=-0.027x . Fig.2. Analysis of evolution of hepatopathy associated with alcoholism for the 4 visits in the witness batch (T.E. 331 people) andtheexperimentalbatch(H.P.202people) The data presented in the figure show that for the witness batch (TE - 331 people) in the first three visits the percentage of patients with alcoholic hepatopathy in relation to the total number of patients has increased and at thefourthvisittheirnumberdecreasedto61,03%. The experimental batch shows that from visit 1 to visit 4, the percentage of patients with alcoholism and associated hepatopathy was continuously decreasing (visit 2 - 82.18%, visit 3-77.77% and at visit 4 it reaches 71,29%).

The trend lines are convergent reflecting flattening following successive visits to detox of the differences in hepatic impairment between the witness batch and the experimental batch, which will be studied extensively in the mathematical and statistical model. The other comorbidities were studied at the relative data level, by frequency weights of the comorbidity incidence in the witness batch and the experimental batch, as shown in the figurebelow: Fig.3. Other comorbidities associated to alcoholism (analysis by frequencyseries ofthetwobatches) There is a higher distribution in patients with hepatopathyassociatedinalcoholism. The analysis of statistical distributions and statistical significancebyp-valueisshown inthetablebelow: Table No.2 Statistical structure of sample on co-morbidities associatedwithalcoholism The biomarker analysis for the witness batch reveals that alcoholism affects predominantly biomarkers, with values ​​above the maximum critical threshold for GGT, GOTand GPT.There are some cases (between 1 and 3%) where the values are below the critical minimum.The average share for the 4 detox visits of the GGT values ​​in the witness batch is around 57.25% for the GOT, the share being 60.73% and the GPT being 45.77% (critical values ​​of the biomarker). The situation will continue dynamically.

The observational study shows that the percentage of patients with elevated GGT is decreasing from visit 1 to visit 4 for detox.Also the number of patients with GOT and GPT values over the limit in alcoholic Claudiu I. Vasile: Biomarkers in Follow-up Treatment of Alcoholism with Hepatic Comorbidity. An Observational Study Coefficient Std. Error t-ratio p-value Urbaniza tion (1-331) 0,00637557 0,000245954 25,92

71 patients and associated hepatopathy decreased as a percentage from visit 1 to visit 4, the detox phenomenon positively influencing the condition of the patient with alcoholismandassociatedalcoholichepatopathy. Table 3 shows that the number of patients with GGT above the limit is higher in the batch of patients with associated hepatopathy as compared to the total batch of patients diagnosed with alcoholism. The number of patients with GOTand GPTabove the limit is higher in the batch of patients with associated alcoholic hepatopathy as comparedtothenumberofpatientsinthetotalbatch. TableNo.3GGT, GOT,GPTvaluesafterthefirstvisitfor detox Fig.4. Impact of alcoholism on changes in biological markers (patients with hepatopathy associated with alcoholism vs total patientswithalcoholism)atfirstadmission for detox From the analysis of the biological markers changes at the first admission for detox, it can be seen that the percentage of GGT with values above the limit is of 79.21%inthebatchofpatientswithalcoholichepatopathy and 58.91% in the total batch of patients with alcoholism. Patients who showed GOT values above the limit were 97.52%inthebatchofpatientswithalcoholichepatopathy and59.52%inthebatchofpatientswithalcoholism. TableNo.4GGT, GOT,GPTvaluesafterthesecondvisit At the second detox visit, the percentage of patients with associated hepatopathy versus total batch was decreasing with respect to GGT (119.09%), GOT (130.13)%andGPT(133.87%).

Fig. 5. Impact of alcoholism on changes in biological markers (patients with hepatopathy associated to alcoholism vs total patientswithalcoholism)atsecondadmission fordetox Table No.5 GGT, GOT, GPT values after the third visit As compared to visit 2, the percentage of patients with associated hepatopathy versus the total batch was continuously decreasing with regard to GGT (112.65%), GOT(115.94)%andGPT(123.15%). Fig.6. Impact of alcoholism on changes in biological markers (patients with hepatopathy associated to alcoholism vs total patients with alcoholism) at third admission for detox At the last detox visit, the percentage of patients with associated hepatopathy continued to decline for GGT (108.67) and GPT (119.57), but GOT (118.39) showed a non-significantstatisticalincrease.

Table No. 6 GGT, GOT, GPT values after the fourth visit Fig. 7. Impact of alcoholism on changes in biological markers (patients with hepatopathy associated to alcoholism vs total patientswithalcoholism)atfourthadmission fordetox Romanian Journal of Psychiatry, vol. XX, No.2, 2018 G G T ABO VE TH E LIM IT G OT ABO VE TH E LIM IT G PT ABO VE TH E LIM IT H P.1 79.21% 97.52% 71.78% T.E.1 58.91% 59.52% 43.81% H P.1/T.E. 1 134.45% 163.86% 163.86% GGT ABOVE THE LIMIT GOT ABOVE THE LIMIT GPT ABOVE THE LIMIT HP.2 65.84% 80.20% 61.88% T.E.2 55.29% 61.63% 46.22% HP.2/T.E.

2 119.09% 130.13% 133.87% GGT ABOVE THELIMIT GOT ABOVE THELIMIT GPT ABOVE THELIMIT HP.3 65.35% 74.26% 59.90% T.E.3 58.01% 64.05% 48.64% HP.3/T.E.3 112.65% 115.94% 123.15% GGT ABOVE THE LIMIT GOT ABOVE THE LIMIT GPT ABOVE THE LIMIT HP.4 62.38% 68.32% 53.47% T.E.4 57.40% 57.70% 44.71% HP.4/T.E. 4 108.67% 118.39% 119.57%

72 Fig.8. Dynamic of GGT changes (patients with hepatopathy associated to alcoholism reported to the total number of patients withalcoholism)in4admission sequencesfor detox The above graph shows that GGTin patients with associated alcoholic hepatopathy has a downward trend in the form of the curve shown above from visit 1 to visit 4, thus detox has a favorable impact on patients with hepatopathyassociatedtoalcoholism. Fig.9. Dynamic of GOT changes (patients with hepatopathy associated to alcoholism reported to the total number of patients withalcoholism)in4admission sequencesfor detox It can be seen in the above graph that in patients with hepatopathy associated to alcoholism the percentage of GOT has a downward trend in the curve shown above from visit 1 to visit 3.At the fourth visit to detox, the curve exhibits a slight ascendant evolution, but insignificant fromastatisticalpointofview.

Fig.10. Dynamic of GPT changes (patients with hepatopathy associated to alcoholism reported to the total number of patients withalcoholism)in4admission sequencesfor detox In the above graph it can be seen that GPT in patients with hepatopathy associated to alcoholism has a downward trend in the above curve from visit 1 to visit 4 so that detox has a favorable impact on patients with hepatopathyassociatedtoalcoholism. DISCUSSIONS: The information presented led to the need to evaluate the changes in GGT sequential values ​​in relation to GPT and GOT biological markers to observe the impact of detox on changes in biomarker values in patients with alcoholism, respectively, with alcoholism and associated hepatopathy.

This evaluation involves the regression analysis of the differences between the relative data of the elevated levels of GGT, GOTand GPTbiomarkers at the four detox visits in the two batches, witness and experimental, as calculatedinTables3-6(H.P. /T.E. values,n=1÷4). n n Regression analysis will reveal valuable data for the treating physician regarding the correlation of biomarkers, data that can be interpreted using a statistical model, so that by applying it, a general image of the patient's clinical picture containing the current and historical data, highlighting possible syncope in treatment orduringtheperiodofrelapsesinalcoholismafterdetox. The statistical model drafted on the basis of observational analysis outlines the impact of alcoholism, as reflected by the GGT(dependent variable) biomarker in relation to the GOT and GPT (regressor) biomarkers for the four detox visits and reflects the analysis of the evolution of hepatopathy associated to alcoholism after detox treatments among an alcoholic population (witness batch) and a population with alcoholism and hepatopathy associated to alcoholism (the experimental batch), which can become a valuable tool for clinician physicians following the implementation of a medical procedure of collecting the patien's medical history data, their centralization and statistical processing based on the proposedmodel.Thecorrelationofthedependentvariable with the regressors reflects the direct relationship of the evolution of hepatic impairment indicators while undergoing detox, so that the proposed model evaluates the achievable predictability degree of the evolutionary curve flattening of the hepatopathy associated in alcoholism, phenomenon highlighted in Figure 1. The regression model determined by the linear regression methodisasfollows: GGT - dependent variable GOT and GOT - regresors α, β - variabile, ε - residual variable The analysis of the observations collected in Tables 4-6 through the Gretl program has generated for the statistical and mathematical model the following equation whose statistical representativity is greater than 99.99%.

Model with equation: ^GGT = - 1.39*TGO + 2.23*TGP (0.872) (0.854) GGT =α*TGO +β*TGP +ε, where H.P./T.E. H.P./T.E. H.P./T.E Claudiu I. Vasile: Biomarkers in Follow-up Treatment of Alcoholism with Hepatic Comorbidity. An Observational Study

73 n = 4, R-squared = 0.999 (standard errors in parentheses), is 99.99% representative for the phenomenon analysed, namely the detox process from alcoholism has significant influence on the reduction of GGT (dependent variable), GPT and GOT (regressive variables), in the sense of flattening the differences between patients with alcoholism and patients with hepatopathy associated to alcoholism. The statistical tests demonstrating the representativenessofthemodelarepresentedbelow: Model 1: OLS, using observations 1-4 Dependent variable: GGT The heteroskedasticity analysis made using the Breusch-Pagan test shows that in the null hypothesis heteroskedasticity is not present, the value p = 0.39, respectively 0.19 in the robust variant of the Chi square testgreaterthan1.84and2,respectively.

Breusch-Pagan test for heteroskedasticity OLS, using observations 1-4 Dependent variable: scaled uhat^2 coefficient std. error t-ratio p-value - - const 8.41810 4.28869 1.963 0.3000 TGO 41.7874 18.3055 2.283 0.2628 TGP −46.3389 20.0987 −2.306 0.2605 Explained sum of squares = 3.69558 Test statistic: LM = 1.847789, with p-value = P(Chi-square(2) > 1.847789) = 0.396970 The evolution on the confidence interval of 95% indicates a minimal difference between the predicted evolution of GGT and the prediction (FORECAST) assessed by the T test through the four observational sequences (visits) with minimum differences of the standarderror(0.01).

Based on the data presented, it results that the model is homogeneous, well-defined and representative of the phenomenon studied, namely the impact of alcoholism on changes in biological markers (flattening differences between patients with hepatopathy associated to alcoholism – experimental batch and total number of patientswithalcoholism-witnessbatch). Fig. 11. Prediction analysis on the confidence interval 95% of the dependentvariableGGT For 95%confidenceintervals,t(2,0.025)=4.303 GGT Prediction Std.error 95%interval I1 1.344504 1.384301 0.067664 1.093167 - 1.675435 I2 1.190905 1.183014 0.058794 0.930044 - 1.435984 I3 1.126547 1.140501 0.070279 0.838116 - 1.442886 I4 1.086660 1.026586 0.058094 0.776628 - 1.276544 CONCLUSIONS: Detoxification (detox) is the first stage in the treatmentofalcoholaddiction.

The detox has a natural direct influence (in the sense of reducing the biomarkers values) on patients with alcoholic hepatopathy. The difference between the biomarkers values for patients with and without hepatopathy in alcoholism tends to decrease after detox. It has been clearly noticed that at patients with two or more detox treatments, there is a clear tendency of normalization of all biomarkers. In the work presented using the observational method, data were collected for a group of patients with repeated relapses in alcoholism (4 visits for detox), the collected data being then statistically interpreted by means ofamathematicalregressionmodel.

For the periods between detox visits the study confirms maintaining sustained treatment effects (detox rd after repeated relapses) up to the III detox visit meaning an average spread of 1.18% between the dependent variable of the model (GGT) and its predicted value for the th confidence interval of 95% (Fig.3). At the IV visit, the prognosis evolution in the 95% confidence interval has a trend change relative to the GGT variation (dependent variable), resulting in a negative spread of 5.53% (1.026586 vs. 1.086660), which represents a 4-time reverse change in the trend registered until the third visit to detox.

The conclusions of the study materialized in the form of a statisticalmodel proposal allow the development of a medical procedure where the patient's historical data are correlated with the data collected at the detox visit so that a diagnosis can be possible based on biomarkers in the context of evaluating changes in biomarkers in patients Romanian Journal of Psychiatry, vol. XX, No.2, 2018 Coefficient Std. Error t-ratio p-value GOT −1.38854 0.871682 −1.593 0.2522 GPT 2.23334 0.853917 2.615 0.1204 Mean dependent var 1.187154 S.D. dependent var 0.113351 Sum squared resid 0.005450 S.E. of regression 0.052200 Uncentered R-squared 0.999040 Centered R- squared 0.858615 F(2, 2) 1040.501 P-value(F) 0.000960 Log- likelihood 7.521219 Akaike criterion −11.04244 Schwarz criterion −12.26985 Hannan- Quinn −13.73590

74 withhepatopathyassociatedtoalcoholism. The proposed statistical and mathematical model reveals the impact of detox on patients with hepatopathy associated with alcoholism, and can be used in early appropriate treatments based on biomarker-assisted diagnosis for patients diagnosed with alcoholic hepatopathy. After the detox stage (detox), the treatment of alcohol addiction requires a relapse prevention stage involving several therapeutic options. The standardized approach that we propose may suggest choosing the right option, time sequence of different bio-psycho-social options, and the assessment of remission and recovery over time of patients in view of the most appropriate plan for resuming vocational activities, their statute and social roles.

The proposed model is an innovative one based on clear information gathered over a period of 2 years from a statistically representative sample of 331 people, which allowed obtaining a statistically representative depiction of the phenomenon of 99.99%. The proposed tool can be integrated into a software program that will ease the mission of the treating physician by enhancing historical information with current information and highlighting possible syncope in treatment or during the periodsofrelapseinalcoholismafterdetox.

For the periods between detox visits, the study confirms the preservation of a treatment redundancy up to the 3rd detox visit in the sense of an average difference of 1.18% between the dependent variable of the model and the predicted dependent variable for the 95% confidence interval (Fig. 3). At the 4th visit, the evolution of the predicted straight line changes its direction from the trend line of the dependent variable, resulting in a negative difference of 5.53% between the two straight lines (1.026586as comparedto1.086660),thedifferencewhich represents a 4 times reverse change of the registered trend untilthethirdvisitfordetox.

The proposed statistical and mathematical model reveals the impact of detox on patients with hepatopathy associated to alcoholism and can be used to establish appropriate early treatments based on diagnosis sustained by the biomarkers values for patients diagnosed with alcoholichepatopathy. REFERENCES: 1.World Health Organisation - Global status report on alcohol and health 2014, Louxembourg, WHO Library Cataloguing-in-Publication Data2014;7-12. 2.Chisholm D, Rehm J, Van Ommeren M, Monteiro M. Reducing the global burden of hazardous alcohol use: a comparative cost- effectivenessanalysis.JStudAlcohol2004;65:782−934. 3.Ghid De Prevenție. Stilul de viață sănătos și alte intervenții preventive prioritare pentru boli netransmisibile, în asistența medicală primară Vol. 3. Intervențiile preventive adresate stilului de viață. Consumul de alcool2016.

4.Ur Rahman I, Idrees M, Salman M, et al.Acomparison of the effect of glitazones on serum sialic acid in patients with Type 2 diabetes. Diab VascDis Res2012;9(3):238–240. 5.Javors MA, Johnson BA. Current status of carbohydrate-deficient transferrin, total serum sialic acid, sialic acid index of apolipoprotein J and serum beta-hexosaminidase as markers for alcohol consumption 2003;Addiction98(Suppl.2):45–50. 6.Mundle G, Ackermann K, Munkes J, Steinle D, Mann K. Influence of age, alcohol consumption and abstinence on the sensitivity of carbohydrate-deficient transferrin, γ- glutamyltransferase and mean corpuscularvolume.AlcoholandAlcoholism1999;34, 760–766. 7.Halvorson MR, Campbell JL, Srague G et al. Comparative evaluation of the clinical utility of three markers of ethanol intake: the effect of gender.AlcoholClinExpRes1993;17:225–9.) 8.Macchia T, Mancinelli R, Dell'Utri Aet al. Quantificazione dell'alcolemia per studi epidemiologici nella prevenzione degli incidenti stradali.BollettinoMediciItalianideiTrasporti 1991;2:5–19. 9.Harper C. The neuropathology of alcohol-related brain damage. AlcoholAlcohol2009, 44:136-140.

10.Imbert-Bismut F, Naveau S, Morra R, Munteanu M, Ratziu V,Abella A, Messous D, Thabut D, Benhamou Y and Poynard T. The diagnostic value of combining carbohydrate-deficient transferrin, fibrosis, and steatosis biomarkers for the prediction of excessive alcohol consumption.Eur JGastroenterolHepatol2009;21:18-27. 11.Sorbi D , Boynton J, Lindor KD. The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease. Am JGastroenterol2001;94:1018–1022 .

12.Charles S L. Blood Markers of alcoholic Liver Disease, World J Gastroenterol2014;15(20):351-365. 13.Prelipceanu D. Abuzul de substanțe psiho-active, în: Prelipceanu D.(ed)-Psihiatrieclinică,Ed.Med.,Buc.2011, 205-350. 14.Vonghia L, Michielsen P, Dom G and Francque S. Diagnostic challenges in alcohol use disorder and alcoholic liver disease. World J Gastroenterol2014;20(25):8024–8032. *** Claudiu I. Vasile: Biomarkers in Follow-up Treatment of Alcoholism with Hepatic Comorbidity. An Observational Study

ORIGINAL ARTICLES MONITORING ALCOHOLIC PATIENTS BY USING THE AUDIT TEST 1 Claudiu I. Vasile 1 MD, Psychiatry Specialist at “Elisabeta Doamna” Psychiatry Hospital Galati,, PhD candidate at „Carol Davila” University of Medicine and Pharmacy, Psychiatry and Psychology Department, Bucharest, Romania;, Assistant Lecturer, at University Dunarea de Jos of Galati, Faculty of Medicine and Pharmacy Correspondence: vasilemclaudiu@yahoo.com; Received December 3, 2017, Revised December 11, 2017, Accepted December 22, 2017 ABSTRACT: The purpose of the study is to identify, by applying the AUDIT test, the stages of alcoholism for patients with relapses in alcoholism. The study was carried out on a group of 331 patients diagnosed with alcoholism, which is the subject of the present paper, by using AUDIT questionnaires during all four visits, with the analysis of the dynamics of the AUDIT indicators and the dissemination of the results through the statistical methods presentedinthisstudy.

The AUDIT test is a relatively easy method of diagnosis because it uses a questionnaire at the beginning ofthedetoxperiodor whenthepatientbecomesconscious. The AUDIT test is addressed to patients in both short (3 questions) and extended versions, aiming at eliminating the error rate due to patient subjectivity. Considering the psychological side and the traceability of the AUDIT test, the study aims at highlighting both the objective and the subjective values in statistically polarized data clouds according to the professional judgment of the physician and the observations collected from thebiomarkeranalyses.

Keywords: Alcoholism, AUDIT, monitoring alcoholism INTRODUCTION The AUDIT test has been developed and assessed over a long period of time, and studies over the past two decades show that it provides a precise measure of the risk for alcoholconsumptionbygender,ageandculture(1-3). Although the AUDIT questionnaire can be applied both orally and in writing, the results may differ from one patient to another depending on how they are applied. It is advisable to provide patients with an explanation of the contentofthequestions,theirpurposeand the need for accurate answers. The usual purpose of the AUDIT test is to determine the patient's evolution after relapse in alcoholism. The AUDIT test can also be regardedasapre-diagnosisforchronicalcoholism. Specialists, such as the biostatistician and alcohol abuse researcher, E.M Jellinek (4), believe that there are four phases in alcoholism. These phases are gradually being installed with the increasing intake of alcohol and the increasing frequency of alcohol ingestion. The pre- alcoholic phase, also called prodromal, corresponds to an occasional consumption of alcohol and a social need for recognition on the background of a melancholic temper or ofsocialisolation.

The clinical stage of the disease, at this moment, does not involve physical and mental dependence, but only the need for "well-being", which becomes manifest by the occasional consumption of alcohol. In the debut phase, the premises for the development of alcohol addiction are created. Symptoms such as amnesia, alcohol concealment, rapid first-time ingestion, feelings of guilt, or avoidance of conversation on alcoholism issues are extremely common. An important factor is the appearance of amnesia almost everytimealcoholisconsumed.

The critical phase is the phase in which alcohol addiction is installed, the patient experiences loss of control over the amount of alcohol he consumes and the frequency of alcohol ingestion, he becomes inebriated and intoxicated, or goes into an alcoholic coma. This is also the stage in which denial, aggressive behaviour, the persistent feeling of guilt, isolation, inactivity at the workplace, self-pity and depressive states occur, in which the patient socializes with other heavy drinkers, in which the patient consumes alcohol in the morning and neglects food and body hygiene,etc.

Once the patient reaches the chronic phase, experts / specialists believe that the patient cannot return, or will return very hard to controlled alcohol consumption. This phase coincides with the significant deterioration of the system of thinking, social relations, lack of periods of abstinence, consumption to avoid withdrawal, denial of the disease and of its effects. In severe cases, alcoholic psychoses such as alcoholic hallucinations, delirium tremens, pathological drunkenness, obsessive jealousy or Wernicke encephalopathy and Korsakov's syndrome occur.

While the primary purpose of theAUDIT test is to identify people with hazardous or harmful alcohol consumption, researchers studying the effectiveness of the AUDIT test were also interested in using the continuity of their overall scoretoensureamorerapidintervention. After studying the domain-related literature, we reached the conclusion that there are several areas of the AUDIT test, as well as intervention/treatment recommendations, dependingonthescoreobtainedbythepatient(5). 75

76 Table 1: AUDIT areas, score, risk level,intervention/treatment recommendations Currently,theAUDITtest(6)isoneofthemostcommonly used screening tools for alcohol addiction (AD) (7). It is also the alcohol screening test most often used in clinical and epidemiological research, as shown by the expansion of its application and the increase in the number of publications in the domain-specific literature. Several studies examined the psychometric properties of the AUDITtest and its ability to correctly identify people with alcohol addiction or alcohol abuse problems (AD) as definedbyDSM-IV.

The monitoring of a group of patients in theAfrican region showed, as a result of the comparison between theAUDIT test, the AUDIT-C test and the biomarker level of phosphatidylethanol, that there is a close correlation between the previously mentioned factors and alcohol consumption. The AUDIT test is thus relevant for analysingalcoholconsumption(8). These findings are also consistent with a study carried out in the emergency department of a German university hospital that found that the AUDIT test is superior in detecting alcohol abuse compared to biomarkers such as Gamma-Glutamyl-Transferase (GGT), Corpuscular Medium Volume (MCV) and Transferrin-Deficient Carbohydrates(CDT)(9).

However, a study carried out in the UK (12, 13) on parents suspected of alcohol abuse in cases investigated in child labour centres shows that, following blood tests, biomarkers of fatty acid ethyl esters (FAEE) have a longer detection period than CDT and GGT and, therefore, increased sensitivity and specificity. This FAEE Alcohol Consumption Test is correlated with AUDIT tests that show that the percentage of alcohol abusers is consistent with the percentage of blood tests (10). High concentrations of phosphatidylethanol (PE) correlate with the results obtained in the alcohol consumption AUDIT test and with the alcohol disorder consumption identification (AUDIT-C) scores. Here we refer to the application of the short version of theAUDIT test, namely AUDIT-C.

Negative EP results correlate with abstinence or alcohol consumption, so 95% of the volunteers were classified as "moderate drinkers" by the AUDIT-C test due to the elevated phosphatidyl ethanol results. Higher concentrations of phosphatidyl ethanol indicate excessive alcoholconsumption(11,14). Thus, the AUDIT test remains a method of determining alcohol consumption by both adolescents and adults, along with the results of blood tests for specific and non- specificbiomarkers(15). The specialists' concerns regarding self-assessment diagnosis tools are increasingly used in medical practice as a cheap source generating quality information. In the present paper, we aim at presenting a transformation of a classic AUDIT test model regarding alcoholism into a complex model of diagnosis based on staging alcoholic pathology.

THEDESIGN OFTHESTUDY The study is based on the screening of patients with relapses in alcoholism, the assessed people being subjected to the AUDIT test successively, during 4 detox visits. The screening procedure is the one used by the domain-specific literature - the AUDIT test, which contains a total of 10 unique-answer questions, which the authors addressed to the patients in the test group who cametofourconsecutivedetoxvisits. Theobjectivesofthestudyarethefollowing: ·Identification of the cognitive factors to which the alcoholic patient sincerely reacts and towards which he develops a sensitivity in solving the effects produced by the manifestation of the factor in the patient's life (social- economic failure or social reintegration of the alcoholic patient).

·Identification of the factors that have a strong emotional impact on the alcoholic patient, factors that generate denialandrejectionoftreatment. ·Quantification of the effects of applying the AUDIT test as a screening method for classifying alcoholism into stages. ·Correlation of screening results with the evolution of the biomarker values (GGT, MCT, TB, HB, HT) in the four stagesofdetoxification. From the point of view of the methods used, we applied statistical methods supported by specific informational resources (dedicated statistical programs - the GRETEL statistical program and the advantages of using the modules of the OFFICE package – the Excel and the Word modules for the systematization, processing and graphical representation of the data from the AUDIT test). The data collected after consolidation generated qualitative outcomes, quantitatively transformed by the value correspondence of the subject's response, correspondence that the specialists made according to the impact of the response option on the general picture provided by the test.

Quantitative data, converted into average scores after all four visits, were centralized at a single average input per patient for the entire AUDIT period. The analytical (values) results were considered relative data (weights of influence), and these relative results were graphically represented by noting patient perception on each AUDIT question. The study is a mathematical-statistical one based on the dissemination of the results obtained by applying a questionnaire / screening test on the different stages of alcoholism in the patient with relapses after detox. The methods used are data pairs, statistical observation, analytical reasoning on the relevance of the information obtained from the screening and also the representation of the data regarding the influence criteria and the impact factors of the results so that the data obtained allow conclusions, which are relevant to the purpose of the Claudiu I. Vasile: Monitoring Alcoholic Patients by Using the Audit Test Score Risk area Risk level Intervention level 0–7 Area I Abstinence, low alcohol consumption Consulting a specialist physician 8–15 Area II Dangerous consumption of alcohol Short interventions from the part of the specialist physician 16–19 Area III Harmful consumption of alcohol Short interventions, permanent intervention , monitoring and diagnosis assessment 20–40 Area IV Addiction Applying specialized treatment

77 proposed research. The criteria for the selection of the test group (inclusion and exclusion criteria) were established in close relationship with the objective of the study, namely the monitoring of alcoholic patients by using the AUDIT test, the main inclusion and exclusion criteria relying on the relapse after detox, on the treatment of the disease in specialized medical units (the Psychiatry Hospital Elisabeta Doamna from Galați) and on the existence of a feedback (response / reaction) from the part of the patients regarding the questionnaire sent to be filled in (the cases in which the patients did not want to express their opinion by filling in the questionnaire were not taken intoconsideration).

RESULTS: The data were collected by applying the questionnaires during each of the 4 visits and were in the database in accordancewithAUDITscoring(0-40). We calculated the total score/patient and the average scores recorded at each visit for the whole group of patients and for each question from the questionnaire. Afterwards, we extracted the average of the resulted scores for all the 4 visits and we applied an impact coefficient in accordance with the development stage of the disease. We calculated the total of the values obtained foreachvisit.

The absolute data were turned into relative data (weights), which were then transposed in a tendency that became manifestinallthevisits(Table1). The average relative values were transformed into a general average so that we could graphically represent the patients' cognitive perception distribution for each question from the AUDIT test. All the values were graphically transposed in Excel with the help of complex graphs, the realistic cognitive factors being separated fromthesubjectivefactors. Table 2 The dissemination of the results obtained after the applicationoftheAUDITtestduringthe4 visits Fig. 1. The dissemination of the results according to the realistic cognitivefactorsandtothesubjectivefactors Fig. 2. Question 1 from theAUDITscreening test – The frequency ofalcoholconsumption(self-assessment steps) As far as the first question of the questionnaire is concerned, we may note that there is a phenomenon of denial of alcoholism among the patients, 45% to 48% of them denying alcoholism. However, we may notice the fact that, due to relapse in alcoholism, visit 2 and visit 3 for detox have the most significant rates of acceptance regarding the frequency of alcohol consumption, which occurs on the background of the psychological shock of thefirstdetoxvisit.

Theresultsarepresentedgraphicallyinthefigurebelow. Fig. 3. AUDIT – Alcohol consumption divided into classes of frequency By applying question 2 from the AUDIT test, we intended to assess the awareness of the amount of alcohol consumed in relation to the GGT biomarker and to quantify the sincerity of the response in relation to the Romanian Journal of Psychiatry, vol. XX, No.2, 2018 Visits AUDIT– The frequency of alcohol consumpt ion AUDIT– The quantity of alcohol ingested AUDIT– The frequency of excessive alcohol consumpt ion AUDIT– Alcohol addiction awarenes s AUDIT– Economic and social failure V1 3.36% 2.06% 10.38% 12.57% 15.58% V2 3.17% 2.03% 10.26% 12.56% 15.39% V3 3.29% 1.99% 10.27% 12.81% 15.41% V4 3.35% 2.03% 10.35% 12.74% 15.52% Average 3.29% 2.03% 10.32% 12.67% 15.47% Average impact percentage (the average of the percentage representati on for each question) 10.00% 10.00% 10.00% 10.00% 10.00% AUDIT– Morning alcohol ingestion AUDIT- Guilt AUDIT– Lapses of memory AUDIT- Violence AUDIT Social inclusion A1-A10 Total 6.18% 12.57% 4.12% 13.34% 19.84% 100.00% 6.08% 12.56% 4.05% 12.51% 21.38% 100.00% 5.98% 12.81% 3.98% 13.18% 20.27% 100.00% 6.08% 12.74% 4.05% 13.21% 19.93% 100.00% 6.08% 12.67% 4.05% 13.06% 20.36% 100.00% 10.00% 10.00% 10.00% 10.00% 10.00%

78 GGTanalysis.The phenomenon of alcoholic denial can be observed here, by assessing the low frequency area answers (80-85%) during each visit in comparison to the critical GGT per visit between 55 and 59%, indicating that 1 out of 2 patients are not sincere in answering this question. Fig. 4. The screening of daily alcohol intake (self-assessment steps) Following the implementation of the second question, it is clear that those who drink more shots of alcohol per day are fewer at the fourth visit but those who drink fewer shots at the fourth visit increase alcohol consumption.

Fig.5. ThequantitativeAUDITofalcoholconsumption This question is correctly perceived (cognitively recognized) by alcoholic patients, a number of 60 to 80% admitting the monthly consumption of alcohol and 14- 15%admittingthedailyconsumptionofalcohol. Fig. 6. The cyclicity of the consumption of significant amounts of alcohol(self-assessment steps) The above results indicate the fact that the patients accepts the disease but the coping mechanisms are not properly activatedtoallowtheregressionofthedisease. Fig. 7. The AUDIT of excessive alcohol consumption on classes offrequency The question of alcohol addiction awareness involves a rate of sincerity above average, and patients recognize it on the background of the desire for social reintegration and the improvement in their condition, whetherpsychological,physicalorsocial. Fig.8.Thealcoholaddictiontest(self-assessment steps) The question regarding the awareness of alcohol addiction implies a rate of sincerity above average and patients recognize it due to the desire for social reintegration and improvement in their condition, be it psychological, physical or social. For this reason, we consider that alcohol addiction is a sensitive cognitive factor, whose emotional impact is strong, being sincerely admittedbypatients.

Fig.9.Auditofalcoholaddictionawareness Socio-economic failure represents a factor acknowledged by the authorities in the domain and the main motivation, besides the clinical factors, for starting Claudiu I. Vasile: Monitoring Alcoholic Patients by Using the Audit Test

79 protection and social inclusion programs of people affected by alcoholism. The socio-economic failure is felt by all participating actors, namely: the patient, his/her family, local and national government bodies. The socio- economic failure is a consequence of the alcoholic crisis, which lowers the patient's standard of living and generates great expenses from the local and national budgets, both in the health and in the economic field, by creating allowances for the support of alcoholic patients. This indicator is assessed by means of a so-called AUDIT, as a sensitive cognitive factor, sincerely admitted by alcoholic patients.

Fig.10. Thefrequencyofsocialfailure(self-assessment steps) Fig.11. The auditofthesocialfactors'impact One may notice that, after the detox treatment, the percentage of patients who do not achieve what they have proposed for a short period of time is decreasing, their number decreasing as they participate in the visits; at the last visit their percentage decreases, fact which indicatestheeffectivenessofthetreatment. Fig. 12. The assessment of alcohol consumption in the morning (self-assessment steps) Alcohol consumption in the morning is inherent in the critical phase of alcoholism (third phase), which is a representative indicator of alcohol addiction. Like other factors, which are directly related to alcoholism, it involves a denial attitude and is poorly represented on the sincerityscaleoftheappliedAUDIT.

Fig.13.AUDIT-Alcoholconsumptioninthemorning Although the vast majority of patients are confronted with alcoholism, a large percentage deny the consumption of alcohol in the morning, the percentage of those who recognize daily consumption also being very low. Fig.14.Assessing theintensityofguilt(self-assessment steps) The sense of guilt is specific to the onset of alcoholism, and is recognized as a cognitive factor that is sensitive to a monthly or weekly average recognition, according to theAUDITtest performed on the 331 patients participatingintheexperiment,inthefourdetoxvisits. Fig.15. Theemotionalaudit–guilt Inaccurate memory occurs in the onset of the disease and worsens as alcoholism becomes chronic. Inaccurate memory is generally denied, having a low Romanian Journal of Psychiatry, vol. XX, No.2, 2018

80 sincerity rate from the part of the alcoholic patients, assessed bymeansoftheAUDIT. Fig.16.Repeatedmemory loss (self-assessment steps) Fig.17.Amnesiaaudit Fig. 18. The daily presence of material or human accidents (self- assessment steps) The violence associated with alcoholism from the critical stage of the disease has strong antisocial effects and causes anguish to people around alcoholics, so they adopt an attitude of avoidance and isolation of the alcoholic. Violence is generally not admitted by the family, the patient moving the frequency of violence to a longer, distant period (longer than a year). In fact, due to the specificity of the disease, people in the critical stage manifest violent acts because of emotional confusion and alcoholicjealousy F ig.19.Theemotionalaudit- Violence Fig. 20. Assessing the possibilities and measures regarding the socialinclusionofthealcoholic Social inclusion is quite high and assessed as such for patients with alcoholism due to the many existing programs in society, including those implemented through European funding (many people benefit from social inclusion activities or have access to national social inclusioncampaigns).

Fig.21. The socialinclusionaudit We may notice the fact that there is a relatively large number of cases in which a relative or physician has been interested in the condition of the alcoholic patient in the last year, which means that there is good communication regardingthedesireforhealing. DISCUSSIONS: The results of the AUDIT reveal the fact that critical factors such as addiction, awareness of adverse social effects, or morning alcohol consumption are increasing during the observation period (4 consecutive DETOX visits followed by relapses in alcoholism), whereas the sensitive cognitive factors relatively improve during detox sessions. In order to assess the impact of screening in relation to traditional diagnose methods (biomarker analysis, detox pre-analysis, biochemical constant analysis (blood pressure, pulse, temperature), in the table below, we present the statistical dissemination of the biomarker analysis (GGT, MCV, TB, HB, HT) of the second detox visit and compare it to the reference period ofthefirstdetoxvisit.

The results of the biomarker assessments were processed by relying on the regression analysis, by means of which the distribution of the statistical phenomenon in dynamics was observed; we drew the conclusion that, within the group of 331 patients, the values have high statistical significance rates and standard errors less than 0.05. The regression coefficients, calculated in the table below in relation to the following detox visits, and compared to the first detox visit, indicate a decrease in the amplitude of the phenomenon (critical values above the standard) in the case of HB, HT and TB, fact which completes the observations from the AUDIT, which were presented above.

Claudiu I. Vasile: Monitoring Alcoholic Patients by Using the Audit Test

81 Table 3: The results of the biomarker analysis for the patients on whom thescreeningtestswerecarriedoutinthe4detoxvisits CONCLUSIONS: Assessing the staging of alcoholism represents a challenge in the context of the evidence we have when the patient is first hospitalized for detox. The opportunity for appropriate staging assessment offers, from the point of view of medical practice, the possibility of a correct diagnosis and directs future clinical and paraclinical investigations and tests towards the area where they are needed.

Staging in alcoholism becomes, in this context, a filter in the application of diagnostic procedures while helping to identify patients who need psychological counseling during treatment. By means of the AUDIT screening test, applied to 331 patients, (a statistically significant group), it was possible to collect relevant observations, which were statistically analysed, and gave rise to a staging assessment model based on the transposition of the classic Audit in alcoholism model, divided on impact categories and classes of influence, in a screening model that can be applied by physicians as an instrument in the diagnosis and treatment of alcoholism in patients with relapses after detox. In order for the AUDIT to maximize its effects, the current aspects must be combined with the historical aspects, resulting in a pertinent and appropriate assessment of the status of alcoholism in the alcohol- addictedpatient.

The audit analysis reveals the general profile of the alcoholic who is tempted to deny the disease but recognizes its effects and wants to improve or even eliminatethem. By means of the performed audit, we have identified the cognitive factors on which psychiatric treatments can be applied in order to obtain the maximization of the cognitive treatment and a maximized drug support, an effort that ultimately has led to an effective control of the diseaseinpre-chronicstages. The audit was designed to track the hazardous and harmful consumption of alcohol, but validity studies were typically used as a criterion for structured diagnostic interviews such as the CIDI journal, which measures more parameters than the hazardous consumption of alcohol. Unlike screening tools, which focus on the presence of alcohol addiction or alcoholism, one benefit of theAUDIT is that it is able to identify individuals across the spectrum of alcohol abuse, providing an opportunity not only for short-term intervention to reduce the hazardous consumption of alcohol, but also for severe alcohol consumptiontreatment.

Further development and improvement in the AUDIT areas may be necessary in order to allow researchers and physicians to find appropriate treatments that are more useful when choosing treatment. Further research should test empirical and gender-specific values for significant areas that reflect the severity of the addiction in people seekingtreatmentforalcohol-relateddisorders. REFERENCES: 1. Saunders JB, Aasland OG, Babor TF, de la Fuente JR and Grant M. Development of theAlcohol Use Disorders IdentificationTest (AUDIT): WHO collaborative project on early detection of persons with harmful alcoholconsumption.II.Addiction1993;88:791-804.

2. Allen JP, Litten RZ, Fertig JB, Babor T. A review of research on the Alcohol Use Disorders Identification Test (AUDIT). Alcoholism: ClinicalandExperimentalResearch1997 21(4):613- 619. 3. Page P B. E. M. Jellinek and the evolution of alcohol studies: a critical essay.Addiction,1997,92(12):1619-1637. 4. Babor T F, Robaina K. The Alcohol Use Disorders Identification Test (AUDIT): A review of graded severity algorithms and national adaptations, IJADR International Journal ofAlcohol and Drug Research 2016,5(2):17 –24.

5. Babor T F, de la Fuente J R, Saunders J, Grant M. AUDITTheAlcohol Use Disorders Identification Test: Guidelines for use in primary health care.WHO/MNH/DAT1989;89. 6. Selin K H. Alcohol Use Disorder Identification Test (AUDIT): What does it screen? Performance of the AUDIT against four different criteria in a Swedish population sample. Substance Use & Misuse 2006, 41(14): 1881–1899. 7. Francis J M, Weiss H A, Helander A, Kapiga S H, Changalucha J, Grosskurth H. Comparison of self-reported alcohol use with the alcohol biomarker phosphatidylethanol among young people in northern Tanzania,Drug andAlcoholDependence 2015;156:289–296. 8. Kader R, Seedat S, Koch JR, Parry CD.Apreliminary investigation of the AUDIT and DUDIT in comparison to biomarkers for alcohol and drug use among HIV-infected clinic attendees in Cape Town, Afr J Psychiatry2012;15:346-351.

9. Schröck A, Wurst F M, Thon N, Weinmann W. Assessing phosphatidylethanol (PEth) levels reflecting different drinking habits in comparison to the alcohol use disorders identification test – C (AUDIT- C) 2017, 178:80-86. 10. Golka K, Sondermann R, Reich S E, Wiese W. Carbohydrate- deficient transferrin (CDT) as a biomarker in persons suspected of alcoholabuse2004Toxicol.Lett,151:235-241. 11. Bush K, Kivlahan D R, Mcdonell M B , Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): An effective brief Romanian Journal of Psychiatry, vol. XX, No.2, 2018 Coefficient Std. Error t-ratio p-value GGT_2 0,478055 0,05593138,547

82 screening test for problem drinking,Arch. Intern. Med. 1998; 158:1789- 1795 12. Babor T F, Higgins-Biddle J, Saunders J B, & Monteiro M G.AUDIT The Alcohol Use Disorders Identification Test: Guidelines for use in primary care (2nd ed.). 2001, Geneva, Switzerland: World Health Organization. 13. Gache P, Michaud P, Landry U, Accietto C, Arfaoui S, Wenger O, & Daeppen JB. TheAlcohol Use Disorders Identification Test (AUDIT) as a screening tool for excessive drinking in primary care: Reliability and validity of a French version. Alcoholism: Clinical and Experimental Research2005;29(11):2001–2007.

14. Kader R, Seedat S, Koch JR, Parry CD. A preliminary investigation of the AUDIT and DUDIT in comparison to biomarkers for alcohol and drug use among HIV-infected clinic attendees in Cape Town, Afr J Psychiatry2015;15:346-351. 15. Joni L, Haravuori H, Lindberg N, Niemelä S, Karlsson L, Marttunen M. AUDIT and AUDIT-C as screening instruments for alcohol problem use inadolescentsDrug andAlcoholDependence2018;188:266-273. *** Claudiu I. Vasile: Monitoring Alcoholic Patients by Using the Audit Test

CLINICAL CASE DIFFERENTIAL DIAGNOSIS: DELUSIONAL DISORDER- SOMATIC TYPE VS ANOREXIA NERVOSA Ana-Anca Tala man , Alexandra Dolfi2 ș ¹ ¹MD, PhD, Clinical Hospital of Psychiatry “Prof. Dr. Al. Obregia” Bucharest, No.10 Berceni Street, email: anaanca@yahoo.com 2 ResidentinPsychiatry, ClinicalHospitalofPsychiatry“Prof.Dr.Al.Obregia”,Bucharest,email:dolfialexa ndra@gmail.com ReceivedNovember1, 2017, Revised November16,2017,AcceptedJanuary9,2018 Abstract: Delusional disorder is an illness characterized by at least 1 month of delusions but no other psychotic symptoms, according to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). (1) Somatic delusions are among the most frequent types of delusion encountered for inpatients, alongside persecutory, referential, grandiose and jealousy type. The differential diagnosis with psychosis is the first to be done and it's suggested by the fact that delusions are persistent and non-bizarre. (2,3) Then all somatic and psychiatric conditions associated with development of delusions must be eliminated. We present the case of a 38-year-old female with delusional disorder-somatic type who was admitted with conflicting symptoms suggesting rather anorexia nervosa associated with somatic symptom disorder. But after a thorough interview and a few days of admission, the delusional symptoms cameoutandthediagnosisbecameclear. Key Words: somatic delusions, anorexia, somatoform disorder Rezumat: Conform Manalului de diagnostic și clasificare statisitcă a tulburărilor mintale, ediția 5 (DSM-5), tulburarea delirantă este caracterizată prin persistența cel puțin o lună a simptomelor delirante neasociate cu alte simptome psihotice. (1) Delirul de tip somatic este printre cele mai frecvente tipuri intalnite la pacienții internați, alături de delirul de persecuție, referință, grandoare și gelozie. Diagnosticul diferențial cu tulburările psihotice este primul luat în calcul și este sugerat de faptul că în tulburarea delirantă delirul este non-bizar. (2,3) Apoi trebuiesc eliminate toate afecțiunile somatice si psihiatrice asociate cu prezența ideilor delirante. Prezentăm cazul unei femei de 38 de ani cu tulburare delirantă- subtipul somatic, care a fost internată pentru simptome specifice mai degrabă anorexiei nervoase asociate cu o tulburare de tip somatoform. Însă simptomatologia delirantă a devenit evidentă după un interviu amănunțit și câteva zile de internare, astfel clarificându-sediagnosticul.

Cuvinte cheie: delir somatic, anorexie, tulburare somatoformă BACKGROUND: Delusions are fixed beliefs that do not change even when the person is confronted with evidence that clearly contradicts them. (2) These persistent delusions are not bizarre and they cannot be attributed to schizophrenia, affective disorders with psychotic symptoms, organic diseases or substance abuse. (3) Delusional disorder- somatic type involves a delirium focused on patient's own body, as an individual thinks that he or she is suffering from a medical condition and/or is experiencing physical sensations or bodily dysfunctions. (4) We report the case of a 38-year-old female, who was admitted in Alexandru Obregia psychiatry hospital on 21/03/2017 for anorexia and severe weight loss, multiple somatizations and somatic delusions. It was her first admission in a psychiatric hospital, the patient being treated in the outpatients' clinic for general anxiety disorder. She was admitted in our ward for one month, between 21/03/2017 and 21/04/2017. A second one, between 19/12/2017 and 29/12/2017, followed this admission.

HISTORY: The patient was firstly admitted in our ward on 21/03/2017 for severe weight loss, anorexia and somatic delusions, after hospitalization in Floreasca Emergency Hospital Bucharest between 24/02/2017 and 07/03/2017. Her admission in Floreasca Emergency Care Unit was due to extreme weight loss (15 kg in three months, the patient weighting 30 kg at the moment of admission) and severe anorexia. She was admitted in the ECU with altered general status, hemodynamically and respiratory stable, h y p o a l b u m i n e m i a a n d h y p o p r o t e i n e m i a , hypocholesterolemia, low triglycerides and severe dehydration. She was administered IV fluids, minimal enteral nutrition, and parenteral nutrition with 1000kcal/day, glutamine, antioxidant therapy and pulmonary embolism prevention therapy. A psychiatrist who recommended admission in a psychiatry hospital and treatment with olanzapine 5mg/day and mirtazapine 45 mg/day examined her. She was discharged with the following diagnoses: anorexia nervosa with secondary severe cachexia, mixed personality disorder, insomnia, constipation,appetitedisorder,andesophagealreflux. From her history we note that she has stopped eating for three months and her weight dropped from 45kg to 30kg during this time. She reports no allergies and no other hospital admissions besides the one in Floreasca ECU. She is being treated in outpatients' clinic for general anxiety disorder for 3 years with Paroxetine 20 mg/day but she stopped the treatment without medical permission three months ago. She is reporting multiple somatizations: abdominal cramps, lump in throat sensation, dysphagia 83

84 and constipation and states that she was diagnosed with irritable bowel syndrome 8 years ago. Her father died by suicide (hanging) 31 years ago. She hasn't been working long term in the past 2 years; she is living alone, is not married and doesn't have children. Until 2 years ago she worked in television as a news reporter but was laid off due to restructuration.After that she worked several short- term jobs (accountant, secretary) but couldn't find a long termone. PHYSICAL EXAMINATION: cachexia- 30kg weight with a severely low BMI (11.2), pale and cold skin, severe dehydration, muscular atrophy, low muscular tonus, kyphosis and scoliosis, high respiratory frequency (20/min), oxygen saturation of 90% and a blood pressure of 90/60 mmHg with tachycardia (regular pulse of 123 bpm).

PSYCHIATRIC EXAMINATION: It revealed a conscious and co operant patient, with a hygiene well kept, oriented in time and space, autopsychic and allopsychic oriented, visual and psychic contact easy to start and maintain, low amplitude mimic and gesture, symmetric and anxious facies, spontaneous and voluntary hypoprosexia, no affirmative perception disturbances, no memory disturbance, slow rate of ideation and speech, spontaneous speech was present. Autolytic ideation was absent. She denied the depressive mood and ideation. Her speech was coherent and she presented somatic delusions related to her digestive symptoms: " I have a very big lump in my throat and it doesn't let me swallow my food. I can't swallow anything, just a drop of water or milk. I didn't eat all month in December because I was very constipated. I have irritable bowel syndrome and this makes me eat less. My abdomen swells very much and the lump in my throat is enormous it really doesn't let me eat at all. I've been so sick because of my colon and I dropped weight because of this. My appetite is low because of my colon problem, my stomach is getting too big and food cannot go inside anymore. Sometimes I want to eat and sometimes I don't. I don't really want to gain too much weight". She didn't present another type of delusions. Her speech was focused on her health state, abdominal symptoms and weight loss. Her mother states that she was a TV reporter and she was always concerned about her weight, being on a diet most of the time. The patient was very anxious, presented low appetite, mixed insomnias and partial insight "I don't think I'm very sick, my weight is just a bit low, I don't think I can die and all my belly symptoms are because of the irritable boweldisease".

PARACLINICALEXAMINATION: first laboratory tests were ready on 22/03/2017 and showed hyperglycemia due to administration of 10% IV glucose (298 mg/dl), a ionic calcium of 4.38 mg/dl, potassium 3.2 mmol/l, urea 58 mg/dl, RBC 3.54 millions with hemoglobin of 11.8 g/dl, MCV 104 fl, VSH 19, fT4 normal with slightly lower T3 (0.33 ng/ml). The other parameters measured were normal. Her EKG, EEG, CT and pulmonary X-Ray were allnormal. The internal medicine consult on 22/03/2018 noted: chronic constipation with abdominal meteorism and extremely low appetite. Recommendations: Drotaverine hydrochloride 40 mg IV(2-0-2), lactulose syrup 20ml/day and active charcoal 2 tablets/day. She was re-examined periodically during her admission. Her abdominal meteorism was ameliorated but on 11/04/2017 she developed a faecaloma and needed a microclism to ameliorate her state as her improvement in weight started tostagnate.

The neurology exam on 14/04/2017 was normal and the ORL examination on the same day showed discrete signs of esophageal reflux and mouth ulcers. She was prescribedomeprazole20mg/day. 03/04/2018: fecal occult blood test negative, potassium of 3.3 mmol/l, increased prothrombin time (13.9) and increased INR (1.24). Her cortisol was normal (17.69 microgram/dl) and she had normal blood proteins. Her labs at discharge on 21/04/2017 were in normal parametersandshewas dischargedwithaBMI of12.6. COURSE AND TREATMENT: on the first day she received 15 mg of mirtazapine and 5 mg of olanzapine associated with intravenous 500 ml of 10% Glucose and 500 ml of 0.9% sodium chloride with 400 mg of vitamin B1 and 100 mg of vitamin B6 (both in injection form, administeredinperfusion).

On 22/03 patient's somatic delusion was persistent "I can't swallow anymore, I don't have the deglutition reflex. I feel how my colon is swollen and the deglutition reflex is linked to the colon. I can't eat but I can lick stuff that's good like coke and chocolate. I can't bite pieces of food". She reported severe constipation and her abdomen was bloated and painful on palpation. Arginine 250 ml IV/ day, active charcoal 3 capsules/day, lactulose syrup 20 ml/day and Drotaverine hydrochloride 40 mg IV twice a day were addedtohertreatmentaftertheinternalmedicineconsult. The next three days her evolution started to improve. She started to eat yogurt and waffles but was still anxious "I feel a bit better, I can bite a bit of food. My deglutition reflex has come back partially. I could eat soup". Her dose of olanzapine was increased to 10 mg while the rest of her treatmentremainedunchanged.

On 28/03 she reports that she can't swallow the 10 mg Olanzapine because "It's way too big and my deglutition reflex is low" so she is administered the velotab and she accepts the treatment. On 29/03 she maintains her delusion but in lower intensity. She starts to refuse the IV treatment because "I developed a low tolerance for pain" but she accepts it after she is administered a local anesthetic. On 03/04 she becomes anxious about her sleep "what if this treatment is way too strong for me and I sleep so deep that if an earthquake comes I won't get up and die?" She is anxious about her health and about the fact that "I'm not sure I want to put on a lot of weight, maybe 35 kg would be enough" but she is not refusing food and is accepting the treatment. She presents high emotional lability, her tolerance to frustration is low and she cries easily. Her olanzapine is increased at 15 mg/day with additional increase in mirtazapine to 30 mg/day on 05/04. On 10/04 her somatic delusions have almost disappeared. She goes down with the other patients to eat (by then her food was brought in the ward) and she eats small portions of all the courses served. She starts to swallow the pills so the IVtreatment is replaced with oral tablets of vitamin B1 and B6. She also administered omeprazole, lactulose and activated charcoal as the constipation persists. On 11/04 she reports abdominal pains, being diagnosed with a Ana-anca Talașman, Alexandra Dolfi: Differential Diagnosis: Delusional Disorder- Somatic Type vs Anorexia Nervosa

85 Romanian Journal of Psychiatry, vol. XX, No.1, 2018 fecaloma so a microclism was necessary. Her delusions returned as her somatic state worsen. So she stopped eating and states that "my deglutition reflux has disappeared" On 13/04 the constipation was resolved so her somatic delusion decreased in intensity and she started toeatlikebefore. The patient was discharged on 21/04/2018.At the moment of discharge her insight was still partial "I know that it's stupid that my colon is related to the deglutition but I still strongly feel that if my colon in bad my deglutition reflex becomes worse" but she had appetite and she was eating three meals a day in small portions (around 1400 kcalories). Her BMI on discharge was 12.6 (34 kg) and her blood parameters were normal. Her constipation was treated with lactulose and capsules of charcoal and she was prescribed 20 ml lactulose/day and 3 capsules of active charcoal in case constipation recidivates. She was also prescribed omeprazole 20 mg/day for her esophageal reflux Her psychiatric treatment on discharge: olanzapine 20mg/dayandmirtazapine30mg/day.

LATER EVOLUTION: A second 10 days admission followed later that year, between 19/12/2017 and 29/12/2017. She was brought by her mother for emotional lability, interpretativity, fragmentary somatic delusions, anorexia and generalized anxiety. Those symptoms were associated with somatic accuses like abdominal cramps, constipation and meteorization of the abdomen. The patient stopped the treatment without medical permissions2monthsbeforethecurrentadmission. Her BMI was lower than after the last discharge (11.9), the patient weighing 32kg. Her physical examination showed integumentary and mucosal pallor with tachycardia and low blood pressure (127 bpm and 80/60 mmHg), abdominal meteorism and painful abdomen on palpation without peritoneal irritation signs. She was examined again by the internal medicine department being prescribed microclism with lactulose and active charcoal inthesamedoses asbefore.

Abnormal blood parameters: creatinin 1.7 mg/dl, total bilirubin 1.7 mg/dl with a direct bilirubin of 0.74 mg/dl, uric acid 8.89 mg/dl, low HDL cholesterol 32,7 mg/dl, high amylase 137.25 UI, thrombocytopenia (93.000), low potassium 2.7 mmol/l with normal sodium, hypocalcemia (total calcium 7 mg/dl with ionic calcium of 3.87 mg/dl) and low total blood proteins 4.5 g/dl. Her hematological parameters and the other biochemical lab tests were normal. A nephrologist examined her on 20/12 and recommended 3 L of IV fluids and glucose 10% with 12 units of insulin associated with potassium supplement 3 tablets/day.

Her psychiatric examination showed delusions centered on the idea that she can't feed herself due to constipation, which affects her deglutition reflex due to the abdominal increase in volume. Her rhythm and speed of speech were low, no spontaneous speech present; she has suspicious, interpretative and circumstantial. Her mood was slightly depressive with high emotional stability. She accused mixed insomnias and low appetite. Her insight was partial " I have a problem with the deglutition reflux because all food comes back. I can't eat because my abdomen swells due to the irritable bowel syndrome and this is strongly linkedtomydeglutitionreflex." On admission she received aripiprazole 10-mg/day associated with sodium valproate 600 mg/day divided in 300 mg doses (1- 0- 1). Her evolution improved as she received additional treatment for constipation and hypokalemia and was hydrated with IV fluids. She demanded discharge against medical advice, on 29/12/2017 when she had gained 2kg and had normal blood parameters with her BMI being 12.6 (similar to the last discharge). The indicated treatment was aripiprazole 20 mg/day; sodium valproate 600 mg/day divided in 300 mg doses for morning and evening, vitamin B1 and B6 complex 3 capsules/day, lactulose syrup 20 ml/day with active charcoal 2 capsules/day in case of constipation and potassiumsupplement3capsules/day.

DISCUSSION: The particularity of this case is in the differential diagnosis. The initial symptoms and hospitalization in the ECU due to extreme weight loss with cachexia were strongly suggesting anorexia nervosa while the associated abdominal symptoms could have been due to a somatic symptom disorder.The admission in Floreasca Emergency Hospital eliminated al the physical causes of weight loss and all somatic diseases that could determine delusions (substance intoxication, metabolic disorders, vitamin deficiency, endocrinopathies, encephalitis, other infectious causes and neurological diseases). (5,6) She was discharged from the ECU with anorexia nervosa but at her admission in Alexandru Obregia hospital, her delusional symptoms were evident but she also had ideas that could have been referred to anorexia (been on diets most of the time in the past years, preoccupied with her weight) but these ideas didn't have pathological intensity so we eliminated anorexia as a secondary diagnosis. Her thoughts were dominated by the somatic delusion of "there is something wrong with my colon and this completely stops my deglutition reflex", fact which directed the diagnosis to delusional disorder- somatic type. We also eliminated body dysmorphic disorder from the possible list of diagnoses as she didn't have any excessive preoccupation related to her body, besidesthedelusionfocusedonhergastricsymptoms. CONCLUSION: The diagnosis of delusional disorder- somatic type can become a challenge when the patient presents symptoms similar to anorexia nervosa such as extreme weight loss and refusal to eat. The case presented above was an example that confirms this challenge and states the importance of differential diagnosis in both delusionaldisorderandanorexianervosa.

REFFERENCES: 1.American PsychiatricAssociation. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. Washington, DC: American PsychiatricAssociation;2013. 2. Silva, Hernan & Ramírez,A& Jerez, S. (1995). [Delusional disorders withdeliriumof somatictype].RevistamédicadeChile.123. 1409-11. 3. Phillips KA, Kim JM, Hudson JI. Body image disturbance in body dysmorphic disorder and eating disorders. Obsessions or delusions? PsychiatrClinNorthAm. 1995 Jun;18(2)317-334.PMID: 7659601. 4. Shibuya, Y., Hayashi, H., Suzuki, A., & Otani, K. (2012). Long-term specificity and stability of somatic delusions in delusional disorder, somatic type. Acta Neuropsychiatrica, 24(5), 314-315. doi:10.1111/j.1601-5215.2011.00642.x 5. Opjordsmoen S. Delusional disorder as a partial psychosis. Schizophr Bull. 2014 Mar.40(2):244-7.[Medline].

6. A.E. Geka, C. Venetis, D. Apatangelos, S. Kalimeris, V. Psarra, N. Drakonakis, G. Doulgeraki, R. Evangelatou, C. Garnetas, Delusional disorder with severe weight loss,European Psychiatry,Volume 26, Supplement1,2011, https://doi.org/10.1016/S0924-9338(11)73424-1

ManuscriptCriteriaand Information Authorship Ethicalconsiderations FinancialDisclosure PeerReviewProcess Submitted manuscripts are screened for completeness and quality of files and will not enter the review process until all files are satisfactory. The Secretariat will announce the corresponding author about the receipt and the status of the manuscript. Manuscriptsandallattachedfilesshouldbesubmittedinelectronicformandonpaper. The electronic form should be submitted, either on compact disk or by e-mail to: aliat@artelecom.net. It is preferable that three copies of the manuscript, printed on one side ofA4 paper format, double-spaced, with 3 cm margins, be alsosubmittedtothesameaddress.

Themanuscriptshouldbeaccompaniedbyacoverletterincluding: -thestatementonauthorship, -thestatementonethicalconsiderations, -thestatementonfinancialdisclosure. Manuscripts are received with the understanding that they have the approval of each author, are not under simultaneous consideration by another publication, and have not been published previously in whole or substantial part.This policy applies to the essential contents, tables, or figures, but does not apply to abstracts.Authors must disclose in their cover letters if the submitted manuscript contains any data, patient information, or other material or results that have already been publishedorareinpress, submitted,ornearlysubmitted.

Accepted manuscripts become the permanent property of the Romanian Journal of Psychiatry. They may not be republishedwithoutpermissionfromthepublisher. All named authors should meet the criteria for authorship as stated in the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication” issued by the International Committee of Medical Journal Editors “ Authorship credit should be based on 1) substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising it critically for important intellectual content; and 3) final approval of the version to be published.Authors should meet conditions 1, 2, and3 ” .

“Acquisition of funding, collection of data, or general supervision of the research group alone does not constitute authorship”. “Allpersons designatedasauthorsshouldqualifyforauthorship,andallthosewho qualifyshouldbelisted.” TheRomanianJournalofPsychiatryconsidersallauthorstoberesponsiblefortheconte ntoftheentirepaper. Authors are requested to describe their individual contributions to a study/ paper in a section that will be signed, attachedtoandsenttogetherwiththe“AuthorshipResponsibilities”form.

Individualswho gaveadviceonthemanuscriptshouldbeacknowledged,butarenotconsideredauthors. If the scientific project involves human subjects or experimental animals, authors must state in the manuscript that the protocol has been approved by the Ethics Committee of the institution within which the research work was undertaken.A statement of informed consent for human investigation should be made in the text, along with the name of the institutional review board that approved the study protocol.Authors must ensure that patient confidentiality is in no way breached. Do not use real names, initials, or disclose information that might identify a particular person without informed consent for publication. When clinical photographs of patients are submitted, consent by the patient must be obtained prior to submission of the article and is the responsibility of the author. The editors reserve the right to reject a paper on ethical grounds.Allauthorsareresponsibleforadheringtoguidelinesongoodpublicationpra ctice.

Theauthorsshouldcertifythat: -allfinancialandmaterialsupportforthisresearchandwork areclearlyidentifiedinthemanuscript. -all the affiliations with or financial involvement (e.g., employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, royalties) with any organization or entity with a financial interest in or in financial conflict with the subject matter or materials discussed in the manuscript are completelydisclosedhereorinanattachment.

-theyhavenorelevantfinancialinterestsinthismanuscript. The absence of funding should also be declared.The statement on conflicts of interest will be published at the end of the paper. Please submit all requested signed documents by regular mail to the Secretariat. Scanned copies sent electronicallyandfaxsubmissions arenotacceptable. www.icmje.org INSTRUCTIONS FOR AUTHORS 86

Asubmitted manuscript will be acknowledged and assigned a manuscript number, which is to be used in all further correspondence. Manuscripts are reviewed and given a priority based on their originality, importance of the findings, scientific merit and significance for the field, interest to readers, lucidity, and suitability for publication. Manuscripts with insufficient priority for publication are rejected promptly. Other manuscripts are sent to expert consultants for peer review. The existence of a manuscript under review is not revealed to anyone other than peer reviewers and editorial staff. Peer reviewers remain anonymous and are expected to maintain strict confidentiality. After the review process has been completed,authorswillbeinformedbymailoftheEditor'sdecision.

Corrections Scientific fraud is rare events; however, they have a very serious impact on the integrity of the scientific community. If the Editorial Board uncovers possible evidence of such problems it will first contact the corresponding author in complete confidence, to allow adequate clarification of the situation. If the results of such interactions are not satisfactory, the Board will contact the appropriate official(s) in the institution(s) from which the manuscript originated. It is then left to the institution(s) in question to pursue the matter appropriately. Depending on the circumstances, the Romanian Journal of Psychiatrymayalsoopttopublisherrata,corrigenda,orretractions.

ManuscriptPreparation Manuscriptorganization 1.Firstpageshouldinclude: Article title: titles should be short, specific, and descriptive, emphasizing the main point of the article.Avoid a 2- part title, if at all possible. Do not number the title, e.g., I or Part I. Do not make a declarative statement in the title. Title length,includingpunctuationandspaces,ideallyshouldbeunder100charactersandmu stnotexceed150characters. 2.Secondpage: a) Author(s). First name, middle initials and surname of the authors, without any scientific, didactic or militarydegrees;(e.g.,MirceaABirţ,AuraVaida,notBirţM.A.,VaidaA.).

b) Footnote that specifies the authors' scientific titles, the name and the address of their workplaces (institution and department) for each author; contact details of the corresponding author (full address, telephone number, fax number, e-mail address) and the address of the institution and department where thestudyhasbeencarriedout.Contactdetailswillbepublishedunlessotherwisereque stedbytheauthor. 3.Thirdpage: a) Abstracts should have no more than 300 words. For original articles they should consist of five paragraphs,labeledBackground,Objective(s),Method(s),Result(s),andConclusion (s). b) Keywords maximum of 6 keywords (minimum of 3), according to Index medicus. Keywords should not repeatthetitleofthemanuscript.

4.Fourthpageandnext: • Originalpapers organizedin: a) Introduction (nomorethan25%ofthetext),materialandmethods,results,commentsordiscussionsan d Romanian authors should send both the Romanian and English version of the article, including title, abstract and keywords. ForeignauthorsshouldsendtheEnglishversionofthearticle. Manuscripts must be prepared in conformity to the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication” issued by the International Committee of Medical JournalEditors(www.icmje.org).

Articles must be written in Microsoft Word, Style: Normal + Justify, Font: Times New Roman, size 12. All manuscripts must be typed double-spaced. Original source files, not PDF files, are required. In text editing, authors should not use spacing with spacebar, tab or paragraph mark, but use the indentation and spacing options in Format -> Paragraph. Automaticpagingispreferred. Subheadingsofthearticleshouldbeleft-justified,typedwithcapitalletters,Font: TimesNew Roman,size12. The abstracts and Key words must be written in MicrosoftWord, Style: Normal + Justify, Font:Times New Roman, size11,italics.

Figures must be cited in order in the text usingArabic numerals, (e.g., fig.2). Their width should be 6,5cm (in order tofitinacolumn)or13,5cm(inordertofitinbothcolumns).Thefigureshavetosatisfyt hefollowingconditions: -blackandwhitephotographswithgoodcontrast,withrecommendedsizes; - scanned photograph with a resolution of 300 dpi and subsequently edited on a computer, original file (*TIF, *JPG); -illustrations(drawings,charts)createdonacomputer,citedinthetext,originalfi le(*XLS, *CDR). Everyfigureshouldbeaccompaniedbyatitleandalegend.

Tables, numbered consecutively with arabic numerals, should have a width of 6,5 cm or 13,5 cm. Every table shouldbealsoaccompaniedbyatitleandalegend.Thedistributionoftablesandfigures inthetextshouldbebalanced. Please do not import tables or figures into the text document, but only specify their insertion in text (e.g., Table No.3 insertion). They have to be sent in separate files. Files should be labeled with appropriate and descriptive file names. 87 Romanian Journal of Psychiatry, vol. XX, No.1, 2018

acknowledgements. b) Material and methods have to be described in enough detail to permit reproduction by other teams. The same product names should be used throughout the text (with the brand name in parenthesis at the first use). c) Results shouldbepresentedconcisely.Tablesandfiguresshouldnotduplicatetext. d) The discussions should set the results in context and set forth the major conclusions of the authors. Information from the Introduction or Results should not be repeated unless necessary for clarity. The discussion should also include a comparison among the obtained results and other studies from the literature, with explanations or hypothesis on the observed differences, comments on the importance of the study and the actual status of the investigated subject, unsolved problems, questions to be answered inthefuture.

e) In addition to the customary recognition of non-authors who have been helpful to the work described, the acknowledgementssectionmustdiscloseanysubstantiveconflictsofinterest. f) Abbreviations shall be preceded by the full term at their first apparition in text. A list of all used abbreviationsshallbemadeattheendofthearticle. g) Separatepages:tables,graphics,picturesandschemeswillappearonseparatepages. • References should be numbered consecutively in the order in which they are first mentioned in the text. Identify referencesintext,tables,andlegendsbyArabicnumeralsinparentheses.

- The reference list will include only the references cited in the text (identified by Arabic numerals in parentheses,not insquarebracketsand not bold). - All authors should be listed when six or less; when seven or more, list only the first three and add 'et al' (IonescuI,PopescuI,GeoregscuIetal). - The name of the Journals cited in the References should be abbreviated according to ISI Journal Title Abbreviations. Examples: INSTRUCTIONS FORMANUSCRIPTS SUBMITTED IN ELECTRONIC FORMAT VERY IMPORTANT:All manuscripts intended for publication will be subject to peer-review by a committee of experts which assesses the scientific and statistical correctness of articles submitted. The committee receives the manuscripts without knowing the authors' name and proposes possible changes, which will be transmitted to the authors by the medium of Editorial Board. The authors have the obligation to oversee the text in English language with the help of a professionaltranslator.

- Reference to a journal publication: VraştiR,MateiVMI.ThecrisiscentreinRomania.EurJPsychiat2002;29:305-311. Reynolds CF, Frank E, Perel JM et al. Treatment of consecutive episodes of major depression in the elderly. Am J Psychiat1994;151(12):1740-3. -Referencetoabook: VrastiR.Thecrisiscentreinpsychiatry.Toronto,London:AcademicPress, 1993,26-52. -Referencetoachapterinaneditedbook: Schuckit MA. Alcohol-Related Disorders. In: Sadock BJ, Sadock VA, Ruiz P (eds). Comprehensive Textbook of Psychiatry.Philadelphia:LippincottWilliamsandWilkins,2009,1268-1287.

The placement of the italics, punctuation and the general aspect of the text format must comply with the rules mentionedabove.Thisisamandatoryandeliminatorycondition. Thetextshouldbeeditedin“WordforWindows”. 1.Use asfewformattingcommandsaspossible: -inputyourtextcontinuously(withoutbreaks); -donotusedifferenttypesoffontstohighlightyourtext; -anyword orphrasethatyouwouldliketoemphasizeshouldbeindicatedthroughoutthetextbyunde rlining; -useonlythe“Enter”keytoindicatetheendoftheendofparagraphs,headings,listsetc .; -donotusethe“SpaceBar”toindicateparagraphs,butonlythe“Tab”key. 2. Charts and tables should be edited in Word or Excel. Please indicate in the text, the place of the table, specifying itsname.

3. You can scan photographs (using Photostyler, Adobe-Photoshop or any other compatible programs) and save themas.tifor.jpgfiles.Pleaseindicateinthetext,theplaceofthephotograph,speci fyingitsname. 4.Youmayuseacommoncompressionprogram:ARJ, RAR orZIP. 5.MakesurethatthetextfilefromCD andtheprint-outcorrespondexactly. 6.MakesurethattherearenoerrorsonyourCD. 7.MakesureyourCD isadequatelypacked. 8.MakesureyourCD hasnoviruses. 88 Instructions for authors

Address tosend themanuscripts is: REVISTAROMÂNĂ DEPSIHIATRIE ASOCIAŢIAROMÂNĂ DEPSIHIATRIEŞI PSIHOTERAPIE Prof. Dr.DanPRELIPCEANU ClinicalHospitalofPsychiatry“Prof.Dr.AlexandruObregia” Şos. Berceni10,sector4,041914Bucureşti Tel./Fax:+40-21-334.84.06 E-mail: Contact: Viorel Roman – web editor E-mail: Tel.+40-21-334.84.06 -printedition -onlineedition aliat@artelecom.net aliat@artelecom.net www.e-psihiatrie.ro/revista www.romjpsychiat.ro 89 Romanian Journal of Psychiatry, vol. XX, No.1, 2018

ROMANIAN JOURNAL OF PSYCHIATRY APR CONTENTS Adult Attachment Pattern. Influence on Parenting Skills 47 Carmen I. Truțescu, Iuliana Dobrescu Personality and Coping Strategies in Age Dynamics AurelNireștean,AndraOltean,EmeseLukacs Conscientiousness Dimension and Pathological Personalities 55 Emese Lukács, Aurel Nireștean, Andra Oltean Dimensional Perspective on the Subvariants of Obsessive-Compulsive Personality Disorder 57 Emese Lukács, Aurel Nireștean, Tudor Nireștean, Andra Oltean The Relationship Between Depression and Socioeconomic Factors 59 Comorbidities of Alcohol Use Disorder 63 Biomarkers in Follow-up Treatment of Alcoholism with Hepatic Comorbidity. An Observational Study 68 Claudiu I. Vasile Monitoring Alcoholic Patients by Using the Audit Test 75 Differential Diagnosis: Delusional Disorder- Somatic Type vs Anorexia Nervosa 83 Ana-Anca Talașman, Alexandra Dolfi REVIEW ARTICLES & SPECIAL ARTICLES & 52 & & ORIGINAL ARTICLES & & & & CLINICAL CASE & INSTRUCTIONS FOR AUTHORS 86 Romanian Journal of Psychiatry and Psychotherapy is recognized in Romanian National Council for Scientific Research in Higher Education, starting with January 2010, at B+ category Romanian Journal of Psychiatry and Psychotherapy is indexed in the international data base Index Copernicus – Journal Master List, starting with 2009.

Ż Doctors subscribed to this journal receive 5 CME credits / year. Scientific articles published in the journal are credited with 80 CME credits / article. Ioana A. Pacearcă, Floris P. Iliuță, Oana Manea, Mirela Manea Maria Bonea, Mădălina C Neacșu, Ioana V Micluția Claudiu I. Vasile Ż www.romjpsychiat.ro EDITOR-IN-CHIEF: Dan PRELIPCEANU CO-EDITORS: Dragoş MARINESCU Aurel NIREŞTEAN ASSOCIATE EDITORS: Doina COZMAN Liana DEHELEAN Marieta GABOŞ GRECU Maria LADEA Cristinel ŞTEFĂNESCU Cătălina TUDOSE Executive editor: Valentin MATEI STEERING COMMITTEE: Vasile CHIRIŢĂ (Honorary Member of the Romanian Academy of Medical Sciences, Iaşi) Michael DAVIDSON (Professor, Sackler School of Medicine Tel Aviv Univ., Mount Sinai School of Medicine, New York) Virgil ENĂTESCU (Member of the Romanian Academy of Medical Sciences, Satu Mare) Ioana MICLUŢIA (UMF Cluj-Napoca) Şerban IONESCU (Paris VIII Universiy, Trois- Rivieres University, Quebec) Mircea LĂZĂRESCU (Honorary Member of the Romanian Academy of Medical Sciences, Timişoara) Juan E. MEZZICH (Professor of Psychiatry and Director, Division of Psychiatric Epidemiology and International Center for Mental Health, Mount Sinai School of Medicine, New York University) Eliot SOREL (George Washington University, Washington DC) Maria GRIGOROIU-ŞERBĂNESCU (senior researcher) Teodor T. POSTOLACHE, MD (Director, Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore)

You can also read