The 8th World Congress on ADHD (2021) - Post-Conference Wrap Up - Doctor Unite
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The 8
World Congress
th
on ADHD (2021)
Post-Conference Wrap Up
2021 ADHD World Congress
Post-Conference Wrap Up
2021 ADHD World Congress Wrap Up
The 2021 ADHD World Congress was held virtually on May 6th-May 9th,
due to the COVID-19 pandemic. Numerous updates were presented on
current research within ADHD, and we summarize some additional
exciting topics from the meeting including hot topics in ADHD
epidemiology.
Plenary: Update on treatment of ADHD over the lifespan
001 –Advances in non-pharmacological treatments (food and nutrition-
based interventions etc.)
• Research paper: Bosch, Annick, et al. "A two arm randomized
controlled trial comparing the short and long term effects of an
elimination diet and a healthy diet in children with ADHD (TRACE
study). Rationale, study design and methods." BMC psychiatry 20
(2020): 1-16.
• Dr Jan K. Buitelaar (Radboud University Nijmegen, Donders Institute
for Brain, Cognition, and Behavior) summarized diet and nutrition
approaches to ADHD treatment. Nutritional psychiatry examines the
relationship between diet and neurobiology and this is a more recent
topic of clinical and research interest. Novel non-pharmacological
advances in nutritional psychiatry are necessary as existing treatments
are limited to short-term efficacy and do not have convincingly
established long-term benefits. Furthermore, additional benefits are
needed beyond symptom reduction including improving quality of life
and more benign side effect profiles. Food interventions have been
investigated two types of studies in ADHD: supplementation and
elimination studies. Dr Buitelaar presented on the supplementation of
omega-3 fatty acids and micro-nutrients as well as the elimination of
artificial food colors and preservatives, sucrose, and a rigorously
restrictive elimination diet.
• Omega-3 levels are reduced in children with ADHD and there is
sufficient evidence to consider omega-3 fatty acids to supplement
established therapies, however it is unclear whether this should be
limited to children with low blood levels. Omega-3 fatty acids are a
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2021 ADHD World Congress Post-Conference Wrap Up main constituent of the brain and cannot be synthesized in the body, thus are essential in external nutrition. A meta-analysis (Bloch et al., 2012) of 9 studies (n=586) highlighted a 0.42 effect size (p
2021 ADHD World Congress
Post-Conference Wrap Up
0.46 to 0.67. A double-blind randomized, controlled trial in ADHD
patients aged 7-12 years old (Rucklidge et al., 2018), demonstrated
clinically meaningful improvement on inattentive symptoms (32%
versus 9%) but no difference in hyperactive-impulsive symptoms.
• Artificial food colors and preservatives may be eliminated as add-on
on treatment for some ADHD cases as it has a small effect size. A
meta-analysis of 20 studies (794 participants) by Nigg et al. found a
small parent-reported effect size of 0.18, while the teacher/observer
effect size was non-significant. In contrast, Sonuga-Barke et al.
highlighted a greater effect size with teacher ratings (0.42) versus
parent ratings (0.32).
• Eliminating sucrose only affords a small effect size and is not qualified
as a stand-alone treatment. Observational studies evaluated in a
meta-analysis by Farsad-Naemi (2020) show a positive relationship
between sugar and symptoms of ADHD. However, additional studies
are required to examine the long-term effects of high sugar intake.
• Children with ADHD have an increased risk of developing adverse
physical reactions to allergenic foods (De Theije et al., 2014). It may be
that adverse physical reactions to food have an impact on the brain
via the microbiome causing adverse behavioral affects. The
elimination diet removing these foods is the most stringent nutritional
approach and long-term effects are unknown. A meta-analysis by
Sonuga-Barke et al. (2013) elicited a 1.48 effect size (p=0.01),
conversely, when a study was taken out due to variability, the effect
size was no longer statistically significant. The elimination diet may be
difficult to implement and research by Pelsser (2020) reported that
only 26% of participants in the intent-to-treat cohort maintained the
diet. The TRACE randomized controlled trial comparing short and
long-term effects of an elimination diet versus a healthy diet in
children with ADHD is ongoing (Bosch et al., 2020).
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2021 ADHD World Congress
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Plenary: Update on the ADHD aetiology and neurobiology
004 –Progress in the genetics and epigenetics research in ADHD
• Dr. Barbara Franke (Radboud University, Netherlands) presented on
the current progress that has been made on the genetics and
epigenetics research within the ADHD field. Currently it is known that
ADHD has high heritability with estimates reaching 74% from studies
in twin siblings (Faraone and Larsson, Mol Psychiatry, 2019). While
there is no one gene that contributes to ADHD, it is known that ADHD
is a complex multifactorial disorder with multiple genes and
environmental factors involved.
• In 2007 the Psychatric Genomics Consortium (PGC) was started in
order to bring together scientists and genomic data on psychiatric
disorders which successfully published a seminal paper in
schizophrenia in 2014. Within ADHD, additional samples were needed
bringing data from both PGC and another consortium, iPsych, which
resulted in 12 genome-wide significant findings associated with ADHD
from over 20,000 ADHD cases and over 35,000 control samples
(Demontis, Walters, et al., Nature Genetics 2019). Further, it has been
found that the 12 gene products interact in pathways that involve
neurite outgrowth, synapse formation, and synaptic plasticity
(Klemann, Poelmans, et al., in preparation; Poelmans et al., Am J
Psychiatry 2011).
• Since ADHD persistence fluctuates by age, a Genome-wide association
study (GWAS) was utilized to compare childhood ADHD and adult
ADHD. Genetic correlations or the overlap between children and
adults was high but there were also some differences found which
agrees with prior research that found only part of those genes
contributing to ADHD onset also play a role in ADHD persistence
(Rovira et al., Neuropsychopharmacology 2020).
• In terms of genetic overlap between ADHD and other psychiatric
comorbidities, it was found that ADHD has significant overlap with
diseases such as anorexia, ASD, bipolar, depression, schizophrenia,
and Tourette syndrome (see next page):
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• Interestingly, genetic overlap of ADHD occurs as well with many non-
psychiatric diseases:
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• Dr. Franke’s group used this data to look at the genetic sharing of
ADHD and BMI/obesity and identified genome-wide significant ADHD-
BMI and ADHD-obesity genes that increased significance by at least
one order of magnitude, and then performed biological pathway
enrichment analyses. One of the main contributors to the overlap
between the ADHD and BMI/obesity comorbidity is dopamine
signaling (Mota et al., Neuropsychopharmacology, 2020). Interestingly,
this finding is consistent with the reversal of risk increase for obesity
in ADHD upon treatment with stimulants (Cortese et al., Am J
Psychiatry, 2016).
• Like the GWAS, arrays have been used for epigenome-wide
association-studies (EWAS) looking at altered DNA-methylation
patterns in ADHD. A meta-analysis performed in Dr. Franke’s group
found that the enriched cellular processes are those involved with
developmental growth, axon guidance, and positive regulation of
neuron differentiation, and the enriched cellular components included
those associated with nucleoplasm, focal adhesion, dendritic spine,
and synapse. Out of these studies, the top brain cell type marker for
these ADHD-specific enrichments are in neurons which were similar to
findings in the GWAS studies. Interestingly, only 1% of the top
epigenetic findings for ADHD were directly explained by genetic
factors involved in ADHD suggesting an important role for epigenetics
as well as genetic studies in ADHD.
• The study of ADHD genetics and epigenetics is largely undeveloped
and additional future studies need to be done for the development of
diagnostic biomarkers and treatment targets for ADHD, prognostic
biomarkers, personalized therapies, and a rethinking of psychiatric
nosology.
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Posters: Pharmacological treatment, children and adolescents
Efficacy and Safety of KP415 (Serdexmethylphenidate and d-
methylphenidate) Capsules in Children with ADHD: A randomized,
double-blind, placebo-controlled laboratory classroom study
• KP415 (Azstarys) is a recently approved once-daily capsule product for
ADHD containing 70% serdexmethylphenidate (SDX) (a novel prodrug
of d-methylphenidate) and 30% d-methylphenidate hydrochloride (d-
MPH HCl). This randomized, double-blind, placebo-controlled
laboratory classroom study demonstrated the favorable efficacy and
safety of KP415 in children with ADHD who were aged 6-12 years.
• After the screening phase, the study included a 3-week open-label
dose optimization phase followed by a 1-week double-blind treatment
phase testing 74 patients in the KP415 group and 76 in the control
group. The following SDX/d-MPH dosage strengths were investigated:
26.1/5.2mg (equivalent to 20mg d-MPH HCl), 39.2/7.8mg (equivalent
to 30mg d-MPH HCl), and 52.3/10.4mg (equivalent to 40mg d-MPH
HCl).
• Statistically significant results were achieved on the pre-specified
primary endpoint with a least-squares (LS) mean change over placebo
of -5.41 in Swanson, Kotkin, Agler, M-Flynn, and Pelham-C (SKAMP-C)
scores collected at the end of the dose optimization period (visit 5)
compared to the end of the treatment period (visit 6) at day 28
(p2021 ADHD World Congress
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was not met at the beginning (30 minutes) and end (12-13 hours)
when assessing SKAMP-C with visit 5 as the baseline.
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• KP415 was generally well-tolerated and reported adverse events were
typical of stimulant treatment. 31.1% of KP415 patients reported any
treatment-emergent adverse events (TEAEs) compared to 14.5% of
the placebo cohort. No serious adverse events were reported,
however the most commonly reported TEAEs included upper
respiratory tract infection (2.7% versus 5.3%), headache (5.4% versus
1.3%), upper abdominal pain (4.1% versus 1.3%), insomnia (2.7%
versus 1.3%), and pharyngitis (2.7% versus 0%). 4 subjects
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experienced adverse events leading to treatment discontinuation
and 2 of these cases reported severe insomnia.
A post hoc analysis of executive function outcome of SPN-812
(viloxazine extended-release) capsules in children and adolescents with
ADHD
• Vilazodone extended-release (ER) (Qelbree) is a recently approved
once-daily capsule nonstimulant for the treatment of ADHD in
pediatric patients 6-17 years of age. The drug was studied in 4 Phase
III clinical trials in children and adolescents and this post-hoc analysis
highlighted the positive effect of viloxazine ER on executive function
deficits (EFDs) in the pooled data for 1154 subjects (viloxazine n=760,
placebo n=394) from these studies.
• Responders were defined as:
• >70 T-score at baseline (defined as severe impairment as this falls
above 2 standard deviations of the population mean) and2021 ADHD World Congress
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• Viloxazine ER improved executive function (EF) and ADHD symptoms.
There were 52.5% of C3PS-EF or ADHD-RS-5 responders in the
viloxazine ER treatment group versus 35.4% in the placebo group
(p70 was 0.12
and a comparable difference of 0.11 was yielded for all subjects.
• Among the patients receiving viloxazine ER, the correlation between
the magnitude of EFD response and ADHD symptom response was r =
0.47 (p2021 ADHD World Congress
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Hot Topic: Diet and ADHD: an epidemiological perspective
001 - Moderating effect of maternal nutrition during pregnancy on the
genetics of ADHD symptoms in children. A longitudinal study in the
Norwegian Mother, Father and Child cohort
• Dr. Berit Skretting Solberg presented the results of a study which
aimed to examine the effects of prenatal maternal fiber intake (as a
proxy of overall diet quality) and common genetic variants (calculated
ADHD polygenic risk scores) on the development of ADHD in offspring
at 3, 5, and 8 years of age (levels of symptoms measured and given
ADHD scores).
• The Norweigen Mother, Father and Child Cohort (MoBa) was
examined in this study, which included ~95,000 mothers, ~75,000
fathers and ~114,000 children who underwent questionnaires and
DNA sampling between 1999-2008. The final study sample included
father, mother, child trios at 3 years (n= ~6,000), 5 years (n=~5,000),
and 8 years (n=~4,500).
• The study concluded that there is a correlation between maternal
fiber intake during pregnancy and ADHD symptoms in offspring, but
the association was very weak. The study also found genetic effects of
common variants were associated with ADHD score at 5 and 8 years of
age, and offspring polygenic risk score showed positive correlation
with change in ADHD scores over the study period. The results must
be interpreted carefully as the sample size was small and a larger
study sample is required to adjust the analysis for confounders.
002 - ADHD symptoms and dietary habits in adulthood: a large
population-based twin study in Sweden
• Lin Li presented details of a study conducted to assess the association
of ADHD in adulthood and dietary habits. The analysis particularly
aimed to understand whether the symptomatic dimensions of ADHD
(such as inattention, hyperactivity, and impulsivity) are specifically
associated with certain dietary habits.
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• The data source used was the Study of Twin Adults: Genes and
Environment (STAGE), which comprised of adult twins aged 20-47
years old whom completed a food frequency questionnaire and were
assessed for ADHD symptom scores (N=17,999). In this study, ADHD
trait dimensions were positively associated with unhealthy dietary
habits, and negatively associated with healthy dietary habits. The
correlation of inattention and dietary habits was stronger than the
correlation between hyperactivity/impulsivity and diet. But, future
longitudinal studies with varying study designs are required to confirm
any associations.
003 - Impulsivity is associated with food intake, snacking, eating
disorders and obesity in a general population
• Sandrine Peneau presents results from the NutriNet-Sante cohort
study investigating the effect of impulsive behaviour traits (measured
using the Barratt Impulsiveness Scale, BIS-11), which are common in
ADHD, and unhealthy dietary behaviour. The cohort consisted of
51,368 adult participants in a web-based questionnaire which asks
specific questions about their behaviour and food intake.
• The results of this study suggest impulsive behaviour correlates with
poorer diet quality, increased snacking, presence of eating disorders
and being overweight or obese. Further longitudinal and experimental
studies are required to understand and confirm these correlations.
004 - Diet, physical activity and behavioral disinhibition in middle-aged
and older adults: a UK Biobank study
• Dr. Lizanne Schweren, PhD presents results from an analysis of the UK
biobank cohort (N=150,000) of middle-aged and older adults (aged
40-69 years), which aimed to answer the following research
questions:
1. Is ADHD associated with poor diet among middle-aged and
older adults?
2. Which dietary features are associated with ADHD?
3. Are these associations age- and/or sex-specific?
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• Participants of UK biobank cohort undergo multiple questionnaires
and multiple metrics are available including self-reported diagnoses of
mental illness (including ADHD), personality traits (e.g. behavioural
disinhibition), substance use, and ICD-10 hospital diagnoses. In this
study, the participants also answered questions about their dietary
habits.
• The study reports, in both women and men, a prudent diet is
associated with lower disinhibition. In men, disinhibition is associated
with meat and full-cream dairy consumption. Surprisingly, dietary
restriction of wheat/eggs/dairy was also associated with higher
disinhibition. This was unexpected as it is assumed disinhibition
affects a person’s ability to restrict oneself. The author suggested
multiple explanations for this including residual confounding caused
by non-Western dietary patterns, high prevalence of food intolerance
in impulsive individuals, effect of response tendency of highly
impulsive individuals. All associations in this study were found to be
very weak, and further research is required to better understand and
confirm correlations.
Hot Topic: New findings on ADHD trajectory from epidemiological
studies
001 - Trajectories of ADHD symptoms into adulthood: Data from five
cohorts
Rachel Blakey presents the results from an analysis of five international
cohorts of ADHD patients. This study modelled the trajectory of illness
based on level of symptoms (measured using DSM and SDQ).
ADHD symptoms typically decline during adolescence, but not for all
people. This study aimed to understand the trajectories of ADHD
symptoms in the general population and describe how symptoms change
across childhood, adolescence and into adulthood. The results suggest
that overall, average symptoms decrease with age. The study also showed
a slight uptick in severity of symptoms in ADHD patients between ages
17-21, which requires further study to understand the explanation why.
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002 - Genetic risk and ADHD trajectories across development
• Dr. Jessica Agnew-Blais presents the results of two projects aiming to
understand the association of genetic risk of ADHD and trajectories
across development:
• Polygenic risk and course of ADHD from childhood to young
adulthood: findings from a nationally representative cohort.
• Polygenic risk and late-onset ADHD: A cross-cohort study
• These projects involved analysis of data from various cohorts,
including the Environmental Risk Longitudinal (E-RISK) study based in
the UK. These cohorts provided data on participant’s ADHD diagnosis
(either through DSM-IV criteria or self/teacher/parent-report) and
genetic data to allow calculation of ADHD polygenic risk score (PRS).
• From early childhood to adolescence, ADHD PRS is associated with an
ADHD diagnosis and symptoms, but only explains a small amount of
the variance. It also showed that during this time, ADHD PRS was
consistently associated with elevated levels of symptoms, but had no
association with the rate of change over time.
• From childhood to young adulthood, persistent ADHD was associated
with higher ADHD PRS (but this association was not significantly
different to the association between PRS and remitted ADHD). This
study also showed that ADHD PRS is not elevated in patients with late-
onset ADHD, which does not support the hypothesis that these cases
were ‘missed’ in childhood. Also, analysis of young adults with
persistent or late-onset ADHD (identified in multiple cohorts; E-Risk,
Children of the 90s, Pelotas, The Dunedin study) showed that there is
no elevated genetic risk for depression, alcohol dependence or
cannabis use disorders in these patients.
003 - The neurobiological signature of the at-risk state for ADHD
• Dr Arthur Caye presents a study which aimed to replicate the risk
score for adult ADHD in a Brazilian cohort, apply the risk score to
separate individuals at low and high risk for ADHD, and compare these
low and high risk groups in terms of neurobiology and psychological
functioning.
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• The baseline sample included a community-based cohort of
children (aged 6-14 years, N=2,511) who were assessed for their
ADHD risk score (based on psychological assessment and
neuroimaging), and then followed up until the age of 12-22 years.
• In comparison of the risk scores (assessed using genetics and
neuropsychology) the relative risk of developing ADHD between
unaffected low and high-risk score groups was 22.76. While,
comparison of risk scores based on neuroimaging suggest the relative
risk of developing ADHD between low and high-risk score groups is
8.16. The neuroimaging analysis was based on relatively small sample
sizes which limited the study and further analysis is required. The
study concludes, based on the assessment of multiple risk factors,
individuals who are at risk of ADHD have a higher genetic load, ADHD
related brain alterations, and impaired neuropsychological
functioning.
004 - Predictors and outcomes of data-driven ADHD developmental
trajectories across three cohorts
• Aja Murray presents a study comparing the predictive characteristics
and outcomes of patients with varying trajectories of ADHD which
aims to find answers to the following questions.
• Are there early markers of later-onset symptoms?
• Are there clinically meaningful differences between later vs early
onset subtypes?
• What differentiates those whose symptoms persist vs remit?
• The Millenium Cohort Study (MCS) includes parent-reported ADHD
symptoms for children aged 3,5,7,11,14 (N=11,316). This dataset was
analysed to understand the predictive characteristics of different
ADHD profiles. Based on analysis of the MCS cohort, patients with late
childhood/adolescent onset vs. pre-school onset were more likely to
be female, have fewer conduct problems at age 3, and higher school
readiness scores at age 3. Those with pre-school onset/persistent
ADHD vs. partially remitting class were more likely to be male and had
more conduct problems at age 3. Those with late
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childhood/adolescent onset ADHD vs. those unaffected were
more likely to be male, premature born, and had more conduct and
peer problems age 3.
• The Zurich Project on social development from childhood to
adulthood (z-proso) cohort includes teacher-reported ADHD
symptoms data at ages 7-15 (N=1,572). This dataset was analysed to
assess how outcomes (including prosociality, internalising, aggression,
violent ideations, delinquency, cigarette smoking, alcohol use, and
self-reported ADHD symptoms) vary by different ADHD trajectories. By
late adolescence, both later onset and earlier onset/persistent ADHD
categories scored significantly worse on a range of psychosocial
outcomes vs. unaffected people. There were few significant
differences between later vs. earlier onset ADHD categories.
• Overall, late onset ADHD subtype was evident in both cohorts and
shows similar psychosocial outcomes to earlier onset ADHD by late
adolescence. Late onset ADHD also shows more early markers relative
to those who never develop symptoms, it seems to be more
characteristic of females and may reflect delayed onset due to
compensatory strengths.
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