Associations between parental psychopathology and markers of severity in children with ADHD

Attention Deficit Hyperactivity Disorder (ADHD) is a disabling neurodevelopmental disorder that has major adverse consequences for individuals and their families. Although ADHD is recognized to be a familial and heritable disorder, little is understood about the relationship between parental psychopathology and variation in the clinical and cognitive presentations of children with ADHD. The first aim of this thesis, which is based on a clinical sample of 570 children with ADHD, was to investigate the association between parental ADHD (based on diagnostic symptom criteria) and offspring clinical features. Results suggest parental ADHD indexes higher risk for a more severe clinical presentation of ADHD in children and higher levels of family conflict. The second aim was to investigate the influence of maternal ADHD and depression on children's clinical presentation outcome, on average two and half years after initial assessment. Maternal depression, but not maternal ADHD, was found to predict an increase in child conduct symptoms, but neither maternal depression nor maternal ADHD contributed to ADHD symptom levels, after adjusting for conduct symptom severity at baseline. Finally the third aim was to assess the role of parental psychopathology (ADHD or depression) in contributing to cognitive variation in children with ADHD. Parent ADHD but not parent depression was found to be associated with lower scores on tasks assessing working memory and set shifting abilities. Overall, these findings extend the understanding of the association between parental psychopathology and phenotype variation in children with ADHD. It indicates that children with more severe clinical presentations and greater pre-frontal cognitive impairments are more likely to have a parent with mental health difficulties. This highlights the importance of considering parent mental health during clinical assessment which can have important implications when considering families’ engagement with services, treatment and intervention strategies as well as planning the intensity of child follow-up

Parent psychopathology and neurocognitive functioning in children with ADHD

Objective: The objective of this study was to examine the association between parent mental health (ADHD and depression) and offspring performance on neurocognitive tasks in children with ADHD. Method: The clinical sample consisted of 570 children (85% males, mean age: 10.77 years) with ADHD who completed neurocognitive tasks measuring working memory, attention set-shifting, and motivational deficits. Questionnaire measures were used to assess ADHD and depression symptom presence in parents. Results: Controlling for ADHD severity, children of parents with ADHD had poorer working memory (B = −0.25, 95% confidence interval [CI] [−0.45, −0.07], p = .01) and increased errors on the extra dimensional shift stage of the set-shifting task (B = 0.26 95% CI [0.02, 0.50], p = .04). Parent depression was not associated with offspring performance on any of the assessed neurocognitive tasks. Conclusion: Children with ADHD who have a parent with ADHD symptom presence are a subgroup of children who may have additional neurocognitive impairments that have potential implications when implementing interventions that target cognition and learning

The presentation of depression symptoms in attention-deficit/hyperactivity disorder: comparing child and parent reports

Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with depression, and out- comes are poor when both are present. Little is known about whether depression symptoms present differ- ently in ADHD compared to the general population, or how reliable young people with ADHD are at reporting these symptoms. This study aimed to describe depression symptoms in a clinical ADHD sample compared to a population sample, and compare self-reports of depression symptoms with parent-reports. Methods: Two hundred and forty-nine children with ADHD and their parents completed follow-up questionnaires around 5 years after taking part in a Cardiff University ADHD study. Child depression symptoms were measured using parent- and child-reported Mood and Feelings Questionnaires (MFQ) and compared to a population sample with MFQ data (n = 1460). Within both samples, child- and parent-reported depression symptoms were com- pared. Results: Although the profile of depression symptoms was similar between young people with ADHD and those in the general population, depression symptoms were much more common in the ADHD sample (parent-rated MFQ score = 24.52 vs. 9.39; child-rated = 21.02 vs. 11.86). The most common symptoms in both samples included irritability, restlessness and concentration difficulties, with core depression symptoms such as feeling miserable/unhappy also prominent. Within the ADHD sample, but not the population sample, children reported depression symptoms less frequently than their parents. Conclusions: Young people with ADHD are at high risk of experiencing symptoms of depression but may under-report the severity of their symptoms. Obtaining parent reports of depression symptoms in this group may be important to avoid missing key indica- tors of risk

Assessment of age-at-onset criterion for adult attention-deficit hyperactivity disorder

To investigate the accuracy of the age-at-onset criterion in those who meet other DSM-5 ADHD criteria (N=138), using a prospective population cohort, we compared four different approaches to asking those at age 25 years when their symptoms started. Receiver Operating Characteristic curves showed variation between the approaches (χ((3)))=8.99, p=0.03); all four showed low discrimination against symptoms that had been assessed when they were children (area under the curve 0.57-0.68). Asking adults to recall specific symptoms may be preferable to recalling at what age symptoms started. However limitations to retrospective recall add to debate on the validity of ADHD age-at-onset assessment

A brief report: de novo copy number variants in children with attention deficit hyperactivity disorder

Recent case–control genetic studies of attention deficit hyperactivity disorder (ADHD) have implicated common and rare genetic risk alleles, highlighting the polygenic and complex aetiology of this neurodevelopmental disorder. Studies of other neurodevelopmental disorders, such as autism spectrum disorder (ASD), Tourette disorder, developmental delay/intellectual disability and schizophrenia indicate that identification of specific risk alleles and additional insights into disorder biology can be gained by studying non-inherited de novo variation. In this study, we aimed to identify large de novo copy number variants (CNVs) in children with ADHD. Children with a confirmed diagnosis of ADHD and their parents were genotyped and included in this sample. We used PennCNV to call large (>200 kb) CNVs and identified those calls that were present in the proband and absent in both biological parents. In 305 parent–offspring trios, we detected 14 de novo CNVs in 13 probands, giving a mutation rate of 4.6% and a per individual rate of 4.3%. This rate is higher than published reports in controls and similar to those observed for ASD, schizophrenia and Tourette disorder. We also identified de novo mutations at four genomic loci (15q13.1–13.2 duplication, 16p13.11 duplication, 16p12.2 deletion and 22q11.21 duplication) that have previously been implicated in other neurodevelopmental disorders, two of which (16p13.11 and 22q11.21) have also been implicated in case–control ADHD studies. Our study complements ADHD case–control genomic analyses and demonstrates the need for larger parent–offspring trio genetic studies to gain further insights into the complex aetiology of ADHD

Preschool development, temperament and genetic liability as early markers of childhood ADHD: A cohort study

Background: ADHD is associated with multiple adverse outcomes and early identification is important. The present study sets out to identify early markers and developmental characteristics during the first 30 months of life that are associated with ADHD 6 years later. Methods: 9201 participants from the prospective Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were included. Outcome measures were parent‐rated ADHD symptom scores (Strengths and Difficulties Questionnaire, SDQ) and ADHD diagnosis (Development and Wellbeing Assessment, DAWBA) at age 7. Seventeen putative markers were identified from previous literature and included: pre‐ and peri‐natal risk factors, genetic liability (ADHD polygenic risk scores, PRS), early development, temperament scores and regulatory problems. Associations were examined using regression analysis. Results: Univariable regression analysis showed that multiple early life factors were associated with future ADHD outcomes, even after controlling for sex and socio‐economic status. In a multivariable linear regression model; temperament activity scores (B = 0.107, CI = 0.083–0.132), vocabulary delay (B = 0.605, CI = 0.211–0.988), fine motor delay (B = 0.693, CI = 0.360–1.025) and ADHD PRS (B = 0.184, CI = 0.074–0.294) were associated with future symptoms (R2 = 10.7%). In a multivariable logistic regression model, ADHD PRS (OR = 1.39, CI = 1.10–1.77) and temperament activity scores (OR = 1.09, CI = 1.04–1.16) showed association with ADHD diagnosis. Conclusion: As well as male sex and lower socio‐economic status, high temperament activity levels and motor and speech delays in the first 30 months of life, are associated with childhood ADHD. Intriguingly, given that genetic risk scores are known to explain little of the variance of ADHD outcomes, we found that ADHD PRS added useful predictive information. Future research needs to test whether predictive models incorporating aspects of early development and genetic risk scores are useful for predicting ADHD in clinical practice

Investigating the associations between irritability and hot and cool executive functioning in those with ADHD

Background Irritability is especially pertinent to those with Attention Deficit Hyperactivity Disorder (ADHD) as it is highly prevalent and associated with a more severe clinical presentation and poorer longitudinal outcomes. Preliminary evidence suggests that top-down cognitive processes taking place in emotional contexts (i.e., hot executive functions) as opposed to those evoked in abstract scenarios (i.e., cool executive functions) may be relevant to the presentation of irritability in ADHD. This study explored the cognitive mechanisms underlying irritability in young people with ADHD, hypothesising that irritability would be associated with hot, but not cool, executive function impairments. Methods Our sample included 219 individuals with ADHD. A composite irritability score was derived extracting items from a parent interview, with scores ranging from 0 to 5. Associations were investigated using linear regression analyses, between irritability and four hot tasks measuring sensitivity to risk, risk-taking behaviour following reward or punishment, acceptance of reward delay and reaction to unfair behaviour from others, and two cool tasks measuring set-shifting and motor inhibition. Results As hypothesised, there were no significant associations between irritability and cool executive functions in those with ADHD; however, contrary to expectations, there was also no significant evidence that hot executive functions were associated with irritability. Conclusions These results, in a large well characterised sample and using a comprehensive task battery, suggest that the variation in irritability in those with ADHD may not be associated with differences in hot or cool executive function performance

Investigating the validity of the Strengths and Difficulties Questionnaire to assess ADHD in young adulthood

Attention Deficit Hyperactivity Disorder (ADHD) symptoms typically onset early and persist into adulthood for many. Robust investigation of symptom continuity and discontinuity requires repeated assessments using the same measure, but research is lacking into whether measures used to assess ADHD symptoms in childhood are also valid in adulthood. The Strengths and Difficulties Questionnaire (SDQ) is widely used to assess ADHD symptoms in children, but little is known about its utility in adulthood. The aim of this study was to assess the validity of the SDQ hyperactivity/ADHD subscale to distinguish between cases and non-cases of DSM-5 ADHD at age 25 years in a UK population cohort (N=4121). ADHD diagnosis was derived using the Barkley Adult ADHD Rating Scale-IV. Analyses suggested that the self-rated SDQ ADHD subscale had high validity in distinguishing ADHD cases/non-cases in young adulthood (area under the curve=0.90, 95% CI=0.87-0.93) and indicated a lower cut-point for identifying those who may have an ADHD diagnosis in this age group compared to that currently recommended for younger ages. Findings were similar for parent-reports. Our findings suggest that the SDQ is suitable for ADHD research across different developmental periods, which will aid the robust investigation of ADHD from childhood to young adulthood

Validation of the short Mood and Feelings Questionnaire in young adulthood

BACKGROUND: Depression often onsets in adolescence and is associated with recurrence in adulthood. There is a need to identify and monitor depression symptoms across adolescence and into young adulthood. The short Mood and Feelings Questionnaire (sMFQ) is commonly used to measure depression symptoms in adolescence but has not been validated in young adulthood. This study aimed to (1) examine whether the sMFQ is valid in young adulthood, and (2) identify cut-points best capturing DSM-5 depression diagnosis at age 25 METHODS: The sample included participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 25 (n = 4098). Receiver Operating Characteristic analyses examined how well the self-rated sMFQ discriminates between cases and non-cases of DSM-5 Major Depressive Disorder (MDD) classified using the self-rated Development and Well Being Assessment. Sensitivity and specificity values were used to identify cut-points on the sMFQ RESULTS: The sMFQ had high accuracy for discriminating MDD cases from non-cases at age 25. The commonly used cut-point in adolescence (≥12) performed well at this age, best balancing sensitivity and specificity. However, a lower cut-point (≥10) may be appropriate when favouring sensitivity over specificity e.g., in context of screening. Sensitivity analyses suggested similar results for males and females LIMITATIONS: ALSPAC is a longitudinal population cohort that suffers from non-random attrition CONCLUSIONS: The sMFQ is a valid measure of depression in young adults in the general population. It can be used to screen for and monitor depression across adolescence and early adulthood