Chronic irritability in ADHD: examining clinical and genetic links with depression

Background: Attention-deficit/hyperactivity disorder (ADHD) and other neurodevelopmental disorders are often associated with depression. Irritability is common in ADHD and other neurodevelopmental disorders, and has been linked to depression in the general population. However, research into the link between irritability and depression in those with neurodevelopmental disorders is lacking. This thesis aimed to examine the association between childhood irritability and depression in young people with ADHD, and in a group with broader neurodevelopmental difficulties. Methods: A clinical ADHD sample, the Study of ADHD Genes and Environment, was used to examine the association between childhood irritability and depression symptoms in young people with ADHD. The same sample was used to examine whether children with ADHD and irritability have an increased genetic liability for depression (indexed by depression polygenic risk scores (PRS)), compared to those with ADHD but no irritability. Finally, a longitudinal population-based cohort, the Avon Longitudinal Study of Parents and Children, was used to examine the role of irritability in the association between childhood neurodevelopmental difficulties and later depression. Results: Childhood irritability was associated with depression symptoms cross-sectionally and longitudinally in the clinical ADHD sample. Persistent irritability across childhood and adolescence was particularly important in the longitudinal association. Childhood irritability was not associated with depression PRS in children with ADHD (although irritability was associated with ADHD PRS). Finally, irritability was important in the association between neurodevelopmental difficulties and later depression in the population-based cohort, specifically in those with ADHD and ASD difficulties. Conclusion: Findings from this thesis suggest that childhood irritability is an important marker of depression risk in children diagnosed with ADHD, as well in children with ADHD and ASD difficulties in the general population. Assessing irritability in children with ADHD and ASD difficulties may allow early identification and treatment of depression, as well as provide an opportunity for prevention

Irritability in ADHD: Associations with depression liability

Background: Irritability and the new DSM-5 diagnostic category of Disruptive Mood Dysregulation Disorder (DMDD) have been conceptualised as related to mood disorder. Irritability is common in Attention Deficit Hyperactivity Disorder (ADHD) but little is known about its association with depression risk in this group. This study aims to establish levels of irritability and prevalence of DMDD in a clinical sample of children with ADHD, and examine their association with anxiety, depression and family history of depression. Methods: The sample consisted of 696 children (mean age 10.9 years) with a diagnosis of ADHD, recruited from UK child psychiatry and paediatric clinics. Parents completed the Child and Adolescent Psychiatric Assessment, a semi-structured diagnostic interview, about their child. This was used to establish prevalence of DMDD, anxiety disorder and depressive disorder, as well as obtain symptom scores for irritability, anxiety and depression. Questionnaires assessed current parental depression, and family history of depression. Result: Irritability was common, with 91% endorsing at least one irritable symptom. 3-month DMDD prevalence was 31%. Children with higher levels of irritability or DMDD were more likely to have comorbid symptoms of anxiety, depression and a family history of depression. Limitations: Results are based on a clinical sample, so may not be generalizable to children with ADHD in the general population. Conclusions: Irritability and DMDD were common, and were associated with markers of depression liability. Longitudinal studies are needed to examine the association between irritability and depression in youth with ADHD as they get older

Adverse childhood experiences and adult mood problems: evidence from a five-decade prospective birth cohort

Background Retrospectively recalled adverse childhood experiences (ACEs) are associated with adult mood problems, but evidence from prospective population cohorts is limited. The aims of this study were to test links between prospectively ascertained ACEs and adult mood problems up to age 50, to examine the role of child mental health in accounting for observed associations, and to test gender differences in associations. Methods The National Child Development Study is a UK population cohort of children born in 1958. ACEs were defined using parent or teacher reports of family adversity (parental separation, child taken into care, parental neglect, family mental health service use, alcoholism and criminality) at ages 7–16. Children with no known (n = 9168), single (n = 2488) and multiple (n = 897) ACEs were identified in childhood. Adult mood problems were assessed using the Malaise inventory at ages 23, 33, 42 and 50 years. Associations were examined separately for males and females. Results Experiencing single or multiple ACEs was associated with increased rates of adult mood problems after adjustment for childhood psychopathology and confounders at birth [2+ v. 0 ACEs – men: age 23: odds ratio (OR) 2.36 (95% confidence interval (CI) 1.7–3.3); age 33: OR 2.40 (1.7–3.4); age 42: OR 1.85 (1.4–2.4); age 50: OR 2.63 (2.0–3.5); women: age 23: OR 2.00 (95% CI 1.5–2.6); age 33: OR 1.81 (1.3–2.5); age 42: OR 1.59 (1.2–2.1); age 50: OR 1.32 (1.0–1.7)]. Conclusions Children exposed to ACEs are at elevated risk for adult mood problems and a priority for early prevention irrespective of the presence of psychopathology in childhood

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

Irritability in ADHD: association with later depression symptoms

Attention-deficit/hyperactivity disorder (ADHD) and depression commonly co-occur. Identifying children with ADHD at risk for later depression may allow early intervention and prevention. Irritability is one possible mechanism linking these two disorders. It is common in ADHD and associated with later depression in the general population. Cross-sectional studies suggest an association between irritability and depression in ADHD, but longitudinal research is limited. This study followed up a clinical ADHD sample longitudinally to examine: (1) the association between childhood irritability and later depression symptoms, and (2) whether irritability persistence is important in this association. At baseline, parents (n = 696) completed semi-structured interviews about their child (mean age = 10.9), providing information on child psychopathology, including irritability. A subsample (n = 249) was followed up after a mean of 5.4 years. Parent-completed Mood and Feelings Questionnaires provided information on depressive symptoms at follow-up. Parent-rated structured diagnostic interviews provided information on ADHD diagnosis and irritability at follow-up. Regression analyses examined associations between (i) baseline irritability and depression symptoms at follow-up, and (ii) persistent (vs. remitted) irritability and depression symptoms at follow-up. Analyses controlled for age, gender, depression symptoms, anxiety, ADHD symptoms, and ADHD medication at baseline. Baseline irritability was associated with depression symptoms at follow-up, but the association attenuated after controlling for anxiety and ADHD symptoms. Persistent irritability was associated with depression symptoms at follow-up, after including all covariates. Children with ADHD with persistent irritability are at elevated risk of developing depression symptoms. They may be a target for early intervention and prevention of depression

Gaining approvals for mental health research in the NHS

When embarking on mental health research it is often necessary to apply for approvals from one or more review bodies to ensure that the research is ethical and that the safety and well-being of participants are safeguarded. This can be complicated and time consuming, particularly to those unfamiliar with the process. In this article we describe the approvals commonly required for National Health Service-based research involving patients and endeavour to clearly explain what is involved at each stage. We then highlight some of the main considerations, including ethical aspects, which are particularly pertinent to conducting research in the field of mental health, and finish with general advice and considerations for future developments in the area

What explains the link between childhood ADHD and adolescent depression? Investigating the role of peer relationships and academic attainment

There is increasing evidence that childhood Attention-Deficit Hyperactivity Disorder (ADHD) elevates risk of later depression, but the mechanisms behind this association are unclear. We investigated the relationship between childhood ADHD symptoms and late-adolescent depressive symptoms in a population cohort, and examined whether academic attainment and peer problems mediated this association. ALSPAC (Avon Longitudinal Study of Parents and Children) is an ongoing prospective longitudinal population-based UK cohort that has collected data since September 1990. 2950 individuals with data on parent-reported ADHD symptoms in childhood (7.5 years) and self-reported depressive symptoms in late adolescence (17.5 years) were included in analyses. 2161 individuals with additional data at age 16 years on parent-reported peer problems as an indicator of peer relationships and formal examination results (General Certificate of Secondary Education; GCSE) as an indicator of academic attainment were included in mediation analyses. Childhood ADHD symptoms were associated with higher depressive symptoms (b = 0.49, SE = 0.11, p < 0.001) and an increased odds of clinically significant depressive symptoms in adolescence (OR = 1.27, 95% CI 1.15–1.41, p < 0.001). The association with depressive symptoms was mediated in part by peer problems and academic attainment which accounted for 14.68% and 20.13% of the total effect, respectively. Childhood ADHD is associated with increased risk of later depression. The relationship is mediated in part by peer relationships and academic attainment. This highlights peer relationships and academic attainment as potential targets of depression prevention and intervention in those with ADHD. Future research should investigate which aspects of peer relationships are important in conferring later risk for depression

Antecedents of new-onset major depressive disorder in adolescence: a longitudinal familial high-risk study

Importance: Early-onset major depressive disorder (MDD) is common in individuals at high familial risk of depression and is associated with poor long-term mental health, social, and educational outcomes. Objectives: To examine the developmental pathways that lead to first-episode adolescent-onset MDD (incident cases) in those at high familial risk and to postulate a theoretically informed model that enables simultaneous testing of different pathways to incident adolescent-onset MDD composed of contributions from familial/genetic and social risk factors, as well as effects via specific clinical antecedents. Design, Setting, and Participants: This investigation was a 4-year longitudinal study (April 2007 to March 2011) among offspring of depressed parents in the general community. Analyses were conducted between September 1, 2015, and May 27, 2016. Participants were 337 families in whom the index parent (315 mothers and 22 fathers) had experienced at least 2 episodes of MDD (recruited through primary care) and among whom there was a biologically related child in the age range of 9 to 17 years living with the index parent (197 girls and 140 boys with a mean [SD] age of 12.4 [2.0] years) at baseline. Offspring with MDD before the study or at baseline (n = 27), offspring with an episode of MDD that had remitted by follow-up (n = 4), and offspring with missing baseline MDD data (n = 2) were excluded. Ninety-two percent (279 of 304) of families completed the follow-up. Main Outcomes and Measures: The primary outcome was new-onset offspring MDD, and the secondary outcome was the total DSM-IV MDD symptom score. Results: On average, children and adolescents had a mean (SD) of 1.85 (1.74) (range, 0-8.5) DSM-IV symptoms of MDD at follow-up. Twenty (6 males and 14 females) had new-onset MDD, with a mean (SD) age at onset of 14.4 (2.0) years (range, 10-18 years). Irritability (β = 0.12, P = .03) and fear and/or anxiety (β = 0.38, P < .001) were significant independent clinical antecedents of new adolescent-onset MDD, but disruptive behavior (β = −0.08, P = .14) and low mood (β = −0.03, P = .65) were not. The results were similar for the DSM-IV symptom count at follow-up. All the measured familial/genetic and social risk indicators directly influenced risk for new-onset MDD rather than indirectly through acting on dimensional clinical antecedents. Conclusions and Relevance: There are multiple pathways to first-onset adolescent depression in individuals at familial risk. Irritability and fear/anxiety may be additional clinical phenomena to be included as targets in primary preventive interventions focusing on the child. In addition to targeting these phenomena in parents and children, depression prevention methods in high-risk groups may need to take into consideration social risks, such as poverty and psychosocial adversity

Exploring ADHD symptoms and associated impairment across development

Objective ADHD symptoms typically decline with age, but less is known about whether the presentation of specific ADHD symptoms differs across development. This study aimed to examine the frequency and associated impairment of specific ADHD symptoms in childhood, adolescence, and young adulthood. Method A prospective, longitudinal cohort, the Avon Longitudinal Study of Parents and Children, was utilized (N = 2,327). ADHD symptoms and impairment were assessed using the Development and Well Being Assessment at ages 7, 15, and 25. Results Specific ADHD symptom frequencies and their associated impairment varied across development for the majority of symptoms, although easily distracted was one of the most commonly reported symptoms at each age, and difficulty sustaining attention was consistently associated with high levels of impairment. Conclusion These findings suggest differences in the presentations of ADHD symptoms across development: current understanding of how ADHD presents in childhood/adolescence may not be generalizable to young adulthood