Irritability in ADHD: Associations with depression liability

Child Psychology Psychiatry

et al. 2019

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Background Children with neurodevelopmental disorders are at increased risk of developing depression. Irritability predicts depression in the general population and is common in children with neurodevelopmental disorders. Thus, it is possible that irritability in children with neurodevelopmental disorders contributes to the link with later depression. This study aimed to (a) examine the association between childhood neurodevelopmental difficulties and adolescent depression and (b) test whether irritability explains this association. Methods Children with any neurodevelopmental difficulty at the age of 7–9 (n = 1,697) and a selected, comparison group without any neurodevelopmental difficulty (n = 3,177) were identified from a prospective, UK population‐based cohort, the Avon Longitudinal Study of Parents and Children. Neurodevelopmental difficulties were defined as a score in the bottom 5% of the sample on at least one measure of cognitive ability, communication, autism spectrum symptoms, attention‐deficit/hyperactivity symptoms, reading or motor coordination. The Development and Well‐Being Assessment measured parent‐reported child irritability at the age of 7, parent‐reported adolescent depression at the age of 10 and 13, and self‐reported depression at the age of 15. Depression measures were combined, deriving an outcome of major depressive disorder (MDD) in adolescence. Logistic regression examined the association between childhood neurodevelopmental difficulties and adolescent MDD, controlling for gender. Path analysis estimated the proportion of this association explained by irritability. Analyses were repeated for individual neurodevelopmental problems. Results Childhood neurodevelopmental difficulties were associated with adolescent MDD (OR = 2.11, 95% CI = 1.24, 3.60, p = .006). Childhood irritability statistically accounted for 42% of this association. On examining each neurodevelopmental difficulty separately, autistic, communication and ADHD problems were each associated with depression, with irritability explaining 29%–51% of these links. Conclusions Childhood irritability appears to be a key contributor to the link between childhood neurodevelopmental difficulties and adolescent MDD. High rates of irritability in children with autistic and ADHD difficulties may explain elevated rates of depression in the neurodevelopmental group.

Section: Discussionmentioning

confidence: 99%

“…Cross‐sectional studies find evidence that irritability is associated with depressive symptoms in children with ADHD (Ambrosini, Bennett, & Elia, ; Eyre et al., ; Seymour et al., ). Further, in a clinical ASD sample, the irritable dimension of ODD was associated with emotional problems (Mandy, Roughan, & Skuse, ).…”

Section: Introductionmentioning

confidence: 99%

Childhood neurodevelopmental difficulties and risk of adolescent depression: the role of irritability

Eyre

Hughes

Child Psychology Psychiatry

et al. 2019

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“…Given the focus by on exploring crossdisorder effects including eight psychiatric disorders and reporting based on statistics across all eight diagnoses, regions impacting only ADHD and MDD are likely to be omitted from the key findings due to insufficient evidence across the remaining six diagnoses. Risk mechanisms that explain the link between ADHD and depression might also involve other phenotypes that have not been previously studied; for example, psychiatric phenotypes such as early irritability and anxiety are known antecedents of depression, including in those with ADHD (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: A GWAS meta-analysis

Powell

Martin

et al. 2020

Preprint

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Attention deficit/hyperactivity disorder (ADHD) demonstrates a high level of comorbidity with major depressive disorder (MDD). One possible contributor to this is that the two disorders show high genetic correlation. However, the specific regions of the genome that may be responsible for this overlap are unclear. To identify variants associated with both ADHD and MDD, we performed a meta-analysis of GWAS of ADHD and MDD. All genome wide significant (p=5x10 -8 ) SNPs in the meta-analysis that were also strongly associated (p=5x10 -4 ) independently with each disorder were followed up. These putatively pleiotropic SNPs were tested for additional associations across a broad range of phenotypes. Fourteen linkage disequilibrium-independent SNPs were identified that were associated with each disorder separately (p=5x10 -4 ) and in the cross-disorder meta-analysis (p=5x10 -8 ). Nine of these SNPs had not been reported previously in either individual GWAS and can be considered as novel signals. Evidence supported nine of the fourteen SNPs acting as eQTL and two of the SNPs as brain eQTL. Index SNPs and their genomic regions demonstrated associations with other mental health phenotypes. Through conducting meta-analysis on ADHD and MDD only, our results build upon the previously observed genetic correlation between ADHD and MDD and reveal novel regions of the genome that may be implicated in this overlap.

“…Thus both trajectory classes are associated with risk of major depression in adolescence, although the mechanisms of this associations are likely different, for example increased risk for MDD in the early-onset irritability subtype may be driven by environmental factors, such as increased life events associated with irritability, rather than genetic risk for MDD -although further work into this would be needed. It is established that child neurodevelopmental disorders such as ADHD, as well as oppositional defiant disorder and conduct problems, are risk factors for later depression so it is perhaps unsurprising that the 'neurodevelopmental' irritability trajectory is also associated with depression, although emerging research suggests that the presence of irritability in those with ADHD confers additional risk of depression (31).…”

Section: Discussionmentioning

confidence: 99%

“…Yet irritability -and, more broadly, emotional dysregulation -is an especially common feature of attention-deficit/hyperactivity disorder (ADHD), which is grouped as a neurodevelopmental disorder under DSM-5. Irritability prevalence rates of 91% have been reported in children with the disorder (10). Evidence of clinical overlap between irritability and ADHD (11,12), genetic overlap with ADHD, as well as features such as its manifestation in early development and male preponderance also have led recently to the suggestion that irritability should perhaps be conceptualised as a neurodevelopmental/ADHD-like problem, rather than a mood problem (12).…”

Section: Introductionmentioning

confidence: 99%

Identifying novel subtypes of irritability using a developmental genetic approach

Riglin

Eyre

et al. 2018

Preprint

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Objective. Irritability is a common reason for referral to services, strongly associated with impairment and negative outcomes, but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. This study used a developmental approach to test the hypothesis that there are several forms of irritability, including a 'neurodevelopmental/ADHD-like' subtype with onset in childhood and a 'depression/mood' subtype with onset in adolescence. Method. Data were analyzed in the Avon Longitudinal Study of Parents and Children, a prospective UK population-based cohort. Irritability trajectoryclasses were estimated for 7924 individuals with data at multiple time-points across childhood and adolescence (4 possible time-points from approximately ages 7 to 15 years). Psychiatric diagnoses were assessed at approximately ages 7 and 15 years. Psychiatric genetic risk was indexed by polygenic risk scores (PRS) for attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) derived using large genome-wide association study results.Results. Five irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), late-childhood limited (5.2%) and high-persistent (2.4%). The early-onset, high-persistent trajectory was associated with male preponderance, childhood ADHD (OR=108. 64 (57.45-204.41), p<0.001) and ADHD PRS (OR=1.31 (1.09-1.58), p=0.005); the adolescent-onset, increasing trajectory was associated with female preponderance, adolescent ), p<0.001) and MDD PRS (OR=1.20, (1.05-1.38), p=0.009). Both trajectory classes were associated with MDD diagnosis and ADHD genetic risk. Conclusions. The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability maybe more 'neurodevelopmental/ADHD-like' and later-onset irritability more 'depression/mood-like'. This has implications for treatment as well as nosology.