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