ADHD and depression: investigating a causal explanation

Abstract

Background Attention-deficit hyperactivity disorder (ADHD) is associated with later depression and there is considerable genetic overlap between them. This study investigated if ADHD and ADHD genetic liability are causally related to depression using two different methods. Methods First, a longitudinal population cohort design was used to assess the association between childhood ADHD (age 7 years) and recurrent depression in young-adulthood (age 18–25 years) in N = 8310 individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC). Second, two-sample Mendelian randomization (MR) analyses examined relationships between genetic liability for ADHD and depression utilising published Genome-Wide Association Study (GWAS) data. Results Childhood ADHD was associated with an increased risk of recurrent depression in young-adulthood (OR 1.35, 95% CI 1.05–1.73). MR analyses suggested a causal effect of ADHD genetic liability on major depression (OR 1.21, 95% CI 1.12–1.31). MR findings using a broader definition of depression differed, showing a weak influence on depression (OR 1.07, 95% CI 1.02–1.13). Conclusions Our findings suggest that ADHD increases the risk of depression later in life and are consistent with a causal effect of ADHD genetic liability on subsequent major depression. However, findings were different for more broadly defined depression.

ADHD in adults with recurrent depression

“…Our findings suggest that a proportion of women in mid-life with a history of early-onset, recurrent depression that has been severely impairing may have undetected ADHD. Previous studies have shown associations of ADHD in childhood and adolescence with more severe depressive outcomes in young adulthood, such as depression recurrence, suicide and hospitalisation (4,5). There is also evidence from a national register-based study that those with ADHD and depression may be at higher risk of antidepressant treatment resistance than those with depression alone (11).…”

“…The SCAN (16) was used to assess self-harm or suicide at each wave with the question “Have you thought about harming yourself or even made an attempt at suicide during the last month?”. Participants responses were coded as ‘absent’ (0), ‘intrusive thoughts but no attempt’ (1), ‘injured self but no serious harm resulted’ (2), ‘injured self and serious harm resulted’ (3) or ‘made an attempt at suicide designed to result in death’ (4). A binary variable capturing whether participants had ever reported self-harm or suicide attempts at any of the four assessment waves was derived.…”

“…Depression is a highly heterogeneous disorder that varies in its origins and clinical presentation (1–3). Individuals with attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder, are at high risk of early-onset, recurrent depression (4,5). Epidemiological and clinical studies report associations between early onset depression and neurodevelopmental disorders and traits, especially ADHD (5–9).…”

Investigating Friendship Difficulties in the Pathway from ADHD to Depressive Symptoms. Can Parent–Child Relationships Compensate?

“…Despite the longitudinal design used, there is a possibility that reverse causation contributed to observed associations. However, evidence suggests that ADHD precedes depression in a potentially causal relationship (Riglin et al, 2020) and that the prospective relationship exists over long periods of time and when adjusting for prior emotional disorder symptomatology (Powell et al, 2020). Moreover, a sensitivity check found that ADHD symptoms were associated with subsequent depressive symptoms when adjusting for baseline self-reported SDQ emotional problems (Goodman, 1997;Supplement 9).…”

“…Attention Deficit/Hyperactivity Disorder (ADHD) is a DSM-5 (American Psychiatric Association, 2013) defined neurodevelopmental disorder that is associated with a range of long term adverse outcomes, including employment and education difficulties, interpersonal problems, substance abuse, suicide and depression (Harpin, 2005;Ljung et al, 2014;Meinzer et al, 2014). There is strong evidence that ADHD precedes depression in a way that is consistent with a potentially causal relationship (Riglin et al, 2020), but the mechanisms that might explain the relationship between ADHD and later depression are unclear. ADHD impacts on many aspects of a young person's life, including functioning in social, school and home life (Harpin, 2005), that might in turn increase the risk of subsequent depression.…”