The Habenula in the Link Between ADHD and Mood Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset, neurodevelopmental disorder, whereas major depressive disorder (MDD) is a mood disorder that typically emerges in adulthood. Accumulating evidence suggests that these seemingly unrelated psychiatric disorders, whose symptoms even appear antithetical [e.g., psychomotor retardation in depression vs. hyperactivity (psychomotor acceleration) in ADHD], are in fact associated with each other. Thus, individuals with ADHD exhibit high comorbidity with MDD later in life. Moreover, genetic studies have shown substantial overlaps of susceptibility genes between ADHD and MDD. Here, we propose a novel and testable hypothesis that the habenula, the epithalamic brain region important for the regulation of monoamine transmission, may be involved in both ADHD and MDD. The hypothesis suggests that an initially hypoactive habenula during childhood in individuals with ADHD may undergo compensatory changes during development, priming the habenula to be hyperactive in response to stress exposure and thereby increasing vulnerability to MDD in adulthood. Moreover, we propose a new perspective on habenular deficits in psychiatric disorders that consider the habenula a neural substrate that could explain multiple psychiatric disorders.