Potential hormonal mechanisms of attention-deficit/hyperactivity disorder and major depressive disorder: a new perspective.

Hormonal influences on the organization of behavior are apparent to neuroendocrinologists but under-examined in relation to childhood and adolescent mental disorders. A central mystery in the field of developmental psychopathology is the preferential male vulnerability to behavior disorders in childhood and female vulnerability to emotional disorders in adolescence. Relative neglect of a hormonal explanation may be due to lack of simple or unifying conceptual paradigms to guide studies. This paper seeks to stimulate research in this area by drawing upon clinical psychology and neuroscience literatures to offer a heuristic paradigm for clinical research. Two syndromes are selected here for illustration: Attention-Deficit/Hyperactivity Disorder (ADHD) and Major Depressive Disorder (MDD), because they have opposite gender risk profiles. Two guiding theories are evaluated. First, prenatal organizational effects of testosterone may modulate striatally-based dopaminergic circuits in such a way as to place boys at greater risk for early developing inattention and disruptive behavioral disorders. Second, activational effects of estradiol at puberty may modulate amygdalar and other circuitry, with particular effects on serotonergic pathways, in such a way as to place girls at greater risk for internalizing and mood disorders. Hypotheses from these theories are evaluated based on the current available literature, and limitations of, and future directions for, this literature are discussed.