Hypothalamic-pituitary-adrenocortical axis function in attention-deficit hyperactivity disorder

The hypothalamic-pituitary-adrenocortical axis plays a critical role in mediating the physiological response to the imposition of stress. There are theoretical reasons to expect reduced basal cortisol secretion and cortisol hyporeactivity in hyperactive/impulsive or combined type attention-deficit hyperactivity disorder (ADHD). Early studies reported profound abnormalities in the diurnal rhythm of cortisol secretion or the cortisol response to stress in children with severe or persistent ADHD. However, subsequent work using larger samples or improved methods has not provided convincing evidence for changes in basal cortisol secretion in non-comorbid forms of ADHD. In contrast, children with ADHD and comorbid oppositional defiant disorder show lower basal cortisol concentrations and a blunted cortisol awakening response. With respect to cortisol reactivity to stress in ADHD, recent evidence has been mixed, with some studies reporting normal cortisol responses and others showing blunted cortisol responses in non-comorbid ADHD. Again, it appears important to consider whether comorbid disorders are present, because children with ADHD and comorbid disruptive behavior disorders exhibit blunted cortisol responses, whereas those with comorbid anxiety disorders show enhanced cortisol responses to stress. Longitudinal studies are required to investigate whether abnormalities in cortisol secretion play a causal role in the etiology of ADHD and related disruptive behavior disorders.