Effects of acute metabolic stress on the dopaminergic and pituitary–adrenal axis activity in patients with schizophrenia, their unaffected siblings and controls

A genetically mediated abnormal sensitivity to stress is thought to play a role in the onset, exacerbation and relapse of schizophrenia. In a double blind, placebo-controlled crossover study, peak increases in plasma ACTH (ΔACTH) and homovanillic-acid, a dopamine metabolite, (ΔHVA) following exposure to a metabolic stressor(2DG) were studied in unaffected siblings of patients with schizophrenia (n = 15), their patient relatives (n = 15) and healthy controls (n = 14). Siblings showed a stress response (both ΔACTH and ΔHVA) that was significantly greater compared to controls and significantly less pronounced compared to patients. The results suggest that the genetic risk for schizophrenia may be characterized by an enhanced sensitivity to stress.