Perspectives on Neuroscience and Behavior.

There is an overlap in genetics, risk factors, symptomatology, and some biologic measures among major depressive disorder, bipolar disorder, and schizophrenia spectrum disorder. Now, a reduction in gray matter volume (GMV) has been found in the left hippocampus in all three disorders. GMV was obtained by utilizing a 3-T MRI scanner in 110 individuals in each of 4 groups matched for age and sex that consisted of healthy controls and DSM-IV-TR–diagnosed major depressive disorder, bipolar disorder, and schizophrenia spectrum disorder. Left hippocampus GMV was not only reduced in the 3 patient groups but associated with current global assessment of functioning and neuropsychological measurement of working memory/executive functioning. Stressful life events experienced during the last 6 months were also associated with left hippocampus GMV in the 3 patient groups and, importantly, also in the controls. Although a specific causal abnormality has been found in many diseases, the pathophysiology can involve multiple factors that overlap diseases at the biologic and symptomatic levels (e.g., inflammation, fever, fatigue). Numerous studies have shown that the hippocampus is highly sensitive to the effects of stress, and this suggests that the reduced GMV seen across the 3 patient groups is at least in part due to stress. Since there are available pharmacologic and behavioral measures to reduce stress, these can be utilized to reduce the effects of stress in major psychiatric disorders.