Prefrontal cortex dysfunction in clinical depression

Abstract The role of specific brain regions in the pathophysiology of clinical depression is poorly understood. However, one brain area, the prefrontal cortex, is emerging as likely being directly involved in clinical depression. The authors review accepted clinical diagnostic criteria for depression and show how these relate to the behavioral changes seen after prefrontal cortex damage in man and other animals. Information from structural (MRI, CT) and functional imaging (SPECT, PET) is then examined for direct evidence of prefrontal cortex abnormalities in clinically depressed subjects. Functional imaging studies, with few exceptions, demonstrate prefrontal lobe hypometabolism in primary and secondary depression, with severity of depression often correlating with the degree of frontal inactivity. These studies imply that dysfunction of the prefrontal cortex, particularly with respect to its role in modulating limbic activity, could conceivably produce many of the symptoms seen in clinical depression. Viewing clinical depression as a disease involving dysfunction of the prefrontal cortex and connected brain regions may prove helpful in both the clinical management of depression and in clarifying future avenues for research. Depression 2:59–72 (1994). © 1994 Wiley‐Liss, Inc.