Prefrontal-subcortical and limbic circuit mediation of major depressive disorder.

Substantial progress has been made in elucidating the pathophysiology of major depressive disorder (MDD) using functional and structural brain imaging. In functional imaging studies comparing MDD subjects to normal controls at baseline, dorsolateral prefrontal cortex (DLPFC) activity has been found to be decreased and ventrolateral prefrontal cortex (VLPFC) activity has been found to be increased in MDD. Other regions found abnormal in baseline studies include the anterior cingulate gyrus (AC), temporal lobe, and basal ganglia. Studies examining mood state change (using sleep deprivation, sadness-induction, and tryptophan depletion) and changes from pre- to posttreatment have generally shown improvement of these abnormalities with improved MDD symptoms and worsening of these abnormalities with worsening symptoms. In structural imaging studies, decreased frontal lobe, hippocampal, and basal ganglia volumes are the most commonly reported findings. Several associations can be made between clinical features of MDD and brain function: (1) active sad thoughts/sadness with both decreased DLPFC and dorsal AC activity and increased VLPFC and ventral AC activity (2) psychomotor retardation with decreased left prefrontal activity (3) anxiety with increased left AC activity (4) impaired episodic memory with left prefrontal and medial temporal dysfunction and (5) impaired sustained attention with right prefrontal and parietal dysfunction.