Distinct regions of prefrontal cortex mediate resistance and vulnerability to depression.
The neuroanatomical correlates of depression remain unclear. Functional imaging data have associated depression with abnormal patterns of activity in prefrontal cortex (PFC), including the ventromedial (vmPFC) and dorsolateral (dlPFC) sectors. If vmPFC and dlPFC are critical neural substrates for the pathogenesis of depression, then damage to either area should affect the expression of depressive symptoms. Using patients with brain lesions we show that, relative to nonfrontal lesions, bilateral vmPFC lesions are associated with markedly low levels of depression, whereas bilateral dorsal PFC lesions (involving dorsomedial and dorsolateral areas in both hemispheres) are associated with substantially higher levels of depression. These findings demonstrate that vmPFC and dorsal PFC are critically and causally involved in depression, although with very different roles: vmPFC damage confers resistance to depression, whereas dorsal PFC damage confers vulnerability.
Koenigs
Michael
M
Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719, USA.
Huey
Edward D
ED
Calamia
Matthew
M
Raymont
Vanessa
V
Tranel
Daniel
D
Grafman
Jordan
J
D000328:Adult; D001930:Brain Injuries / Q000150:complications / Q000473:pathology; D001931:Brain Mapping; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology; D003863:Depression / Q000150:complications / Q000209:etiology / Q000473:pathology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000150:complications / Q000473:pathology; D017397:Prefrontal Cortex / Q000473:pathology*; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed / Q000379:methods; D014728:Veterans