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The Journal of Neuroscience, November 19, 2008, 28(47):12341-12348; doi:10.1523/JNEUROSCI.2324-08.2008

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Behavioral/Systems/Cognitive
Distinct Regions of Prefrontal Cortex Mediate Resistance and Vulnerability to Depression

Michael Koenigs,¹ Edward D. Huey,² Matthew Calamia,³ Vanessa Raymont,^2,4 Daniel Tranel,³ and Jordan Grafman²

¹Department of Psychiatry, University of Wisconsin–Madison, Madison, Wisconsin 53719, ²Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke–National Institutes of Health, Bethesda, Maryland 20892-1440, ³Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, and ⁴Vietnam Head Injury Study, Henry M. Jackson Foundation, National Naval Medical Center, Bethesda, Maryland 20889

Correspondence should be addressed to Dr. Jordan Grafman, National Institutes of Health, 10 Center Drive, MSC 1440, Bethesda, MD 20892-1440. Email: grafmanj{at}ninds.nih.gov

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.

Key words: depression; emotion; prefrontal cortex; ventromedial; dorsolateral; neuropathology

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Received May 22, 2008; revised Oct. 13, 2008; accepted Oct. 14, 2008.

Correspondence should be addressed to Dr. Jordan Grafman, National Institutes of Health, 10 Center Drive, MSC 1440, Bethesda, MD 20892-1440. Email: grafmanj{at}ninds.nih.gov

This article has been cited by other articles:

				M. Koenigs and J. Grafman Posttraumatic Stress Disorder: The Role of Medial Prefrontal Cortex and Amygdala Neuroscientist, October 1, 2009; 15(5): 540 - 548. [Abstract] [PDF]

				E. J CHURCH Medical Imaging Looks Inside Depression Radiol. Technol., September 1, 2009; 81(1): 33 - 51. [Abstract] [Full Text] [PDF]

				M. B. Stein and T. W. McAllister Exploring the Convergence of Posttraumatic Stress Disorder and Mild Traumatic Brain Injury Am J Psychiatry, July 1, 2009; 166(7): 768 - 776. [Abstract] [Full Text] [PDF]

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