Gray matter reduction associated with psychopathology and cognitive dysfunction in unipolar depression: a voxel-based morphometry study

J Affect Disord. 2008 Jul;109(1-2):107-16. doi: 10.1016/j.jad.2007.11.011. Epub 2008 Jan 9.


Background: Functional neuroimaging studies on both cognitive processing and psychopathology in patients with major depression have reported several functionally aberrant brain areas within limbic-cortical circuits. However, less is known about the relationship between psychopathology, cognitive deficits and regional volume alterations in this patient population.

Methods: By means of voxel-based morphometry (VBM) and a standardized neuropsychological test battery, we examined 15 patients meeting DSM-IV criteria for major depression disorder and 14 healthy controls in order to investigate the relationship between affective symptoms, cognitive deficits and structural abnormalities.

Results: Patients with depression showed reduced gray matter concentration (GMC) in the left inferior temporal cortex (BA 20), the right orbitofrontal (BA 11) and the dorsolateral prefrontal cortex (BA 46). Reduced gray matter volume (GMV) was found in the left hippocampal gyrus, the cingulate gyrus (BA 24/32) and the thalamus. Structure-cognition correlation analyses revealed that decreased GMC of the right medial and inferior frontal gyrus was associated with both depressive psychopathology and worse executive performance as measured by the Wisconsin Card Sorting Test (WCST). Furthermore, depressive psychopathology and worse performance during the WCST were associated with decreased GMV of the hippocampus. Decreased GMV of the cingulate cortex was associated with worse executive performance.

Limitations: Moderate illness severity, medication effects, and the relatively small patient sample size should be taken into consideration when reviewing the implications of these results.

Conclusions: The volumetric results indicate that regional abnormalities in gray matter volume and concentration may be associated with both psychopathological changes and cognitive deficits in depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brief Psychiatric Rating Scale
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology*
  • Depressive Disorder / diagnosis
  • Depressive Disorder / epidemiology*
  • Depressive Disorder / psychology*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Prefrontal Cortex / anatomy & histology
  • Prefrontal Cortex / pathology*
  • Severity of Illness Index