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Cumulative Adversity and Smaller Gray Matter Volume in Medial Prefrontal, Anterior Cingulate, and Insula Regions

  • Emily B. Ansell

      Affiliations

    • Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
  • ,
  • Kenneth Rando

      Affiliations

    • Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
  • ,
  • Keri Tuit

      Affiliations

    • Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
  • ,
  • Joseph Guarnaccia

      Affiliations

    • Department of Neurology, Yale University School of Medicine, New Haven, Connecticut
  • ,
  • Rajita Sinha

      Affiliations

    • Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
    • Corresponding Author InformationAddress correspondence to Rajita Sinha, Ph.D., Yale University School of Medicine, Department of Psychiatry, Yale Stress Center, 2 Church Street, South, Suite 209, New Haven, CT 06519

Received 5 July 2011; received in revised form 22 November 2011; accepted 30 November 2011. published online 05 January 2012.
Corrected Proof

Background

Cumulative adversity and stress are associated with risk of psychiatric disorders. While basic science studies show repeated and chronic stress effects on prefrontal and limbic neurons, human studies examining cumulative stress and effects on brain morphology are rare. Thus, we assessed whether cumulative adversity is associated with differences in gray matter volume, particularly in regions regulating emotion, self-control, and top-down processing in a community sample.

Methods

One hundred three healthy community participants, aged 18 to 48 and 68% male, completed interview assessment of cumulative adversity and a structural magnetic resonance imaging protocol. Whole-brain voxel-based-morphometry analysis was performed adjusting for age, gender, and total intracranial volume.

Results

Cumulative adversity was associated with smaller volume in medial prefrontal cortex (PFC), insular cortex, and subgenual anterior cingulate regions (familywise error corrected, p < .001). Recent stressful life events were associated with smaller volume in two clusters: the medial PFC and the right insula. Life trauma was associated with smaller volume in the medial PFC, anterior cingulate, and subgenual regions. The interaction of greater subjective chronic stress and greater cumulative life events was associated with smaller volume in the orbitofrontal cortex, insula, and anterior and subgenual cingulate regions.

Conclusions

Current results demonstrate that increasing cumulative exposure to adverse life events is associated with smaller gray matter volume in key prefrontal and limbic regions involved in stress, emotion and reward regulation, and impulse control. These differences found in community participants may serve to mediate vulnerability to depression, addiction, and other stress-related psychopathology.

Key Words:  Brain MRI , chronic stress , cumulative adversity , gray matter volume , life trauma , prefrontal cortex , recent adverse life events

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PII: S0006-3223(11)01193-0

doi:10.1016/j.biopsych.2011.11.022

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