Fronto-limbic volumetric changes in major depressive disorder

J Affect Disord. 2012 Feb;136(3):1104-13. doi: 10.1016/j.jad.2011.10.038. Epub 2011 Nov 30.


Background: Fronto-limbic dysregulation in major depressive disorder (MDD) may be influenced by early life stress and antidepressant treatment. The present structural MRI study aimed to determine the relationship between amygdala, cingulate and subgenual prefrontal cortex volumes in MDD and their associations with child abuse and antidepressants.

Methods: Right-handed subjects (21-50 years), meeting DSM-IV criteria for MDD, either with (n=19) or without (n=20) childhood sexual or physical abuse. Healthy controls (n=34) were matched for age, sex, education and smoking. 3D-MPRAGE images with a spatial resolution of 1.5 mm×1.0 mm×1.0 mm were acquired with a Siemens Sonata 1.5 T system. Volumes of subgenual prefrontal cortex, amygdala and affective, cognitive, superior and posterior divisions of cingulate cortex were analyzed using DISPLAY software using reliable volumetric protocols. Groups were compared using ANCOVA, with intracranial volume as a covariate.

Results: MDD subjects had low cingulate (cognitive division) and high amygdala volumes. Low cingulate volume was related to abuse and treatment history. Amygdala volume was predicted by subgenual prefrontal and cingulate (cognitive division) volumes and the presence of paracingulate cortex.

Limitations: This study was cross sectional and the sample size was limited for subgroup and correlational analyses.

Summary: Our data suggest that MDD may be associated with alterations in anterior cingulate cortex and amygdala. Morphological variation, early stress and stress-protective factors may contribute to differences in fronto-limbic structures in MDD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Child
  • Child Abuse / psychology*
  • Depressive Disorder, Major / diagnosis*
  • Depressive Disorder, Major / drug therapy
  • Female
  • Humans
  • Limbic System / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size
  • Prefrontal Cortex / pathology*


  • Antidepressive Agents