Mapping the depressed brain: A meta-analysis of structural and functional alterations in major depressive disorder

Background: Depression has a lifetime prevalence of up to 20 percent. Neuroimaging methods have revealed various structural and functional changes that occur in a human brain during a depressive episode. However, we still lack information concerning the extent to which structural and functional changes co-occur in a depressed brain. Furthermore, it is difficult to evaluate from a merely qualitative literature review what regional brain changes in volume and activation are robust across depressed patient samples and consistent across imaging centers. Methodology and Principle Findings: This study is a meta-analysis from 10 selected studies published previously. We applied the statistical anatomical/activation likelihood estimate method (ALE) in a total of 176 depressed patients and 175 controls for the MRI modality and in a total of 102 depressed patients and 94 controls for the PET modality to quantitatively identify those brain regions that show concordant alteration in the midst of a depressive episode across imaging modalities and study sites. We find a convergent change in the limbic-cortical brain circuit in depression compared to controls of both Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) data. The specific changes include lower gray matter volumes in the amygdala, the dorsal frontomedian cortex, and the right paracingulate cortex, as well as increases in glucose metabolism in the right subgenual and pregenual anterior cingulate cortices. Conclusions/Significance: Our current findings represent an important first step towards a more focused approach to neuroimaging unipolar depression. The regions identified could serve as a specific region-of-interest-for-disease template for both individual in vivo imaging studies and postmortem histopathologic exploration