A meta-analytic study of changes in brain activation in depression

Hum Brain Mapp. 2008 Jun;29(6):683-95. doi: 10.1002/hbm.20426.


Objective: A large number of studies with considerably variable methods have been performed to investigate brain regions involved in the pathophysiology of major depressive disorder. The aim of this study was to use a quantitative meta-analytic technique to synthesise the results of much of this research.

Methods: Three separate quantitative meta-analytical studies were conducted using the Activation Likelihood Estimation technique. Analysis was performed on three types of studies: (1) those conducted at rest comparing brain activation in patients with depression and controls; (2) those involving brain changes following antidepressant treatment; and (3) those comparing brain activation patterns induced by the induction of positive or negative emotion in patients with depression compared with controls.

Results: There appears to be a complex series of areas of the brain implicated in the pathophysiology of depression although limited overlap was found across imaging paradigms. This included a network of regions including frontal and temporal cortex as well as the insula and cerebellum that are hypoactive in depressed subjects and in which there is increase in activity with treatment. There was a corresponding set of subcortical and limbic regions in which opposite changes were found.

Conclusions: There is limited overlap between the brain regions identified using differing imaging methods. The most consistently identified regions include areas of the anterior cingulate, dorsolateral, medial and inferior prefrontal cortex, insula, superior temporal gyrus, basal ganglia and cerebellum. Further research is required to identify if different imaging methods are identifying complementary networks that are equally involved in the disorder.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / diagnostic imaging
  • Brain / physiopathology
  • Depressive Disorder, Major / diagnostic imaging*
  • Depressive Disorder, Major / physiopathology*
  • Humans
  • Magnetic Resonance Imaging*
  • Positron-Emission Tomography*
  • Tomography, Emission-Computed, Single-Photon*