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

Abstract

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.

Copyright 2007 Wiley-Liss, Inc.

Figures

Figure 1

Demonstration of the areas of significant differences across the four analyses. (a) Decreased (blue) and increased (red) activation in depressed patients at rest compared with controls (x = 0, z = +9). (b) Increased activation (red) and decreased activation (blue) with SSRI treatment in depressed patients (x = −10, z = +9). (c) Increased (red) and decreased (blue) activation in depressed patients compared with controls in response to happy stimuli (x = 0, z = +9). (d) Decreased (blue) and increased (red) activation in depressed patients compared with controls in response to sad stimuli (x = 0, z = +1). Images are neurological.

Figure 2

Demonstration of the areas of overlap between analyses. (a) Decreased activation in patients at rest (red); increased activation in patients with treatment (blue); decreased activation in patients compared with controls with sad stimuli (green); overlap between decreased activation at rest and increased activation with treatment (yellow); overlap between increased activation with treatment and decreased activation with sad stimuli (pink). There were no areas of overlap between decreased at rest and decreased with sad stimuli or for the three comparisons. (b) Increased activation in patients at rest (red); decreased activation in patients with treatment (blue); increased activation in patients compared with controls with sad stimuli (green); overlap between increased activation at rest and decreased activation with treatment (yellow). There were no areas of overlap between increased activation with treatment and decreased activation with sad stimuli, decreased at rest and decreased with sad stimuli or for the three comparisons.