Brain effects of antidepressants in major depression: A meta-analysis of emotional processing studies

Abstract Background A consistent brain activity pattern has been identified in major depression across many resting positron emission tomography (PET) studies. This dysfunctional pattern seems to be normalized by antidepressant treatment. The aim of this meta-analysis was to identify more clearly the pattern associated with clinical improvement of depression following an antidepressant drug treatment, in emotional activation studies using functional magnetic resonance imaging (fMRI). Methods A quantitative Activation Likelihood Estimation (ALE) meta-analysis was performed across 9 emotional activation fMRI and PET studies (126 patients) using the Activation Likelihood Estimation technique. Results Following the antidepressant drug treatment, the activation of dorsolateral, dorsomedial and ventrolateral prefrontal cortices was increased whereas the activation of the amygdala, hippocampus, parahippocampal region, ventral anterior cingulate cortex, orbitofrontal cortex, and insula was decreased. Additionally, there was a decreased activation in the anterior (BA 32) and posterior cingulate cortices, as well as in the precuneus and inferior parietal lobule, which could reflect a restored deactivation of the default mode network. Limitations The small number of emotional activation studies, using heterogeneous tasks, included in the ALE analysis. Conclusions The activation of several brain regions involved in major depression, in response to emotional stimuli, was normalized after antidepressant treatment. To refine our knowledge of antidepressants' effect on the neural bases of emotional processing in major depression, neuroimaging studies should use consistent emotional tasks related to depressive symptoms and that involve the default mode network, such as self-referential processing tasks.