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Brain Imaging Behav. 2016 Jun;10(2):619-27. doi: 10.1007/s11682-015-9429-x.

How treatment affects the brain: meta-analysis evidence of neural substrates underpinning drug therapy and psychotherapy in major depression.

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  • 1Department of Psychology, "Sapienza" University of Rome, Via dei Marsi, 78, 00185, Rome, Italy.
  • 2Neuropsychology Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
  • 3Neuropsychology Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
  • 4Department of Life, Health and Environmental Sciences, L'Aquila University, L'Aquila, Italy.
  • 5Department of Human Science and Society, University of Enna "Kore", Enna, Italy.


The idea that modifications of affect, behavior and cognition produced by psychotherapy are mediated by biological underpinnings predates the advent of the modern neurosciences. Recently, several studies demonstrated that psychotherapy outcomes are linked to modifications in specific brain regions. This opened the debate over the similarities and dissimilarities between psychotherapy and pharmacotherapy. In this study, we used activation likelihood estimation meta-analysis to investigate the effects of psychotherapy (PsyTh) and pharmacotherapy (DrugTh) on brain functioning in Major Depression (MD). Our results demonstrate that the two therapies modify different neural circuits. Specifically, PsyTh induces selective modifications in the left inferior and superior frontal gyri, middle temporal gyrus, lingual gyrus and middle cingulate cortex, as well as in the right middle frontal gyrus and precentral gyrus. Otherwise, DrugTh selectively affected brain activation in the right insula in MD patients. These results are in line with previous evidence of the synergy between psychotherapy and pharmacotherapy but they also demonstrate that the two therapies have different neural underpinnings.


ALE meta-analysis; Cognitive-behavioral therapy; Drug therapy; Insula; Major depression; Treatment effect

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