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Distinct brain activity alterations of treatment for bipolar disorders with psychotherapy and drug therapy: activation likelihood estimation meta-analysis

Published online by Cambridge University Press:  01 February 2023

Jingyi Luo
Centre for Translational Medicine, Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China Department of Medical Psychology, School of Mental Health and Psychological Science, Anhui Medical University, Hefei, China
Pengcheng Yi
Department of Clinical Psychology, the Third People's Hospital of Xiangshan County, Ningbo, China
Meng Liang
Department of Medical Psychology, School of Mental Health and Psychological Science, Anhui Medical University, Hefei, China
Shuyu Zhang
School of Psychology, the Australian National University, Canberra, Australia
Qian Tao*
Department of Psychology, School of Basic Medicine, Jinan University, Guangzhou, China
Ni Li
Department of Medical Psychology, School of Mental Health and Psychological Science, Anhui Medical University, Hefei, China
Han Zhang
Department of Medical Psychology, School of Mental Health and Psychological Science, Anhui Medical University, Hefei, China
Jialin Wen
Department of Medical Psychology, School of Mental Health and Psychological Science, Anhui Medical University, Hefei, China
Xinrong Xue
Department of Medical Psychology, School of Mental Health and Psychological Science, Anhui Medical University, Hefei, China
Chuan Fan*
Department of Psychiatry, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
Xiaoming Li
Centre for Translational Medicine, Second Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China Department of Medical Psychology, School of Mental Health and Psychological Science, Anhui Medical University, Hefei, China
Authors for correspondence: Xiaoming Li, E-mail:; Chuan Fan, E-mail:; Qian Tao, E-mail:
Authors for correspondence: Xiaoming Li, E-mail:; Chuan Fan, E-mail:; Qian Tao, E-mail:



Many studies suggest that both psychotherapy and drug therapy are effective in the treatment of bipolar disorders (BDs). However, the pathophysiology of both types of intervention has not been established definitively.


An activation likelihood estimation meta-analysis was performed to identify the distinct brain activity alterations between psychotherapy and drug therapy for the treatment of BDs. Articles were identified by searching databases including PubMed, Embase, Cochrane Library, and Web of Science databases. Eligible studies on BDs were published up until 10 June 2021.


21 studies were included and we conducted a meta-analysis for different therapies and imaging tasks. After receiving psychotherapy, BD patients showed increased activation in the inferior frontal gyrus (IFG) and superior temporal gyrus. While after taking drug therapy, BD patients displayed increased activation in the anterior cingulate cortex, medial frontal gyrus, IFG, and decreased activation in the posterior cingulate cortex. The regions of brain activity changes caused by psychotherapy were mostly focused on the frontal areas, while drug therapy mainly impacted on the limbic areas. Different type of tasks also affected brain regions which were activated.


Our comprehensive meta-analysis indicates that these two treatments might have effect on BD in their own therapeutic modes. Psychotherapy might have a top-down effect, while drug therapy might have a bottom-up effect. This study may contribute to differential diagnosis of BDs and would be helpful to finding more accurate neuroimaging biomarkers for BD treatment.

Review Article
Copyright © The Author(s), 2023. Published by Cambridge University Press

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These authors contribute equally to this work.

This article has been updated since its original publication. A notice detailing the edits can be found here:


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