A quantitative meta-analysis of fMRI studies in bipolar disorder


  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

Corresponding author:
Chi-Hua Chen, Ph.D.
Department of Psychiatry
University of California, San Diego
8950 Villa La Jolla Drive, #0841
La Jolla, CA 92093-0841, USA
Fax: (858) 534-7653
E-mail: chc101@ucsd.edu


Chen C-H, Suckling J, Lennox BR, Ooi C, Bullmore ET. A quantitative meta-analysis of fMRI studies in bipolar disorder.
Bipolar Disord 2011: 13: 1–15. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S.

Objectives:  Functional magnetic resonance imaging (fMRI) has been widely used to identify state and trait markers of brain abnormalities associated with bipolar disorder (BD). However, the primary literature is composed of small-to-medium-sized studies, using diverse activation paradigms on variously characterized patient groups, which can be difficult to synthesize into a coherent account. This review aimed to synthesize current evidence from fMRI studies in midlife adults with BD and to investigate whether there is support for the theoretical models of the disorder.

Methods:  We used voxel-based quantitative meta-analytic methods to combine primary data on anatomical coordinates of activation from 65 fMRI studies comparing normal volunteers (n = 1,074) and patients with BD (n = 1,040).

Results:  Compared to normal volunteers, patients with BD underactivated the inferior frontal cortex (IFG) and putamen and overactivated limbic areas, including medial temporal structures (parahippocampal gyrus, hippocampus, and amygdala) and basal ganglia. Dividing studies into those using emotional and cognitive paradigms demonstrated that the IFG abnormalities were manifest during both cognitive and emotional processing, while increased limbic activation was mainly related to emotional processing. In further separate comparisons between healthy volunteers and patient subgroups in each clinical state, the IFG was underactive in manic but not in euthymic and depressed states. Limbic structures were not overactive in association with mood states, with the exception of increased amygdala activation in euthymic states when including region-of-interest studies.

Conclusions:  In summary, our results showed abnormal frontal-limbic activation in BD. There was attenuated activation of the IFG or ventrolateral prefrontal cortex, which was consistent across emotional and cognitive tasks and particularly related to the state of mania, and enhanced limbic activation, which was elicited by emotional and not cognitive tasks, and not clearly related to mood states.