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The Amygdala in Schizophrenia and Bipolar Disorder

A Synthesis of Structural MRI, Diffusion Tensor Imaging, and Resting-State Functional Connectivity Findings

Ho, New Fei, PhD; Chong, Pearlynne Li Hui, BA; Lee, Daryl Renick, BEng; Chew, Qian Hui, BA; Chen, Guoyang, BSocSci; Sim, Kang, MBBS, MMed (Psychiatry), MSc HPE (MGH IHP), FAMS

doi: 10.1097/HRP.0000000000000207

Frequently implicated in psychotic spectrum disorders, the amygdala serves as an important hub for elucidating the convergent and divergent neural substrates in schizophrenia and bipolar disorder, the two most studied groups of psychotic spectrum conditions. A systematic search of electronic databases through December 2017 was conducted to identify neuroimaging studies of the amygdala in schizophrenia and bipolar disorder, focusing on structural MRI, diffusion tensor imaging (DTI), and resting-state functional connectivity studies, with an emphasis on cross-diagnostic studies. Ninety-four independent studies were selected for the present review (49 structural MRI, 27 DTI, and 18 resting-state functional MRI studies). Also selected, and analyzed in a separate meta-analysis, were 33 volumetric studies with the amygdala as the region-of-interest. Reduced left, right, and total amygdala volumes were found in schizophrenia, relative to both healthy controls and bipolar subjects, even when restricted to cohorts in the early stages of illness. No volume abnormalities were observed in bipolar subjects relative to healthy controls. Shape morphometry studies showed either amygdala deformity or no differences in schizophrenia, and no abnormalities in bipolar disorder. In contrast to the volumetric findings, DTI studies of the uncinate fasciculus tract (connecting the amygdala with the medial- and orbitofrontal cortices) largely showed reduced fractional anisotropy (a marker of white matter microstructure abnormality) in both schizophrenia and bipolar patients, with no cross-diagnostic differences. While decreased amygdalar-orbitofrontal functional connectivity was generally observed in schizophrenia, varying patterns of amygdalar-orbitofrontal connectivity in bipolar disorder were found. Future studies can consider adopting longitudinal approaches with multimodal imaging and more extensive clinical subtyping to probe amygdalar subregional changes and their relationship to the sequelae of psychotic disorders.

From the Research Division (all), and West Region (Dr. Sim), Institute of Mental Health, Singapore.

Original manuscript received 17 February 2018, accepted for publication subject to revision 13 May 2018; revised manuscripts received 29 May and 26 June 2018.

Correspondence: Kang Sim, Institute of Mental Health, 10 Buangkok View, Buangkok Medical Park, Singapore 539747. Email: Or: New Fei Ho, Institute of Mental Health, 10 Buangkok View, Buangkok Medical Park, Singapore 539747. Email:

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© 2019 President and Fellows of Harvard College
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