New Fei Ho, PhD;* Zhengjun Li, PhD;* Fang Ji, MSc; Mingyuan Wang, BSocSc; Carissa N. Kuswanto, MSc; Min Yi Sum, BA; Han Ying Tng, BSc; Yih Yian Sitoh, MBBS; Kang Sim, MMed;† Juan Zhou, PhD†
Background: Hemispheric lateralization of the brain occurs during development and underpins specialized functions. It is posited that aberrant neurodevelopment leads to abnormal brain lateralization in individuals with psychotic illnesses. Here, we sought to examine whether white matter hemispheric lateralization is abnormal in individuals with the psychotic spectrum disorders of schizophrenia and bipolar disorder.
Methods: We examined the white matter microstructure lateralization in patients with schizophrenia, bipolar disorder with psychotic features and healthy controls by measuring the laterality indices of fractional anisotropy (FA) and mean diffusivity (MD). We also correlated the laterality indices with clinical measures.
Results: We included 150 patients with schizophrenia, 35 with bipolar disorder and 77 healthy controls in our analyses. Shared FA lateralization abnormalities in patients with schizophrenia and bipolar disorder were found in the cerebral peduncle and posterior limb of internal capsule, with more extensive abnormalities in patients with bipolar disorder than in those with schizophrenia. The shared MD lateralization abnormalities were more widespread, extending to the subcortical, frontal–occipital, limbic and callosal tracts, with patients with bipolar disorder showing greater abnormalities than patients with schizophrenia. While lateralization was decreased in patients with schizophrenia, the lateralization was reversed in those with bipolar disorder, underpinned by the more pronounced microstructural abnormalities in the right hemisphere. The loss of FA lateralization in patients with schizophrenia was associated with lower quality of life and psychosocial functioning.
Limitations: Owing to the cross-sectional study design, we cannot confirm whether the lateralization abnormalities are neurodevelopmental or a consequence of psychosis onset or chronicity.
Conclusion: Shared and distinct white matter lateralization abnormalities were found in patients with schizophrenia and bipolar disorder. In distinct regions of abnormalities, the lateralization was attenuated in patients with schizophrenia and reversed in those with bipolar disorder.
*Share first authorship; †share senior authorship.
Submitted May 11, 2016; Revised Sept. 21, 2016; Accepted Nov. 6, 2016; Early-released Jan. 31, 2017
Acknowledgements: This research was supported by the Agency for Science, Technology, and Research (A*STAR) Singapore under the Biomedical Research Council (13/1/96/19/687 awarded to J. Zhou) and the Duke-NUS Graduate Medical School Signature Research Program, funded (awarded to J. Zhou) by the Ministry of Health, Singapore. This research was also supported by funding from the National Medical Research Council Centre Grant (Institute of Mental Health; awarded to N.F. Ho), the National Healthcare Group (NHG 11003, 12003 awarded to K. Sim) and the Agency for Science, Technology, Research/ Singapore BioImaging Consortium (ASTAR/SBIC 009/2006 awarded to K. Sim). The authors thank all the research staff and patients who participated in this study.
Affiliations: From the Center for Cognitive Neuroscience and the Behavioral Disorders Program, Duke-NUS Medical School, Singapore (Ho, Li, Ji, Tng, Zhou); the Research Division, Institute of Mental Health/Woodbridge Hospital, Singapore (Ho, Wang, Kuswanto, Sum, Sim); the Department of Neuroradiology, National Neuroscience Institute, Singapore (Sitoh); and the Clinical Imaging Research Centre, The Agency for Science, Technology and Research-National University of Singapore, Singapore (Zhou).
Competing interests: None declared.
Contributors: Z. Li, K. Sim and J. Zhou designed the study. F. Ji, C. Kuswanto, M.-Y. Sum, Y.-Y. Sitoh, K. Sim and J. Zhou acquired the data, which N.-F. Ho, Z. Li, M. Wang, H.-Y. Tng, K. Sim and J. Zhou analyzed. N.-F. Ho, Z. Li, K. Sim and J. Zhou wrote the article, which all authors reviewed and approved for publication.
Correspondence to: J. Zhou, Neuroscience & Behavioral Disorders Program, Duke-NUS Medical School, Singapore, 8 College Rd, #06-15, Singapore 169857; email@example.com