Association between functional and structural connectivity of the corticostriatal network in people with schizophrenia and unaffected first-degree relatives

Association between functional and structural connectivity of the corticostriatal network in people with schizophrenia and unaffected first-degree relatives

J Psychiatry Neurosci 2020;45(6):395-405 | PDF | Appendix

Peng Li, MD, PhD*; Ri-Xing Jing, PhD*; Rong-Jiang Zhao, MD; Le Shi, PhD; Hong-Qiang Sun, MD, PhD; Zengbo Ding, MD, PhD; Xiao Lin, MS; Lin Lu, MD, PhD†; Yong Fan, PhD†

Background: Dysfunction of the corticostriatal network has been implicated in the pathophysiology of schizophrenia, but findings are inconsistent within and across imaging modalities. We used multimodal neuroimaging to analyze functional and structural connectivity in the corticostriatal network in people with schizophrenia and unaffected first-degree relatives.

Methods: We collected resting-state functional magnetic resonance imaging and diffusion tensor imaging scans from people with schizophrenia (n = 47), relatives (n = 30) and controls (n = 49). We compared seed-based functional and structural connectivity across groups within striatal subdivisions defined a priori.

Results: Compared with controls, people with schizophrenia had altered connectivity between the subdivisions and brain regions in the frontal and temporal cortices and thalamus; relatives showed different connectivity between the subdivisions and the right anterior cingulate cortex (ACC) and the left precuneus. Post-hoc t tests revealed that people with schizophrenia had decreased functional connectivity in the ventral loop (ventral striatum–right ACC) and dorsal loop (executive striatum–right ACC and sensorimotor striatum–right ACC), accompanied by decreased structural connectivity; relatives had reduced functional connectivity in the ventral loop and the dorsal loop (right executive striatum–right ACC) and no significant difference in structural connectivity compared with the other groups. Functional connectivity among people with schizophrenia in the bilateral ventral striatum–right ACC was correlated with positive symptom severity.

Limitations: The number of relatives included was moderate. Striatal subdivisions were defined based on a relatively low threshold, and structural connectivity was measured based on fractional anisotropy alone.

Conclusion: Our findings provide insight into the role of hypoconnectivity of the ventral corticostriatal system in people with schizophrenia.


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Submitted Jan. 24, 2019; Revised July 14, 2019; Accepted Sep. 4, 2019; Published online May 20, 2020

Acknowledgements: This work was supported in part by the National Basic Research Program of China (no. 2015CB856400), the National Natural Science Foundation of China (no. 81501158), and an NIH grant (EB022573).

Affiliations: From the Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), and National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, Beijing, China (Li, Shi, Sun, Lin, Lu); the National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China (Jing); the University of Chinese Academy of Sciences, Beijing, China (Jing); the Department of Alcohol and Drug Dependence, Beijing Hui-Long-Guan Hospital, Peking University, Beijing, China (Zhao); the National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China (Ding); the Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China (Lin, Lu); and the Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA (Fan).

Competing interests: None declared.

Contributors: P. Li, L. Lu and Y. Fan designed the study. P. Li, R.-J. Zhao, L. Shi, H.-Q. Sun and Z. Ding acquired the data, which P. Li, R.-X. Jing, X. Lin and Y. Fan analysed. P. Li, R.-X. Jing and Y. Fan wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.190015

Correspondence to: Y. Fan, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, yong.fan@ieee.org; L. Lu, Peking University Sixth Hospital/Peking University Institute of Mental Health, Peking University, 51 Huayuan Bei Rd, Haidian District, Beijing 100191, China, linlu@bjmu.edu.cn