Neuregulin 1 genetic variation and anterior cingulum integrity in patients with schizophrenia and healthy controls

Neuregulin 1 genetic variation and anterior cingulum integrity in patients with schizophrenia and healthy controls


J Psychiatry Neurosci 2010; 34(3): 181-186

Fei Wang, MD, PhD; Tianzi Jiang, PhD; Zhiguo Sun, MD; Siew-leng Teng, PhD; Xingguang Luo, MD, PhD; Zhongjun Zhu, MD; Yufeng Zang, MD, PhD; Handi Zhang, MD;
Weihua Yue, MD, PhD; Mei Qu, PhD; Tianlan Lu, BS; Nan Hong, MD; Haiyan Huang, PhD; Hilary P. Blumberg, MD; Dai Zhang, MD, PhD

Wang, Jiang, Zang — National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences; Wang, Zhu, H. Zhang, Yue, Qu, Lu, D. Zhang — Institute of Mental Health, Peking University, Beijing, China; Wang, Luo, Blumberg — Department of Psychiatry, Yale School of Medicine, New Haven, Conn.; Sun, Hong — Department of Radiology, People’s Hospital, Peking University, Beijing, China; Teng, Huang — Department of Statistics, University of California, Berkeley, Calif.


Background: Neuregulin1 (NRG1) influences the development of white matter connectivity and is implicated in genetic susceptibility to schizophrenia. The cingulum bundle is a white matter structure implicated in schizophrenia. Its anterior component is especially implicated, as it provides reciprocal connections between brain regions with prominent involvement in the disorder. Abnormalities in the structural integrity of the anterior cingulum in patients with schizophrenia have been reported previously. The present study investigated the potential contribution of NRG1 variation to anterior cingulum abnormalities in participants with schizophrenia.

Methods: We studied 31 men with schizophrenia and 36 healthy men using diffusion tensor imaging to investigate the association between fractional
anisotropy in the anterior cingulum and a single-nucleotide polymorphism (SNP8NRG221533: rs35753505) of NRG1.

Results: Consistent with previous reports, fractional anisotropy was significantly reduced in the anterior cingulum in the schizophrenia group. Moreover, the results revealed a significant group (schizophrenia, control) by genotype (C/C, T carriers, including CT and TT) interaction between genetic variation in NRG1 and diagnosis of schizophrenia, such that the patients with the T allele for SNP8NRG221533 had significantly decreased anterior cingulum fractional anisotropy compared with patients homozygous for the C allele and healthy controls who were T carriers.

Limitations: Limitations of our study included the small sample size of the TT subgroup and our use of only fractional anisotropy as an index of myelin integrity. In addition, the use of diffusion tensor imaging acquisition methods limited our ability to study other brain regions that may be involved in schizophrenia.

Conclusions: Our results suggest that NRG1 variation may play a role in the pathophysiology of anterior cingulum abnormalities in patients with schizophrenia.

Submitted May 6, 2008; Revised Sep. 26, 2008; Accepted Sep. 29, 2008

Acknowledgements: The authors thank R. Todd Constable, PhD; Marcel Jackowski, PhD; Xenios Papademetris, PhD; Maolin Qiu, PhD; Gaolang Gong, PhD; and Linda Spencer, BS, for assistance with the study, and the study participants. Funding for this study was provided by the following sources: the National Natural Science Foundation of China (30530290, 30870896), the National High Technology Research and Development Program of China (2006AA02Z195), and the Capital Foundation of Medical Developments (2007-1001) for Dr. Dai Zhang.

Competing interests: None declared.

Contributors: Drs. Wang, Jiang, Zang and D. Zhang designed the study. Drs. Wang, Sun, Zhu, H. Zhang, Yue, Qu, Lu and Hong acquired data. Drs. Wang, Teng, Luo, Zhu, Zang, Yue, Qu, Hong, Huang and Blumberg analyzed data. Drs. Wang and Blumberg wrote the article. Drs. Wang, Jiang, Sun, Teng, Luo, Zhu, Zang, H. Zhang, Yue, Qu, Lu, Hong, Huang, Blumberg and D. Zhang reviewed the article. All authors provided approval for publication.

Correspondence to: Dr. D. Zhang, Institute of Mental Health, Peking University, 51 Huayuan Bei Rd., Beijing 100083, China; fax 8610-6207-8246;