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


CONCLUSIONS
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.
Wang
Fei
F
National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, China.
Jiang
Tianzi
T
Sun
Zhiguo
Z
Teng
Siew-Leng
SL
Luo
Xingguang
X
Zhu
Zhongjun
Z
Zang
Yufeng
Y
Zhang
Handi
H
Yue
Weihua
W
Qu
Mei
M
Lu
Tianlan
T
Hong
Nan
N
Huang
Haiyan
H
Blumberg
Hilary P
HP
Zhang
Dai
D
D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009186:Myelin Sheath / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D012559:Schizophrenia / Q000473:pathology*; D017422:Sequence Analysis, DNA; D055815:Young Adult
C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1