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Cognitive and serum BDNF correlates of BDNF Val66Met gene polymorphism in patients with schizophrenia and normal controls

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Abstract

Studies suggest that a functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) may mediate hippocampal-dependent cognitive functions. A few studies have reported its role in cognitive deficits in schizophrenia including its association with peripheral BDNF levels as a mediator of these cognitive deficits. We assessed 657 schizophrenic inpatients and 445 healthy controls on the repeatable battery for the assessment of neuropsychological status (RBANS), the presence of the BDNF Val66Met polymorphism and serum BDNF levels. We assessed patient psychopathology using the Positive and Negative Syndrome Scale. We showed that visuospatial/constructional abilities significantly differed by genotype but not genotype × diagnosis, and the Val allele was associated with better visuospatial/constructional performance in both schizophrenic patients and healthy controls. Attention performance showed a significant genotype by diagnosis effect. Met allele-associated attention impairment was specific to schizophrenic patients and not shown in healthy controls. In the patient group, partial correlation analysis showed a significant positive correlation between serum BDNF and the RBANS total score. Furthermore, the RBANS total score showed a statistically significant BDNF level × genotype interaction. We demonstrated an association between the BDNF Met variant and poor visuospatial/constructional performance. Furthermore, the BDNF Met variant may be specific to attentional decrements in schizophrenic patients. The association between decreased BDNF serum levels and cognitive impairment in schizophrenia is dependent on the BDNF Val66Met polymorphism.

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Acknowledgment

This study was funded by the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639.

Conflict of interest

No conflict of interest was disclosed for each author.

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Authors and Affiliations

  1. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA

    Xiang Yang Zhang, Colin N. Haile, Therese A. Kosten & Thomas R. Kosten

  2. Center for Psychiatric Research, Beijing HuiLongGuan Hospital, Beijing, People’s Republic of China

    Da Chun Chen & Mei Hong Xiu

  3. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Xingguang Luo, Ke Xu, Hui Ping Zhang & Lingjun Zuo

  4. Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, People’s Republic of China

    Zhijun Zhang & Xiangrong Zhang

  5. VA Medical Center, Research Building 109, Room 130, 2002 Holcombe Boulevard, Houston, TX, 77030, USA

    Xiang Yang Zhang

  6. VA Medical Center, Research Building 110, Room 229, 2002 Holcombe Boulevard, Houston, TX, 77030, USA

    Thomas R. Kosten

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  1. Xiang Yang Zhang
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  2. Da Chun Chen
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  9. Zhijun Zhang
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Correspondence to Xiang Yang Zhang or Thomas R. Kosten.

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Zhang, X.Y., Chen, D.C., Xiu, M.H. et al. Cognitive and serum BDNF correlates of BDNF Val66Met gene polymorphism in patients with schizophrenia and normal controls. Hum Genet 131, 1187–1195 (2012). https://doi.org/10.1007/s00439-012-1150-x

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  • DOI: https://doi.org/10.1007/s00439-012-1150-x

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