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Neural mechanisms of oxytocin receptor gene mediating anxiety-related temperament

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Abstract

A common variant (rs53576) of the OXTR gene has been implicated in a number of socio-emotional phenotypes, such as anxiety-related behavior. Previous studies have demonstrated that A-allele carriers have higher levels of physiological and dispositional stress reactivity and depressive symptomatology compared to those with the GG genotype, but the mediating neural mechanisms remain poorly understood. We combined voxel-based morphometry and resting-state functional connectivity analyses in a large cohort of healthy young Chinese Han individuals to test the hypothesis that the OXTR gene polymorphism influences an anxiety-related temperamental trait, as assessed by the harm avoidance subscale from the Tridimensional Personality Questionnaire via modulating the gray matter volume and resting-state functional connectivity of the brain, especially the limbic system. We revealed that female subjects with the AA genotype showed increased harm avoidance scores relative to G-carrier females. We also found that, compared to female individuals with the GG/GA genotype, female individuals with the AA genotype exhibited significantly smaller amygdala volumes bilaterally (especially the centromedial subregion), with a trend of allele-load-dependence. Compared to female individuals with the GG/GA genotype, female subjects with the AA genotype demonstrated reduced resting-state functional coupling between the prefrontal cortex and amygdala bilaterally, also with an allele-load-dependent trend. Furthermore, the magnitude of prefrontal-amygdala coupling in the left hemisphere was positively correlated with harm avoidance scores in female subjects. Our findings highlight a possible neural pathway by which a naturally occurring variation of the OXTR gene may affect an anxiety-related temperamental trait in female subjects by modulating prefrontal-amygdala functional connectivity.

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Acknowledgments

We would like to thank our volunteers for participating in this study. This work was supported by the Natural Science Foundation of China (Grant No. 81271551), the National Basic Research Program of China (973 program, No. 2011CB707801), and the International Cooperation and Exchanges NSFC (No. 81061120533).

Conflict of interest

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China

    Junping Wang, Wen Qin, Dawei Wang, Yunting Zhang & Chunshui Yu

  2. LIAMA Center for Computational Medicine, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, 100190, Beijing, China

    Bing Liu & Tianzi Jiang

  3. Center for Social and Economic Behavior, Institute of Psychology, Chinese Academy of Sciences, Beijing, China

    Yuan Zhou

  4. School of Medical Imaging, Tianjin Medical University, Tianjin, China

    Chunshui Yu

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  1. Junping Wang
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  2. Wen Qin
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  3. Bing Liu
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  4. Yuan Zhou
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  5. Dawei Wang
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  6. Yunting Zhang
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  7. Tianzi Jiang
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  8. Chunshui Yu
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Correspondence to Tianzi Jiang or Chunshui Yu.

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Drs. J. Wang and W. Qin contributed equally to this work.

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Wang, J., Qin, W., Liu, B. et al. Neural mechanisms of oxytocin receptor gene mediating anxiety-related temperament. Brain Struct Funct 219, 1543–1554 (2014). https://doi.org/10.1007/s00429-013-0584-9

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