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Sex differences in orbitofrontal gray as a partial explanation for sex differences in antisocial personality

Abstract

Attention is increasingly being given to understanding sex difference in psychopathology to better understand the etiology of disorders. This study tests the hypothesis that sex differences in ventral and middle frontal gray volume contribute to sex differences in antisocial personality disorder (APD) and crime. Participants were recruited from temporary employment agencies, consisting of normal controls, substance/alcohol-dependent controls, axis I/II psychiatric controls and individuals with APD. An independent sample of female volunteers was also recruited. Magnetic resonance imaging volumes of superior frontal, middle frontal, inferior frontal, orbital frontal and rectal gyral frontal gray matter, and dimensional scores of APD and criminal behavior were assessed. APD males when compared with male controls showed an 8.7% reduction in orbitofrontal gray volume, a 17.3% reduction in middle frontal gray and a 16.1% reduction in right rectal gray. Reduced middle and orbitofrontal volumes were significantly associated with increased APD symptoms and criminal offending in both males and females. Males as a whole had reduced orbitofrontal and middle frontal gray volume when compared with females, and controlling for these brain differences reduced the gender difference in the antisocial personality/behavior by 77.3%. Findings were not a function of psychiatric comorbidity, psychosocial risk factors, head injury or trauma exposure. Findings implicate structural differences in the ventral and middle frontal gray as both a risk factor for APD and as a partial explanation for sex differences in APD.

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Acknowledgements

This study was supported by the NIH grants to A Raine (K02 MH01114 and RO3 MH50940), Y Yang (1F31MH079592) and KL Narr (K01MH073990). KL Narr and AW Toga were also supported by grants from the National Center for Research Resources (P41 RR13642), the NIH Roadmap Initiative (P20 RR020750), the National Library of Medicine (R01 LM05639) and the NIH Roadmap for Medical Research, Grant U54 RR021813 entitled Center for Computational Biology (CCB). We wish to thank Samantha Henry, Elizabeth Culley, Donna Kha, Reimar Macaranas, Henry Wu, Lydia Lee, Sum-yan Ng, Lori Lacasse and Todd Lencz, for assistance in data collection and analysis.

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Raine, A., Yang, Y., Narr, K. et al. Sex differences in orbitofrontal gray as a partial explanation for sex differences in antisocial personality. Mol Psychiatry 16, 227–236 (2011). https://doi.org/10.1038/mp.2009.136

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