Literature DB >> 30768381

Beyond a Binary Classification of Sex: An Examination of Brain Sex Differentiation, Psychopathology, and Genotype.

Owen R Phillips1, Alexander K Onopa2, Vivian Hsu2, Hanna Maria Ollila2, Ryan Patrick Hillary2, Joachim Hallmayer2, Ian H Gotlib2, Jonathan Taylor2, Lester Mackey2, Manpreet K Singh2.   

Abstract

OBJECTIVE: Sex differences in the brain are traditionally treated as binary. We present new evidence that a continuous measure of sex differentiation of the brain can explain sex differences in psychopathology. The degree of sex-differentiated brain features (ie, features that are more common in one sex) may predispose individuals toward sex-biased psychopathology and may also be influenced by the genome. We hypothesized that individuals with a female-biased differentiation score would have greater female-biased psychopathology (internalizing symptoms, such as anxiety and depression), whereas individuals with a male-biased differentiation score would have greater male-biased psychopathology (externalizing symptoms, such as disruptive behaviors).
METHOD: Using the Philadelphia Neurodevelopmental Cohort database acquired from database of Genotypes and Phenotypes, we calculated the sex differentiation measure, a continuous data-driven calculation of each individual's degree of sex-differentiating features extracted from multimodal brain imaging data (magnetic resonance imaging [MRI] /diffusion MRI) from the imaged participants (n = 866, 407 female and 459 male).
RESULTS: In male individuals, higher differentiation scores were correlated with higher levels of externalizing symptoms (r = 0.119, p = .016). The differentiation measure reached genome-wide association study significance (p < 5∗10-8) in male individuals with single nucleotide polymorphisms Chromsome5:rs111161632:RASGEF1C and Chromosome19:rs75918199:GEMIN7, and in female individuals with Chromosome2:rs78372132:PARD3B and Chromosome15:rs73442006:HCN4.
CONCLUSION: The sex differentiation measure provides an initial topography of quantifying male and female brain features. This demonstration that the sex of the human brain can be conceptualized on a continuum has implications for both the presentation of psychopathology and the relation of the brain with genetic variants that may be associated with brain differentiation.
Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Entities:  

Keywords:  differentiation; gender; genotype; mosaic; sex

Year:  2018        PMID: 30768381      PMCID: PMC6456435          DOI: 10.1016/j.jaac.2018.09.425

Source DB:  PubMed          Journal:  J Am Acad Child Adolesc Psychiatry        ISSN: 0890-8567            Impact factor:   8.829


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