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Diagnostics Genetics and epigenetics, Neurology

Examining Sex-Dependent Psychiatric Risks

Previous research suggests there may be sex-dependent risks for several major psychiatric disorders (1). However, according to Jill M. Goldstein, founder and executive director of the Innovation Center on Sex Differences in Medicine at Massachusetts General Hospital, “medicine, essentially, has been built on models of men’s health and male animals. We need to develop our precision medicine models incorporating the effect of sex (2).”

Recognizing the need for a genotype-by-sex (GxS) interaction study, an international collaboration of researchers conducted a large-scale genome-wide study to assess the sex-dependent and sex-specific risks of schizophrenia, major depressive disorder (MDD), and bipolar disorder (3). Though there was some genetic overlap between the sexes, they found significant sex-dependent effects for genes associated with neuronal development and immune and vascular pathway functioning across the disorders.

Heritability estimates differed between males and females for schizophrenia and MDD, but not for bipolar disorder, suggesting there are sex differences in incidence for schizophrenia and MDD. For all disorders, a single nucleotide polymorphism (SNP)-by-sex interaction was found at a locus encompassing NKAIN2 – a gene associated with cognitive ability and risk of schizophrenia. They also found a significant GxS interaction for the STLM gene and a SNP adjacent to AMIGO1.

The authors did note that the study lacked access to detailed clinical data, preventing them from delving deeper into GxS associations with age of onset, symptom type and severity, and cognitive deficits. However, their research still demonstrates a vital call for reform in genetics research.

“Our study underscores the importance of designing large-scale genetic studies that have the statistical power to test for interactions with sex,” said Goldstein (2). “Dissecting the impact of sex, genes, and pathophysiology will identify potential targets for sex-dependent or sex-specific therapeutic interventions – creating more effective therapies for both men and women.”

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  1. HE Jongsma et al., Lancet Public Health, 4, e229 (2019). PMID: 31054641.
  2. N Brown (2021). Available at:
  3. GAM Blokland et al., Biol Psych, [Preprint] (2021).
About the Author
Liv Gaskill

During my undergraduate degree in psychology and Master’s in neuroimaging for clinical and cognitive neuroscience, I realized the tasks my classmates found tedious – writing essays, editing, proofreading – were the ones that gave me the greatest satisfaction. I quickly gathered that rambling on about science in the bar wasn’t exactly riveting for my non-scientist friends, so my thoughts turned to a career in science writing. At Texere, I get to craft science into stories, interact with international experts, and engage with readers who love science just as much as I do.

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