Amazing stuff! I protest, this is unfair, gender discrimination that women have a "protective effect"! (just kidding) 😊
"Autism spectrum disorder diagnoses are about four times as common in boys than in girls. Nearly two times as many men are diagnosed with schizophrenia as women. In fact, for many neuropsychiatric conditions, there appear to be gendered differences in prevalence, severity, and at what age the disease first manifests. ... Now, researchers have found evidence for a somewhat controversial idea: that for women, more has to go awry before these diseases develop.
The team, who are part of a research consortium called PsychENCODE, examined gene expression in postmortem brain tissue from more than 2000 people. By comparing the genes expressed in the brains of people diagnosed with neuropsychiatric conditions with those expressed in people who had no history of these diseases, the researchers identified sets of genes that are expressed differently in patients diagnosed with autism, schizophrenia, or bipolar disorder. But most telling was the greater magnitude of difference between putatively healthy and diagnosed women compared to men.
The findings support a debated theory known as the “female protective effect.” Essentially, it posits that it takes a certain number of factors coming together—such as mutations and environmental exposures—to trigger neuropsychiatric disease, and this threshold is higher in women. As for why that is, the researchers found evidence for particularly strong divergence in expression of genes related to immunity and how neurons connect, so it may stem from differences in how male and female brains develop and differences in their immune systems."
From the editor's summary and abstract:
"Editor’s summary
Xia et al. analyzed transcriptomics data from 2,160 postmortem adult brain samples from patients with schizophrenia, bipolar disorder or autism spectrum disorder. They found that females exhibited a higher burden of transcriptomic dysfunction and greater connectivity variability compared to males. They report enrichment for genes associated with immune and synaptic-related pathways such as SCN2A, FGF14, and C3 in the transcriptomic burden of females compared to males. Understanding this sex-specific difference may lead to better treatments for psychiatric disorders. ...
Abstract
Many psychiatric disorders exhibit sex differences, but the underlying mechanisms remain poorly understood. We analyzed transcriptomics data from 2,160 postmortem adult prefrontal cortex brain samples from the PsychENCODE consortium in a sex-stratified study design. We compared transcriptomics data of postmortem brain samples from patients with schizophrenia (SCZ), bipolar disorder (BD), and autism spectrum disorder (ASD) to transcriptomics data of postmortem control brains from individuals without a known history of psychiatric disease. We found that brain samples from females with SCZ, BD and ASD showed a higher burden of transcriptomic dysfunction than did brain samples from males with these disorders. This observation was supported by the larger number of differentially expressed genes (DEGs) and a greater magnitude of gene expression changes observed in female versus male brain specimens. Additionally, female patient brain samples showed greater overall connectivity dysfunction, defined by a higher proportion of gene co-expression modules with connectivity changes and higher connectivity burden, indicating a greater degree of gene co-expression variability. We identified several gene co-expression modules enriched in sex-biased DEGs and identified genes from a genome-wide association study that were involved in immune and synaptic functions across different brain cell types. We found a number of genes as hubs within these modules including those encoding SCN2A, FGF14, and C3. Our results suggest that in the context of psychiatric diseases, males and females exhibit different degrees of transcriptomic dysfunction, and implicate immune and synaptic-related pathways in these sex differences."
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