Normal Sex Differences in Mentalizing Are Reversed in Schizophrenia

November 5, 2018

By Will Boggs MD 

NEW YORK—Normal sex differences in the ability to mentalize are reversed in people with schizophrenia, researchers report.

"It was most surprising to find that mental-state identification was related to intelligence in healthy women and affective processes in healthy males," Dr. Julie Walsh-Messinger of the University of Dayton, in Ohio, told Reuters Health by email. "In individuals with schizophrenia, the sex differences were reversed."

Deficits in the ability to accurately identify other people's emotions and interpret their intentions, known as mentalizing or "theory of mind" (ToM), have been well documented in schizophrenia.

Dr. Walsh-Messinger and colleagues tested ToM in sex-stratified samples of 37 individuals with schizophrenia and 31 healthy controls to probe differential cognitive (indexed by intelligence) and affective (indexed by olfactory tasks) contributions to ToM performance.

For ToM, the researchers used Reading the Mind in the Eyes (RME) to assess the ability to identify another person's mental state and Strange Stories Task (SST) to assess the ability to infer intentions of others, a reflective process that entails reasoning.

Higher intelligence best correlated with more accurate mental-state identification in female controls and males with schizophrenia, whereas better smell-identification accuracy best correlated with more accurate mental-state identification in male controls and females with schizophrenia.

SST inferring intentions correlated significantly with intelligence in female controls and males with schizophrenia, again showing a reversal of sex effects in the schizophrenia group, the researchers report in Social Neuroscience, online October 29.

In male controls and in the schizophrenia group, performance on both ToM tasks was not significantly associated with any of the Positive and Negative Syndrome Scale (PANSS) symptom scales. But in female controls, less accurate mental-state identification was related to more general psychopathology symptoms.

Higher negative-symptom severity was associated with lower smell-identification scores in males with schizophrenia, while higher positive-symptom severity was associated with less sensitive odor detection in females with schizophrenia.

In post hoc sex-specific multivariable analyses, intelligence was the only significant predictor of mental-state identification in female controls and males with schizophrenia (but not in male controls or females with schizophrenia), whereas only smell identification predicted mental-state identification in male controls.

"Our findings suggest that sex differences in healthy individuals may interact with schizophrenia-related pathology to produce different symptom profiles that vary by sex," Dr. Walsh-Messinger said. "Healthy males appear to rely on limbic processing for mental state identification and disruption to this circuitry by schizophrenia pathology may contribute to development of negative symptoms, which tend to be more severe in males with schizophrenia."

"Most importantly, our findings highlight the importance of considering sex differences in treatment research, as men and women are different and important findings may be obscured by not using sex-stratified designs in schizophrenia research, including treatment studies," she said.

"Do not assume that research findings obtained in predominantly male samples will generalize to females, and vice versa," she said.


Soc Neurosci 2018.

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