Lack of Sexual Dimorphism in Language Processing Gray Matter Regions in Early Psychosis

Principal Investigator: Martha Shenton

Authors: Emily Johns, A.B., Amanda E. Lyall, Ph.D., Johanna Seitz-Holland, M.D., Ph.D., Sylvain Bouix, Ph.D., Michael J. Coleman, M.A., Marek Kubicki, M.D., Ph.D., Ofer Pasternak, Ph.D., Raquelle Mesholam-Gately, Ph.D., Eve Lewandowski, Ph.D., Daphne Holt, M.D., Ph.D., Matcheri S. Keshavan, M.D., Dost Ongur, M.D., Ph.D., Alan Breier, M.D., Martha E. Shenton, Ph.D.
Lay Abstract

The two hemispheres of a healthy brain are asymmetrical, especially in regions related to processing language. However, when we use neuroimaging techniques to examine the brains of individuals suffering from psychosis, we do not see these same structural differences that we normally see in healthy brains. Yet, there is little research examining whether structural differences exist in brain areas that process language between males and females who suffer from early psychosis. In this study, we examined the extent of this asymmetry and thickness of the brain’s cortex in three key areas regions related to language on both sides of the brain to determine if there are structural differences between males and females. We found that there was a significant asymmetry in one region in individuals with psychosis compared to healthy individuals. We also found that there were only significant differences in the thickness of one of the three regions between males and females in the sample of healthy people, but not in the sample of people with early psychosis. This suggests that individuals suffering from early psychosis lack the structural differences related to sex that are characteristic of the normal, healthy brain.

Scientific Abstract

It is well established that individuals with psychosis show diminished anatomical lateralization in language processing brain regions compared to healthy controls. However, there are few neuroimaging studies that explore sex-related differences in lateralization related to language processing in early course psychosis. Therefore, we characterized the variation in hemispheric lateralization and cortical thickness of regions implicated in language processing to determine if the presence and extent of sexually dimorphic cortical characteristics is similar across groups. Cortical thickness of 3 bilaterally represented language processing regions approximating to Geschwind’s, Wernicke’s, and Broca’s areas were compared between 134 individuals suffering from early psychosis (EP) and 67 healthy individuals (HC) matched 2:1 on age, sex, handedness, and education. Welch’s t-tests revealed a significantly diminished left lateralization only in Broca’s area in EP compared to HC, yet there was no group by sex interaction. Subsequent morphological analyses of cortical thickness for each bilateral region revealed greater right and left cortical thickness in Wernicke’s area in HC males compared to HC females. This was not seen when comparing EP males and EP females. This suggests that individuals suffering from early psychosis lack the sex-related structural differences that are characteristic of the normal, healthy brain.

Clinical Implications
Understanding how the biomarkers of early course psychosis differ between sexes can increase the specificity and thus the efficacy of treatment for psychosis and related disorders.

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