Sexual Dimorphism in Psychiatric Illness: Who is More Susceptible?

    Anyone can develop psychiatric illnesses like depression and anxiety, but some individuals are genetically predisposed; there exists a gender disparity within the development of cognitive disorders, and women are more prone to doing so. The distinction can be attributed to biological differences in cellular signaling pathways and levels of gene expression in the brain, but also environmental and sociocultural factors.

    There are critical differences between males and females in their expression levels of genes encoding for proteins that associate with neurotransmitters, and these variations are evident in the differences observed in patients with depressive disorders. In “Sex differences in the transcription of glutamate transporters in major depression and suicide” by Sodhi et al., the glutamate system is investigated to figure out how it contributes to the biological basis of major depressive disorder (MDD) and suicide through acting on the dorsolateral prefrontal cortex (DLPFC). Susceptibility to developing the disorder was found to indeed be sexually dimorphic, with mRNA expression levels of glutamate receptors and glutamate transporter genes in dorsolateral DLPFC being upregulated in females with MDD. Abnormalities in glutamate signaling can lead to cell death, thus explaining reduced glial and neuronal cells in the DLPFC of female MDD patients. This reduced number of cells would lead to lower activity levels in the DLPFC, causing issues in decision making and problem solving and issues in these cognitive functions could lead to greater susceptibility to suicide.

    Also discussing sexual dimorphisms in the brain, “Sexual Dimorphism in Brain Development: Influence on Affective Disorders” by López-Ojeda et al. emphasizes the significance of sex hormones and their effects on brain structure and function, as well as their roles in behavioral outputs like stress response. Environmental stimuli also serve to highlight differences in male versus female brain activation; positive stimuli for males and the counterpart negative stimuli for females generates higher levels of activity in the amygdala. Additionally, even in cases where males and females alike experience the same level of anxiety and/or stress, it is the behavioral differences in how they react to adverse stimuli that further distinguishes the gender disparity in mood disorders.

    Both articles discuss the role of sex differences in developing and managing cognitive disorders, with females being more susceptible to major depressive and mood disorders. These studies underscore the importance of creating therapies tailored to account not only these biological differences among males and females, but behavioral differences as well; the sociocultural impact on health and its role in the development of cognitive disorders is often overlooked.

López-Ojeda, Wilfredo, and Robin A. Hurley. “Sexual dimorphism in brain development: Influence on Affective Disorders.” The Journal of Neuropsychiatry and Clinical Neurosciences, vol. 33, no. 2, 2021, https://doi.org/10.1176/appi.neuropsych.20100269.

Powers, B., Joyce, C., Kleinman, J. E., Hyde, T. M., Ajilore, O., Leow, A., & Sodhi, M. S. (2020). Sex differences in the transcription of glutamate transporters in major depression and suicide. Journal of affective disorders, 277, 244–252. https://doi.org/10.1016/j.jad.2020.07.055.