Sex Differences Regarding Major Depressive Disorder

     The article “Sex- and suicide-specific alterations in the kynurenine pathway in the anterior cingulate cortex in major depression” delves into a study that describes how alterations in the kynurenine pathway (KP) contribute to the pathology of major depressive disorder (MDD.) Initially, there is a discussion on how MDD affects women at a rate that is double that of males, and how there is evidence of sex differences regarding KP dysregulation in non-psychiatric control. In addition, there is evidence that the concentration of the metabolites of KP changes when dysregulation of the KP exists. Activation of the KP is thought to lead to the formation of neuroactive metabolites, including kynurenic acid and quinolinic acid. By obtaining a postmortem anterior cingulate cortex from the NIH NeuroBioBank, the changes in the KP were tested. MDD subjects were found to have increased IL6 and IL1B expression, but female subjects, in particular, were found to have decreased KYNA.

    Sex differences in MDD were also investigated in the article “Sex differences in the transcription of glutamate transporters in major depression and suicide.” Here, however, the main focus is on the role of glutamatergic transmission in the prefrontal cortex and how that relates to major depressive disorder. The utilization of a multivariate analysis of covariance helped determine that there was a significant effect of diagnosis on the expression of glutamate transporters in female subjects with MDD. An increase in glutamate signaling has been shown to be therapeutic in MDD. By testing the hypothesis that glutamate transporter gene expression is abnormal in the DLPFC of MDD patients, the findings gave credence to the hypothesis that glutamatergic genes are abnormally expressed in the DLPFC of females with MDD, specifically.

    What is so interesting regarding both of these findings is the fact that both deal with different biochemical pathways. It sheds light on the complexity of MDD, and how researchers can’t necessarily ascertain a single pathway that causes that specific disorder. Much more work lies ahead in investigating the biochemical complexities of MDD. For example, researchers should look into whether the kynurenine pathway relates to glutamatergic transmission in the prefrontal cortex. By doing this, one can understand why the sex difference in MDD exists and how to better address it via specific interventions.

References:

Brown, Samara J., et al. “Sex- and Suicide-Specific Alterations in the Kynurenine Pathway in the Anterior Cingulate Cortex in Major Depression.” Nature News, Nature Publishing Group, 21 Sept. 2023, www.nature.com/articles/s41386-023-01736-8.

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.