Expression and Underlying Mechanisms of Depression Differ According to Gender

     Depression, and especially Major Depressive Disorder (or MDD), is known to be extremely difficult to treat for many sufferers. Some researchers trying to improve treatment efficacy have taken the route of focusing on the possible differences between depression in females vs. males. Researching the different manifestations and underlying mechanisms of depression for females vs. males has the potential to completely change the way we understand and treat it.

    In the study “Sex differences in the transcription of glutamate transporters in major depression and suicide,” Brian Powers and his colleagues investigated glutamate transporter gene expression in the dorsolateral prefrontal cortex (DLPFC) of females vs. males (Powers et al., 2020). There is known to be less PFC activity in those with MDD, but only males treated with ketamine show increased PFC spine density. They ended up finding that there was increased gene expression in only female MDD subjects, as well as upregulated mRNAs encoding glutamate transporters (GLUTS) in only females. In the article “Boys experience depression differently than girls. Here’s why that matters,” journalist Sujata Gupta reports on the actual manifestation of depression in adolescent boys vs. girls (Gupta, 2023). There has been an overall increase in reports of depressive symptoms in teenagers from 2011 to 2021, and although there is a large gap between the amount of girls and boys with depression (with girls being much higher), the size of that gap may not be entirely accurate.

    A leading prediction for why girls report higher rates of depression than boys is their tendency to internalize emotions, while boys more often externalize them. Screenings typically use words like “sadness” and “hopelessness,” but boys may be more likely to engage in risky, impulsive, or violent behavior (Gupta, 2023). Additionally, despite the lower rates of depression, males have a higher rate of death by suicide. Part of this could be that men with suicidal ideation are less likely to seek help and more likely to be dismissed by healthcare professionals when they do. Another explanation is that while girls report more suicidal thinking, planning, and attempts, boys are more likely to impulsively follow through with their suicidal ideation. In the Powers et al. study, a discrepancy between depressed individuals who die by suicide and those who don’t was also indicated by different expression of GLUTs in subjects who died by suicide vs. otherwise (Powers et al., 2020). To try and improve the accuracy of the screening process for men with depression, clinical psychologist Simon Rice developed the Male Depression Risk Scale. It focused on things like emotion suppression, anger, aggression, drug and alcohol use, risk-taking, etc. After using this scale and a traditional scale to survey 1,000 men, 11% of respondents met the criteria for depression on the men’s scale, but not on the traditional one (Gupta, 2023).

    Historically, we have treated depression similarly for men and women under the idea that it’s all the same disorder, but research like Powers et al. and Gupta have presented point towards an understanding that treatment may be more effective if it was more highly customized according to gender. The initial screenings could be more inclusive by accounting for more male-specific symptoms (especially externalizing factors), and medical treatment for MDD could eventually be different based on gender as well.

Sources: 

Powers, Brian, et al. “Sex differences in the transcription of glutamate transporters in major depression and suicide.” Journal of Affective Disorders, vol. 277, 2020, pp. 244–252, https://doi.org/10.1016/j.jad.2020.07.055.

Gupta, Sujata. “Boys Experience Depression Differently than Girls. Here’s Why That Matters.” Science News, Science News, 30 June 2023, www.sciencenews.org/article/boys-experience-depression-differently-girls.