Women carry a higher genetic risk of depression, according to a groundbreaking study published Wednesday in Nature Communications. This research, which claims to be the largest genetic study to date on sex differences in major depression, identified 16 genetic variants linked to depression in women compared to eight in men.
The study, spearheaded by Australia’s QIMR Berghofer Medical Research Institute, reveals that while many genetic variants associated with depression are shared between sexes, women bear a “higher burden of genetic risk.” This could be attributed to female-specific genetic variants.
Dr. Brittany Mitchell, a senior researcher at QIMR Berghofer’s genetic epidemiology lab, noted, “We already know that females are twice as likely to suffer from depression in their lifetime than males.” She added, “Depression looks very different from one person to another. Until now, there hasn’t been much consistent research to explain why depression affects females and males differently, including the possible role of genetics.”
Understanding the Genetic Landscape
The study’s findings underscore the complexity of depression, suggesting that a multifaceted approach is necessary to unravel its underlying mechanisms. Previous explanations have spanned behavioral, environmental, and biological domains. For instance, men are less likely to seek help, leading to under-diagnosis, while women face greater exposure to sexual abuse and interpersonal violence.
However, the study proposes that differences in genetics could be a key component of the biological mechanisms underlying these disparities. Researchers analyzed DNA from five international cohorts—Australia, the Netherlands, the United States, and two from the United Kingdom—comprising 130,471 women and 64,805 men with major depression, alongside 159,521 women and 132,185 men without the diagnosis.
Genetic Correlations and Metabolic Traits
The research also uncovered stronger genetic correlations in women between depression and metabolic traits, such as body mass index and metabolic syndrome, compared to men with the same traits. Dr. Jodi Thomas, the lead researcher, explained, “These genetic differences may help explain why females with depression more often experience metabolic symptoms, such as weight changes or altered energy levels.”
Despite the study’s robust findings, the authors acknowledged limitations, including the overrepresentation of women with depression and the restriction of analyses to European populations, which may limit the applicability of the findings to other groups.
Implications for Future Research and Treatment
Prof. Philip Mitchell from the University of New South Wales, who was not involved in the study, commented on the longstanding debate regarding why depression is more prevalent among females. He noted, “Most studies report that women have 2 to 3 times the risk of depression compared to men.”
“This very interesting novel genetic study in a very large global study provides strong evidence that these differences in rates of depression may in fact be due to genetic factors,” Prof. Mitchell said. “As well as strengthening the evidence that the differences in depression rates between men and women may be largely due to biological factors, it also points to the future possibility of different pharmacological treatments for depression in women and men.”
The announcement comes as researchers continue to explore the biological systems coded for by these genetic regions, potentially paving the way for more tailored and effective treatments for depression. As the understanding of these genetic differences deepens, it could lead to significant advancements in how depression is diagnosed and treated across genders.
Meanwhile, the study’s findings highlight the urgent need for further research across diverse populations to ensure that these insights can be applied globally. As genetic research progresses, the hope is to develop more personalized approaches to mental health care that consider both genetic and environmental factors.
