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Important genetic differences in how females and males experience depression have been revealed for the first time, in findings that could pave the way for more targeted intervention and treatments.
In the study, published in Nature Communications, scientists found that genetic factors contribute more to depression risk in females than in males. The team discovered about twice as many genetic ‘flags’ for depression in the DNA of females compared with males.
“We already know that females are twice as likely to suffer from depression in their lifetime than males,” said Dr Brittany Mitchell, Senior Researcher at QIMR Berghofer’s Genetic Epidemiology Lab.
“And we also know that 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.”
The team identified about 7,000 changes in the DNA that could cause depression in both sexes, and about a further 6,000 DNA changes (a total of 13,000) that could cause depression in females only.
Researcher Dr Jodi Thomas said the study also pinpointed how depression could show up differently for females and males.
The team found that the genetic factors linked to depression overlap more with those associated with metabolic traits in females.
“We found some genetic differences that may help explain why females with depression more often experience metabolic symptoms, such as weight changes or altered energy levels.”
The global study is the largest of its kind to look at males and females in this way. Scientists analysed DNA from hundreds of thousands of people with and without depression including around 130,000 females and 65,000 males with depression.*
The changes in DNA the scientists have identified are genetic differences people are born with, not changes that happen because of life experiences.
Traditionally, most drug trials and therapies are tested on males, but Drs Mitchell and Thomas hope their work will also translate to a greater clinical understanding of female depression.
“Unpacking the shared and unique genetic factors in males and females gives us a clearer picture of what causes depression - and opens the door to more personalised treatments,” Dr Thomas said.
“The findings highlight the importance of considering sex-specific genetic influences in studying depression and other health conditions.”
In the spirit of advancing scientific knowledge in this area, Drs Thomas and Mitchell have also made their results publicly available, allowing other scientists to analyse them further.
Please note: for the purposes of this study, genetic information was categorised via DNA samples with an XX chromosome (female) and XY chromosome (male). The authors did not analyse intersex DNA samples or gender identity information but acknowledge this will be an important future step.
*The authors wish to highlight that the study included roughly twice as many female participants as male participants, which means the statistical power to detect effects is higher in females than in males. To account for this, they performed additional analyses to ensure the findings were not simply due to the difference in sample sizes. These analyses confirmed that their findings were robust. For example, that genetic factors contribute more strongly to depression risk in females than in males, and that there are roughly twice as many DNA changes that could cause depression in females compared to males.
Read the full journal article here: https://www.nature.com/articles/s41467-025-63236-1
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