Depression is one of the leading causes of disability worldwide, affecting around 322 million people, yet it remains a complex and poorly understood condition. About 15% of the global population will experience depression at some point in their lifetime, with women being twice as likely to be affected as men. It is characterized by persistent low mood, loss of interest in activities, and a range of associated psychological and physical symptoms lasting at least two weeks.

Depression is also a chronic and recurrent illness, with the risk of relapse increasing after each episode. It is a major risk factor for suicide, with nearly two-thirds of those affected experiencing suicidal thoughts, and up to 15% dying by suicide. 

Despite its staggering prevalence, only about one-third of people with depression receive effective treatment. In low and middle-income countries, this rate drops to less than 10%, highlighting a critical gap in mental health care. 

One of the biggest challenges in treating depression is the complexity of the brain, which is still not fully understood despite decades of research. Scientists now recognize that major depressive disorder (MDD) arises from an interplay of biological, genetic, environmental, and psychosocial factors. 

A recent landmark study led by the MDD Working Group, part of the Psychiatric Genetics Consortium, has provided pivotal insights into the genetics of depression. It stands as the world’s largest and most diverse genetic study of depression to date. 

Historically, research in this field has largely centered on white, affluent populations. This has led to treatments that often overlook and/or ineffectively address the needs of diverse ethnic groups, further deepening the health disparities. However, this study analyzed anonymized genetic data from over 5 million people across 29 countries, including groups that have been historically underrepresented in research. Notably, one in four participants were from non-European ancestries, addressing a significant gap in previous research.

By including a broader and more diverse sample, researchers identified 700 genetic variations linked to the development of depression—nearly 293 of them were previously unknown. The inclusion of participants from African, East Asian, Hispanic, and South Asian backgrounds led to the discovery of 100 genetic variations that had never been linked to the condition before.

While each individual genetic factor contributes only a small risk, the study found that having multiple depression-linked genes together can significantly increase a person’s likelihood of developing the condition.

The study also provides a more precise understanding of where depression-related genes are expressed in the body. Mark J. Adams, a leading co-author and senior research fellow at University of Edinburgh’s Centre for Clinical Brain Sciences, explains, “We’ve long known that these genes are related to brain function, but now we have a clearer picture of their specific roles—particularly in brain regions involved in reward processing and stress resilience.” These insights could pave the way for more targeted research and treatments for depression.

Nonetheless, translating these findings into new treatments is no easy task. Fabian Streit, another leading co-author and senior research fellow at Central Institute of Mental Health in Germany, points out, “Developing new medications is a complex and costly process, requiring multiple stages, including rigorous safety assessments in humans. As a result, there is a lack of new drugs for treating mental health disorders.” 

One promising approach researchers are exploring is drug repurposing, which means identifying existing medications developed for other diseases that could also be effective in treating depression.

In this study, the team used large databases that show how different drugs interact with specific genes. By matching this information with their newly identified depression-related genes, they were able to flag medications—such as those used to treat nerve pain and narcolepsy—as potentially promising candidates for further study. While this doesn’t guarantee effectiveness, it’s an important step toward accelerating the discovery of new treatment options.

Despite progress, significant gaps remain in our understanding of depression, limiting the ability to improve outcomes for those affected. As Fabian notes, “This study paves the way for future genetic studies that might help to develop personalized treatments for depression. It could help guide the selection of the most effective treatment combinations for patients, improving outcomes, and reducing the long phases of trial-and-error often involved in finding the right medication.” In this sense, the study has revealed a crucial missing piece of the puzzle.

To make meaningful strides in the fight against depression, larger and more globally representative studies are essential. They will provide insights to develop more effective therapies, prevent illness in high-risk populations, and ultimately help improve the lives of millions. Studies like these reignite the hope that early diagnosis and targeted treatments for depression could soon become a reality.

Image Credits: 

Feature Image: Photo by digitale.de on Unsplash, Creative Commons

Body Image 1: Photo by K. Mitch Hodge on Unsplash, Creative Commons

Body Image 2: Photo by Christina Victoria Craft on Unsplash, Creative Commons

– Japneet Kaur, Contributing Writer