Millions of people take antidepressants each year, often during periods of intense emotional strain when daily functioning becomes difficult. For patients, questions about why one person needs medication while another copes without it remain deeply personal and unresolved. New genetic research suggests that the answer may lie partly in inherited biological differences linked not just to depression itself, but to the likelihood of being treated with antidepressants.
A large international study, published in HGG Advances, has examined the genetics of selective serotonin reuptake inhibitor use, the most commonly prescribed class of antidepressants. Rather than focusing only on diagnosed depression, researchers analysed genetic data from nearly 900,000 people to understand what distinguishes those who go on to use these medications from those who do not .
The analysis combined data from the UK Biobank and the US Million Veteran Program, allowing researchers to compare patterns across different healthcare systems and populations. They identified 40 genetic regions associated with SSRI use, many of which are involved in brain signalling, reward processing, and emotional regulation. Some of these genetic markers overlap with known risk factors for depression, while others appear to reflect distinct biological pathways.
One striking finding was that genetic signals linked to antidepressant use were stronger and more numerous than those linked to depression diagnoses alone. This suggests that medication use may capture aspects of mental health severity, persistence, or complexity that are not fully reflected in diagnostic labels. In practical terms, people who carry certain genetic profiles may be more likely to experience symptoms that lead to treatment, rather than brief or self limiting distress.
The study also found strong genetic overlap between antidepressant use and anxiety related traits, headaches, and measures of psychological distress. This aligns with real world prescribing patterns, where SSRIs are commonly used for anxiety disorders as well as depression. At the same time, antidepressant use showed a clearer genetic link to lower cognitive performance and educational attainment than depression alone, pointing to possible differences in how severe symptoms affect daily functioning.
Researchers also explored the role of sex chromosomes, an area often overlooked in genetic studies. Two significant genetic variants were found on the X chromosome, highlighting the importance of including sex based biology when studying mental health and treatment response. These findings may help explain why antidepressant use and side effects sometimes differ between men and women.
While the study does not suggest that genes determine who should take antidepressants, it adds weight to the idea that treatment seeking and treatment need are influenced by biology as well as environment. Depression is shaped by life events, social context, and personal coping resources, but these findings show that underlying genetic vulnerability may affect how intensely symptoms are felt and whether medication becomes part of recovery.
The authors caution that antidepressant use is a complex marker, influenced by healthcare access, prescribing practices, and personal choice. Still, understanding its genetic foundations could help future research move towards more personalised mental health care, where treatment decisions are better matched to individual risk profiles and symptom patterns.