Sex Differences in Depression and Treatment Responses
Summary
Depression exhibits a consistent female preponderance in prevalence and clinical presentation, yet men often manifest more severe outcomes such as higher suicide rates and substance misuse. Biological factors, including sex hormones, genetic predispositions and neurobiological pathways, interact with psychosocial influences to shape divergent symptom profiles and help-seeking behaviours. Emerging evidence points to sex-dependent molecular mechanisms, from neurotransmitter receptor expression to inflammatory and metabolic pathways, which may underlie differential vulnerability. Treatment responses also vary: women more commonly receive selective serotonin reuptake inhibitors and report distinct side-effect burdens, while men may benefit more from tricyclic antidepressants. Rapid-acting interventions, psychotherapy uptake and adherence patterns further diverge by sex, underscoring the need for tailored strategies. A nuanced appreciation of these differences is crucial to optimise diagnosis, personalise therapy and address under-diagnosis and under-treatment, particularly among men.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Sex Differences in Depression and Treatment Responses publication trend
The graph below shows the total number of articles in sex differences in depression and treatment responses across all publications each year (not limited to Nature Index journals).
Technical terms
Genome-wide association study (GWAS): A method that scans the genome for common genetic variants to identify associations with traits or disorders.
Polygenic risk score (PRS): An aggregate measure of genetic liability for a trait, calculated by summing the effects of multiple risk variants.
Treatment-resistant depression (TRD): Major depressive disorder that fails to respond adequately to at least two standard antidepressant therapies.
Selective serotonin reuptake inhibitor (SSRI): A class of antidepressant medications that increase serotonin levels by inhibiting its reuptake into presynaptic neurons.
References
- A sex-specific genome-wide association study of depression phenotypes in UK Biobank. Molecular Psychiatry (2023).
- The influence of general practitioner and patient sex on the treatment of major depression. Frontiers in Pharmacology (2023).
- Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials. Archives of Women's Mental Health (2022).
About these summaries
This Nature Research Intelligence Topic summary is created with the cited references and a large language model. We take care to ground generated text with facts, and have systems in place to gain human feedback on the overall quality of the process in line with our AI principles. We strive to create accurate and useful summaries for people unfamiliar with the research topic and that supports this goal. These pages are a beta release and will be updated as we learn how best to help people gain value from a research topic summary.
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.