Associations of modifiable risk factors with depression and anxiety in women and men: evidence from the UK Biobank

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Depression and anxiety (n=87648). Intervention: Neuroticism symptoms vs. Lower neuroticism symptoms. Primary outcome: Incident depression in men (HR 3.50, 95% CI 3.07, 3.98).

Q: What does this research mean for the field?

Neuroticism symptoms account for the largest population attributable fraction of incident depression and anxiety in both sexes, with modifiable risk factors jointly accounting for over 60% of incident cases. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Zeyu Luo; Weidi Sun; Shiyi Shan; Jing Wu; Yajie Zhu; Peige Song

doi:10.1038/s41398-026-04185-1

June 22, 2026Translational PsychiatryOpen Access

Associations of modifiable risk factors with depression and anxiety in women and men: evidence from the UK Biobank

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Key result

Combined modifiable risk factors tied to ~70% of incident depression cases, driven primarily by neuroticism.

HR 3.50
95% CI 3.07, 3.98
n=87,648

Figures

Why the study?

Do modifiable physiological, psychosocial, and reproductive factors increase the risk of incident depression and anxiety in men and women?

Key Points

To evaluate the associations of modifiable physiological, psychosocial, and reproductive risk factors with incident depression and anxiety in women and men, and to estimate their population attributable fractions.
Prospective cohort study analyzing 87,648 participants from the UK Biobank (44,383 women and 43,265 men) recruited between 2006 and 2010, followed for a median of 13.7 years.
Assessed incident depression and anxiety based on the first recorded ICD-10 diagnosis or new-onset symptom positivity during follow-up among participants free of the respective condition at baseline.
Calculated sex-stratified hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox proportional hazards models, and estimated individual and combined population attributable fractions (PAFs).
During follow-up, 5.65% of women and 4.21% of men developed depression, while 6.02% of women and 3.60% of men developed anxiety.
Neuroticism symptoms drove the highest population attributable fractions for depression (women: HR 2.61, 95% CI: 2.36, 2.88, PAF 48.61%; men: HR 3.50, 95% CI: 3.07, 3.98, PAF 59.93%) and anxiety (women: HR 2.82, 95% CI: 2.56, 3.11, PAF 51.75%; men: HR 2.94, 95% CI: 2.58, 3.36, PAF 53.80%).
Obesity had the largest physiological PAF for depression (women: HR 1.33, PAF 14.85%; men: HR 1.25, PAF 15.32%), hormone replacement therapy led reproductive contributions in women (depression: HR 1.48, PAF 13.43%; anxiety: HR 1.32, PAF 9.43%), and overall additive combined PAFs reached 67.54% in women and 69.71% in men for depression.

Study Design

Type

Cohort (n=87,648)

Multicenter

Yes

Structured PICO

Do modifiable physiological, psychosocial, and reproductive factors increase the risk of incident depression and anxiety in men and women?

P

Population

87,648 adults aged 37-73 years from the UK Biobank, free of depression and anxiety at baseline, followed for a median of 13.7 years.

E

Exposure

Modifiable physiological, psychosocial, and female-specific reproductive risk factors

O

Outcome

Incident depression and anxiety (first recorded ICD-10 diagnosis or new-onset symptom positivity during follow-up)

Main Result

Hazard Ratio: 3.5 (95% CI 3.07–3.98)

Psychosocial factors, especially neuroticism, contribute the largest population attributable fraction for incident depression and anxiety in both men and women.

Limitations

Assessment of depression and anxiety based on hospital records and self-reports may lead to underdiagnosis.
Retrospective self-reporting of psychosocial exposures is susceptible to recall bias.
Complete-case approach for missing data may introduce selection bias.
Dichotomization of continuous variables may result in loss of information.
Observational design precludes definitive causal inference.
UK Biobank cohort is not fully representative of the general population.

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Neuroticism symptoms warrant consideration in depression risk models; leaves open whether screening or modification alters outcomes.

Abstract

Depression and anxiety are common mental disorders with substantial public health burden, yet the relative contributions of potentially modifiable physiological, psychosocial, and female-specific reproductive factors to their development remain incompletely understood, particularly across sex and age groups. We aimed to examine the associations of these factors with incident depression and anxiety in women and men and to estimate their population attributable fractions (PAFs). This prospective cohort study included 87,648 participants from the UK Biobank (44,383 women and 43,265 men) recruited between 2006 and 2010 and followed for a median of 13.7 years. Incident depression and anxiety were defined as the first recorded ICD-10 diagnosis or new-onset symptom positivity during follow-up among participants free of the respective condition at baseline. Sex-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and individual and combined PAFs were calculated separately in women and men. During follow-up, 5.65% of women and 4.21% of men developed depression, while 6.02% and 3.60% developed anxiety, respectively. Psychosocial factors contributed the largest population burden in both sexes. Neuroticism symptoms had the largest PAFs for depression (women: HR 2.61, 95% CI: 2.36, 2.88; PAF 48.61%, 95% CI: 44.71%, 52.68%; men: HR 3.50, 95% CI: 3.07, 3.98; PAF 59.93%, 95% CI: 55.41%, 64.13%) and anxiety (women: HR 2.82, 95% CI: 2.56, 3.11; PAF 51.75%, 95% CI: 47.93%, 55.68%; men: HR 2.94, 95% CI: 2.58, 3.36; PAF 53.80%, 95% CI: 48.89%, 58.62%). The additive combined PAF of psychosocial factors was 61.17% in women and 66.90% in men for depression, and 59.98% and 56.80% for anxiety. Among physiological factors, obesity contributed the largest PAF for depression in both sexes, while chronic inflammation was associated with both outcomes in both sexes. In women, reproductive factors provided additional contributions, with hormone replacement therapy showing the largest PAFs for depression (HR 1.48, 95% CI: 1.34, 1.62; PAF 13.43%, 95% CI: 10.15%, 16.84%) and anxiety (HR 1.32, 95% CI: 1.20, 1.44; PAF 9.43%, 95% CI: 6.38%, 12.80%). Age-stratified analyses showed that psychosocial contributions remained substantial across age groups, whereas physiological and reproductive contributions were more pronounced in later life. When all factors were considered jointly, the overall additive combined PAFs were 67.54% in women and 69.71% in men for depression, and 61.23% and 57.82% for anxiety. These findings support sex-informed and life course-oriented prevention strategies for depression and anxiety.

Discussion

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Cite This Study

Luo et al. (2026) conducted a cohort in Depression and anxiety (n=87,648). Neuroticism symptoms vs. Lower neuroticism symptoms was evaluated on Incident depression in men (HR 3.50, 95% CI 3.07, 3.98). Neuroticism symptoms had the largest population attributable fractions for incident depression, with a hazard ratio of 2.61 in women and 3.50 in men, while all modifiable risk factors combined accounted for 67.54% and 69.71% of depression cases, respectively.

synapsesocial.com/papers/6a3c2323d15afadd906f9d37 https://doi.org/10.1038/s41398-026-04185-1

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Associations of modifiable risk factors with depression and anxiety in women and men: evidence from the UK Biobank

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Associations of modifiable risk factors with depression and anxiety in women and men: evidence from the UK Biobank

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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