A 13-year UK Biobank analysis suggests that neuroticism, adversity and other psychosocial pressures may explain more of the population burden of depression and anxiety than physiological risk factors alone.
Study: Associations between modifiable risk factors and depression and anxiety in women and men: Evidence from the UK Biobank. Image credit: manka_web / Shutterstock
Given the large global burden of depression and anxiety, it is important to understand the relative importance of modifiable risk factors. Journal’s recent “press articles” translational psychiatry They found that psychosocial factors were estimated to contribute most significantly to the population burden of depression and anxiety in both men and women.
background
As of 2021, approximately 332 million people worldwide have depression and 359 million people of all ages have anxiety disorders. Both disorders develop early in life, are often chronic, and can impair social, educational, and occupational functioning, as well as reduce quality of life.
Administrative costs are high and economic and social productivity is reduced. However, it is treatable if diagnosed early, highlighting the need for early detection and prevention strategies.
The causes of these disorders are thought to be related to multiple factors, including physiological, psychosocial, metabolic, and female-specific reproductive factors. For example, people who have experienced adverse childhood experiences (ACEs) are more likely to develop anxiety and depression.
Gender differences have long been recognized in these conditions, with women being almost twice as likely to be diagnosed and having more severe symptoms and earlier onset. These differences may partially reflect biological, hormonal, reproductive, social, and behavioral differences across women’s life courses.
In the current study, researchers examined the effects of modifiable physiological, psychosocial, and female-specific reproductive factors on the long-term risk of depression and anxiety in women and men. They calculated the population attributable fraction (PAF) for each factor, which is the proportion of disease cases in a population that could theoretically be prevented if the risk factor was removed, assuming that the risk factor caused the outcome. This allows us to quantitatively estimate the impact of these factors at the population level, which can help determine policy priorities.
The study used data from 87,648 UK Biobank participants, followed for a median of 13.7 years. Participants had no depression or anxiety at baseline. During the follow-up period, 5.7% of women and 4.2% of men developed depression. For anxiety, the corresponding figures were 6% and 3.6%, respectively.
Psychosocial factors were the strongest factor
Among the factors studied, neuroticism, which refers to elevated neuroticism-related traits rather than clinical diagnosis, may be the most significant contributor to the overall burden of depression based on PAF estimates. PAFs for depression ranged from 49% to 60%, whereas PAFs for anxiety ranged from 52% to 54%.
Women with neurotic symptoms were 2.6 times more likely to develop depression, while men were 3.5 times more likely. For anxiety, the corresponding figures were 2.8 and 2.9 times higher, respectively. The authors suggest that although women are more likely to be neurotic, the association between neuroticism and depression is stronger in men, perhaps due to lower psychological thresholds or reduced ability to regulate emotions.
Other important factors were adverse childhood and adult experiences. For depression, these patients had a PAF of approximately 18% to 25%, while for anxiety, the PAF was lower, approximately 11% to 14%. Such events can disrupt stress responses, cause emotional dysregulation, and increase susceptibility to depression and anxiety. The authors note that the higher prevalence among women may reflect increased exposure to such situations, particularly within the household, and a tendency to internalize such stress.
Unhealthy lifestyle habits such as lack of sleep, smoking, and sedentary behavior also increase the risk of depression and anxiety, along with lower socio-economic status. These associations were more pronounced in men, likely reflecting a higher concentration of unhealthy behaviors and less frequent use of stress-reducing and help-seeking behaviors.
Collectively, psychosocial factors contributed to 61% of the PAF for depression in women and 67% in men. They contributed 60% of the PAF to anxiety in women and 56.8% in men. In particular, psychosocial factors continue to significantly contribute to PAF across all age groups.
physiological factors
Among physiological factors, obesity contributed the most to the PAF of depression, at 15% in both men and women. Obese women had a 33% higher risk, while men had a 25% higher risk. This may reflect the bidirectional risk posed by obesity, both in terms of metabolic and psychosocial stress.
Obesity is also associated with chronic inflammation. It also contributes to insulin resistance and other negative metabolic effects, all of which can contribute to an increased risk of depression.
Chronic inflammation was associated with increased risk of depression and anxiety in both women and men. PAF for depression was 6% to 7%, and PAF for anxiety was 3% to 5%. This is consistent with evidence of central endocrine dysregulation and immune dysfunction associated with chronic inflammation, which may contribute to depression and anxiety.
Diabetes also increased the risk of depression in both men and women, but the PAF was less than 3%.
Collectively, physiological factors contributed 21% to 22% of PAF in depression but less so in anxiety. Across age groups, obesity contributed the most to the burden of depression among participants under 60, and chronic inflammation contributed across all age groups. For anxiety, the physiological contribution was generally modest at a young age but increased in later life. Total PAF for depression was higher in women aged 55 to 59 years and men aged 60 to 64 years.
Reproductive factors unique to women
Hormone replacement therapy (HRT) had the largest individual reproductive factor PAFs, 13% for depression and 9% for anxiety. However, this continues to be reported and more detailed exposure data are essential to properly interpret this.
Early menarche, history of abortion, and early age at first birth were other significant factors for depression. Regarding anxiety, HRT remained the main reproductive factor, with history of abortion making a modest contribution.
The combined PAF of reproductive factors and depression was 19%, with the greatest impact occurring later in life. However, for anxiety, the combined PAF of the reproductive domain was minimal at 0.13%, suggesting that this domain is more related to depression than anxiety.
PAF with additives
Taking all factors together, the PAF for depression was 68% in women and 70% in men. For anxiety, the corresponding PAFs were 61% and 58%, respectively.
Health effects
These findings demonstrate the importance of considering a wide range of emotional characteristics, physiological parameters, and psychosocial factors, as well as gender-specific factors, when assessing mental health risk. These findings suggest that, although estimates are theoretical, targeting modifiable psychosocial, lifestyle, and physiological factors could potentially reduce the population burden of depression and anxiety.
Potential strategies include interventions targeting trauma and socio-economic stress, as well as mental health screening for chronic diseases, older populations, and women undergoing transitions such as menopause.
strengths and limitations
This study used data from a large prospective UK Biobank cohort with detailed data on health and risk factors. Researchers are incorporating a variety of modifiable risk factors across multiple areas of health. They used PAF estimates to provide actionable population-level impact figures. We also stratified by age and gender to identify the most vulnerable groups.
That said, “the estimated PAF should be interpreted as an indication of potential population-level associations rather than as a precise causal relationship.”
This study has some limitations. Since this is an observation, we cannot infer cause and effect relationships. Multiple sources of information were used to assess depression and anxiety, which could have resulted in misclassification errors. Retrospective self-reports of adverse experiences in childhood and adulthood may also have led to recall bias.
The majority of participants did not provide complete data, reducing the sample size, which may have affected the final estimates and possibly limited the generalizability of the results.
The estimates were based on “yes/no” classification for some variables, which may have prevented the observation of a dose-response relationship. Unmeasured confounding may affect the final estimates. A large number of statistical comparisons increases the likelihood of finding results by chance. UK Biobank is not representative of the general population.
conclusion
This study highlights the contribution of multiple modifiable physiological, psychosocial, and reproductive factors to the risk of depression and anxiety in middle-aged and older adults.
This finding reveals the important role of psychosocial factors, particularly neuroticism and adversity. Finally, if these risk factors can be effectively addressed, the total PAF is approximately 58% to 70%, indicating the potential for prevention. This will require the use of “gender-sensitive, life-course-oriented strategies that integrate psychological, metabolic, and reproductive health considerations into mental health prevention and clinical practice.”
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Reference magazines:
- Luo, Z., Sun, W., Shan, S., et al. (2026). Associations of modifiable risk factors with depression and anxiety in women and men: Evidence from the UK Biobank. Translational psychiatry. Toi: 10.1038/s41398-026-04185-1, https://www.nature.com/articles/s41398-026-04185-1
