Migraine Associated With Increased Risk of Depression in Women

MIGRAINE and depression have been linked in women, with migraine associated with a higher risk of incident depression in a large prospective cohort, although female-specific genetic analyses found no statistical evidence of a direct causal effect.

Migraine and Depression in Women

Migraine and depression disproportionately affect women, yet their global trends, prospective associations, and genetic causal mechanisms have remained largely uninvestigated. This study has therefore integrated multi-level evidence from the Global Burden of Disease (GBD) Study, the UK Biobank (UKB), and Mendelian randomisation (MR) analyses to dissect the relationship between migraine and depression in women.

Study Methods

Temporal trends in incidence and disability-adjusted life year (DALY) rates were analysed using GBD data from 1990 to 2023. Within the UKB prospective cohort (N=249,322), Cox proportional hazards models were used to examine the association between migraine and incident depression. Two-sample MR analyses were performed to evaluate genetic causality between the two disorders, with supplementary bidirectional analysis using FinnGen data.

Is Migraine Linked to Depression?

Between 1990 and 2023, age-specific incidence and DALY rates of depression in women rose across all age groups, and those of migraine remained essentially stable, with slight increases only at middle and older ages. In 2023, migraine DALY rates remained high across ages 35–59 years, whereas depression rates declined steadily with age. In the UKB, migraine was associated with a significantly increased risk of incident depression (hazard ratio: 1.46), with a stronger association in individuals aged under 60 years (hazard ratio: 1.62). MR analysis using current female-specific genome-wide association study data provided no statistical evidence for a direct causal effect of migraine on depression (odds ratio: 1.03), although limited power due to a small number of instrumental variables precluded definitive exclusion of a subtle causal link. Conversely, genetically predicted depression was linked to an increased risk of migraine in the sex-unspecific FinnGen cohort, which may reflect a shared cross-sex liability.

Future Research

Migraine has been associated with an increased risk of incident depression in women, but female-specific MR analysis, with limited power, found no statistical evidence of a direct causal effect, so a subtle causal link cannot be excluded. Future studies should integrate multi-omics and longitudinal designs in larger female-specific cohorts.

Reference

Hu X et al. Migraine and depression risk in women: integrated evidence from the global burden of disease, UK Biobank, and Mendelian randomization. J Headache Pain. 2026;DOI:10.1186/s10194-026-02560-3.