Lower Plasma Dopamine β-hydroxylase Levels Are Associated with Suicide Mortality in the UK Biobank

Objective: Suicide remains a major global public health concern, yet its biological underpinnings remain incompletely understood at the population level.Although monoaminergic dysregulation has been implicated in suicidal behavior, population-based studies directly examining circulating proteomic profiles in suicide mortality remain limited.Methods: We conducted an exploratory, population-based case-control study as a secondary analysis of existing UK Biobank plasma proteomic data generated with the Olink proximity extension assay, comparing 22 individuals who subsequently died by suicide with 1,781 rigorously defined supernormal controls without major psychiatric, neurological, or medical conditions.Associations between plasma protein abundance and suicide mortality were examined using protein-wise linear regression models adjusted for age, sex, and assay date, with multiple-testing correction applied across all analyzed proteins.Results: Among the assayed proteins, dopamine -hydroxylase (DBH) was the only protein significantly associated with suicide mortality after multiple-testing correction (Benjamini-Hochberg false discovery rate q = 0.006; equivalent Bonferroni-adjusted p = 0.006), with lower DBH abundance in suicide decedents; no other protein remained significant.Protein-protein interaction analysis suggested that DBH represented an isolated association rather than part of widespread proteomic dysregulation.In a male-only sensitivity analysis, including 655 controls and 17 suicide decedents with complete DBH and covariate data after proteomic quality control, lower DBH abundance remained significantly associated with suicide mortality after adjustment for age and assay date ( = -1.362,95% confidence interval = -1.888 to -0.837, p = 4.67 × 10 -7 ).Conclusion: Given the role of DBH in catecholaminergic regulation, lower circulating DBH abundance may reflect a peripheral biological correlate associated with suicide mortality.Because the number of suicide decedents was small and no independent validation was available, these findings should be interpreted as strictly hypothesis-generating and warrant replication in larger, independent cohorts.The association was also preserved in a male-only sensitivity analysis; however, because the suicide group was overwhelmingly male, the findings cannot be reliably generalized to females and should remain hypothesis-generating.