Peripheral immune-vascular correlates of suicidal thoughts and behaviors in bipolar disorder and schizophrenia: cross-sectional and prospective analyses from the FACE-BD and FACE-SZ cohorts.

BACKGROUND

Bipolar disorder (BD) and schizophrenia-spectrum disorders (SZ) are associated with high rates of suicidal ideation (SI) and suicide attempts (SA). Peripheral immune-vascular abnormalities may contribute to suicidal vulnerability in these disorders, but their specificity, temporal meaning, and diagnostic patterning remain unclear.

METHODS

We quantified 28 peripheral immune-vascular variables (cytokines/chemokines, vascular-injury markers, blood counts, lipids) in 980 French FACE (FondaMental Advanced Centres of Expertise) outpatients with BD (n = 529) or SZ (n = 451). Elastic-net logistic regression and partial least-squares regression for binary outcomes examined associations with SA, baseline SI, and SI over 12 months in pooled and diagnosis-stratified samples. Models adjusted for age, sex, and body mass index, with sensitivity analyses for depression severity, medication classes, smoking, phenotype overlap, attrition, and missing data.

RESULTS

In pooled analyses, SA was associated with higher vascular endothelial growth factor; stratified analyses suggested this signal was mainly driven by BD (OR = 1.33, 95% CI 1.08-1.64). In SZ, SA showed weaker platelet/SAA-related associations. Baseline SI showed more consistent multivariate signals than individual analytes; in BD, higher IL-7 and SAA remained associated with SI after adjustment, whereas SZ findings were more medication-sensitive. SI over 12 months showed the least stable associations; in BD, lower IL-7 was associated with follow-up SI (OR = 0.72, 95% CI 0.54-0.96). Internal validation indicated stronger performance for baseline SI than for SA or follow-up SI.

CONCLUSIONS

We found modest, phenotype-dependent and partly diagnosis-specific peripheral immune-vascular correlates of SI and SA in BD and SZ. Replication and direct biological validation are needed.