Alterations in the levels of cerebrospinal fluid (CSF) metabolites among individuals dying by suicide: a systematic review and meta-analysis

Objectives Suicidal behaviour is biologically heterogeneous, and dysregulation of cerebrospinal fluid (CSF) metabolites has been implicated in suicidal death. We conducted a systematic review and meta-analysis to evaluate these alterations in individuals dying by suicide compared with non-suicidal deaths.Methods This review followed PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420251242059). PubMed, Web of Science, and Scopus were systematically searched. Random-effects meta-analyses were performed, calculating standardised mean differences (SMDs) with 95% confidence intervals (CIs). Quality assessment and sensitivity analyses of included studies were done and heterogeneity assessed using I2 statistic.Results Of 1,814 records, seven case-control studies (195 suicidal deaths; 267 controls) met inclusion criteria and were rated moderate-to-good quality on the Newcastle-Ottawa scale. Eight metabolites were reported, but meta-analysis was feasible for serotonin and 5-hydroxyindoleacetic acid (5-HIAA) only. No significant differences were observed for serotonin (SMD (95%CI) = −0.43 (−1.62–0.76); p = 0.48) and 5-HIAA (SMD (95%CI) = 0.34 (−0.54–1.21); p = 0.45). Substantial heterogeneity was present, but sensitivity analyses showed robust estimates.Conclusions Current evidence does not demonstrate significant differences in CSF serotonin or 5-HIAA levels in suicidal deaths. Methodological heterogeneity and limited data underscore the need for rigorously designed standardised post-mortem studies.