Cerebrospinal fluid levels of monoamines among suicide attempters: A systematic review and random-effects meta-analysis

Abstract : Background: It remains unclear whether the dopaminergic and noradrenergic systems may be implied in suicide attempt risk. In addition, although the serotonergic system has been extensively studied, no formal meta-analysis has been performed to examine its association with suicide attempt. Methods: Using PRISMA methodology, we performed a systematic literature review and random-effects meta-analyses of the differences in cerebrospinal fluid (CSF) levels of 5-HIAA, HVA and MHPG between suicide attempters and individuals who never attempted suicide. Results: We identified 30 studies including 937 suicide attempters and 1128 non-attempters; 29 of them measured CSF levels of 5-HIAA, 22 measured CSF levels of HVA and 14 measured CSF levels of MHPG. CSF levels of 5-HIAA and HVA were significantly lower in suicide attempters than in non-attempters [SMD = -0.43 (95% CI: -0.71 to -0.15; p < 0.01) and SMD = -0.45 (95% CI: -0.72 to -0.19; p < 0.01), respectively]. We did not find a significant association between CSF MHPG levels and suicide attempt. Limitations: Our analyses relied on a limited number of studies of good quality and most studies included small sample sizes. Conclusion: Both serotonin and dopamine systems may play a role in suicide attempt risk. Our findings suggest that a silo approach to biomarkers should be phased out in favor of the study of multiple systems in parallel and in the same populations to progress in the identification of the biological components independently associated with suicide risk, with the goal of identifying new treatment targets and improving suicide risk prediction.