Neurobiological basis of suicidal behavior: a narrative review of cerebrospinal fluid monoamine metabolites
- 1Laboratory of Forensic Toxicology, Section of Forensic Medicine and Toxicology, Department of Biomedicine and Prevention, University of Rome Tor Vergata
Abstract
Background: Suicide is a multifactorial phenomenon resulting from the interaction of psychiatric, biological, genetic, psychological, environmental and sociocultural factors. Evidence suggests that alterations in central neurotransmitter systems may contribute to vulnerability to suicidal ideation. Among the biological markers investigated, cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), have received particular attention.
Methods: A literature review was conducted using Medline/PubMed and Google Scholar to identify studies published between 2005 and 2026 addressing suicidal behavior, suicide attempts, lethality, and their biological and clinical correlates, and 5-HIAA and HVA, with particular emphasis on their CSF concentrations. Studies published in languages other than English and review articles were excluded. Studies investigating 5-HIAA and HVA in other biological matrices were considered when they provided relevant contextual evidence for the interpretation of suicidal behavior. A total of 23 studies were included in the review.
Results: Evidence supports an association between suicidal behavior and alterations in central monoaminergic neurotransmission. Reduced CSF 5-HIAA concentrations were the most consistent finding, particularly in mood disorders and violent or high-lethality suicidal behavior. Lower 5-HIAA levels were associated with greater lethality of suicide attempts, suggesting a relationship between impaired serotonergic turnover, behavioral disinhibition, impulsivity, and the severity of suicidal acts. CSF HVA concentrations were also reduced in some populations, although findings were more heterogeneous and less consistent than those observed for 5-HIAA. Studies suggested that monoaminergic abnormalities may be more strongly related to the severity or lethality of suicidal behavior than to its occurrence alone. The neurobiological substrate of suicidality may involve interactions between monoaminergic, inflammatory, metabolic, and neuroendocrine pathways rather than isolated biomarkers.
Conclusions: Evidence supports the relevance of CSF monoamine metabolites, particularly 5-HIAA and, to a lesser extent, HVA, as biological correlates of suicidal behavior. However, heterogeneity across psychiatric diagnoses, small sample sizes, differences in CSF collection and analytical procedures, and predominantly cross-sectional study designs limit the generalizability and clinical translation of these findings. The invasive nature of lumbar puncture makes CSF biomarkers unsuitable for routine suicide-risk screening currently. Further longitudinal research is needed to determine whether their integration with clinical and peripheral biological measures could contribute to objective risk stratification and more personalized suicide prevention strategies.
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BibTeX
@article{stefani2026neurobiological,
title = {{Neurobiological basis of suicidal behavior: a narrative review of cerebrospinal fluid monoamine metabolites}},
author = {Lucrezia Stefani and Luigi Tonino Marsella and Roberta Tittarelli},
journal = {Frontiers in Psychiatry},
year = {2026},
month = oct,
doi = {10.3389/fpsyt.2026.1968256},
url = {https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1968256/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neurobiological basis of suicidal behavior: a narrative review of cerebrospinal fluid monoamine metabolites
AU - Lucrezia Stefani
AU - Luigi Tonino Marsella
AU - Roberta Tittarelli
PY - 2026
DA - 2026/10/19
JO - Frontiers in Psychiatry
DO - 10.3389/fpsyt.2026.1968256
UR - https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1968256/full
AB - Background: Suicide is a multifactorial phenomenon resulting from the interaction of psychiatric, biological, genetic, psychological, environmental and sociocultural factors. Evidence suggests that alterations in central neurotransmitter systems may contribute to vulnerability to suicidal ideation. Among the biological markers investigated, cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), have received particular attention. Methods: A literature review was conducted using Medline/PubMed and Google Scholar to identify studies published between 2005 and 2026 addressing suicidal behavior, suicide attempts, lethality, and their biological and clinical correlates, and 5-HIAA and HVA, with particular emphasis on their CSF concentrations. Studies published in languages other than English and review articles were excluded. Studies investigating 5-HIAA and HVA in other biological matrices were considered when they provided relevant contextual evidence for the interpretation of suicidal behavior. A total of 23 studies were included in the review. Results: Evidence supports an association between suicidal behavior and alterations in central monoaminergic neurotransmission. Reduced CSF 5-HIAA concentrations were the most consistent finding, particularly in mood disorders and violent or high-lethality suicidal behavior. Lower 5-HIAA levels were associated with greater lethality of suicide attempts, suggesting a relationship between impaired serotonergic turnover, behavioral disinhibition, impulsivity, and the severity of suicidal acts. CSF HVA concentrations were also reduced in some populations, although findings were more heterogeneous and less consistent than those observed for 5-HIAA. Studies suggested that monoaminergic abnormalities may be more strongly related to the severity or lethality of suicidal behavior than to its occurrence alone. The neurobiological substrate of suicidality may involve interactions between monoaminergic, inflammatory, metabolic, and neuroendocrine pathways rather than isolated biomarkers. Conclusions: Evidence supports the relevance of CSF monoamine metabolites, particularly 5-HIAA and, to a lesser extent, HVA, as biological correlates of suicidal behavior. However, heterogeneity across psychiatric diagnoses, small sample sizes, differences in CSF collection and analytical procedures, and predominantly cross-sectional study designs limit the generalizability and clinical translation of these findings. The invasive nature of lumbar puncture makes CSF biomarkers unsuitable for routine suicide-risk screening currently. Further longitudinal research is needed to determine whether their integration with clinical and peripheral biological measures could contribute to objective risk stratification and more personalized suicide prevention strategies.
SN - 1664-0640
ER -