The influence of the serotonin transporter gene 5-HTTLPR polymorphism on suicidal behaviors: a meta-analysis
Abstract
Suicidal Behavior (SB) is the second leading cause of death among youths worldwide and the tenth among all age groups. Inherited genetic differences have a role in suicidality with heritability ranging from 30 to 55%. The SLC6A4 5-HTTLPR gene variant has been largely investigated for association with SB, with controversial results. In this work, we sought to determine whether the results of previous meta-analyses were confirmed or modified subsequent to the inclusion of more recent literature data. An electronic literature search was performed to identify relevant studies published until July 2018. Data were analysed through RevMan v5.3. Subgroup and sensitivity meta-analyses were performed considering different SB sub-phenotypes, ethnicity, gender and psychiatric diagnostic categories. Our literature search yielded 1186 articles; among these, we identified 45 pertinent case-control studies (15,341 subjects). No association was found between low-expressing alleles or genotypes (S + L G alleles or S' carrier genotypes) and SB in the primary analyses. However, low-expressing alleles (S + L G) were associated with an increased risk of Violent Suicide Attempt (OR = 1.44, C.I. 1.17-1.78, p = .0007). An effect of the same alleles on SB was found in a subpopulation of substance abusers, but this result was not confirmed after the exclusion of healthy subjects from the control group. The other sensitivity meta-analyses did not show any significant effect. Our findings contribute to clarify the conflicting previous evidence by suggesting an association between the 5-HTTLPR and Violent SB. Nonetheless, many other modulators, including environmental factors and epigenetic mechanisms may act to further increase the level of complexity.
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Variants in tryptophan hydroxylase (TPH1, TPH2), serotonin transporter (5-HTTLPR), and serotonin receptors (5-HTR1A, 5-HTR2A) have been associated with suicidal behaviors in adults, though replication in pediatric cohorts remains limited.
“Variants in tryptophan hydroxylase (TPH1, TPH2), serotonin transporter (5-HTTLPR), and serotonin receptors (5-HTR1A, 5-HTR2A) have been associated with suicidal behaviors in adults, though replication in pediatric cohorts remains limited (44, 45).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [45]
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Salehi, M., Saeidi, M., Amanat, M., Barias, T., Anyeji, U., Alzein, O., & Gunturu, S. (2026) · Frontiers in Pediatrics · doi:10.3389/fped.2026.1738009
“Variants in tryptophan hydroxylase (TPH1, TPH2), serotonin transporter (5-HTTLPR), and serotonin receptors (5-HTR1A, 5-HTR2A) have been associated with suicidal behaviors in adults, though replication in pediatric cohorts remains limited (44, 45).”
- Authors
- Fanelli, G., & Serretti, A.
- Affiliations
- University of Bologna (IT)
- Corresponding author
- Serretti, Alessandro
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 88
- Pages
- 375-387
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2885157060
- Cited by
- 52
- References
- 149
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 13 · 2020: 12 · 2019: 6 · 2018: 2
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- serotonin transporter gene, 5-HTTLPR polymorphism, suicidal behavior, violent suicide attempts, serotonin transporter, genetic susceptibility to suicide, substance abuse, epigenetic mechanisms
- MeSH terms
- Alleles, Gene Frequency, Humans, Polymorphism, Genetic, Suicide, Serotonin Plasma Membrane Transport Proteins
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