Cited by 53Neurotransmitter Receptor Influence on BehaviorGenetic Associations and EpidemiologyAttention Deficit Hyperactivity Disorder

Evidence for epistasis between the 5-HTTLPR and the dopamine D4 receptor polymorphisms in externalizing behavior among 15-year-olds

Hohmann, Sarah, Becker, Katja, Fellinger, Johannes, Banaschewski, Tobias, Schmidt, Martin H., Esser, Günter, Laucht, Manfred·2009·Journal of Neural Transmission

Abstract

The present study aimed to clarify the functional role of genes in the dopamine and serotonin systems by examining whether polymorphisms in these genes are related to adolescent externalizing behavior either alone or in interaction with each other. Participants were selected from an ongoing prospective study of the outcome of early risk factors. At age 15 years, 298 adolescents (144 males, 154 females) completed the Youth Self Report, 296 primary caregivers the Child Behavior Checklist and 253 teachers the Teacher Report Form. DNA was genotyped for the DRD4 exon III VNTR and the 5-HTTLPR polymorphisms. Results revealed that individuals with the DRD4 7r allele reported significantly more externalizing behavior than carriers of other variants. In addition, a significant interaction emerged, indicating that adolescents carrying two copies of the 5-HTTLPR short allele and the DRD4 7r variant scored highest on aggressive and/or delinquent behavior compared to other genotypes. This result suggests an effect of 5-HTTLPR on externalizing behavior in the presence of DRD4 7r but no effect in its absence.

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Crossref · 10.1007/s00702-009-0290-1

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  • Several studies on European children and adolescents and Chinese adolescents did not report a significant main effect of 5-HTTLPR on aggressive behaviors and related phenotypes.

    “Several studies on European children and adolescents [78, 89] and Chinese adolescents [51] did not report a significant main effect of 5-HTTLPR on aggressive behaviors and related phenotypes.”

    From Genetics of child aggression, a systematic review (2024) · cites this paper as [78]

  • The larger repeat (7 R or 6-8 R) DRD4 alleles were associated with high aggression in an Italian sample, the Mannheim Study of Children at Risk, and the Ben-Gurion University Infant Developmental Study.

    “The larger repeat (7 R or 6-8 R) alleles were associated with high aggression in an Italian sample [77], the Mannheim Study of Children at Risk study [78], and the Ben-Gurion University Infant Developmental Study [79]”

    From Genetics of child aggression, a systematic review (2024) · cites this paper as [78]

  • Some studies failed to report a significant main effect of 5-HTTLPR on aggressive behaviors but demonstrated a significant gene-gene interaction on behavior.

    “Although some studies failed to report a significant main effect of 5-HTTLPR on aggressive behaviors, they demonstrated a significant gene-gene interaction on behavior.”

    From Genetics of child aggression, a systematic review (2024) · cites this paper as [78]

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Authors
Hohmann, S., Becker, K., Fellinger, J., Banaschewski, T., Schmidt, M. H., Esser, G., & Laucht, M.
Affiliations
  • Central Institute of Mental Health (DE)
  • Philipps University of Marburg (DE)
  • University of Potsdam (DE)
Corresponding author
Laucht, Manfred
Venue
Journal of Neural Transmission
Published
2009-08-21
Volume
116
Issue
12
Pages
1621-1629
ISSN
  • 0300-9564 (ISSN-L)
  • 1435-1463
OpenAlex
W2030150836
Cited by
53
References
63
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 3 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 5 · 2012: 3
FWCI
1.38
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neural Transmission (publishedVersion)
  • PubMed (publishedVersion)
  • publish.UP (University of Potsdam) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • Bundesministerium für Bildung und Forschung
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Keywords
epistasis, 5-HTTLPR, externalizing problems, adolescent aggression, delinquency, gene-gene interaction, 7-repeat allele
MeSH terms
Adolescent, Aggression, Alleles, Mental Disorders, Epistasis, Genetic, Faculty, Female, Humans, Juvenile Delinquency, Male, Parents, Polymorphism, Genetic, Psychiatric Status Rating Scales, Risk Factors, Cohort Studies, Sequence Analysis, DNA, Serotonin Plasma Membrane Transport Proteins, Receptors, Dopamine D4

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