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Cited by 60Neurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesGenetic Associations and Epidemiology

Serotonin Transporter Promoter Polymorphism Genotype Is Associated With Behavioral Disinhibition and Negative Affect in Children of Alcoholics

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Twitchell, Geoffrey R., Hanna, Gregory L., Cook, Edwin H., Stoltenberg, Scott F., Fitzgerald, Hiram E., Zucker, Robert A.·2001·Alcoholism: Clinical and Experimental Research
DOI 10.1111/j.1530-0277.2001.tb02302.x
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Abstract

Background : Serotonergic (5‐HT) dysfunction has been implicated in the etiology of both behavioral disinhibition (BD) and negative affect (NA). This work extends our previous finding of relationships between whole blood 5‐HT and both BD and NA in pubescent, but not prepubescent, children of alcoholics and continues examination of a hypothesized role of 5‐HT dysfunction in alcoholism risk. The long and short (L and S) variants of the 5‐HT transporter gene‐linked polymorphic region (5‐HTTLPR) are responsible for differing transcriptional efficiencies in 5‐HT uptake. Although associations have been found between the SS 5‐HTTLPR genotype and severe alcoholism and neuroticism, recent reports describe relationships between the LL genotype and both low level of response to alcohol and alcoholism diagnosis and a predominance of the LL genotype in early‐onset alcoholics. Methods: This report is from an ongoing prospective study of the development of risk for alcoholism and other problematic outcomes in a sample of families classified by father's alcoholism subtype. This study examines relationships between 5‐HTTLPR genotype and both child BD (Child Behavior Checklist Aggressive Behavior) and NA (Child Behavior Checklist Anxious/Depressed) in offspring from 47 families. Results: Results showed significantly higher levels of BD and NA in the 16 children with the LL genotype than the 46 SS or SL children. Conclusions: Behaviors of undercontrol, which occur at increased rates in children of alcoholics, may be genetically influenced through the regulation of the 5‐HT transporter. Due to the small sample size and the preliminary nature of our findings, replication is necessary.

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  • A smaller sample of 62 European participants reported an increased risk for behavioral disinhibition and aggressive behaviors with the L/L genotype when compared to S/S and S/L.

    “A smaller sample consisting of 62 European participants similarly reported an increased risk for behavioral disinhibition and aggressive behaviors with the L/L genotype when compared to S/S and S/L [34].”

    From Genetics of child aggression, a systematic review (2024) · cites this paper as [34]

    The Sample section describes 62 non-Hispanic white children in a Michigan longitudinal study, not participants identified as European. The Abstract reports significantly higher behavioral disinhibition—measured using the Child Behavior Checklist Aggressive Behavior scale—in the 16 LL children than in the 46 SS or SL children. It reports higher measured scores, rather than a demonstrated increase in future risk. (LLM, conf=0.84)

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  • The first research study retrieved using the search strategy was by Twitchell and colleagues in 2001, examining the genetics of child aggression among offspring of alcoholic fathers.

    “The first research study retrieved using our search strategy was by Twitchell and colleagues in 2001 [34], which examined the genetics of child aggression among offspring of alcoholic fathers.”

    From Genetics of child aggression, a systematic review (2024) · cites this paper as [34]

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Authors
Twitchell, G. R., Hanna, G. L., Cook, E. H., Stoltenberg, S. F., Fitzgerald, H. E., & Zucker, R. A.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Twitchell, Geoffrey R.
ORCID
Venue
Alcoholism: Clinical and Experimental Research
Publisher
Wiley
Published
2001-07
Volume
25
Issue
7
Pages
953-959
ISSN
  • 0145-6008 (ISSN-L)
  • 1530-0277
DOI
10.1111/j.1530-0277.2001.tb02302.x
OpenAlex
W2166137433
Cited by
60
References
69
Citations by year
2025: 1 · 2024: 2 · 2020: 1 · 2019: 2 · 2016: 1 · 2014: 3 · 2013: 1 · 2012: 6
FWCI
1.47
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1745 d)
Locations
  • Alcoholism Clinical and Experimental Research (publishedVersion)
  • PubMed (publishedVersion)
  • Deep Blue (University of Michigan) (submittedVersion)
  • Lincoln (University of Nebraska) (submittedVersion)
Funders
  • University of Michigan
  • Michigan State University
  • National Institutes of Health (5k01aa000295-03)
  • College of Engineering, Michigan State University
  • National Institute on Alcohol Abuse and Alcoholism (K01 AA00295, 2 RO1 AA07065, AA 07065, R01AA007065)
  • National Institute on Drug Abuse (DA07272, T32DA007272)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
serotonin transporter, 5-HTTLPR, promoter polymorphism, behavioral disinhibition, negative affect, children of alcoholics, alcoholism risk, serotonergic dysfunction, aggression, pubertal children
MeSH terms
Adolescent, Affect, Alcoholism, Carrier Proteins, Child, Child Behavior Disorders, Female, Genotype, Humans, Male, Membrane Glycoproteins, Nerve Tissue Proteins, Polymorphism, Genetic, Promoter Regions, Genetic, Psychiatric Status Rating Scales, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins

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