Serotonin transporter promoter polymorphism genotype is associated with behavioral disinhibition and negative affect in children of alcoholics.
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.
Twitchell
G R
GR
Integrated Substance Abuse Programs (GRT), University of California, Los Angeles, California 90025, USA. twitche2@ucla.edu
Hanna
G L
GL
Cook
E H
EH
Stoltenberg
S F
SF
Fitzgerald And
H E
HE
Zucker
R A
RA
D000293:Adolescent; D000339:Affect / Q000502:physiology*; D000437:Alcoholism / Q000235:genetics*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002648:Child; D002653:Child Behavior Disorders / Q000235:genetics* / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins