HTR3B is associated with alcoholism with antisocial behavior and alpha EEG power--an intermediate phenotype for alcoholism and co-morbid behaviors.
Alcohol use disorders (AUD) with co-morbid antisocial personality disorder (ASPD) have been associated with serotonin (5-HT) dysfunction. 5-HT3 receptors are potentiated by ethanol and appear to modulate reward. 5-HT3 receptor antagonists may be useful in the treatment of early-onset alcoholics with co-morbid ASPD. Low-voltage alpha electroencephalogram (EEG) power, a highly heritable trait, has been associated with both AUD and ASPD. A recent whole genome linkage scan in one of our samples, Plains American Indians (PI), has shown a suggestive linkage peak for alpha power at the 5-HT3R locus. We tested whether genetic variation within the HTR3A and HTR3B genes influences vulnerability to AUD with comorbid ASPD (AUD+ASPD) and moderates alpha power. Our study included three samples: 284 criminal alcoholic Finnish Caucasians and 234 controls; two independent community-ascertained samples with resting EEG recordings: a predominantly Caucasian sample of 191 individuals (Bethesda) and 306 PI. In the Finns, an intronic HTR3B SNP rs3782025 was associated with AUD+ASPD (P=.004). In the Bethesda sample, the same allele predicted lower alpha power (P=7.37e(-5)). Associations between alpha power and two other HTR3B SNPs were also observed among PI (P=.03). One haplotype in the haplotype block at the 3' region of the gene that included rs3782025 was associated with AUD+ASPD in the Finns (P=.02) and with reduced alpha power in the Bethesda population (P=.00009). Another haplotype in this block was associated with alpha power among PI (P=.03). No associations were found for HTR3A. Genetic variation within HTR3B may influence vulnerability to develop AUD with comorbid ASPD. 5-HT3R might contribute to the imbalance between excitation and inhibition that characterize the brain of alcoholics.
Ducci
Francesca
F
Division of Psychological SGDP Centre, P080 Institue of Psychiatry 16 De Crespigny Park, London SE58AF, United Kingdom. Francesca.Ducci@iop.kcl.uk
Enoch
Mary-Anne
MA
Yuan
Qiaoping
Q
Shen
Pei-Hong
PH
White
Kenneth V
KV
Hodgkinson
Colin
C
Albaugh
Bernard
B
Virkkunen
Matti
M
Goldman
David
D
D000328:Adult; D001741:Black or African American; D000437:Alcoholism / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D000483:Alleles; D000513:Alpha Rhythm; D000987:Antisocial Personality Disorder / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D016022:Case-Control Studies; D004569:Electroencephalography; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007198:Indians, North American; D008297:Male; D001523:Mental Disorders / Q000235:genetics / Q000523:psychology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D011985:Receptors, Serotonin / Q000235:genetics*; D044406:Receptors, Serotonin, 5-HT3; D012307:Risk Factors; D044465:White People; D055815:Young Adult
C509410:HTR3B protein, human; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3