title: HTR3B is associated with alcoholism with antisocial behavior and alpha EEG power--an intermediate phenotype for alcoholism and co-morbid behaviors.
abstract: 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.
authors.affiliation: Division of Psychological SGDP Centre, P080 Institue of Psychiatry 16 De Crespigny Park, London SE58AF, United Kingdom. Francesca.Ducci@iop.kcl.uk
authors.forename: Francesca
authors.initials: F
authors.lastname: Ducci
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Enoch
authors.forename: Qiaoping
authors.initials: Q
authors.lastname: Yuan
authors.forename: Pei-Hong
authors.initials: PH
authors.lastname: Shen
authors.forename: Kenneth V
authors.initials: KV
authors.lastname: White
authors.forename: Colin
authors.initials: C
authors.lastname: Hodgkinson
authors.forename: Bernard
authors.initials: B
authors.lastname: Albaugh
authors.forename: Matti
authors.initials: M
authors.lastname: Virkkunen
authors.forename: David
authors.initials: D
authors.lastname: Goldman
mesh_terms: 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
chemical_list: C509410:HTR3B protein, human; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3