Personality traits and dopamine receptors (D2 and D4): linkage studies in families of alcoholics.
Activation of the mesolimbic dopamine pathway appears to promote drug- and alcohol-seeking behavior in laboratory animals. Results for association and linkage analysis between various alcohol dependence phenotypes and the dopamine receptors have been quite mixed. Similarly, both positive and negative results have been presented concerning dopamine receptor genes and temperament. Cloninger has postulated that the novelty seeking factor from the Tridimensional Personality Questionnaire (TPQ) may be related to the dopamine neurotransmitter system. As novelty seeking is a trait of some importance for substance-dependent individuals, our goal was to test this relationship within a sample of families of alcoholics. No evidence favoring linkage between D2, D4, or DAT1 was found for TPQ novelty seeking. However, the harm-avoidance trait from the TPQ showed evidence for linkage to both the D4 and one of the D2 loci (TaqI A). The Multidimensional Personality Questionnaire (MPQ) was used to provide converging evidence for these results. The TPQ harm-avoidance scale loads heavily on introversion (worry, pessimism, shyness), characteristics that may be especially salient in alcoholic families. Thus, planned comparisons were made between selected MPQ traits measuring the affective dimension (negative affectivity, stress reaction, alienation, and well-being). We find evidence favoring linkage between the D2 and D4 receptor loci and these MPQ traits, with stronger evidence being seen for the D2 polymorphisms. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:634-641, 1999.
Hill
S Y
SY
Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Zezza
N
N
Wipprecht
G
G
Locke
J
J
Neiswanger
K
K
D000293:Adolescent; D017668:Age of Onset; D000374:Aggression; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology; D001007:Anxiety / Q000235:genetics; D001362:Avoidance Learning; D002352:Carrier Proteins / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins; D005106:Exploratory Behavior; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010551:Personality / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D019655:Quantitative Trait, Heritable; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4; D012201:Reward; D012918:Social Alienation; D013315:Stress, Psychological / Q000235:genetics
D002352:Carrier Proteins; C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4