The ability to inhibit a response is an important component of normal behavioral control and is an aspect of psychopathology when diminished. Converging evidence implicates the serotonergic neurotransmitter system in response inhibition circuitry. Objectives The present study examined potential associations between serotonergic genetic markers and response inhibition as indexed by Stop Task performance. Methods College-age participants (N=199) completed self-report questionnaires, the computerized Stop Task, and donated buccal cells for genetic analyses. Statistics were analyzed by ANOVA. Results Stop Signal reaction time was not associated with allelic variation at a monoamine oxidase A promoter length polymorphism or a serotonin 1B terminal autoreceptor polymorphism (G861C). An intronic genetic marker of the neuronal tryptophan hydroxylase-2 (the rate-limiting enzyme for serotonin biosynthesis) gene, however, was associated with the Stop Signal reaction time. Individuals homozygous for the T variant at an intron-8 polymorphism had the longest Stop Signal reaction time (i.e. greater impulsivity, P=0.01), and this effect was stronger in males (P=0.01) than in females (P=0.10). Conclusions A genotype at an intron-8 tryptophan hydroxylase-2 polymorphism was associated with response inhibition as indexed by the Stop Task. These results, if replicated, would implicate dorsal raphe serotonin neurons in response inhibition. It may be that individuals with the T/T genotype may have reduced tryptophan hydroxylase-2 function and correspondingly lower central serotonin levels; however, further investigation of the reported association is required.

BACKGROUND:Dopamine receptor genes are candidates for hypertension susceptibility. Locally released dopamine increases renal sodium excretion, and defective renal dopamine receptor signaling has been shown to play a role in hypertension. Dopamine-4 receptors are expressed in juxtaglomerular and cortical collecting cells, where dopamine activation could alter sodium and water metabolism and affect blood pressure (BP). The dopamine-4 receptor (DRD4) gene has a 16 amino acid (48 base pairs [bp]) repeat polymorphism located in exon 3 where a G-protein binding area is encoded. The long allele (defined as at least one 7 to 10 repeat) has been associated with the personality trait Novelty Seeking and with substance abuse, but associations between dopamine-4 receptor polymorphisms and BP have not been reported.METHODS:We genotyped 479 female and 385 male subjects of white ethnicity at the DRD4 repeat polymorphism site and classified each subject as having either the long or short genotype.RESULTS:We found associations between the DRD4 long allele and increased systolic BP (P = .031), diastolic BP (P = .034), and a history of regular alcohol use (P = .008). Furthermore, for systolic BP (P = .009) and pulse pressure (P = .002), we found evidence for an interaction between dopamine-4 receptor alleles and age, indicating that the effects of dopamine-4 receptor variants on BP increase with age.CONCLUSION:In this white population, the long variant of the DRD4 gene is associated with a 3-mm Hg higher systolic and 2-mm Hg higher diastolic BP.

, but with traits, such as personality factors, that are themselves associated with risk for the disorder (Lander and Schork, 1994; Stolten-berg and Burmeister, 2000). Often such traits have a higher heritability than the disease status (Almasy and Blangero, 2001). Neuroticism, as measured by the NEO personality inventory (NEO-PI) (Costa and McCrae, 1997), a psycho-metrically sound and widely used instrument, is one such trait. High scorers on the Neuroticism domain are char-acterized by frequent experience of “negative emotional-ity” such as anxiety, low mood, and hostility. Converging lines of evidence point to brain-derived neurotrophic fac-tor (BDNF) as a factor in the pathophysiology of depres-sion. To explore the possibility that variation in the BDNF gene is, in part, responsible for the population variation in Neuroticism, we studied a community sample of 441 sub-jects, genotyping a G→A single-nucleotide polymorphism (SNP) responsible for a valine→methionine substitution in the prodomain of BDNF. The less common, nonconserved Met allele was associated with significantly lower mean Neuroticism scores (

Central serotonin dysfunction appears to be related to a subtype of alcoholism with antisocial impulsive features (type II; antisocial alcoholism). The serotonergic deficit may be associated with greater impulsivity, which in turn facilitates both alcohol dependence and antisocial behavior. The present study tested association of antisocial impulsive alcoholism with candidate genes related to serotonergic neurotransmission, using families. Eight markers were assayed using polymerase chain reaction: tryptophan hydroxylase (intron 7), the serotonin transporter SLC6A4 (VNTR 9/12), HTTLPR, the three serotonin receptor types HTR1B (G861C), HTR2A (T102C) and HTR2C (Cys23Ser), monoamine oxidase A (T1460C), and (CA)(n),. Eligible probands had early age of onset of alcoholism, child conduct disorder, and two or more symptoms of adult Antisocial Personality Disorder. This sample included 35 probands, their parents, and some siblings (n = 116). Association tests were conducted using the Haplotype Relative Risk method for antisocial alcoholism diagnosis and the George-Elston regression method (the S.A.G.E. program ASSOC) for quantitative antisocial alcoholism severity. Haplotype Relative Risk analyses were not significant at the 0.05 level for any of the markers. Trends suggestive for future research occurred for tryptophan hydroxylase and HTR2A. Quantitative ASSOC analyses showed significant marker effects (P < 0.05) for both monoamine oxidase A markers, which were in linkage disequilibrium. Antisocial alcoholism symptom severity was higher with monoamine oxidase A C homozygotes or hemizygotes, indicating that low monoamine oxidase activity may be important. Future studies are needed to examine joint and interactive effects of serotonin-related markers. (C) 2002 Lippincott Williams Wilkins.