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Scott F Stoltenberg

Publications and source records attributed to Scott F Stoltenberg.

8 recordsLinked to original sources
PubMed2006

Possible association between response inhibition and a variant in the brain-expressed tryptophan hydroxylase-2 gene.

UNLABELLED: 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.

Adult↗
PubMed2005

Epistasis among presynaptic serotonergic system components.

Epistatic interactions among regulatory components of the serotonin (5-HT) neurotransmitter system may be an important aspect of 5-HT function. Because 5-HT dysregulation is associated with several common psychiatric disorders, the potential for epistasis among genetic variants in the 5-HT transporter (SERT), 5-HT1B terminal autoreceptor and the 5-HT1A somatodendritic autoreceptor should be examined. In this study, output from a dynamic minimal model of 5-HT function was compared to empirical results in the literature. Parameters representing extracellular 5-HT clearance rates (SERT), 5-HT release levels (5-HT1B) and inhibitory thresholds (the amount of extracellular 5-HT above which cell firing is inhibited, an indication of 5-HT1A autoreceptor sensitivity) were varied to simulate genetic deletion (i.e. knockout) of each component singly, and in combination. Simulated knockout effects on extracellular 5-HT level and presynaptic neural firing rates were in the same direction and of similar relative magnitude as studies in the literature. Epistasis among presynaptic components appears to be important in the 5-HT system's regulation of extracellular 5-HT levels, but not of firing rates.

Animals↗
PubMed2005

Association between a dopamine-4 receptor polymorphism and blood pressure.

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.

Adult↗
PubMed2004

Serotonin transporter and GABAA alpha 6 receptor variants are associated with neuroticism.

BACKGROUND: A tendency to experience negative affect, as measured by the neuroticism component of the Neuroticism, Extraversion, and Openness Personality Inventory (NEO-PI), is a trait marker for major depression. Epidemiologic studies indicate a strong genetic component, but to date few specific genetic variants have been definitively implicated. A serotonin transporter promoter polymorphism (5-HTTLPR) has been extensively studied in neuroticism and several psychiatric disorders, with inconclusive results. A GABA(A) receptor alpha6 subunit variant (Pro385Ser) has been associated with alcohol-related traits but has not been studied in neuroticism or depression. METHODS: A total of 384 subjects who completed the NEO-PI were genotyped at 5-HTTLPR and Pro385Ser. Associations between polymorphisms and both alcohol use and personality domains were tested. RESULTS: The 5-HTTLPR short allele (p =.008) and Pro385Ser Pro allele (p =.003) are associated with higher neuroticism scores. The 5-HTTLPR long allele (p =.006), but not Pro385Ser, is also associated with an increased presence of alcohol use. In addition, there is a nonsignificant suggestion of an interaction: the effect of 5-HTTLPR on neuroticism might be dependent on the Pro385Ser genotype. CONCLUSIONS: These findings support a role for the serotonin transporter and GABA(A) alpha6 subunit in depression-related traits.

Adult↗
PubMed2003

Serotonergic agents and alcoholism treatment: a simulation.

BACKGROUND: Those with early-onset alcoholism may better respond to ondansetron (a 5-HT3 receptor antagonist) than to selective serotonin reuptake inhibitor (SSRI) treatment, whereas those with late-onset alcoholism may present the reverse response pattern. Johnson and colleagues proposed a model that attempts to explain the observed treatment response patterns of those with early and late alcoholism onset by focusing on the influence of a common genetic variant in the serotonin transporter regulatory region (5-HTTLPR) on serotonin (5-HT) and dopamine (DA) system function. METHODS: The present study formalizes and extends Johnson's descriptive model into a computer simulation consisting of differential equations. For each of 16 conditions defined by genotype, drinking status, diagnostic status, and drug treatment, data were generated by 100 simulation runs. RESULTS: In every condition, the S/_ genotype (S/S and S/L) had higher extracellular 5-HT levels than did the L/L genotype. The S/_ genotype also had higher rates of postsynaptic DA firing than did the L/L genotype with the exception of the SSRI treatment condition, where the firing rates were similar. Drinking generally increased levels of extracellular 5-HT, reduced rates of presynaptic 5-HT firing, and increased rates of postsynaptic DA firing. Drinking produced increases in DA activation that were greater for the L/L genotype in the SSRI treatment condition and for the S/_ genotype in the ondansetron treatment condition. CONCLUSIONS: Genotype at 5-HTTLPR may influence relative reward of drinking alcohol while a person is under pharmacological treatment for alcoholism. Alternatively, 5-HTTLPR genotype may influence pathways of alcohol craving. Clinical studies should examine these hypotheses.

Alcoholism↗
PubMed2002

Serotonin transporter promoter polymorphism, peripheral indexes of serotonin function, and personality measures in families with alcoholism.

A functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) is considered to be a plausible candidate gene for anxiety-related personality traits and for alcoholism. Empirical support for the association between 5-HTTLPR and psychological traits has been somewhat inconsistent; however, observations of the functional dominance of the low-activity s-allele over the l-allele have been more consistent. When studying the influence of particular genes on psychological traits, it seems useful also to assess more biological intermediate traits that may mediate the effects of those genes on the traits of interest. The present study examined relationships between 5-HTTLPR genotype, whole blood serotonin (5-HT) level, and platelet 5-HT binding in 150 Caucasian subjects from 50 biological families. Individuals with the s-allele had lower average platelet 5-HT binding availability than those with the l/l genotype (P<0.025). Whole blood 5-HT level was not associated with 5-HTTLPR genotype. In adult men, those with the s-allele had higher mean scores on the NEO-FFI personality trait of openness than did those with the l/l genotype (P=0.002). The effect was not statistically significant in women (P=0.42), although it was in the same direction. Our findings do not support an association of 5-HTTLPR genotype with alcoholism diagnosis, alcoholism subtype, or the personality trait of neuroticism. The results of this pilot study suggest that further work should examine the mediation of the genetic effects on personality traits by biochemical measures and their moderation by gender.

Alcoholism↗
PubMed2002

Antisocial alcoholism and serotonin-related polymorphisms: association tests.

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.

Adult↗