Neuroimaging and 5-HT<sub>2C</sub>Receptor Polymorphism: A HMPAO-SPECT Study in Healthy Male Probands Using mCPP-Challenge of the 5-HT<sub>2C</sub>Receptor

Ku, Kühn; Ay, Joe; Meyer, Klaus; Reichmann, K.; Maier, Wladislaw; Ml, Rao; Mj, Reinhardt; Hj, Biersack; Quednow, Boris B.

doi:10.1055/s-2004-832685

Cited by 15 publications

(14 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite this relevance, there is poor experiment evidence on animals and genetic investigations that focused on this part of the brain with a specific attention devoted to the serotonin receptor 2C. Anyway, a recent interesting experiment reported that the presence of the Ser or Cys allele of the well known rs6318 mutation is associated with a list of diverse distributions of the blood flow in the brain of normal subjects [Kuhn et al, 2004]. …”

Section: Anterior Cingulate Relevance To Psychiatric Disordersmentioning

confidence: 99%

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Drago

Serretti

2009

American J of Med Genetics Pt B

View full text Add to dashboard Cite

HTR2C is one of the most relevant and investigated serotonin receptors. Its role in important brain structures such as the midbrain, the lateral septal complex, the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior cingulated gyrus candidate it as a promising target for genetic association studies. The biological relevance of these brain structures is reviewed by way of the focus on HTR2C activity, with a special attention paid to psychiatric disorders. Evidence from the genetic association studies that dealt with HTR2C is reviewed and discussed alongside the findings derived from the neuronatmic investigations. The reasons for the discrepancies between these two sets of reports are discussed. As a result, HTR2C is shown to play a pivotal role in many different psychiatric behaviors or psychiatric related disrupted molecular balances, nevertheless, genetic association studies brought inconsistent results so far. The most replicated association involve the feeding behavior and antipsychotic induced side effects, both weight gain and motor related: Cys23Ser (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of association found in other independent studies dampens the clinical impact of these reports. Here, we report a possible explanation for discrepant findings that is poorly or not at all usually considered, that is that HTR2C may exert different or even opposite activities in the brain depending on the structure analyzed and that mRNA editing activity may compensate possible genetically controlled functional effects. The incomplete coverage of the HTR2C variants is proposed as the best cost-benefit ratio bias to fix. The evidence of brain area specific HTR2C mRNA editing opens a debate about how the brain can differently modulate stress events, and process antidepressant treatments, in different brain areas. The mRNA editing activity on HTR2C may play a major role for the negative association results.

show abstract

Section: Anterior Cingulate Relevance To Psychiatric Disordersmentioning

confidence: 99%

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Drago

Serretti

2009

American J of Med Genetics Pt B

View full text Add to dashboard Cite

show abstract

“…Identification and validation of single nucleotide polymorphisms ( SNPs ) that predict impulsivity, cue reactivity or treatment success could also be useful in guiding prevention efforts (Ducci and Goldman, 2012). Impulsivity has been associated with genotypes that predict reduced 5-HT function (Bevilacqua, et al, 2010; Bevilacqua and Goldman, 2013; Bjork, et al, 2002; Stoltenberg, et al, 2012) and we have recently demonstrated that cocaine-dependent subjects who carry a SNP in the HTR2C (rs6318) (Lappalainen, et al, 1995) predicted to alter 5-HT 2C R functionality (Brasch-Andersen, et al, 2011; Kuhn, et al, 2004; Okada, et al, 2004; Walstab, et al, 2011), exhibit significantly higher attentional bias on the cocaine-word Stroop task. As convergent evidence links genotypes to phenotypes important in addictive processes, it will be possible to best understand the shared genetic liability for impulsivity and cue reactivity, and to integrate this information into more effective clinical care for afflicted patients.…”

Section: Implications For Treatment Of Cocaine Addictionmentioning

confidence: 99%

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

2014

View full text Add to dashboard Cite

Cocaine abuse and addiction remain great challenges on the public health agendas in the U.S. and the world. Increasingly sophisticated perspectives on addiction to cocaine and other drugs of abuse have evolved with concerted research efforts over the last 30 years. Relapse remains a particularly powerful clinical problem as, even upon termination of drug use and initiation of abstinence, the recidivism rates can be very high. The cycling course of cocaine intake, abstinence and relapse is tied to a multitude of behavioral and cognitive processes including impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to the negative consequences), and cocaine cue reactivity (responsivity to cocaine-associated stimuli) cited as two key phenotypes that contribute to relapse vulnerability even years into recovery. Preclinical studies suggest that serotonin (5-hydroxytryptamine; 5-HT) neurotransmission in key neural circuits may contribute to these interlocked phenotypes well as the altered neurobiological states evoked by cocaine that precipitate relapse events. As such, 5-HT is an important target in the quest to to understand the neurobiology of relapse-predictive phenotypes, to successfully treat this complex disorder and improve diagnostic and prognostic capabilities. This review emphasizes the role of 5-HT and its receptor proteins in key addiction phenotypes and the implications of current findings to the future of therapeutics in addiction.

show abstract

“…Male carriers of the less common Ser23 C allele show a trend toward faster and stronger adrenocorticotropic hormone ACTH responses to the 5HTR2C agonist m-chlorophenylpiperazine (m-CPP) [7], as well as a different pattern of change in regional cerebral blood flow following m-CPP infusion compared to men carrying the 5HTR2C Cys23 G allele [8]. In related work [9] we recently found that rs6318 was associated with stress responses to an emotional stress task in the laboratory.…”

Section: Introductionmentioning

confidence: 99%

A Functional Polymorphism in the 5HTR2C Gene Associated with Stress Responses Also Predicts Incident Cardiovascular Events

et al. 2013

View full text Add to dashboard Cite

Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-up time = 5.3 years, interquartile range = 3.3–8.2). Unadjusted Cox time-to-event regression models showed, compared to Cys23 G carriers, males hemizygous for Ser23 C and females homozygous for Ser23C were at increased risk for the composite endpoint of all-cause death or MI: Hazard Ratio (HR) = 1.47, 95% confidence interval (CI) = 1.17, 1.84, p = .0008. Adjusting for age, rs6318 genotype was not related to body mass index, diabetes, hypertension, dyslipidemia, smoking history, number of diseased coronary arteries, or left ventricular ejection fraction in either males or females. After adjustment for these covariates the estimate for the two Ser23 C groups was modestly attenuated, but remained statistically significant: HR = 1.38, 95% CI = 1.10, 1.73, p = .005. These findings suggest that this functional polymorphism of the 5HTR2C gene is associated with increased risk for CVD mortality and morbidity, but this association is apparently not explained by the association of rs6318 with traditional risk factors or conventional markers of atherosclerotic disease.

show abstract

Neuroimaging and 5-HT_2CReceptor Polymorphism: A HMPAO-SPECT Study in Healthy Male Probands Using mCPP-Challenge of the 5-HT_2CReceptor

Abstract: These findings suggest that differences in the 5-HT (2C) receptor gene polymorphism has functional consequences due to a different responsiveness of the expressed 5-HT (2C) receptor variants.

Cited by 15 publications

References 21 publications

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

A Functional Polymorphism in the 5HTR2C Gene Associated with Stress Responses Also Predicts Incident Cardiovascular Events

Contact Info

Product

Resources

About

Neuroimaging and 5-HT2CReceptor Polymorphism: A HMPAO-SPECT Study in Healthy Male Probands Using mCPP-Challenge of the 5-HT2CReceptor

Abstract: These findings suggest that differences in the 5-HT (2C) receptor gene polymorphism has functional consequences due to a different responsiveness of the expressed 5-HT (2C) receptor variants.

Cited by 15 publications

References 21 publications

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction

A Functional Polymorphism in the 5HTR2C Gene Associated with Stress Responses Also Predicts Incident Cardiovascular Events

Contact Info

Product

Resources

About

Neuroimaging and 5-HT_2CReceptor Polymorphism: A HMPAO-SPECT Study in Healthy Male Probands Using mCPP-Challenge of the 5-HT_2CReceptor