Antidepressive Agents/therapeutic use* ; Serotonin ; Serotonin Plasma Membrane Transport Proteins

The knowledge of gene regulation of serotonin transporter mRNA may provide clues to understanding how antidepressants affect their therapeutic actions. Recently, the effects of antidepressants on the serotonin transporter have been investigated but yielded controversial results. To study this further, we performed in situ hybridization for serotonin transporter mRNA in rats(treatment group, n=5)receiving long term(14 days)treatment with a selective serotonin reuptake inhibiting antidepressant, sertraline(10mg/kg, i.p) Following sertraline treatment, a significant(p<0.05)ncrease in hybridization of serotonin transporter mRNA was observed compared to that observed in vehicle-treated rats(control group, n=5) This result may be interpreted as a compensatory mechanism to reduce synaptic levels of serotonin which were increased by long term sertraline treatment.
Animals ; Antidepressive Agents ; Brain* ; In Situ Hybridization ; Rats* ; RNA, Messenger* ; Serotonin Plasma Membrane Transport Proteins* ; Serotonin* ; Sertraline*

SKL10406, triple monoamine reuptake inhibitor, is a novel antidepressant candidate. A PET study was performed to investigate the occupancies of serotonin and dopamine transporters (SERT and DAT) in human brain, and the relationship between SKL10406 concentration and SERT occupancy was assessed using pharmacokinetic-pharmacodynamic (PK-PD) modeling methods. Fifteen healthy volunteers were given SKL10406 100 mg/day for 6 days or 150 mg/day for 6 days after 100 mg/day for 4 days. Each subject underwent full PK sampling for SKL10406 and PET scans at predose, 4 h and 16 h after dosing at a steady state to investigate the occupancies of SERT and DAT using 11C-DASB and 11C-PE2I, respectively. Naive pooled method (NPM) and nonlinear mixed-effect methods (ME) including a direct ME (DME) and an effect compartmental ME (EME) were used (NONMEM Ver. 7.2). Six and five subjects completed the studies for SERT and DAT, respectively. The final estimates of Emax (53.4%) and EC50 (11.8 ng/mL) from DME were relatively lower than those from NPM (Emax, 74.1%; EC50, 36.8 ng/mL) and EME (Emax, 68.6%; EC50, 40.2 ng/mL). DAT occupancy results were not modeled because of lower occupancies. The results showed that the dosage regimens may be applied in patient studies. However, difference between estimation methods alerts that ME may not be a recommendable analysis tool for sparsely sampled PET scan data.
Brain ; Dopamine ; Healthy Volunteers ; Humans ; Positron-Emission Tomography ; Serotonin ; Serotonin Plasma Membrane Transport Proteins*

ele frequency analysis, a significant association was also observed between the short allele and social phobia(p=.030). A significant associations between S genotype and each subgroup were observed(GEN p=.045 ; NGEN p=.033), but there were no differences in allele frequency. And, no differences in genotype and allele distribution between two subgroups were found. CONCLUSION: The results in our Korean sample suggest that S genotype of 5-HTTLPR may be associated with social phobia and s allele may be an important genetic factor that activates social phobic symptoms. But, further studies including large number of samples are necessary to elucidate these present findings.
Alleles ; Gene Frequency ; Genotype ; Phobic Disorders* ; Serotonin Plasma Membrane Transport Proteins* ; Serotonin*

Neurotransmitter imaging with radiopharmaceuticals plays major role for understanding of neurological and psychiatric disorders such as Parkinson's disease and depression. Radiopharmaceuticals for neurotransmitter imaging can be divided to dopamine transporter imaging radiopharmaceuticals and serotonin trnasporter imaging radiopharmaceuticals. Many kinds of new dopamine transporter imaging radiopharmcaeuticals has a tropane ring and they showed different biological properties according to the substituted functional group on tropane ring. After the first clinical trials with [123I]beta-CIT, alkyl chain substituent introduced to tropane ring amine to decrease time for imaging acquisition and to increase selectivity. From these results, [123I]PE2I, [18F]FE-CNT, [123I]FP-CIT and [18F]FP-CIT were developed and they showed high uptake on the dopamine transporter rich regions and fast peak uptake equilibrium time within 4 hours after injection. [11C]McN 5652 was developed for serotonin trnasporter imaging but this compound showed slow kinetics and high background radioactivity. To overcome these problems, new diarylsulfide backbone derivatives such as ADAM, ODAM, AFM, and DASB were developed. In these candidates, [11C]AFM and [11C]DASB showed high binding affinity to serotonin transporter and fast in vivo kinetics. This paper gives an overview of current status on dopamine and serotonin transporter imaging radiopharmaceuitcals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.
Chemistry, Pharmaceutical ; Depression ; Dopamine ; Dopamine Plasma Membrane Transport Proteins ; Kinetics ; Neurotransmitter Agents* ; Parkinson Disease ; Radioactivity ; Radiopharmaceuticals* ; Serotonin ; Serotonin Plasma Membrane Transport Proteins ; Tomography, Emission-Computed, Single-Photon

OBJECTIVES: Psychological resilience is the ability to cope with stress. The genetic background behind psychological resilience is not much known. The serotonin transporter and dopamine transporter are implicated in stress related psychology and emotional processing. The aim of this study is to investigate a possible genetic role of functional polymorphisms of serotonin and dopamine transporters for psychological resilience. METHODS: A total of 951 healthy adult subjects were included. Psychological resilience was measured using Connor-Davidson Resilience Scale (CD-RISC). Genotyping was performed for serotonin transporter gene (SERT) promoter variable number tandem repeat (VNTR) and dopamine transporter gene (DAT1) 3'-untranslated region (UTR) VNTR. Genetic association analysis was conducted between genotypes and the CD-RISC score. RESULTS: No genetic association was observed for SERT promoter VNTR or DAT1 3'-UTR VNTR with CD-RISC score. No genetic interaction between SERT promoter VNTR and DAT1 3'-UTR VNTR with CD-RISC score was detected. CONCLUSIONS: Either serotonin or dopamine transporter did not seem to play a significant role for psychological resilience in this sample.
Adult ; Dopamine Plasma Membrane Transport Proteins ; Dopamine* ; Genetic Background ; Genotype ; Humans ; Psychology ; Resilience, Psychological* ; Serotonin Plasma Membrane Transport Proteins ; Serotonin* ; Tandem Repeat Sequences

OBJECTIVE: Many studies suggest an association between the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and anxiety-related personality traits (e.g., neuroticism) in healthy subjects. This study investigated the interaction of 5-HTTLPR genotype on body dissatisfaction by neuroticism and to evaluate the interaction of 5-HTTLPR genotype on self-esteem by body dissatisfaction in a young adult Korean population. METHODS: Two hundred and eighty three subjects were included in this study. The Eysenck Personality Questionnaire-Korean version was used to evaluate neuroticism, the Body Dysmorphic Disorder Examination-Self Report (BDDE-SR)-Korean version was used to evaluate body dissatisfaction, and the Self-Esteem Scale (SES)-Korean version was used to evaluate self-esteem. The 5-HTTLPR genotype by neuroticism (high : low) interaction was assessed according to the total BDDE-SR score, and 5-HTTLPR genotype by BDDE-SR (high : low) interaction was assessed according to the total SES score. RESULTS: The analysis of 5-HTTLPR genotype and neuroticism (high : low) with respect to body dissatisfaction showed no main effects of genotype whereas neuroticism did influence the BDDE-SR score and no interaction of the genotype with neuroticism. The analysis of 5-HTTLPR genotype and BDDE-SR (high : low) with respect to self-esteem score showed no main effects of genotype whereas BDDE-SR did influence the self-esteem score and no interaction of the genotype with body dissatisfaction. CONCLUSION: These results suggest that an interaction between 5-HTTPLR genotype and neuroticism does not affect body dissatisfaction and an interaction between 5-HTTPLR genotype and body dissatisfaction does not affect self-esteem in a young adult Korean population.
Body Dysmorphic Disorders ; Genotype* ; Humans ; Serotonin Plasma Membrane Transport Proteins ; Young Adult*

BACKGROUND: Serotonin transporter gene-linked polymorphism region(5-HTTLPR) and catechol-O-methyltransferase(COMT) genes are thought to be important factors in some personality traits and the etiology of anxiety disorder. The goal of this study was to determine the role of these genes in personality traits. METHOD: The participants included 116 healthy adults with no history of psychiatric disorders and other physical illness for the last 6 months. All participants were tested by Temperament and Character Inventory(TCI). The 5-HTTLPR, COMT val158met gene polymorphisms were analyzed with PCR(Polymerase Chain Reaction). Differences on TCI dimensions and sub-scales among groups were examined with t-test and ANOVA. RESULT: There were possible relationships of the 5-HTTLPR with self-transcendence(P=0.050) and COMT val158met polymorphism with cooperativeness(P=0.053). CONCLUSION: We found associations between 5-HTTLPR, COMT polymorphisms and the some TCI character dimensions. Further studies of polymorphisms of other genes and their interactions may clarify the complex relationship between personality and genes.
Adult ; Anxiety Disorders ; Humans ; Polymorphism, Genetic ; Serotonin Plasma Membrane Transport Proteins ; Temperament

Premature ejaculation (PE), as one of the most common male sexual dysfunctions, has a serious negative impact on the sexual satisfaction of the patients and their sexual partners. Lifelong PE is a most common type and a current focus of research as well. The etiology and pathogenesis of this disease are not yet clear and genetic factors are considered to be closely related to lifelong PE. Studies show that the 5-hydroxytryptamine transporter (5-HTT) gene plays an important role in the development and progression of lifelong premature ejaculation and the 5-HTT-linked polymorphic region (5-HTTLPR) has attracted much attention in recent years. This article presents an overview on the correlation between 5-HTTLPR and lifelong PE.
Adult ; Ejaculation ; Humans ; Male ; Polymorphism, Genetic ; Premature Ejaculation ; genetics ; Serotonin Plasma Membrane Transport Proteins ; genetics

OBJECTIVE: To assess the association of SLC6A4 gene c.*670T>G polymorphism with the risk for asthma and peripheral blood cytological characteristics among ethnic Zhuang Chinese from Guangxi, China. METHODS: From May 2017 to March 2020, 258 patients diagnosed with asthma and 244 healthy controls were recruited from the Affiliated Hospital of Youjiang Minzhu Medical College and the People's Hospital of Hechi. Genotypes of the c.*670T>G polymorphism were determined by Sanger sequencing. Flow cytometry was used in combination with an electrical impedance method for the counting and classification of peripheral blood cells. RESULTS: Compared with the T allele, the G allele of the c.*670T>G polymorphism was associated with the risk for asthma in the population (OR = 1.54, 95%CI = 1.15-2.06; P = 0.004). Compared with the GT and TT genotypes, homozygous GG genotype also comprised a risk factor (OR = 1.66, 95%CI = 1.16-2.38; P = 0.005). Stratification of the risk factors showed that the homozygous GG genotype has increased the risk of asthma in males and urban residents (P < 0.01). The erythrocyte, hemoglobin and platelet counts of the asthma group were significantly higher than the control group (P < 0.001). The GG, GT and TT genotypes have respectively accounted for 82.35%, 17.65% and 0% of the samples with platelets exceeding the normal value. The overall platelet level of GG genotype was higher than GT+TT genotype (P < 0.05). The significant association was verified by the false positive report probability, and at a prior probability level of 0.1, G vs. T false positive probability was 0.071, and GG vs. GT+TT false positive probability was 0.153. CONCLUSION The GG genotype of the c.*670T>G polymorphism is associated with the risk for asthma among ethnic Zhuang Chinese from northwest Guangxi. Above finding has also enriched the genotypic data and peripheral blood phenotype for this polymorphism.
Male ; Humans ; East Asian People ; China ; Genotype ; Alleles ; Asthma/genetics* ; Serotonin Plasma Membrane Transport Proteins