No association between serotonin transporter gene polymorphisms and personality traits

Human family and twin studies have established considerable heritable components in personality traits as assessed by self-report questionnaires. Recently, an association between a functional polymorphism in the upstream regulatory region of the serotonin transporter gene and neuroticism-related personality traits was reported. Two different serotonin transporter polymorphisms including the previously associated variant were genotyped in two samples of healthy Swedish subjects (n = 127 and n = 178, respectively) assessed with the Karolinska Scales of Personality (KSP) inventory. No statistically significant association between serotonin transporter polymorphisms and any of the eight neuroticism-related KSP scales was found. Thus, the previously reported association between serotonin transporter alleles and neuroticism-related personality traits could not be replicated in the present study. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:430–436, 1999. © 1999 Wiley-Liss, Inc.     

Serotonin transporter gene polymorphisms are associated with anxiety‐related personality traits in women

Several studies have reported an association between anxiety‐related personality traits and a promoter polymorphism in the human serotonin transporter (5‐HTT) gene (5‐HTT gene‐linked polymorphic region, 5‐HTTLPR). In the present study, a population of 251 subjects was assessed with the Karolinska Scales of Personality (KSP) and genotyped both for the 5‐HTTLPR and for a variable number of tandem repeats polymorphism in the second intron of the same gene. The interpretation of previous studies has to some extent been confounded by the studied subjects differing with respect to ethnicity, sex, and age. To circumvent this problem, all included subjects were Caucasians, women, and born in the same year (1956). Associations were found between the 5‐HTTLPR and four of the five anxiety‐related KSP scales (psychic anxiety, muscular tension, psychasthenia, and lack of assertiveness), subjects being homozygous for the short allele displaying higher anxiety scores than those of the long/long or long/short genotype. In addition, an association was found between the intron 2 polymorphism and one anxiety‐related personality trait (somatic anxiety). © 2001 Wiley‐Liss, Inc.     

Intact coding region of the serotonin transporter gene in obsessive-compulsive disorder

Epidemiologic studies indicate that obsessive-compulsive disorder is genetically transmitted in some families, although no genetic abnormalities have been identified in individuals with this disorder. The selective response of obsessive-compulsive disorder to treatment with agents which block serotonin reuptake suggests the gene coding for the serotonin transporter as a candidate gene. The primary structure of the serotonin-transporter coding region was sequenced in 22 patients with obsessive-compulsive disorder, using direct PCR sequencing of cDNA synthesized from platelet serotonin-transporter mRNA. No variations in amino-acid sequence were found among the obsessive-compulsive disorder patients or healthy controls. These results do not support a role for alteration in the primary structure of the coding region of the serotonin-transporter gene in the pathogenesis of obsessive-compulsive disorder. © 1996 Wiley-Liss, Inc.     

5-HT转运体基因多态性与孤独症核心家系的关联研究

目的:探讨中国汉族人群5-HT转运体基因多态性(HTT SNP18)与孤独症的关系.方法:应用聚合酶链式反应与限制性片断长度多态性(PCR-RFLP)分析方法对175个孤独症核心家系测定基因型和等位基因.结果:孤独症患儿与父母的基因频率和基因型频率的分布呈基本一致的趋势.传递不平衡检验(TDT)显示等位基因传递无统计学意义,(McNemar χ2 =0.00,P>0.05).结论:本研究未发现5-HT转运体基因多态性(HTT SNP18)与孤独症存在关联,提示该基因多态性不影响孤独症的易感性,在中国汉族孤独症发病中不起主要作用.     

Involvement of human histamine N-methyltransferase gene polymorphisms in susceptibility to atopic dermatitis in korean children

Purpose

Histamine N-methyltransferase (HNMT) catalyzes one of two major histamine metabolic pathways. Histamine is a mediator of pruritus in atopic dermatitis (AD). The aim of this study was to evaluate the association between HNMT polymorphisms and AD in children.

Methods

We genotyped 763 Korean children for allelic determinants at four polymorphic sites in the HNMT gene: -465T>C, -413C>T, 314C>T, and 939A>G. Genotyping was performed using a TaqMan fluorogenic 5'' nuclease assay. The functional effect of the 939A>G polymorphism was analyzed.

Results

Of the 763 children, 520 had eczema and 542 had atopy. Distributions of the genotype and allele frequencies of the HNMT 314C>T polymorphism were significantly associated with non-atopic eczema (P=0.004), and those of HNMT 939A>G were significantly associated with eczema in the atopy groups (P=0.048). Frequency distributions of HNMT -465T>C and -413C>T were not associated with eczema. Subjects who were AA homozygous or AG heterozygous for 939A>G showed significantly higher immunoglobulin E levels than subjects who were GG homozygous (P=0.009). In U937 cells, the variant genotype reporter construct had significantly higher mRNA stability (P<0.001) and HNMT enzyme activity (P<0.001) than the common genotype.

Conclusions

Polymorphisms in HNMT appear to confer susceptibility to AD in Korean children.     

Recent developments in the management of patients with atopic dermatitis

Management of most patients with AD should be directed toward basic therapy--lubricants, moderate potency topical steroids, and antihistamines. Only the severe or unresponsive patient should be considered for management with some of the techniques that have been discussed previously. In part, this is because the addition of extra therapy will substantially decrease long-term compliance, increase the cost of medical care, and produce a dissatisfied patient. There are, however, definite situations in which dietary manipulation, topical and systemic antiseptics, dietary supplementation, and ultraviolet light may be useful. The uses of environmental control, biofeedback, and coal tar were not discussed but may also be useful in certain situations. Finally, all physicians should realize that Herpes simplex infection in patients with AD can be a serious and sometimes life-threatening problem. Rapid, accurate diagnosis is the key to effective management with the newer anti-viral agents.     

Platelet serotonin transporter density and related parameters in endurance-trained and sedentary male subjects

A number of peripheral indices of serotonergic function were examined in endurance-trained (ET) and sedentary males using the blood platelet as a model of the serotonergic neurone. The aim of the study was to investigate possible involvement and adaptation of the central serotonergic system in exercise-induced fatigue. The [³H] paroxetine-defined density of platelet serotonin transporters, platelet serotonin content and the plasma concentration of amino acids were determined in 10 ET and eight sedentary males. The mean (standard deviation) density of the serotonin transporter in the platelet membranes of the ET subjects was greater [1237 (182) fmol mg protein^?1] than that of the sedentary subjects [910 (119) fmol mg protein^?1; P = 0.013]. No difference (P = 0.51) could be seen between the median (range) platelet serotonin content of the ET subjects [0.98 (0.37–3.04) nmol platelet^?10] and that of the sedentary subjects [0.82 (0.18–1.49) nmol platelet^?10]. The platelet poor plasma concentrations of tryptophan and tyrosine were lower in the ET subjects (P = 0.028 and 0.015, respectively). The present study suggests that the platelet membrane of the ET subjects has a greater density of the serotonin transporter and that this is inversely related to the circulating concentration of the serotonin precursor, tryptophan. It remains to be resolved whether the increase in serotonin transporter density in the platelet membrane of ET subjects is reflected centrally and whether the ET platelet population may be sufficiently different from that of sedentary individuals to alter serotonin transporter density.     

Association study of serotonin transporter gene regulatory region polymorphism and alcoholism

Previous studies have indicated associations between a functional biallelic repetitive element in the 5′ regulatory region of the serotonin transporter gene (5‐HTTLPR) and alcoholic subjects who have either dissocial personality disorder or severe withdrawal symptoms. To replicate these associations under the hypothesis that genetic polymorphism plays some role in the susceptibility or vulnerability of some subgroup of alcoholics, the associations between alcoholic subjects' genetic polymorphisms, clinical characteristics, and personality traits were examined. This case control study comprised 697 alcoholic and 270 control subjects. A questionnaire focusing on family and social background, history of drinking and alcohol withdrawal, DSM‐III‐R criteria for the evaluation of psychiatric conditions, and Feighner's criteria for the lifetime diagnosis and assessment of overall severity of alcoholism was administered to 373 alcoholic subjects. Temperament and Character Inventory (TCI) and Sensation Seeking Scale (SSS) were used to evaluate the other 324 alcoholics. The frequency of the homozygous short allele was significantly higher in alcoholic binge drinkers than in nonbinge drinking alcoholics. There were no significant differences in the frequencies of either the 5‐HTTLPR genotype or the short vs. long allele in alcoholic and control subjects. The alcoholics' 5‐HTTLPR genotype and allele frequencies did not differ significantly by the severity of withdrawal symptoms or by the number of positive Feighner's diagnostic criteria. Although these results indicate an association between 5‐HTTLPR and a subgroup of alcoholics characterized by binge drinking, the authors found no differences in SSS and TCI subscale scores for alcoholics with different 5‐HTTLPR genotypes. Future studies of the association in other alcoholic population should take into account personality traits. © 2001 Wiley‐Liss, Inc.     

Regulation of the human serotonin transporter mediated by long-term action of serotonin in Caco-2 cells

Aim: The aim of this study was to determine the effect of long‐term serotonin (5‐hydroxytryptamine, 5‐HT) treatment on the human serotonin transporter (hSERT) function and its expression. Methods: This study was carried out in the enterocyte‐like cell line Caco‐2. These cells constitutively express the hSERT and have been shown to be an excellent model for the study of this protein. We measured serotonin transport, levels of mRNA expression and of the SERT protein after treating the cells with serotonin. Results: Serotonin treatment diminished hSERT activity in a concentration and period‐dependent way by increasing the K_t value and reducing V_max. This inhibition was reversible and was not mediated by either the action of 5‐HT₂, 5‐HT₃ or 5‐HT₄ receptors, or by the intracellular second messengers, protein kinase C and cAMP. 5‐HT did not seem to affect either the mRNA level of the SERT or the protein transporter measured in either the membrane or the cell lysate. The 5‐HT treatment effect was additive to the inhibitory effect of treatment with a low concentration of citalopram and fluoxetine. Nevertheless, 5‐HT did not increase the inhibition yielded by treatment with high concentration citalopram. Conclusion: The chronic increase in serotonin in the extracellular medium diminishes the function of the SERT. This effect seems to be due to an effect on the transporter molecule itself in the membrane, without altering protein synthesis, intracellular traffic, or its availability.     

The modulatory influence of polymorphism of the serotonin transporter gene on characteristics of mental maladaptation in relatives of patients with endogenous psychoses

A number of studies have reported an association between 5-HTTLPR, a polymorphism of the serotonin transporter gene, and the development of depressive states in response to a variety of distal and proximal stressors. We report here studies of the effects of the 5-HTTLPR polymorphism on the probability that an individual will develop mental maladaptation in 224 close relatives of patients with severe chronic mental disorders — schizophrenia and schizoaffective and affective psychoses. The ss genotype of the serotonin transporter gene contributes to the formation predominantly of manifestations of distress, reflected by increases on the hypochondriasis scale of the MMPI scale of factors such as the extent of the autonomic component of anxiety reactions and increased attention to own health, as well as increases in sensitivity. At the same time, the ss genotype was less likely to influence the appearance of depression and anxiety, as determined on the depression scale. These tendencies were more marked in males than females. Furthermore, males with the ss genotype were characterized by some increase in tension, suspicion, detachment, and attention difficulty (on the paranoia and schizophrenia scales). These data can be regarded as supporting the role of the short allele of the serotonin transporter gene in enhancing and modulating psychopathological reactions to chronic stress situations in relatives of mental patients. __________ Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 107, No. 1, pp. 46–51, January, 2007.     

Association of verbal and figural creative achievement with polymorphism in the human serotonin transporter gene

The purpose of this study was to examine the potential association between the S (short) and L (long) alleles of the 5-HTTLPR polymorphism of the serotonin transporter (5-HTT) gene and verbal and figural creative ability. Sixty-two unrelated Caucasian university students (29 men and 33 women) participated in the experiment. The results showed a significant association between verbal and figural creativity scores and the 5-HTTLPR polymorphism. The subjects with S/S and L/S genotypes demonstrated higher verbal creativity scores in comparison with the L/L genotype carriers. The carriers of S/S genotype demonstrated also higher figural creativity scores in comparison with the carries of L/S and L/L genotypes. Thus, it is the first report on a significant association between the 5-HTTLPR polymorphism and creative achievements. As the 5-HTTLPR polymorphism is associated with genetically defined alteration in the brain serotonergic neurotransmission our result provides an evidence of the involvement of the central serotonin system in creativity regulation.     

睡眠呼吸暂停综合征与5-羟色胺转运体基因多态性的关联分析

目的 初步探讨睡眠呼吸暂停综合征（sleep apnea syndrome，SAS）的遗传易感因素。方法 采用聚合酶链反应技术，检测104例SAS患者和150名健康对照者的5．羟色胺转运体（5-hydroxytryptamine transporter，5-HTT）基因启动子的基因连锁多态区（gene-hnked polymorphic region，LRR）和第2内含子的可变数目串联重复区（variable number tandem repeat，VNTR）多态性，分别对所得基因型和等位基因的频率进行相关统计学分析。结果 SAS患者5-HTT LPR多态性的基因型和等位基因频率与正常对照组之间的差异无统计学意义（P〉0．05）。SAS患者的5-HTT-VNWR的基因型10／10、12／10频率高于正常对照组（P〈0．05），其等位基因10的频率高于正常对照组（P〈0.01，OR=2.536，95％ CI：1．071～6．783）。结论 5-HTILPR可能不是SAS患者的遗传位点，第2内含子VNTR的等位基因10可能与SAS有一定的关联。     

Serotonin transporter gene polymorphism and psychiatric disorders in NF1 patients

Neurofibromatosis type 1 (NF1) is an autosomal‐dominant genetic disease characterized by a broad clinical expression. Comorbid affective disorders, anxiety disorders, and suicide are frequently observed during NF1. The promoter marker (5‐HTTLPR) of the serotonin transporter gene (5‐HTT) has been shown to be associated with major affective disorders, anxiety‐related trait, and more recently with suicidal behavior. This gene is adjacent to the NF1 gene, raising the question of the implication of the 5‐HTT gene in the psychiatric comorbidity during NF1. Eighty‐eight patients with NF1 and 184 screened controls were typed for the 5‐HTTLPR. No deviation from the Hardy‐Weinberg equilibrium in patients was observed. In addition, allele and genotype frequencies were similar in the two groups. Our data do not support the implication of the 5‐HTT gene in the psychiatric comorbidities of NF1. © 2001 Wiley‐Liss, Inc.     

Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese

We determined polymorphism in the serotonin (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) in 501 healthy Japanese, individuals, using the polymerase chain reaction of Lesch et al., with minor modifications. The distribution of allele frequencies was determined and found to differ from that in Caucasians. We also investigated the relationship of polymorphism in 5-HTTLPR to anxiety traits, by having 189 of the 501 subjects complete a self-rating questionnaire for anxiety and depression. Subjects with the short/short (s/s) genotype had significantly higher anxiety scores than those with the long/long (l/l) or l/s genotype. It is suggested that populations with the s/s genotype of 5-HTTLPR have stronger anxiety-related personality traits than those with the l allele. Received: July 16, 1998 / Accepted: August 25, 1998     

Personality and the serotonin transporter gene: Associations in a longitudinal population-based study

Associations between the promoter polymorphism of the serotonin transporter gene (5-HTTLPR) and anxiety-related personality traits in healthy adult subjects have been inconsistent. We assessed personality in participants of the Estonian Children Personality Behaviour and Health Study, using parental reports and self-reports. In the younger cohort, according to parental assessments at ages 9 and 15, children homozygous for the S allele had significantly higher scores of Neuroticism and lower scores of Openness, Agreeableness and Conscientiousness. Parental assessment of the older cohort at ages 15 and 18 did not yield any genotype effect on personality; however, interaction of cohort and genotype was not significant. According to self-reports, SS homozygotes had higher Neuroticism at age 15 but not at age 18. Thus, homozygocity for the S allele of the 5-HTTLPR is related to anxiety-related personality traits in general population, but this is easier to detect before adolescence.