Association of a functional polymorphism in the serotonin transporter gene with personality traits in females in a Polish population

The aim of our study was to determine whether the 5-HTTLPR polymorphism is related to temperamental traits measured using the Formal Characteristics of Behavior - Temperament Inventory (FCB-TI) and personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI) questionnaire. The sample comprised 200 unrelated females, aged 18-29 years. DNA of the subjects was isolated from buccal epithelial cells, and 5-HTTLPR polymorphism was genotyped using PCR. The subjects were divided into SS, SL and LL groups according to their genotype. The differences in results on the endurance scale (F = 11.29, p = 0.001), measured using FCB-TI and neuroticism measured using NEO-FFI (F = 15.32, p = 0.000) between the S group (short-form allele; genotypes SS and SL) and the L group (long-form allele; genotype LL) were statistically significant. Additionally, statistically significant differences between the LL and SS groups, and between the SL and SS groups with respect to 'activity' (FCB-TI) were found (F = 4.5, p = 0.012). These findings support a role of the 5-HTTLPR polymorphism in the modulation of personality and temperamental traits.     

An interaction between the serotonin transporter promoter region and dopamine transporter polymorphisms contributes to harm avoidance and reward dependence traits in normal healthy subjects

Summary. There is evidence for an association between polymorphisms of serotonin- and dopamine-related genes and temperamental personality traits. Recent findings have shown that interactions between allelic variants of the different genes may contribute to personality traits. We examined the effects of serotonin transporter-linked promoter region (5-HTTLPR) and dopamine transporter (DAT1) gene polymorphisms for associations with the Temperament and Character Inventory (TCI) temperament subscales in 209 Koreans. We found that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI. Neither of these two genes affected any subscales of TCI alone. Controlling for the effects of gender and age, we found significant interactions between 5-HTTLPR and DAT1 genes on Harm Avoidance (HA) and Reward Dependence (RD) as measured by the TCI (Hotelling’s Trace = 3.0, P = 0.02). In the presence of the DAT1 10/10 genotype, subjects of group L of 5-HTTLPR had a significantly higher HA score and significantly lower RD score than those of group S (F = 5.04, df = 1, p = 0.03 and F = 8.35, df = 1, p = 0.004, respectively). These findings suggest that the variants of 5-HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD temperament subscales of TCI.     

No association between the TPH A218C polymorphism and personality traits in Japanese healthy subjects

It has been suggested that the central serotonergic activity is implicated in personality traits. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. In the present study, the association between the TPH A218C polymorphism and personality traits assessed by the Temperament and Character Inventory (TCI) was examined in 345 Japanese healthy subjects. The TPH A218C polymorphism was determined by a PCR-RFLP method. There were no significant differences in the seven dimension scores of TCI among the A/A, A/C, and C/C genotype groups by the one-way ANOVA. There was a significant negative correlation between age and the NS scores. Females showed significantly higher scores of HA, RD, and ST, and significantly lower scores of SD than males. The multiple regression analysis using age, gender, and the TPH genotype as independent variables also showed no significant association between any dimension score and the genotype. The present study thus suggests that the TPH A218C polymorphism does not affect personality traits in Japanese healthy subjects.     

Possible association between serotonin transporter promoter region polymorphism and impulsivity in Koreans

Serotonin has become the major focus of biological studies of suicidal behavior and impulsive-aggressive behavior in humans. The serotonin transporter (5-HTT) gene is one of the important genes involved in the regulation of serotonin transmission. We examined the association of impulsivity in Korean populations with a functional polymorphism of the promoter region of the 5-HTT gene (5-HTTLPR). We recruited 186 adolescent prisoners and 64 medical students. Impulsivity was measured using the Barratt Impulsiveness Scale and we divided all subjects into three groups: impulsive subjects (IS, N=121), non-impulsive subjects (NIS, N=115) and an intermediate group (excluded, N=14). The 5-HTTLPR genotype was determined by polymerase chain reaction. All subjects were Korean men unrelated to each other. There were no significant differences in the genotype frequency of 5-HTTLPR-S/S, S/L and -L/L between the two groups in the Korean population (IS vs. NIS: 47.9 vs. 61.7%; 43.0 vs. 32.2%; and 9.1 vs. 6.1%, respectively). However, there was a statistically significant difference in allelic frequency of 5-HTTLPR-S and 5-HTTLPR-L between the two groups in the Korean population (IS vs. NIS: 69.4 vs. 77.8%; and 30.6 vs. 22.2%, respectively. From our results, this 5-HTTLPR polymorphism appears to be a possible candidate gene for impulsivity in the Korean population.     

Genetic variation in serotonin transporter alters resting brain function in healthy individuals.

BACKGROUND: Perfusion functional magnetic resonance imaging (fMRI) was used to investigate the effect of genetic variation of the human serotonin transporter (5-HTT) gene (5-HTTLPR, SLC6A4) on resting brain function of healthy individuals. METHODS: Twenty-six healthy subjects, half homozygous for the 5-HTTLPR short allele (s/s group) and half homozygous for the long allele (l/l group), underwent perfusion functional and structural magnetic resonance imaging during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores. RESULTS: Compared with the l/l group, the s/s group showed significantly increased resting cerebral blood flow (CBF) in the amygdala and decreased CBF in the ventromedial prefrontal cortex. The effect of functional modulation in these regions by 5-HTTLPR genotype cannot be accounted for by variations in brain anatomy, personality, or self-reported mood. CONCLUSIONS: The 5-HTTLPR genotype alters resting brain function in emotion-related regions in healthy individuals, including the amygdala and ventromedial prefrontal cortex. Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.     

Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationship to temperamental dimensions measured by the Temperament and Character Inventory in healthy volunteers

There is evidence for an association between polymorphisms of monoamine transporter genes and temperamental personality traits. Recent findings have shown that interaction of allelic variants of the different genes may contribute to the personality factors. We studied the association between temperamental personality dimensions measured with the Temperament and Character Inventory (TCI) and polymorphisms of the dopamine (DAT), norepinephrine (NET) and serotonin (5-HTT) transporter genes in 127 healthy Polish volunteers. There were no significant differences between means of TCI temperamental dimensions (novelty seeking, reward dependence, persistence and harm avoidance) and the transporter genes compared by ANOVA. There were some significant associations between genotypes and TCI subdimensions. Individuals carrying the A9/A9 DAT genotype have lower RD4 scores (dependence vs. independence) than A10/A10 individuals (3.0 +/- 1.4 vs. 3.5 +/- 1.3); p = 0.01. Examining 5-HTT gene promoter polymorphism, heterozygous individuals (l/s) and individuals with 44-bp deletion (s/s) scored significantly lower in the HA1 subdimension (anticipatory worry and pessimism vs. uninhibited optimism; 4.3 +/- 2.3 vs. 5.5 +/- 2.6) in comparison with individuals without deletion (l/l); p = 0.021. The NET transporter gene polymorphism showed no significant association with any of the temperamental TCI subdimensions.     

Serotonin transporter gene polymorphism and schizoid personality traits in the patients with psychosis and psychiatrically well subjects.

BACKGROUND AND OBJECTIVES: serotonin transporter (5-HTT) gene allelic variants were shown to be associated with Neuroticism and Harm Avoidance but the results were not replicated in other studies. The current investigation was undertaken in a further attempt to study the relationship between 5-HTT polymorphism and personality traits. SUBJECTS AND METHODS: to evaluate a spectrum of personality traits, MMPI was administered to a sample including patients with affective disorders (n=114), patients with schizophrenia spectrum illnesses (n=110) and psychiatrically well controls (n=124). All groups were genotyped for VNTR-17 and functional insertion-deletion (5-HTTLPR) polymorphisms. RESULTS: an association was found between 5-HTTLPR polymorphism and scores on three MMPI scales: Psychopathic deviance, Paranoia and Schizophrenia in patients with affective disorders and S chizophrenia in normal subjects. Both affected and control individuals with 'ss' genotype exhibited lower scores on these scales. CONCLUSION: we demonstrated that functional deletion/insertion allelic variation associated with decreased expression of serotonin transporter ('s' allele or 'ss' genotype) may restrict expression of schizoid traits in normal subjects and patients with affective disorders.     

A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder

Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fisher's exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression.     

Influence of serotonin-transporter-linked promoter region polymorphism on platelet activation in geriatric depression.

OBJECTIVE: Depression has been associated with increased platelet activation. Variations in the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism may influence the degree of activation. The authors examined the association among depression, platelet activation, and 5-HTTLPR genotype. METHOD: Elderly subjects with (N=61) and without (N=12) major depression were assessed for cognitive impairment, cardiovascular disease, and two indices of platelet activation. The depressed subjects were genotyped for the 5-HTTLPR polymorphism. RESULTS: The depressed subjects were older, were more cognitively impaired, and had higher platelet factor 4 and beta-thromboglobulin levels; cardiovascular disease was minimal in both groups. In the depressed group, subjects with the 5-HTTLPR l/l genotype had significantly higher platelet factor 4 and beta-thromboglobulin levels. CONCLUSIONS: Platelet activation is increased in elderly depressed patients, especially those with the 5-HTTLPR l/l genotype. This finding suggests how genetic differences may influence cardiovascular mortality in depressed patients with ischemic heart disease.     

中国汉族人群5-羟色胺转运体基因多态性与神经性厌食的关联研究

目的:探讨中国汉族人群5-羟色胺转运体基因启动子区域(5-HTTLPR)多态性与神经性厌食的关系。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对198例神经性厌食患者和225例正常健康对照者进行基因分型和关联分析。结果:①5-HTTLPR基因的3种基因型S/S、L/S和L/L在神经性厌食组的分布频率分别为65.7%、26.8%、7.6%,对照组为48.8%、37.8%、13.4%,两组差异有统计学意义(P<0.05)。等位基因S、L在神经性厌食组的分布分别为79.0%、21.0%,对照组为69.3%、30.7%,差异有统计学意义(P<0.05)。患病与携带L等位基因成负关联(OR=0.52,95%CI:0.35～0.77),患病与L/S基因型成负关联(OR=0.52,95%CI:0.34～0.79)。②5-HTTLPR功能三等位基因型(LA/LA、S/LA+LA/LG、S/S+S/LG+LG/LG)在神经性厌食组分布频率分别为2.0%、12.2%、85.8%,对照组为4.1%、23.4%、72.5%,两组差异有统计学意义(P<0.05)。患病与携带LA等位基因成负关联(OR=0.44,95%CI:0.25～0.77),患病与S/LA基因型成负关联(OR=0.44,95%CI:0.24～0.81)。结论::5-HTTLPR基因启动子区域多态性与中国汉族人群AN可能存在关联,L、LA等位基因及L/S、S/LA基因型为AN患病的保护等位基因及基因型。     

Impulsive-disinhibited personality and serotonin transporter gene polymorphisms: Association study in an inmate’s sample

The association between different impulsive-disinhibited personality traits with 5-HTTLPR and 5-HTTVNTR genetic polymorphisms was examined in an imprisoned male sample. Higher scores of the impulsive-disinhibited personality traits tended to be associated with carrying one or two copies of the 5-HTTPLR S allele (S/S homozygous and S/L heterozygous), and carrying two copies of the 5-HTTVNTR 12 allele (12/12 homozygous). Genotype, allele, haplotype and extended genotype distribution between low and high impulsive-disinhibited groups confirmed this association. Allele S and genotypes S/S+S/L at the 5-HTTLPR locus and allele 12 and genotype 12/12 at the 5-HTTVNTR locus were overrepresented in the high scoring group. Accordingly, allele S and allele 12 conferred a trend for risk to be in the high scoring group with an odds ratio (OR) of 1.8 (p < 0.035) and 1.7 (p < 0.014), respectively. In addition, extended genotype distribution shows that those S allele carriers (S/S homozygote and S/L heterozygote) that were also 12/12 homozygote, were overrepresented in the high scoring group (OR = 3.2; p < 0.004). The main risk of being in the high scoring group was assigned to those carrying two copies of the S-12 haplotype (OR = 5.7; p < 0.0007). We discuss the possible relationship between the two genetic serotonin polymorphisms and the personality impulsive-disinhibited traits investigated.     

No association between polymorphism in tyrosine hydroxylase and personality traits in healthy Japanese subjects

The aim of the present study was to investigate whether there is an association between the (TCAT)_n repeat polymorphism in the tyrosine hydroxylase (TH) gene and personality. The (TCAT)_n repeat polymorphism in the TH gene was genotyped in 898 healthy Japanese subjects. Personality traits were evaluated using the Temperament and Character Inventory (TCI). There was no significant difference in the TCI scores of subjects with and without the T9 allele. Furthermore, no significant association was found between each genotype and the TCI scores, even when the TCI scores were compared with the homozygous genotype. These findings suggest that the (TCAT)_n repeat polymorphism in the TH gene does not contribute to the personality traits evaluated on the TCI in healthy Japanese subjects.     

Does self-construal predict activity in the social brain network? A genetic moderation effect

Neural activity in the social brain network varies across individuals with different cultural traits and different genetic polymorphisms. It remains unknown whether a specific genetic polymorphism may influence the association between cultural traits and neural activity in the social brain network. We tested whether the serotonin transporter promoter polymorphism (5-HTTLPR) affects the association between self-construals and neural activity involved in reflection of personal attributes of oneself and a significant other (i.e., mother). Using functional MRI, we scanned Chinese adults with short/short (s/s) or long/long (l/l) variants of the 5-HTTLPR during reflection of personal attributes of oneself and one’s mother. We found that, while s/s and l/l genotype groups did not differ significantly in self-construals measured by the Self-Construal Scale, the relationship between self-construal scores and neural responses to reflection of oneself and mother was significantly different between the two genotype groups. Specifically, l/l but not s/s genotype group showed significant association between self-construal scores and activity in the medial prefrontal cortex, bilateral middle frontal cortex, temporoparietal junction, insula and hippocampus during reflection on mental attributes of oneself and mother. Our findings suggest that a specific genetic polymorphism may interact with a cultural trait to shape the neural substrates underlying social cognition.     

Serotonin Transporter Gene Polymorphism and Schizoid Personality Traits in Patients with Psychosis and Psychiatrically Well Subjects

Background and Objectives: Serotonin transporter (5-HTT) gene allelic variants were shown to be associated with Neuroticism and Harm Avoidance but the results were not replicated in other studies. The current investigation was undertaken in a further attempt to study the relationship between 5-HTT polymorphism and personality traits.

Subjects and Methods: To evaluate a spectrum of personality traits, MMPI was administered to a sample including patients with affective disorders (n=114), patients with schizophrenia spectrum illnesses (n=110) and psychiatrically well controls (n=124). All groups were genotyped for VNTR-17 and functional insertion-deletion (5-HTTLPR) polymorphisms.

Results: An association was found between 5-HTTLPR polymorphism and scores on three MMPI scales: Psychopathic deviance, Paranoia and Schizophrenia in patients with affective disorders and Schizophrenia in normal subjects. Both affected and control individuals with ‘ss’ genotype exhibited lower scores on these scales.

Conclusion: We demonstrated that functional deletion/insertion allelic variation associated with decreased expression of serotonin transporter (‘s’ allele or ‘ss’ genotype) may restrict expression of schizoid traits in normal subjects and patients with affective disorders.     

No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism.

BACKGROUND: A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. METHODS: SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus-hypothalamus and mesencephalon-pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. RESULTS: Specific binding ratios in the thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n = 3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s; n = 4). None of these differences was statistically significant. CONCLUSIONS: Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects.