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).     

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.     

Neuroticism-related personality traits are related to symptom severity in patients with premenstrual dysphoric disorder and to the serotonin transporter gene-linked polymorphism 5-HTTPLPR

Neuroticism has been linked to a functional polymorphism in the serotonin transporter gene (5-HTTLPR), with short-allele carriers being overrepresented among high-scorers on neuroticism. Studies evaluating neuroticism-related personality traits in relation to the 5-HTTLPR polymorphism among patients with premenstrual dysphoric disorder (PMDD) and are lacking. The primary aim of this study was to evaluate the relationship between PMDD and neuroticism-related personality traits, and secondly, to relate the personality trait scores of PMDD patients to experienced symptom severity and to the 5-HTTLPR short allele. Thirty PMDD patients and 55 asymptomatic healthy controls were included in the study. The Swedish Universities Scale of Personality was used to evaluate personality traits. Genotype analyses were available in 27 PMDD patients and 18 healthy controls. Women with PMDD displayed higher levels of neuroticism-related personality traits (psychic trait anxiety, somatic trait anxiety, embitterment, stress susceptibility and mistrust) than healthy controls, and these effects were most prominent in women with more severe luteal phase symptoms. Furthermore, PMDD patients with at least one copy of the short allele of the 5-HTTLPR polymorphism scored higher on psychic trait anxiety and lack of assertiveness than PMDD patients who were homozygous for the long allele. PMDD patients who suffer from more severe luteal phase symptoms also display increased scores of neuroticism-related personality traits in comparison with healthy controls. Within the group of PMDD patients, differences in certain personality trait scores are associated with the short allele of the 5-HTTLPR polymorphism.     

Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits.

Anxiety-related personality traits, such as NEO neuroticism and TCI/TPQ harm avoidance, have been shown to have significant genetic components. To date, however, no specific genetic variants that contribute to these traits have been conclusively identified. At least 26 studies have investigated a putative association between a functional serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits. The results of these studies have been inconsistent with some studies finding evidence for an association, and others not. We performed a meta-analysis of all applicable studies investigating this association. In the overall analysis (N = 5,629 subjects), we found suggestive evidence for an association between the 5-HTTLPR short allele (s) and increased anxiety-related personality trait scores (P = 0.087). However, we also found strong evidence for heterogeneity. This heterogeneity is largely explained by substantial variation between the studies in the inventory used. When the analysis was stratified by inventory type, there was a significant association between 5-HTTLPR and NEO neuroticism (P = 0.000016), a non-significant association between 5-HTTLPR and TCI/TPQ harm avoidance (P = 0.166), and no association between 5-HTTLPR and other anxiety-related personality traits (P = 0.944). There was no evidence that these results were either due to publication bias or accounted for by any one single study. We conclude that there is a strong association between the serotonin transporter promoter variant and neuroticism as measured in the NEO personality inventory and that non-replications are largely due to small sample size and the use of different inventories.     

Combination of the serotonin transporter and norepinephrine transporter gene promoter polymorphisms might influence harm avoidance and novelty seeking in healthy females

It has been demonstrated that the interaction between serotonin transporter (5HTT) and norepinephrine transporter (NET) functions affects each transporter function and behavior in studies using knockout mice model. In the present study, we examined the effects of the 5HTT and NET gene promoter polymorphisms on personality traits in 575 Japanese healthy subjects. The 5HTT (long/short, L/S) and NET (-3081 A/T) genotypes were identified by PCR methods, and personality traits were assessed by the Temperament and Character Inventory (TCI). Neither of the two polymorphisms affected any TCI dimension, but the interaction between them had significant effects on harm avoidance and novelty seeking in females. Subsequent analyses showed that the females with the combination of the SS genotype reducing 5HTT function and the TT genotype reducing NET function had higher harm avoidance and lower novelty seeking. The present study suggests that the combination of 5HTT and NET polymorphisms influences harm avoidance and novelty seeking in females.     

Search for association between suicide attempt and serotonergic polymorphisms

Serotonergic neurotransmission has been implicated in suicidal behavior. Polymorphisms in the genes coding for tryptophan hydroxylase, serotonin receptor 2A and serotonin transporter were investigated in a sample of suicide attempters (n = 165) and healthy control subjects (n = 99). No significant differences were found for any of the investigated polymorphisms. Neither did any significant differences emerge in comparison with control subjects when the suicide attempters were grouped into different diagnostic categories: unipolar disorder (n = 45), adjustment disorder (n = 37), substance use disorder (n = 37) and personality disorder, cluster B (n = 36). The results suggest that alleles defined by the investigated polymorphisms do not represent a major determinant in suicide attempt. However, a highly significant (P = 0.001; odds ratio, 1.47; 99% confidence interval, 1.42-1.53) allelic association between tryptophan hydroxylase and suicide attempt is indicated after pooling our data with literature data. In light of previous data, a possible association between the tryptophan hydroxylase polymorphism and a phenotype that may become differently stratified within differently selected samples of suicide attempters is discussed.     

Lack of association between polymorphisms of the dopamine receptor D4 and dopamine transporter genes and personality traits in a Korean population

Human personality traits have a considerable genetic component. Cloninger et al. were the first to postulate that certain personality traits, such as novelty seeking, are related to the dopamine neurotransmitter system. In this study, we investigated the associations between dopamine receptor D4 (DRD4) exon III and dopamine transporter (DAT1) polymorphisms and personality traits. The DRD4 and DAT1 gene polymorphisms were genotyped in 214 healthy Korean subjects, whose personality traits were assessed with the Temperament and Character Inventory (TCI). There were no significant differences between scores of TCI temperament dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and DRD4 gene polymorphism. The DAT1 gene polymorphisms also showed no significant association with any of the temperament subscales of the TCI. These data suggest that DRD4 and DAT1 gene polymorphism may not associated with personality traits in a Korean population.     

An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder

Serotonergic pathways have been implicated in impulsive and aggressive behavior. Polymorphisms in the regulatory region of the serotonin transporter (5-HTT), in intron 7 of the tryptophan hydroxylase (TPH) gene and in the MAOA gene were previously reported to be associated with mood and anxiety disorders, impulsivity and aggression. In this study, we analyzed these polymorphisms in men and women with schizophrenia or schizoaffective disorder (n = 84) who met our criteria for violence (history of two or more assaults on others) or nonviolence (no history of either assaultive or threatening behavior). In males, a modest association between TPH genotype and history of violence (chi-square test = 6.703, degrees of freedom = 2, P = 0.035) was not statistically significant after correction for multiple comparisons (corrected P = 0.21). The TPH L allele was more frequent in violent males (chi-square = 5.323, degrees of freedom = 1, P = 0.021) but this difference also failed to withstand correction (corrected P = 0.126). No significant associations were found for either the 5-HTT or MAOA polymorphisms in males or females. These results tend to support previous reports by New et al. (1996; 1998) of an association between the TPH L allele and impulsive aggression in males with personality disorder, but larger studies are needed.     

Serotonergic genes and personality traits in the Korean population

Serotonergic genes have been implicated in mood disorders, alcoholism and certain personality traits. The goal of this study was to investigate the relationship between personality traits and several important genes in the serotonin system. The participants included 146 healthy adults with no history of psychiatric disorders or other physical illness during the last 6 months. All participants were tested by the Temperament and Character Inventory (TCI) and genotyped serotonin transporter, serotonin receptors (5-HT(2A) and 5-HT(6)) and tryptophan hydroxylase gene polymorphisms. Genotyping was analyzed with polymerase chain reaction. Differences in TCI dimensions and sub-scales among three groups were examined with ANOVA. Our result suggested that 5-HT(2A) receptor gene polymorphism (A-1438G) appears to be associated with self-determinism and self-transcendence (ST). Our result also indicated a significant relationship between 5-HT(6) receptor gene polymorphism (C267T) and ST. Further studies of polymorphisms of other genes and their interactions may clarify the complex relationship between personality and genes.     

Lack of association between the serotonin transporter promoter polymorphism (5-HTTLPR) and personality traits in asymptomatic patients with panic disorder

The serotonin transporter promoter polymorphism (5-HTTLPR) has been investigated regarding its association with neuroticism, which, in its turn, is a personality dimension often found in patients with panic disorder (PD). It has been recently evidenced that the long 5-HTTLPR polymorphism has a genetic variation (Lg), which is related to its lower expression. The objective of this study was to assess the association between the 5-HTTLPR polymorphism in the triallelic system and the neurotic personality traits in patients in PD remission. Sixty-seven Caucasian patients with PD diagnosis according to the DSM-IV-TR assessed with the MINI (mini international neuropsychiatric interview) were included. The MMPI (Minnesota multiphasic personality inventory) was used to assess the personality. The remission of PD symptoms was defined as CGI (clinical global impression) 相似文献   

No association of 5-HT2C, 5-HT6, and tryptophan hydroxylase-1 gene polymorphisms with personality traits in the Japanese population

Serotonin 2C receptor (5-HT(2C)), serotonin 6 receptor (5-HT(6)), and tryptophan hydroxylase-1 (TPH1) genes could be candidates for personality-related genes considering the role of serotonin in various mental functions and behavior. However, a limited number of studies have investigated the association between these genes and personality traits. In the present study, we investigated the three serotonin-related genes, 5-HT(2C), 5-HT(6), and TPH1 genes, in relation to personality traits in the Japanese population. The Cys23Ser polymorphisms in the 5-HT(2C) gene, the 267T/C polymorphism of the 5-HT(6) gene, and the 779A/C polymorphisms in the TPH1 gene were genotyped in 253 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). As a result, no significant association was observed between the polymorphisms and the NEO PI-R or the STAI scores. The present results did not provide evidence for the association between the three serotonin-related genes and personality traits. The genes might not have major role in the development of personality traits, although further investigation with larger sample size may be recommended for conclusion.     

Evidence for associations between MDGA2 polymorphisms and harm avoidance: replication and extension of a genome-wide association finding

In 2008, van den Oord et al. identified in a genome-wide association study the MAM domain containing glycosylphosphatidylinositol anchor 2 gene (MDGA2 or MAMDC1) as a new candidate for neuroticism. In addition to the replication attempt of this association, we further investigated the role of MDGA2 with respect to harm avoidance (HA), a personality trait highly related to neuroticism. In a sample of mentally healthy volunteers (n=541) and depressed patients (n=199), neuroticism and HA were assessed with Eysenck's Revised Personality Questionnaire and Cloninger's Tridimensional Personality Questionnaire. Genotypic information (Illumina Bead Chip HumanHap300) of 100 single nucleotide polymorphisms (SNPs) located in the MDGA2 gene (±5 kb) was available, and additional four SNPs for replication were imputed. We were able to replicate the association between MDGA2 and neuroticism for the strongest SNPs of the genome-wide association study. It could further be shown that volunteers homozygous for the T-allele of SNP rs2416054 showed higher scores in the HA4 subscale 'Fatigability and asthenia' (Pnominal=0.0006), remaining significant after correction for multiple testing (Pwy-corrected=0.045). The same SNP also showed an association with HA4 in the patients' sample (Pnominal=0.03). Our finding provides further support for a link between variants in the MDGA2 gene and specific neuroticism-related phenotypes.     

Norepinephrine transporter and α2c adrenoceptor allelic variants and personality factors

It has been suggested that reward dependence, as measured by the Tridimensional Personality Questionnaire (TPQ), is related to central noradrenergic activity, a proposition supported by two studies of urinary norepinephrine metabolite. In the current investigation, 190 normal young Han Chinese were examined, with genetic polymorphisms determined for the norepinephrine transporter (1287G/A) and the α_2c‐adrenoceptor (Del322–325) to test the association with TPQ personality traits. No significant association was demonstrated for these two polymorphisms and any of the TPQ personality‐factor scores, including reward dependence and its subscales. Our negative findings suggest that the investigated polymorphisms of the norepinephrine transporter and the α_2c adrenoceptor do not play a major role in the reward‐dependence personality trait as assessed by TPQ. © 2002 Wiley‐Liss, Inc.     

No association between 5-HTTLPR and harm avoidance in Korean college students

There have been numerous studies on the association between 5-HTTLPR (polymorphisms in the promoter region of the serotonin transporter gene) and anxiety-related personality traits, with conflicting results. In this study, we administered Korean version of the Temperament and Character Inventory (K-TCI) to a sample of 158 Korean college students and genotyped for the 5-HTTLPR in order to compare the TCI dimensional scores including harm avoidance according to the 5-HTTLPR genotype and sex. We could not find the association between 5-HTTLPR and harm avoidance and other TCI measures. Considering known allele frequencies differences of 5-HTTLPR among different ethnic groups, further cross-cultural studies with a larger sample would be needed.     

Norepinephrine transporter and alpha(2c) adrenoceptor allelic variants and personality factors

It has been suggested that reward dependence, as measured by the Tridimensional Personality Questionnaire (TPQ), is related to central noradrenergic activity, a proposition supported by two studies of urinary norepinephrine metabolite. In the current investigation, 190 normal young Han Chinese were examined, with genetic polymorphisms determined for the norepinephrine transporter (1287G/A) and the alpha(2c)-adrenoceptor (Del322-325) to test the association with TPQ personality traits. No significant association was demonstrated for these two polymorphisms and any of the TPQ personality-factor scores, including reward dependence and its subscales. Our negative findings suggest that the investigated polymorphisms of the norepinephrine transporter and the alpha(2c) adrenoceptor do not play a major role in the reward-dependence personality trait as assessed by TPQ.     

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.