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Background: The μ-opioid receptor (MOR) plays an important role in social bonding behaviors, while it is implicated in the pathophysiology of depression. It is shown that the A118G polymorphism (rs1799971) of the MOR gene (OPRM1) causes amino-acid exchange from Asn to Asp, and that this polymorphism is associated with altered mu-opioid receptor function. Meanwhile, sociotropy/autonomy and interpersonal sensitivity are personality vulnerabilities to depression characterized by distinctive interpersonal styles. The present study tested the hypothesis that the functional A118G OPRM1 polymorphism influences these personality traits., Methods: The subjects were 402 physically and mentally healthy Japanese volunteers. Sociotropy and autonomy were measured by the Sociotropy-Autonomy Scale, and interpersonal sensitivity was evaluated by the Interpersonal Sensitivity Measure. The A118G polymorphism of the OPRM1 was determined by the PCR method., Results: In one factor analysis of covariance, there were differences in scores of sociotropy (uncorrected p < .001, corrected p < .003) and interpersonal sensitivity (uncorrected p = .015, corrected p = .045), but not autonomy, among the A/A, A/G, and G/G genotypes. Post hoc LSD tests showed that sociotropy scores were higher in the A/A group than in the A/G (p = .029) and G/G (p < .001) groups, and higher in the A/G group than in the G/G group (p = .004). Interpersonal sensitivity scores were higher in the A/A group than in the A/G (p = .023) and G/G (p = .009) groups., Conclusion: This study suggests that the A118G OPRM1 polymorphism is associated with sociotropy and interpersonal sensitivity, interpersonal vulnerabilities to depression., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Aims: The diacylglycerol kinase η gene (DGKH) is one of the few replicated risk genes for bipolar disorder. Meanwhile, specific personality traits, especially openness to experience, have been suggested as premorbid personality traits of the disorder. The aim of the present study was to examine the relation of the DGKH genotype with broad dimensions of personality, to obtain further evidence for its implication in the etiology of bipolar disorder., Methods: The subjects were 319 Japanese healthy volunteers. Personality was assessed by the NEO Personality Inventory-Revised, which has the neuroticism, extraversion, openness to experience, agreeableness and conscientiousness dimensions. The A/G polymorphism of DGKH (rs9525580) was detected by a PCR-RFLP method. The subjects were divided into two groups with respect to the presence or absence of the A allele, which is a putative risk allele for bipolar disorder., Results: The group with the A allele had significantly (p < 0.05) higher scores of openness to experience compared to that without this allele. Scores of other dimensions were not different between the two groups., Limitations: The subjects had a homogeneous but rather specific background, and we did not employ a longitudinal design., Conclusions: The present study shows that a bipolar-risk allele of DGKH is associated with higher openness to experience, providing further evidence for the implication of this gene in the etiology of bipolar disorder., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Telomeres are repetitive DNA sequences located at the ends of chromosomes, and telomere length represents a biological marker for cellular aging. Interpersonal sensitivity, excessive sensitivity to the behavior and feelings of others, is one of the vulnerable factors to depression. In the present study, we examined the effect of interpersonal sensitivity on telomere length in healthy subjects., Methods: The subjects were 159 unrelated healthy Japanese volunteers. Mean age ± SD (range) of the subjects was 42.3 ± 7.8 (30-61) years. Interpersonal sensitivity was assessed by the Japanese version of the Interpersonal Sensitivity Measure (IPSM). Leukocyte telomere length was determined by a quantitative real-time PCR method., Results: Higher scores of the total IPSM were significantly (β = -0.163, p = 0.038) related to shorter telomere length. In the sub-scale analysis, higher scores of timidity were significantly (β = -0.220, p = 0.044) associated with shorter telomere length., Conclusions: The present study suggests that subjects with higher interpersonal sensitivity have shorter leukocyte telomere length, implying that interpersonal sensitivity has an impact on cellular aging.

Background and Aim: Interpersonal sensitivity is defined as undue and excessive awareness of, and sensitivity to, the behavior and feelings of others. Previous studies suggested that interpersonal sensitivity is one of the vulnerable factors to depression, and that genetic factors and cortisol are involved in the formation of interpersonal sensitivity. On the other hand, P-glycoprotein, which is encoded by the multidrug resistance 1 (MDR1) gene, serves as a barrier to entry and as an active eliminator for xenobiotics and cellular metabolites including cortisol, which is implicated in multiple brain functions. In the present study, we examined the effects of the MDR1 C3435T polymorphism (rs1045642) on interpersonal sensitivity in healthy subjects., Methods: The subjects were 842 healthy Japanese volunteers (mean age = 26.7 years, male/female ratio = 490/352). The C3435T polymorphism of MDR1 gene was detected by a PCR method, and interpersonal sensitivity was assessed by the Interpersonal Sensitivity Measure (IPSM)., Results: The 2-factor analysis of covariance (ANCOVA) showed a significant main effect of the MDR1 genotype on the IPSM scores with a significant interaction between the genotype and gender. The subsequent 1-factor ANCOVA showed that in females the C/C genotype group had higher IPSM scores than the C/T genotype group (p < 0.001) and the T/T genotype group (p < 0.001), and the C/T genotype group had higher IPSM scores than the T/T genotype group (p = 0.014). In males no significant association was found between the MDR1 genotype and the IPSM scores. In allelic analyses using the χ(2) tests, the C allele frequency in females was significantly higher (p < 0.001) in the high IPSM group than in the low IPSM group, while there was no significant difference in the C allele frequency between the high and low IPSM groups in total subjects and males., Conclusion: The present study suggests that the C3435T polymorphism of the MDR1 gene affects the formation of a depression-prone personality trait in Japanese females.

GTP cyclohydrolase 1 (GCH1) is the initial and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin, which is an essential cofactor for biosynthetic enzymes of dopamine, serotonin, and nitric oxide. In the present study, the association of functional polymorphism of the GCH1 gene (C+243T, rs841) with personality traits was examined in 902 healthy Japanese subjects. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the GCH1 genotype was detected by a PCR-RFLP method. There were no significant main effects of the GCH1 genotype on the seven TCI dimension scores, but significant interaction effects between the GCH1 genotype and gender were found on the scores of novelty seeking. Post-hoc analysis revealed that males with the C/C genotype had higher scores of novelty seeking than those with the C/T genotype or those with the T/T genotype, while in females the scores of novelty seeking were not different among the genotype groups. The present study thus suggests that the C+243T polymorphism of the GCH1 gene affects the personality trait of novelty seeking in males., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Previous studies have shown that the function of hypothalamic-pituitary-adrenal (HPA) axis is involved in the characterization of personality traits. FK506-binding protein 51 (FKBP51 or FKBP5) is a co-chaperone of heat-shock protein 90, and plays an important role in the negative feedback regulation of HPA axis function. It has been reported that a C/T single nucleotide polymorphism in the intron 2 of FKBP5 gene (rs1360780) affects FKBP5 protein levels and cortisol response to dexamethasone and psychological stress tests. Therefore, it is hypothesized that the FKBP5 polymorphism affects personality traits. In the present study, we studied the association between this polymorphism and personality traits in 826 Japanese healthy subjects. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the FKBP5 genotype was detected by a real-time PCR and cycling probe technology for SNP typing. In total subjects, the group with the T allele predictive of impaired negative feedback regulation of the HPA axis had higher scores of harm avoidance (HA) (p=0.043) and lower scores of cooperativeness (CO) (p=0.019) compared to that without the T allele. The T allele was associated with higher scores of HA in females (p=0.020) and lower scores of CO in males (p=0.015). The present study thus suggests that the FKBP5 polymorphism affects HA and CO in healthy subjects, with gender specificity., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

According to the Cloninger's theory, personality consists of temperaments, which are automatic emotional reactions and habits, and characters, which are the self-concepts about goals and values. It has been suggested that temperaments are highly heritable and related to catecholaminergic neurotransmission. Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme in the biosynthesis of catecholamines such as dopamine and norepinephrine, which are deeply involved in human mental functions and behaviors. It has recently been reported that the C-824T single nucleotide polymorphism in the promoter region of the TH gene (rs10770141) affects promoter activity of the TH gene and urinary catecholamine levels. In the present study, the association of this polymorphism with personality traits was examined in 740 healthy Japanese subjects. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the TH genotype was detected by a PCR-RFLP method. In total subjects, there were no significant differences in the seven TCI dimension scores between the TH genotype groups. In males, the subjects with the T allele predictive of elevated levels of dopamine and norepinephrine had lower scores of novelty seeking than those without this allele, while in females none of the TCI scores was different between the two genotype groups. The present study thus suggests that the C-824T polymorphism in the TH gene promoter may affect the personality trait of novelty seeking in healthy males. However, taken the effects of multiple comparisons into account, the present result should be interpreted with caution, necessitating a replication in a different sample., (Copyright 2009 Elsevier B.V. All rights reserved.)

There have been several studies showing the relationship between sex hormones and personality traits. Cytochrome P450 19 (CYP 19, aromatase) is the rate-limiting enzyme for the conversion of androgens into estrogens, and it has been reported that the C/T single nucleotide polymorphism in the 3'-untranslated region (3'UTR) of CYP19 gene (rs10046) affects dispositions of estradiol and testosterone. Therefore, it is hypothesized that this polymorphism affects personality traits. In the present study, the association of this polymorphism with personality traits was examined in 633 healthy Japanese subjects. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the CYP19 genotype was detected by a PCR-RFLP method. In males, the group with the T allele predictive of elevated levels of estradiol and decreased levels of testosterone had lower scores of harm avoidance than that without the T allele (p=0.015). In females, none of the seven TCI dimensions was different between the two genotype groups. The present study thus suggests that the C/T polymorphism in the 3'UTR of CYP19 gene affects personality trait of harm avoidance in healthy males.

Dopamine transporter (DAT) plays a major role in terminating dopamine neurotransmission, which may be involved in the characterization of personality traits. Recently, polymorphisms of the promoter region (-67 A/T) and intron 8 (40-bp variable number of tandem repeats, VNTRs) in the DAT gene were reported to affect DAT expression. In the present study, we examined the associations of these polymorphisms with personality traits in 654 healthy Japanese. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the DAT polymorphisms were identified by PCR-based methods. Regarding the -67 A/T promoter polymorphism, the females without the A allele predictive of high DAT activity had lower scores of self-directedness (p=0.005) and cooperativeness (p=0.038) than those with the A allele. In males, none of the TCI scores was different between the two genotype groups. The intron 8 VNTR polymorphism did not affect any TCI score either in males or in females. The present study thus suggests that the -67 A/T promoter polymorphism, but not intron 8 VNTR polymorphism, in the DAT gene affects personality traits of Japanese healthy females.

Dopamine and norepinephrine are implicated in the characterization of personality traits. Dopamine-beta-hydroxylase (DBH) is the enzyme responsible for conversion of dopamine to norepinephrine, and thus plays an important role in controlling dispositions of these neurotransmitters. Previous studies have shown that the -1021C/T polymorphism of the DBH gene promoter influences plasma DBH activity. Therefore, we examined the association between the -1021C/T DBH polymorphism and personality traits in 627 Japanese healthy volunteers. The DBH genotypes were identified by a PCR-RFLP method, and personality traits were assessed by the Temperament and Character Inventory (TCI). In the two-factor analysis of covariance with the DBH genotype and sex as factors and with age as a covariate, there was no main effect of the DBH genotype on any TCI score, while the interaction between the factors was significant in harm avoidance. In the post hoc analysis, the group with the T allele predictive of lower DBH activity had higher scores of harm avoidance than that without the T allele in females (p=0.006), but not in males. The present study suggests that the -1021C/T DBH polymorphism affects the personality trait of harm avoidance in healthy females.

There have been several studies suggesting that sex hormones are involved in characterization of human mental function and behaviour. Recently, it has been reported that the -34T/C polymorphism of cytochrome P450 17 (CYP17) gene affects sex hormone dispositions. Therefore, it is possible that the CYP17 -34T/C polymorphism affects personality traits. In the present study, the association of this genetic polymorphism with personality traits was examined in 595 healthy Japanese. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the CYP17 -34T/C polymorphism was detected by a PCR-RFLP method. In males, the scores of novelty seeking, cooperativeness, and self-transcendence were higher in the group with the C allele than in that without this allele. In females, none of the seven TCI dimensions was different between the two genotype groups. The present study thus suggests that the -34T/C polymorphism of the CYP17 gene affects personality traits of healthy males, but not females, and this gender-dependent effect may be mediated by the action of sex hormones such as estradiol and testosterone.

There have been some animal and human data suggesting that excitatory amino acid transporter (EAAT)-2, the major subtype of EAAT, is involved in human mental function and behavior. Recently, it has been shown that the -181 A/C polymorphism in the EAAT2 gene promoter affects plasma glutamate concentrations in humans. In the present study, the association of this genetic polymorphism with personality traits was examined in 575 Japanese healthy volunteers. Personality traits were assessed by the Temperament and Character Inventory, and the EAAT2 polymorphism was detected by a PCR-RFLP method. The scores of reward dependence were significantly (p=0.017) lower in the group with the A allele (A/A and A/C) than in that without this allele (C/C). When males and females were analyzed separately, the significant difference between the two genotype groups was observed in females (p=0.021) but not in males. The present study thus suggests that the -181 A/C polymorphism in the EAAT2 gene promoter affects the personality trait of reward dependence in healthy subjects.

There have been several data suggesting that norepinephrine neurotransmission is involved in the characterization of personality traits. Recently, the -3081A/T polymorphism in the promoter region of the norepinephrine transporter (NET) gene affecting promoter activity has been reported. In the present study, we studied the association between this NET polymorphism and personality traits in 553 Japanese healthy subjects. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the NET genotypes were identified by a PCR-RFLP method. Multivariate two-factor analysis of covariance with genotype and gender as factors and with age as a covariate showed no association between the NET genotypes and the TCI dimension scores. The present study thus suggests that the -3081A/T polymorphism in the NET gene promoter is not involved in the characterization of personality traits in healthy subjects.

Introduction: Oxytocin receptor (OXTR) gene polymorphism reportedly moderates effects of negative environments during childhood on mental function and behavior such as depressive symptoms and externalizing problems. This study examined OXTR gene polymorphism effects on personality traits in healthy participants, considering interaction effects of polymorphism with affectionless control (AC) parenting which is one of the dysfunctional and pathogenic parenting styles. Methods: For 496 Japanese volunteers, personality was evaluated using the Temperament and Character Inventory. The Parental Bonding Instrument, which has subscales of care and protection, was used to assess perceived parental rearing. AC parenting was defined as low care and high protection. A/G polymorphism of the OXTR gene (rs53576) was detected using TaqMan SNP Genotyping Assay. Results: Two‐way analysis of covariance revealed significant interaction effects between the genotype and the number of AC parents on scores of harm avoidance, with no significant main effect of genotype on any personality. Post‐hoc analysis revealed that the harm avoidance scores were increased in a stepwise manner with respect to the increase of the number of AC parents in the A allele carriers. No similar association was observed in the A allele noncarriers. Conclusion: The results of this study suggest that OXTR polymorphism influences characterization of harm avoidance by moderating susceptibility to AC parenting. [ABSTRACT FROM AUTHOR]

Abstract: Catechol-O-methyltransferase (COMT) is one of the major enzymes for the degradation of catecholamines. It has been suggested that catecholaminergic neurotransmission is involved in characterization of personality. Previous studies on the association between the COMT Val158Met polymorphism and personality traits in healthy subjects have produced inconsistent results. Therefore, the relationship between this polymorphism and personality was re-examined in 478 Japanese healthy volunteers. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the COMT genotypes were determined by a PCR-RFLP method. In total, there were no significant differences among the Val/Val, Val/Met, and Met/Met genotypes in seven TCI dimension scores. Similarly, no significant relationship was found between the COMT genotypes and the TCI dimensions when males and females were analyzed separately. The present study thus suggests that the COMT Val158Met polymorphism is not associated with personality traits in Japanese healthy subjects. [Copyright &y& Elsevier]