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Objective The Japanese Psycho-Oncology Society and the Japanese Association of Supportive Care in Cancer have recently revised the clinical practice guidelines for delirium in adult cancer patients. This article reports the process of developing the revised guidelines and summarizes the recommendations made. Methods The guidelines were developed in accordance with the Medical Information Network Distribution Service creation procedures. The guideline development group, consisting of multi-disciplinary members, created three new clinical questions: non-pharmacological intervention and antipsychotics for the prevention of delirium and trazodone for the management of delirium. In addition, systematic reviews of nine existing clinical questions have been updated. Two independent reviewers reviewed the proposed articles. The certainty of evidence and the strength of the recommendations were graded using the grading system developed by the Medical Information Network Distribution Service, following the concept of The Grading of Recommendations Assessment, Development, and Evaluation system. The modified Delphi method was used to validate the recommended statements. Results This article provides a compendium of the recommendations along with their rationales, as well as a short summary. Conclusions These revised guidelines will be useful for the prevention, assessment and management of delirium in adult cancer patients in Japan.

Delirium occurs very frequently in cancer patients. Insomnia is a symptom of delirium. Lemborexant is a drug that regulates sleep-wake rhythms without causing extrapyramidal symptoms. Based on its ability to improve sleep, lemborexant is expected to have efficacy for insomnia with delirium. The purpose of this study was to determine the efficacy of lemborexant for insomnia in cancer patients with delirium. A retrospective observational study was conducted between July 2020 and February 2021. Fourteen patients (six females; mean age,69 years) were included. Lemborexant was effective in 11 of 14 (78.6%) patients. Of 14 patients, 10 had hyperactive delirium. Lemborexant might have similar efficacy for insomnia with and without delirium when compared with previous studies. The efficacy rate of lemborexant was 70% for patients with insomnia and hyperactive delirium. This study might lead to dose reductions of antipsychotic medications and fewer extrapyramidal symptoms in cancer patients with delirium.

Inflammatory factors in the peripheral blood, such as the C-reactive protein level and neutrophil-to-lymphocyte ratio (NLR), are prognostic markers in multiple types of cancer, including non-small cell lung cancer (NSCLC). However, the association between inflammatory factors and prognosis based on histological types has not been adequately reported. In addition, the relationship between these factorsand the immune condition of the tumor microenvironment (TME) is unclear. In this study, we first investigated the relationship between preoperative inflammatory markers and clinical outcomes in 176 patients with NSCLC who underwent surgery. Lung adenocarcinoma (LUAD) showed no significant prognostic marker, whereas for lung squamous cell carcinoma (LUSC), a multivariate analysis showed that a high NLR was significantly associated with postoperative recurrence. In LUSC patients, the median time of postoperative recurrence-free survival in patients with a low NLR was longer than that in patients with a high NLR. We then compared the tumor-infiltrating lymphocyte (TIL) profile with inflammatory markers in peripheral blood and found that the NLR was negatively correlated with the frequencies of T cells and B cells in LUSC tissues. Thus, the NLR is a useful predictive biomarker for postoperative recurrence and may reflect the immune condition of the TME in LUSC.

Objective Preventing postoperative delirium with agitation is vital in the older population. We examined the preventive effect of yokukansan on postoperative delirium with agitation in older adult patients undergoing highly invasive cancer resection. Methods We performed a secondary per-protocol analysis of 149 patients’ data from a previous clinical trial. Patients underwent scheduled yokukansan or placebo intervention 4–8 days presurgery and delirium assessment postoperatively. Delirium with agitation in patients aged ≥75 years was assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the Japanese version of the Delirium Rating Scale-Revised-98. We assessed odds ratios for yokukansan (TJ-54) compared with placebo for the manifestation of postoperative delirium with agitation across patients of all ages (n = 149) and those aged ≥65 years (n = 82) and ≥ 75 years (n = 21) using logistic regression. Results Delirium with agitation manifested in 3/14 and 5/7 patients in the TJ-54 and placebo groups, respectively, among those aged ≥75 years. The odds ratio for yokukansan vs. placebo was 0.11 (95% confidence interval: 0.01–0.87). An age and TJ-54 interaction effect was detected in patients with delirium with agitation. No intergroup differences were observed in patients aged ≥65 years or across all ages for delirium with agitation. Conclusions This is the first study investigating the preventive effect of yokukansan on postoperative delirium with agitation in older adults. Yokukansan may alleviate workforce burdens in older adults caused by postoperative delirium with agitation following highly invasive cancer resection.

Surgery is an invasive procedure evoking acute inflammatory and immune responses that can influence risk for postoperative complications including cognitive dysfunction and delirium. Although the specific mechanisms driving these responses have not been well-characterized, they are hypothesized to involve the epigenetic regulation of gene expression. We quantified genome-wide levels of DNA methylation in peripheral blood mononuclear cells (PBMCs) longitudinally collected from a cohort of elderly patients undergoing major surgery, comparing samples collected at baseline to those collected immediately post-operatively and at discharge from hospital. We identified acute changes in measured DNA methylation at sites annotated to immune system genes, paralleling changes in serum-levels of markers including C-reactive protein (CRP) and Interleukin 6 (IL-6) measured in the same individuals. Many of the observed changes in measured DNA methylation were consistent across different types of major surgery, although there was notable heterogeneity between surgery types at certain loci. The acute changes in measured DNA methylation induced by surgery are relatively stable in the post-operative period, generally persisting until discharge from hospital. Our results highlight the dramatic alterations in gene regulation induced by invasive surgery, primarily reflecting upregulation of the immune system in response to trauma, wound healing and anaesthesia.

Postoperative delirium is a common and important complication in cancer patients. We need to identify patients at high risk of postoperative delirium such that it can be prevented preoperatively or in early postoperative phase. The aim of this study was to investigate whether preoperative anxiety predicted onset of postoperative delirium in cancer patients, not only in order to identify high-risk groups but also to help develop new preventive approaches. This was a prospective observational cohort study of cancer patients undergoing tumor resections. Postoperative delirium was assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Preoperative anxiety was evaluated with the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), and we defined HADS-A > 7 as clinical anxiety. We conducted multivariate logistic regression to determine which factors were predictors of delirium. The final analysis included 91 patients, 29 of whom met the criteria for postoperative delirium. In multivariable logistic regression, age (5-year increments; odds ratio (OR) = 1.565, 95% confidence interval (CI) = 1.057–2.317, p = 0.025) and HADS-A > 7 (OR = 4.370, 95% CI = 1.051–18.178, p = 0.043) predicted delirium onset. These variables explained 74.2% of the variance. Preoperative anxiety strongly predicted postoperative delirium in cancer patients. Our findings suggest that preoperative anxiety may be a new target for prevention of postoperative delirium. Trial registration number This study was registered at UMIN000018980

BackgroundSurgery is an invasive procedure evoking acute inflammatory and immune responses that are believed to mediate risk for postoperative complications including cognitive dysfunction and delirium. Although the specific mechanisms driving these responses have not been well-characterized, they are hypothesized to involve the epigenetic regulation of gene expression. We quantified genome-wide levels of DNA methylation in purified peripheral blood mononuclear cells (PBMCs) longitudinally collected from 55 elderly patients undergoing three types of major surgery (elective colorectal and hip replacement surgery, and emergency hip fracture surgery), comparing samples collected at baseline to those collected immediately post-operatively and at discharge from hospital.ResultsMajor surgery was associated with acute changes in DNA methylation at sites annotated to immune system genes, paralleling changes in serum-levels of markers including C-reactive protein (CRP) and Interleukin 6 (IL-6) measured in the same individuals. Although many of the observed changes in DNA methylation are consistent across the three types of surgery, there is notable heterogeneity between surgery types at certain loci. The acute changes in DNA methylation induced by surgery are relatively stable in the postoperative period, generally persisting until discharge from hospital.ConclusionsOur results highlight the dramatic alterations in gene regulation induced by invasive surgery, primarily reflecting upregulation of the immune system in response to trauma, wound healing and anaesthesia.

Surgery is one of the main treatments component against cancer. Although the basic principle of surgical treatment of cancer is curability, safety, and functionality, early recovery after surgery is also important. While some previous studies focus on physical recovery, there are few studies regarding the perioperative period of cancer patients and their impact on postoperative recovery. This study is aim to clarify psychosocial factors that affect postoperative recovery in cancer patients. The study design is a secondary data analysis of a prospective observational cohort study whose primary purpose was to investigate whether preoperative anxiety predicted onset of postoperative delirium in cancer patients at the National Cancer Center Hospital in Japan. The primary outcome of this study was the length of postoperative hospital stay, and the secondary outcome was postoperative complications. We conducted multivariable regression analysis to determine psychosocial predictors of primary and secondary outcomes. The final analysis included 109 patients. The mean length of postoperative hospital stay was 23.4 (SD = 12.4) days and the incidence rate of postoperative complications was 32.1%. In multivariable regression, preoperative anxiety was positively associated with the length of postoperative hospital stay, while sex (female) and alcohol dependence showed a negative association. Cognitive function was marginally associated with postoperative complications. In conclusion, Appropriate management of preoperative anxiety contributes to early discharge after surgery in cancer patients.

Background Preoperative anxiety and postoperative delirium affect both short- and long-term prognoses in patients with cancer; therefore, these conditions require early prevention and treatment. However, no standard preventive or therapeutic methods have been established for them. Yokukansan, a Japanese herbal medicine for the treatment of insomnia and anxiety, causes relatively few adverse drug reactions and effectively improves the behavioral and psychological symptoms of dementia. Thus, it is expected to be useful for treating and/or preventing perioperative psychiatric symptoms in patients with cancer. The objective of this study is to clarify the therapeutic effect of Yokukansan for preoperative anxiety and its preventive effect on postoperative delirium in cancer patients, as well as to confirm its safety profile. Methods This study is a randomized, double-blind, placebo-controlled study in cancer patients scheduled to undergo tumor resection. Patients who provide consent are randomly allocated to receive oral administration of Yokukansan or placebo, and study drug administration is continued for 4 days or longer prior to surgery. We defined two primary endpoints, change in preoperative anxiety and incidence of postoperative delirium. Secondary endpoints are severity score of postoperative delirium, duration of postoperative delirium, amount of benzodiazepines used prior to surgery, amount of antipsychotic agents used after surgery, and number of postoperative hospitalization days. We plan to complete the analysis on March 31, 2021. The target number of registered patients is 110 per group, or 220 in total. Discussion This study is the first randomized, double-blind, placebo-controlled study intended to clarify the effects of a Japanese herbal medicine, Yokukansan, in the prevention and treatment of perioperative psychiatric symptoms in patients with cancer. The trial was initiated on August 14, 2017, with 195 subjects randomized by October 5, 2018. Trial registration UMIN Clinical Trials Registry (UMIN-CTR), UMIN000027561. Registered on 31 May 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3202-1) contains supplementary material, which is available to authorized users.

Background:It has been shown that certain personality traits are related to mortality and disease morbidity, but the biological mechanism linking them remains unclear. Telomeres are tandem repeat DNA sequences located at the ends of chromosomes, and shorter telomere length is a predictor of mortality and late-life disease morbidity. Thus, it is possible that personality traits influence telomere length. In the present study, we examined the relationship of leukocyte telomere length with personality traits in healthy subjects.Subjects and methods:The subjects were 209 unrelated healthy Japanese who were recruited from medical students at 4th–5th grade. Assessment of personality traits was performed by the Revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI). Leukocyte relative telomere length was determined by a quantitative real-time PCR method for a ratio of telomere/single copy gene.Results:In the stepwise multiple regression analysis, shorter telomere length was related to lower scores of neuroticism (P < 0.01) and conscientiousness (P < 0.05) of the NEO-PI-R, and lower scores of harm avoidance (P < 0.05) and reward dependence (P < 0.05) of the TCI.Conclusions:The present study suggests that leukocyte telomere length is associated with some personality traits, and this association may be implicated in the relationship between personality traits and mortality.

Background: Beck's cognitive theory of depression postulates personality vulnerability factors termed sociotropy and autonomy, which are accompanied by characteristic interpersonal styles. Meanwhile, Bartholomew contends that negative working models of the self and other built through insecure attachment relationships are externalized as distinctive interpersonal styles. The present study examined the relationships of sociotropy and autonomy with the self- and other-models, and attempted to promote understanding of the two personality traits from an attachment perspective. Methods: The subjects were 510 healthy Japanese medical students or hospital staffs. Sociotropy and autonomy were assessed by the Sociotropy–Autonomy Scale, and working models of the self and other were evaluated by the Relationship Scales Questionnaire. Results: The sociotropy score was correlated negatively with the self-model score (β = −0.52, p

FK506-binding protein 51 (FKBP5) is a co-chaperone of the glucocorticoid receptor, and plays an important role in the negative feedback regulation of the hypothalamic-pituitary-adrenal axis. The C/T single nucleotide polymorphism in the intron 2 of the FKBP5 gene affects cortisol secretion, and has been implicated in the pathophysiology of depression. In this study, the relationship of the FKBP5 C/T polymorphism with dysfunctional attitudes predisposing to depression was examined. The subjects were 300 healthy Japanese. The FKBP5 genotypes were determined by a real-time PCR and cycling probe technology for SNP typing. Dysfunctional attitudes were assessed by the 24-item version of the Dysfunctional Attitude Scale (DAS-24), which has the Achievement, Self-control, and Dependency subscales. DAS-24 total scores were significantly higher in the group with the T allele than in that without this allele (p = 0.001). Regarding the subscales, scores of the Achievement (p = 0.003) and Self-control (p = 0.009) subscales, but not those of the Dependency subscale, were significantly higher in the former group than in the latter group. The present study suggests that the FKBP5 C/T polymorphism is implicated in formation of dysfunctional attitudes, especially those about achievement and self-control.

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 χ2 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.

There have been few studies which examined the developmental origins of cognitive vulnerability of depression. The purpose of the present study was to examine the effects of parental rearing on sociotropy and autonomy, the personality vulnerability factors in the cognitive theory of depression.The subjects were 416 healthy subjects. Perceived parental rearing was assessed by the Parental Bonding Instrument (PBI), which has care and protection factors, and sociotropy and autonomy were assessed by the Sociotropy-Autonomy Scale.In males, neither sociotropy nor autonomy was affected by paternal rearing or maternal rearing. In females, higher levels of sociotropy were related to higher maternal protection (β=0.308, p0.01), while autonomy was affected neither by paternal rearing nor by maternal rearing.Parental behaviors not covered by the PBI may affect formation of autonomy.The present study suggests that parental overprotection increases sociotropy with gender specificity in parents and recipients.

The relationships of sociotropy and autonomy, the 2 personality traits postulated as vulnerability factors for depression, with 7 dimensions of the Temperament and Character Inventory, a comprehensive measure of personality, were studied in 305 healthy subjects. Sociotropy and autonomy were assessed by the sociotropy and autonomy subscales, respectively, of the original 60-item Sociotropy-Autonomy Scale. In multiple regression analysis, sociotropy was significantly correlated with higher harm avoidance, reward dependence (RD), and self-transcendence (ST), and lower self-directedness; and the correlation was strongest with higher RD ( β = 0.27) and second strongest with lower self-directedness ( β = −0.25). Meanwhile, autonomy was significantly correlated with higher persistence and ST, and lower RD; and the correlations were especially strong with higher ST ( β = 0.37) and lower RD ( β = −0.28). These results support Beck's concepts of these personality traits, that is, the orientation toward interpersonal relationships of sociotropy, and that toward mastery and independence of autonomy.

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.

Background There have been several reports suggesting that adverse childhood experiences such as physical maltreatment and long institutionalization influence telomere length. However, there has been no study examining the relationship of telomere length with variations in parental rearing. In the present study, we examined the relationship of leukocyte telomere length with parental rearing in healthy subjects. Methods The subjects were 581 unrelated healthy Japanese subjects. Perceived parental rearing was assessed by the Parental Bonding Instrument consisting of the care and protection factors. Leukocyte relative telomere length was determined by a quantitative real-time PCR method for a ratio of telomere/single copy gene. Results In the multiple regression analyses, shorter telomere length in males was related to lower scores of paternal care (β = 0.139, p

A 69-year-old man was admitted to the emergency department 3 hours after ingestion of a bleaching agent containing hypochlorous acid and sodium hydroxide in a suicide attempt. Enhanced chest computed tomography scans taken on admission indicated an edematous esophagus and air bubbles in the mediastinum. He underwent endotracheal intubation and mechanical ventilation until day 9 because of laryngeal edema. On day 10, his endoscopy indicated diffuse reddish mucosal hyperemia, erosions, and lacerated mucosal lesions in the esophagus that were indicative of grade 2b corrosive esophagitis. Treatment with a proton pump inhibitor was initiated, with which the condition of the esophagus improved, and on day 44, a slight stricture of the upper part of the esophagus was observed. He was discharged on day 64 without any complaints. The ingestion of sodium hypochlorite induces corrosive esophagitis and acute phase of gastritis. Ingestion of any corrosive agent is known as a risk factor for esophagus cancer in the long-term. In such cases with esophageal stricture, esophagectomy is recommended for preventing esophagus cancer. Considering the age of the patient, however, he did not undergo esophagectomy.

Background It has been suggested that dysfunctional attitudes, cognitive vulnerability to depression, have developmental origins. The present study examined the effects of parental rearing on dysfunctional attitudes in three areas of life with special attention to gender specificity. Methods The subjects were 665 Japanese healthy volunteers. Dysfunctional attitudes were assessed by the 24-item Dysfunctional Attitude Scale, which has the Achievement, Dependency and Self-control subscales. Perceived parental rearing was assessed by the Parental Bonding Instrument, which has the Care and Protection subscales. Results Higher scores of the Achievement (β = 0.293, p

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.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).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 (p0.001) and the T/T genotype group (p0.001), 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 (p0.001) 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.The present study suggests that the C3435T polymorphism of the MDR1 gene affects the formation of a depression-prone personality trait in Japanese females.

The 24-item Dysfunctional Attitude Scale (DAS-24) has three subscales to evaluate dysfunctional attitudes predisposing to depression in the areas of achievement, dependency and self-control.The purpose of the present investigation was to characterize the three subscales in relation to broad dimensions of personality.The subjects were 528 healthy Japanese volunteers. Personality assessment was conducted by the Temperament and Character Inventory (TCI), which has seven dimensions. The correlations of the DAS-24 subscales with the TCI dimensions were examined by the multiple regression analysis.All DAS-24 subscales had negative correlations with the self-directedness dimension. However, the three subscales had differential patterns of correlations with the reward dependence, persistence, cooperativeness and harm avoidance dimensions.The present study suggests that dysfunctional attitudes measured by the DAS-24 are closely related to low self-directedness of the TCI. Also, the differential patterns of correlations with some TCI dimensions support the content-specificity of the three subscales.

Interpersonal sensitivity is a depression-prone personality trait closely related to anxious attachment, whereas sociotropy and autonomy are personality vulnerability factors in the cognitive theory of depression. In the present study, the relationships of interpersonal sensitivity with sociotropy and autonomy were studied in 362 healthy subjects. Interpersonal sensitivity was assessed using the Interpersonal Sensitivity Measure (IPSM), whereas sociotropy and autonomy were evaluated using the Sociotropy and Autonomy subscales, respectively, of the Sociotropy-Autonomy Scale. The IPSM was significantly correlated with the Sociotropy subscale (β = 0.61, p < 0.001) but not with the Autonomy subscale. All subscales of the IPSM correlated significantly with the Sociotropy subscale, and the correlation for the Separation Anxiety subscale (β = 0.56, p < 0.001) was strongest. The present study suggests that interpersonal sensitivity is correlated with sociotropy but not with autonomy in healthy subjects.

There is a growing body of data suggesting that gene-environment interaction is critical in the characterization of personality traits; however, previous studies have not taken into consideration variability in parental rearing as an environmental factor. In this study, we examined the effects of the interaction between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and parental rearing on personality traits in 710 healthy Japanese subjects. Perceived parental rearing was assessed by the Parental Bonding Instrument (PBI), which consists of the care and protection factors. Assessment of personality traits was performed by the temperament and character inventory (TCI), which has seven dimensions, i.e. novelty seeking, harm avoidance, reward dependence, persistence, self-directedness, cooperativeness and self-transcendence. Parental rearing has significant main effects on some TCI dimensions, but no significant main effects of the BDNF genotype on the TCI scores were found. The interaction between the BDNF genotype and maternal care of the PBI had significant effects on harm avoidance and self-directedness of the TCI. Post hoc analyses showed that decreased maternal care was correlated with increased harm avoidance and decreased self-directedness, and for both personality traits the partial correlation coefficient was highest in the Met/Met genotype group and lowest in the Val/Val genotype group and the value of the Val/Met genotype group was in the middle. Data from this study suggest that the BDNF Val66Met polymorphism modulates the effects of parental rearing, especially maternal care, on harm avoidance and self-directedness in healthy subjects.

P-glycoprotein, which is encoded by the multidrug resistance 1 (MDR1) gene, serves as a barrier to entry and as an active elimination for xenobiotics and cellular metabolites including cortisol, which is implicated in multiple brain functions. Meanwhile, previous studies suggested that genetic factors and cortisol are involved in formation of interpersonal sensitivity, a personality trait predisposing to depression. In the present study, we examined the effects of the C3435T MDR1 polymorphism on interpersonal sensitivity. The subjects were 842 healthy Japanese volunteers. The mean age ±SD of the subjects was 26.7±8.1 (490 males and 352 females). The C3435T polymorphism of MDR1 gene was detected by a PCR method, and interpersonal sensitivity was assessed by the Interpersonal Sensitivity Measure (IPSM). In total subjects, the C allele of the C3435T MDR1 polymorphism was associated with higher scores of the IPSM. In females the C/C genotype group had higher IPSM scores than the C/T genotype group and the T/T genotype group, and the C/T genotype group had higher IPSM scores than the T/T genotype group. In males no significant association was found between the MDR1 genotype and the IPSM scores. The present study suggests that the C3435T polymorphism of the MDR1 gene affects formation of a depression-prone personality trait in Japanese females.

Interpersonal sensitivity is defined as undue and excessive awareness of, and sensitivity to, the behavior and feelings of others and is one of the vulnerable factors to depression. In a twin study, it was suggested that this personality trait was characterized by both genetic and environmental factors. In the present study, we examined the effects of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and parental rearing on interpersonal sensitivity. The subjects were 725 unrelated healthy Japanese volunteers (mean age±SD=27.1±8.5, 405 males and 320 females). Assessment of interpersonal sensitivity was performed by the Japanese version of the Interpersonal Sensitivity Measure (IPSM). Perceived parental rearing was assessed by the Parental Bonding Instrument (PBI), which consists of the care and protection factors. The BDNF polymorphism was detected by the PCR-RFLP method. There was no main effect of the BDNF genotype on the IPSM score, while the PBI factors except maternal care had significant main effect on the IPSM score. There was significant interaction effect between the BDNF genotype and maternal care of the PBI on the IPSM score. Post-hoc analysis of simple slopes showed that the negative relationship between the IPSM score and maternal care was strongest and significant in the Met/Met genotype group, intermediate in the Val/Met genotype group, and weakest in the Val/Val genotype group. The present study suggests that the interaction between the BDNF Val66Met polymorphism and parental rearing, especially maternal care, influences interpersonal sensitivity in healthy subjects.

It has been reported that certain personality traits are related to mortality and disease morbidity, but the biological mechanism linking them remains unclear. Telomeres are tandem repeat DNA sequences located at the ends of chromosomes, and shorter telomere length is a predictor of mortality and late-life disease morbidity. Thus, it is possible that personality traits influence telomere length. In the present study, we examined the relationship of leukocyte telomere length with personality traits in healthy subjects. The subjects were 209 unrelated physically healthy Japanese who were recruited from medical students at 4th-5th grade. None had psychiatric disorders. 128 subjects were males, and 81 were females. The mean±SD (range) of age was 23.3±1.7 (20-30) years. Personality traits were assessed by the revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI). Leukocyte relative telomere length was determined by a quantitative real-time PCR method for a ratio of telomere/single copy gene. In the stepwise multiple regression analysis, shorter telomere length was related to lower scores of Neuroticism (β=0.208, p

AimsPrevious 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 healthy subjects.MethodsSubjects were 826 Japanese healthy volunteers. 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.ResultsIn total subjects, the group with the T allele predictive of impaired negative feedback regulation of the HPA axis had higher scores of harm avoidance (p = 0.043) and lower scores of cooperativeness (p = 0.019) compared to that without the T allele. The T allele was associated with higher scores of harm avoidance in females (p = 0.020) and lower scores of cooperativeness in males (p = 0.015).ConclusionThe present study thus suggests that the FKBP5 polymorphism affects harm avoidance and cooperativeness in healthy subjects, with gender specificity.

AimsPrevious studies have shown that the function of hypothalamic-pituitary-adrenal (HPA) axis is involved in the characterization of personality traits. Glucocorticoid receptor (GR) is the most important regulator of the HPA axis negative feedback system, and several polymorphisms of the GR gene are associated with altered glucocorticoid sensitivity. In the present study, we examined the associations between the GR polymorphisms and personality traits in healthy subjects.MethodsSubjects were 880 Japanese healthy volunteers. Personality traits were assessed by the Temperament and Character Inventory (TCI). Two polymorphisms of the GR gene, i.e., G/C SNP in the intron 2 (BcII polymorphism, rs41423247) and A/G SNP in the exon 9β (9β polymorphism, rs6198), were detected by a real-time PCR and cycling probe technology for SNP typing.ResultsThe genotype distributions were G/G = 614, G/C = 240, and C/C = 26 for the BcII polymorphism, and A/A = 879 and A/G = 1 for the 9β polymorphism, respectively. There were no significant associations between the BcII genotype groups in any TCI dimension score.ConclusionThe present study suggests that these two GR polymorphisms (BcII and 9β polymorphism) are not involved in the characterization of personality traits in healthy subjects.

AimsThere is a growing body of data suggesting the gene-environment interaction in the characterization of personality traits, but variation in ordinary parental rearing among environmental factors has not been focused yet. We examined the effects of the interaction between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and parental rearing on personality traits.MethodsSubjects were 710 Japanese healthy volunteers. Perceived parental rearing was assessed by the Parental Bonding Instrument (PBI), which consists of the care and protection factors. Personality assessment was performed by the Temperament and Character Inventory (TCI), which has 7 dimensions, i.e., novelty seeking, harm avoidance, reward dependence, persistence, self-directedness, cooperativeness, and self-transcendence. The BDNF Val66Met polymorphism was detected by the PCR-RFLP method.ResultsParental rearing has significant main effects on all TCI dimensions except novelty seeking, while no significant main effects of the BDNF genotype on the TCI scores were found. The interaction between the BDNF genotype and maternal care of the PBI had significant effects on harm avoidance and self-directedness of the TCI. Post-hoc analyses showed that decreased maternal care was correlated with increased harm avoidance and decreased self-directedness in most of the genotype groups, and for both personality traits the correlation was highest in the Met/Met genotype and lowest in the Val/Val genotype and that for the Val/Met genotype was in between the two values.ConclusionThe present study suggests that the BDNF Val66Met polymorphism moderates the effects of parenting rearing, especially maternal care, on harm avoidance and self-directedness in healthy subjects.

Background It has been suggested that interpersonal sensitivity, a personality trait associated with depression and anxiety disorders, is linked with attachment insecurity. To confirm this link, we studied the correlations of interpersonal sensitivity with working models of the self and other. Methods The subjects were 301 healthy Japanese. Interpersonal sensitivity and working models of the self and other were assessed by the Interpersonal Sensitivity Measure (IPSM) and the Relationship Scales Questionnaire, respectively. The correlations of the IPSM total scores with the self-model or other-model scores were analyzed by the multiple regression analysis. Results The IPSM total scores were correlated negatively with the self-model scores (β = −0.48, p