Cluster analysis of patients with alcohol use disorder featuring alexithymia, depression, and diverse drinking behavior.

AIM: This study aimed to identify subgroups of alcohol use disorder (AUD) based on a multidimensional combination of alexithymia, depression, and diverse drinking behavior. METHOD: We recruited 176 patients with AUD, which were initially divided into non-alexithymic (n = 130) and alexithymic (n = 46) groups using a cutoff score of 61 on the Toronto Alexithymia Scale (TAS-20). Subsequently, the profiles of the two groups were compared. Thereafter, a two-stage cluster analysis using hierarchical and K-means methods was performed with the Z-scores from the TAS-20, the Quick Inventory of Depressive Symptomatology Self-Report Japanese Version, the 12-item questionnaire for quantitative assessment of depressive mixed state, and the 20-item questionnaire for drinking behavior pattern. RESULTS: In the first analysis, Alexithymic patients with AUD showed greater depressive symptoms and more pathological drinking behavior patterns than those without alexithymia. Cluster analysis featuring alexithymia, depression, and drinking behavior identified three subtypes: Cluster 1 (core AUD type) manifesting pathological drinking behavior highlighting automaticity; Cluster 2 (late-onset type) showing relatively late-onset alcohol use and fewer depressive symptoms or pathological drinking behavior; and Cluster 3 (alexithymic type) characterized by alexithymia, depression, and pathological drinking behavior featuring greater coping with negative affect. CONCLUSION: The multidimensional model with alexithymia, depression, and diverse drinking behavior provided possible practical classification of AUD. The alexithymic subtype may require more caution, and additional support for negative affect may be necessary due to accompanying mood problems and various maladaptive drinking behaviors.

Drinking behavior patterns may be associated with persistent depressive symptoms after alcohol abstinence in alcohol use disorder.

AIM: This study examined the association between drinking behavior patterns and depressive symptoms after alcohol abstinence in patients with alcohol use disorder (AUD). METHOD: We recruited 102 AUD inpatients with baseline depressive symptoms, indicated by scores ≥6 on the Quick Inventory of Depressive Symptomatology Self-Report Japanese Version (QIDS-SR-J) pre-detoxification. Post-4-week abstinence, remission was defined as QIDS-SR-J scores <6. Patients were classified into remitted (n = 51) and persistent (n = 51) groups. Comparative analyses were conducted using patient profiles and the Drinking Behavior Pattern 20-item Questionnaire (DBP-20). Logistic regression identified factors related to post-abstinence persistent depression. Receiver operating characteristic curve analysis determined DBP-20 cutoff scores differentiating between persistent and remitted depression. RESULTS: The persistent group exhibited higher scores in the DBP-20 "coping with negative affect" subscale. Logistic regression showed low education, unemployment, and using alcohol for coping as significant factors for persistent depression. Conversely, an automatic drinking pattern indicated natural remission post-abstinence. A subscale score of ≥8 in alcohol use for coping, especially among unemployed patients, predicted persistent depression (sensitivity 86.8%, positive predictive value 73.3%). CONCLUSION: Unemployed patients with AUD using alcohol to cope with negative affect may experience residual depression even after detoxification. In contrast, patients with AUD with predominantly automatic drinking behavior may exhibit natural remission post-abstinence.

Prevalence of somatic diseases in adults with attention deficit hyperactivity disorder in Japan is highest in people aged ≥40 years with mental disorders: a cross-sectional study of a Japanese health insurance claims database.

Introduction: Studies have reported an association between attention deficit hyperactivity disorder (ADHD) and somatic diseases; however, the correlation of mental disorders with the association between ADHD and somatic diseases remains uninvestigated. This study investigated and compared the prevalence of somatic diseases among adults with/without ADHD, stratified by the presence or absence of mental disorders. Methods: This cross-sectional study (October 2020-September 2021), using data (June 2013-September 2021) from a Japanese health insurance claims database, included adult participants with a medical record of and receiving medication for ADHD (ADHD group); the control group (matched 1:5 by age/sex) comprised participants without ADHD. The prevalence and odds ratio (OR; ADHD versus control) of type 2 diabetes mellitus (T2DM), diabetes complications, hypertension, cardiovascular disease (CVD), dyslipidemia, gout and hyperuricemia, chronic obstructive pulmonary disease (COPD), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH), and atopic dermatitis were investigated. Pooled ORs for stratified analysis were calculated using the Mantel-Haenszel method. Results: In the matched analysis sets, the ORs for all somatic diseases were significantly higher for the ADHD group (n=15,028) versus the control group (n=74,796). On stratified analysis, the Mantel-Haenszel ORs were significant for NAFLD/NASH (1.53; 95% confidence interval [CI]: 1.34, 1.73), diabetes complications (1.39; 95% CI: 1.09, 1.77), and gout and hyperuricemia (1.34; 95% CI: 1.19, 1.51). Furthermore, the stratum-specific ORs for T2DM, hypertension, and dyslipidemia were >1 and <1 in the presence and absence of mental disorders, respectively. The prevalence of all somatic diseases except atopic dermatitis increased with age. For participants aged ≥40 years, the Mantel-Haenszel ORs were significant for all somatic diseases except CVD, COPD, and atopic dermatitis. Conclusions: The prevalence of several somatic diseases, including chronic disorders, was high among adults with ADHD, particularly in those aged ≥40 years and those with mental disorders.

Associations between relapse and drinking behaviors in patients with alcohol use disorders: A 6-month prospective study.

BACKGROUND: Habitual behaviors, rather than goal-oriented behaviors, mainly characterize drinking patterns in patients with alcohol use disorder (AUD). However, few studies have focused on the influence of drinking behavior on AUD relapse. This prospective study examined associations between drinking behavior patterns and alcohol-use relapse using the 20-item questionnaire for drinking behavior patterns (DBP-20). METHODS: We enrolled patients with AUD and compared the cohort's demographic data and 6-month outcomes based on the DBP-20 and the Alcohol Use Disorders Identification Test between two groups (alcohol use relapse vs. abstinence). We also assessed the results for significant factors related to relapse. RESULTS: We included 105 patients with AUD. More patients in the relapse group (n = 63) were active smokers and lived alone, while fewer took medication with cyanamide or disulfiram than those in the abstinence group (n = 42). The DBP-20 automaticity subscale score was higher in the relapse group than that in the abstinence group. Current smoker, living alone, and automatic drinking habits were significantly associated with AUD relapse. CONCLUSIONS: Automaticity may be a risky drinking behavior that leads to future relapse in patients with AUD, justifying behavioral strategies to combat automatic drinking for relapse prevention.

Elevated Brain-Derived Neurotrophic Factor Levels During Depressive Mixed States.

OBJECTIVE: Neurotrophin-like brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines may modulate the pathophysiology of mood disorders. Although several studies show alterations in these biomarkers during the depressive, manic, and euthymic states of mood disorders, evidence is lacking for those in a mixed state. Therefore, this study aimed to investigate the relationship between the depressive mixed state (DMX) and peripheral neurobiological factors. METHODS: We enrolled 136 patients with major depressive episodes. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J). The severity of DMX was assessed using the self-administered 12-item questionnaire (DMX-12). Categorical screening as DMX-positive (n=54) was determined by a cutoff score of 13 or more in the specific eight symptoms from the DMX-12; the remaining were DMX-negative (n=82). Serum BDNF, tumor necrosis factor-α, highsensitivity C-reactive protein, and interleukin-6 levels were measured. RESULTS: When comparing biomarkers between the DMX-positive and DMX-negative groups, higher serum BDNF concentration in the DMX-positive group than in the DMX-negative group was the only significant finding (p=0.009). A positive correlation existed between the total score of the eight specific symptoms of DMX-12 and the BDNF concentration (r=0.190, p=0.027). After adjustment for confounders, logistic regression analysis revealed that BDNF (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.00-1.14, p=0.045), bipolar diagnosis (OR=3.43, 95% CI=1.36-8.66, p=0.009), and total QIDS-SR-J score (OR=1.29, 95% CI=1.15-1.43, p<0.001) were significantly associated with DMX positivity. CONCLUSION: BDNF was positively associated with DMX severity, suggesting that higher BDNF concentrations may be involved in the pathophysiology of DMX.

Age-related cognitive decline is accelerated in alcohol use disorder.

This study aimed to examine potential cognitive impairments in patients with alcohol use disorder (AUD), and explore the factors affecting them. We recruited 97 inpatients with AUD, showing superficially normal cognitive function (mini-mental state examination score ≥24) for this study. We assessed cognitive function after a 4-week post-abstinence period using the Brief Assessment of Cognition in Schizophrenia-Japanese version (BACS-J). Relationships between BACS-J subcategory/composite raw scores and Z-scores (deviation from standard data in healthy Japanese) and background factors such as age, sex, education, smoking status, mini-mental state examination score, body mass index, systolic blood pressure, severity of depression, alcohol consumption, and laboratory findings were analyzed. Multiple regression analysis showed that the age (p < 0.001) and total bilirubin level (p = 0.014) were worsening factors for the BACS-J composite raw score, whereas education (p < 0.001) was a protective factor. An inverse correlation was apparent between the age and the composite Z-score of the BACS-J (r = -0.431, p < 0.001). Receiver operating characteristic (ROC) analysis identified 53 years as the cutoff age for predicting more than -2SD cognitive decline from the normal standard, with a high negative predictive value (95%). Patients with AUD aged ≥53 years showed more pronounced impairments in verbal memory, working memory, verbal fluency, and attention than those younger than 53 years (p < 0.05). These findings clearly demonstrate accelerated age-related cognitive decline in patients with AUD, especially those aged ≥53 years, suggesting the necessity of early intervention in patients with AUD to prevent progressive cognitive impairment and preserve their quality of life.

CYP1A2*F Polymorphism contributes at least partially to the Variability of Plasma Levels of Dehydroaripiprazole, an active Metabolite of Aripiprazole, in Schizophrenic Patients.

AIM: The relationship between CYP1A2 polymorphisms and the steady-state plasma levels of aripiprazole and its active metabolite, dehydroaripiprazole, were investigated in Japanese schizophrenic patients. BACKGROUND: It has been implied that cytochrome P450 (CYP) 1A2 may play a role in the metabolism of aripiprazole. Genetic variations in the CYP1A2 gene have been reported. OBJECTIVE: The authors investigated the relationship between 2 CYP1A2 polymorphisms, CYP1A2*C (-3860G>A) and CYP1A2*F (-163C>A), and the steady-state plasma levels/dose (C/D) ratios of aripiprazole and dehydroaripiprazole in Japanese schizophrenic patients. METHODS: All 89 subjects (46 males and 43 females) had been receiving 2 fixed daily doses of aripiprazole (24 mg; n=56 and 12 mg: n=33) for more than 2 weeks. No other drugs were used except flunitrazepam and biperiden. The plasma drug levels were determined by LC/MS/MS. These CYP1A2 polymorphisms were detected using polymerase chain reaction analysis. RESULTS: The mean C/D ratios of dehydroaripiprazole were significantly (P < 0.05) lower in patients with the A/A allele of CYP1A2*F than in those without the allele. No differences were found in the values of aripiprazole and the combination of aripiprazole and dehydroaripiprazole among the CYP1A2*F genotype. There were no differences in the values of aripiprazole, dehydroaripiprazole, or the combination of the 2 compounds among the CYP1A2*C genotype. The absence of the A allele of CYP1A2*F was correlated with the mean C/D ratios of dehydroaripiprazole (standardized partial correlation coefficient = 0.276, P < 0.01) by multiple regression analysis. CONCLUSION: The findings of this study suggest that the CYP1A2*F polymorphism contributes at least partially to the variability in the steady-state plasma levels of dehydroaripiprazole.

Generation of four iPSC lines from a family harboring a 1p36-35 haplotype linked with bipolar disorder and recurrent depressive disorder: Three-generation patients and a healthy sibling.

Induced pluripotent stem cells (iPSCs) obtained from genetically characterized patients benefit the biological study of bipolar disorder (BD). Here, we present iPSC lines from three-generation patients with BD and recurrent depressive disorder (RDD) and a healthy control sibling in a family. All patients shared the specified haplotype in the 1p36-35, previously reported as the susceptibility locus of mood disorders. iPSCs were generated with the reprogramming factors OTC3/4, l-MYC, LIN28, SOX2, KLF4, and p53 shRNA through non-integrated episomal vectors. All iPSC lines strongly expressed pluripotency markers and proved the ability to differentiate into three germ lineages in vitro.

Haplotype phasing of a bipolar disorder pedigree revealed rare multiple mutations of SPOCD1 gene in the 1p36-35 susceptibility locus.

BACKGROUND: The etiology of bipolar disorder (BD) is poorly understood. Considering the complexity of BD, pedigree-based sequencing studies focusing on haplotypes at specific loci may be practical to discover high-impact risk variants. This study comprehensively examined the haplotype sequence at 1p36-35 BD and recurrent depressive disorder (RDD) susceptibility loci. METHODS: We surveyed BD families in Okinawa, Japan. We performed linkage analysis and determined the phased sequence of the affected haplotype using whole genome sequencing. We filtered rare missense variants on the haplotype. For validation, we conducted a case-control genetic association study on approximately 3000 Japanese subjects. RESULTS: We identified a three-generation multiplex pedigree with BD and RDD. Strikingly, we identified a significant linkage with mood disorders (logarithm of odds [LOD] = 3.61) at 1p36-35, supported in other ancestry studies. Finally, we determined the entire sequence of the 6.4-Mb haplotype shared by all affected subjects. Moreover, we found a rare triplet of missense variants in the SPOCD1 gene on the haplotype. Notably, despite the rare frequency, one heterozygote with multiple SPOCD1 variants was identified in an independent set of 88 BD type I genotyping samples. LIMITATIONS: The 1p36-35 sequence was obtained from only a single pedigree. The replicate sample was small. Short-read sequencing might miss structural variants. A polygenic risk score was not analyzed. CONCLUSION: The 1p36-35 haplotype sequence may be valuable for future BD variant studies. In particular, SPOCD1 is a promising candidate gene and should be validated.

Development of a 20-item questionnaire for drinking behavior pattern (DBP-20) toward personalized behavioral approaches for alcohol use disorder.

Although screening tools are available for alcohol use disorders (AUD), such as the Alcohol Use Disorders Identification Test (AUDIT), these tools do not directly characterize individual drinking behavior for patients with AUD. Therefore, the aim of this study was to develop a new self-report questionnaire to identify the characteristics of drinking behavior patterns in patients with AUD.The study team developed a self-administered 20-item questionnaire for drinking behavior pattern (DBP-20) based on semi-structured interviews of patients with AUD. The DBP-20 and AUDIT were administered to 232 patients with AUD and 222 normal drinkers (1 ≤ AUDIT <20) as controls. Exploratory factor analysis of the DBP-20 was conducted for patients with AUD, followed by comparisons of its item and subscale scores between patients with AUD and controls. Correlations of AUDIT with total and subscale scores of the DBP-20 were also analyzed. Receiver operating characteristic (ROC) analyses for the DBP-20 and its subscales were performed to distinguish patients with AUD from controls.Exploratory factor analysis revealed a multidimensional 4-factor model of the DBP-20: coping with negative affect, automaticity, enhancement, and social use. Significant differences in DBP-20 total and subscale scores were observed for patients with AUD versus controls for all factors, except the social use subscale. Both the coping with negative affect and automaticity subscale scores as well as total DBP-20 scores were highly correlated with AUDIT scores. Total DBP-20 scores showed the greatest sensitivity, negative predictive value, and area under the ROC curve to distinguish patients with AUD from normal drinkers.Drinking as a means of coping with negative affect and automaticity may be specific for patients with AUD. DBP-20 may help patients with AUD to be aware of their own targeted problematic drinking behaviors and to seek their personalized behavioral approaches in a collaborative relationship with therapists.

Efficient spin current source using a half-Heusler alloy topological semimetal with back end of line compatibility.

Topological materials, such as topological insulators (TIs), have great potential for ultralow power spintronic devices, thanks to their giant spin Hall effect. However, the giant spin Hall angle (θSH > 1) is limited to a few chalcogenide TIs with toxic elements and low melting points, making them challenging for device integration during the silicon Back-End-of-Line (BEOL) process. Here, we show that by using a half-Heusler alloy topological semi-metal (HHA-TSM), YPtBi, it is possible to achieve both a giant θSH up to 4.1 and a high thermal budget up to 600 °C. We demonstrate magnetization switching of a CoPt thin film using the giant spin Hall effect of YPtBi by current densities lower than those of heavy metals by one order of magnitude. Since HHA-TSM includes a group of three-element topological materials with great flexibility, our work opens the door to the third-generation spin Hall materials with both high θSH and high compatibility with the BEOL process that would be easily adopted by the industry.

Prevalence and profile of depressive mixed state in patients with autism spectrum disorder.

PURPOSE: The present study aimed to clarify prevalence and profile of depressive mixed state (DMX) in depressed individuals with autism spectrum disorder (ASD). PATIENTS AND METHODS: The Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J) and global assessment of functioning (GAF) were administered to 182 consecutive patients (36 ASD and 146 non-ASD subjects) with a major depressive episode (MDE). DMX was categorically diagnosed according to the criteria for mixed depression (MD) by Benazzi and mixed features (MF) specifier by DSM-5. Severity of DMX was assessed by the self-administered 12-item questionnaire for DMX (DMX-12). Clinical backgrounds and incidence/severity of DMX were compared between the ASD and non-ASD groups. RESULTS: ASD patients showed higher prevalence of MD than non-ASD patients (36.1% versus 18.5%). Mood lability, distractibility, impulsivity, aggression, irritability, dysphoria and risk-taking behavior as mixed symptoms were more prevalent in ASD patients than those in non-ASD patients, together with higher scores of total DMX-12 and its disruptive emotion/behavior cluster. Multiple regression analysis revealed significant contribution of ASD to the disruptive emotion/behavior symptoms. CONCLUSION: Careful monitoring and management of potential DMX are warranted in depressed ASD individuals.

The 12-Item Self-Rating Questionnaire for Depressive Mixed State (DMX-12) for Screening of Mixed Depression and Mixed Features.

For simultaneous screening of mixed features (MF) by DSM-5 and mixed depression (MD) by Benazzi, useful symptoms were extracted from our 12-item dimensional scale for depressive mixed state (DMX-12). Subjects were 190 consecutive cases with major depressive episode (MDE) who visited our clinic. Associations between symptomatological combinations of the DMX-12 and MF or MD were analyzed using receiver operating characteristic (ROC). The rate of MF was 4.2% while that of MD was 22.6%. Eight symptoms (overreactivity, inner tension, racing/crowded thought, impulsivity, irritability, aggression, risk-taking behavior, and dysphoria) with their AUC > 0.6 for ROC curves were specially focused on distinguishing patients with MF or MD from non-mixed patients. By using these 8 symptoms, 40.5% of the overall patients were screened as positive at the same cut-off value (≥13) for both MD and MF. The AUC of ROC curve and sensitivity/specificity were well balanced together with sufficient negative predictive values. The abovementioned 8 symptoms seem to be helpful for primary screening and negative check of DMX with considerable severity during MDE.

A High Plasma Lamotrigine Concentration at Week 2 as a Risk Factor for Lamotrigine-Related Rash.

BACKGROUND: Reportedly, a high plasma concentration of lamotrigine plays a role in the development of lamotrigine-related rash. The relationship between plasma concentrations of lamotrigine at week 2 and the lamotrigine-related rash was prospectively studied in 84 patients (22 males and 62 females) with treatment-resistant depressive disorder during an 8-week treatment of lamotrigine augmentation. METHODS: Eighty-four depressed patients with an insufficient response to at least 3 psychotropics, including antidepressants, mood stabilizers, and atypical antipsychotics, were included. The diagnoses were major depressive disorder (n = 39), bipolar I disorder (n = 10), and bipolar II disorder (n = 35). The final doses of lamotrigine were 100 mg/d for 57 subjects who were not taking valproate and 75 mg/d for 27 subjects taking valproate. Blood sampling was performed at week 2. Lamotrigine plasma concentrations were measured using high-performance liquid chromatography. The development of lamotrigine-related rash was assessed during the 8-week treatment. RESULTS: Six females developed lamotrigine-related rash. The mean plasma lamotrigine concentrations at week 2 were significantly (P = 0.009) higher in the rash group (4.81 ± 1.23 µmol/L) than in the nonrash group (3.35 ± 1.39 µmol/L). Receiver-operating characteristic analysis indicated that a plasma lamotrigine concentration of 4.38 µmol/L or greater at week 2 was significantly (P < 0.0001) predictive of lamotrigine-related rash. The proportion of patients with a lamotrigine concentration of 4.38 µmol/L or greater was significantly divided by the cutoff point into the rash group and the nonrash group (5/1 versus 13/65, P = 0.001). CONCLUSIONS: This study suggests that a high plasma lamotrigine concentration during week 2 is a risk factor for lamotrigine-related rash and a plasma lamotrigine concentration of 4.38 µmol/L may be a considered a threshold for rash in treatment-resistant depressive disorder.

Development of the 12-item questionnaire for quantitative assessment of depressive mixed state (DMX-12).

BACKGROUND: Conventional categorical criteria have limitations in assessing the prevalence and severity of depressive mixed state (DMX). Thus, we have developed a new scale for screening and quantification of DMX and examined the symptomatological structure and severity of DMX in individuals with major depressive episode (MDE). METHODS: Subjects were 154 patients with MDE (57 males and 97 females; age 13-83 years). Our original Japanese version of the self-administered 12-item questionnaire to assess DMX (DMX-12), together with the Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J) and global assessment of functioning, were administered to each participant. The symptomatological structure of the DMX-12 was examined by exploratory factor analysis. Multiple regression analyses were used to analyze factors contributing to the DMX-12 scale. The relationships of this scale with categorical diagnoses (mixed depression by Benazzi and mixed features by DSM-5) were also investigated. RESULTS: A three-factor model of the DMX-12 was extracted from exploratory factor analysis, namely, "spontaneous instability", "vulnerable responsiveness", and "disruptive emotion/behavior". Multiple regression analyses revealed that age was negatively correlated with total DMX-12 score, while bipolarity and the QIDS-SR-J score were positively correlated. A higher score on the disruptive emotion/behavior subscale was observed in patients with mixed depression and mixed features. CONCLUSION: The DMX-12 seems to be useful for screening DMX in conjunction with conventional categorical diagnoses. Severely depressed younger subjects with potential bipolarity are more likely to develop DMX. The disruptive emotion/behavior subscale of the DMX-12 may be the most helpful in distinguishing patients with DMX from non-mixed patients.

Effects of attitudes towards ambiguity on subclinical depression and anxiety in healthy individuals.

This study aims to examine the effects of multidimensional attitudes towards ambiguity on subclinical depression and anxiety in healthy individuals. Attitudes Towards Ambiguity Scale, consisting of four clusters (enjoyment, anxiety, exclusion, and noninterference), Self-Rating Depression Scale, and State-Trait Anxiety Inventory-trait version were administered to 1019 Japanese volunteers. The result of a regression analysis suggested that the score of Attitudes Towards Ambiguity Scale-enjoyment factor significantly contributed to the Self-Rating Depression Scale score while that of Attitudes Towards Ambiguity Scale-anxiety factor significantly contributed to the State-Trait Anxiety Inventory-trait score. Among attitudes toward ambiguity, enjoyment may have protective effects against subclinical depression whereas anxiety can enhance anxiety-trait in nonclinical individuals.

Relationship Between UGT1A4 and UGT2B7 Polymorphisms and the Steady-State Plasma Concentrations of Lamotrigine in Patients With Treatment-Resistant Depressive Disorder Receiving Lamotrigine as Augmentation Therapy.

BACKGROUND: In a previous study, the authors had shown that in treatment-resistant depressive disorder, an early therapeutic response to lamotrigine augmentation therapy is dependent on its plasma concentrations. Lamotrigine is mainly metabolized by UGT1A4 and UGT2B7, and polymorphisms of said UGTs that affect enzyme activities have been reported. This study investigated the effect of these polymorphisms on the steady-state plasma concentrations (Css) of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy. METHODS: The subjects were 103 depressed patients who had already shown insufficient response to at least 3 psychotropics including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 46), bipolar II disorder (n = 44), and bipolar I disorder (n = 13). They received augmentation therapy with lamotrigine for 8 weeks. The final doses of lamotrigine were 100 mg/d for 67 subjects who were not taking valproate and 75 mg/d for 36 subjects taking valproate, respectively. Blood sampling was performed at the 8th week. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography. The genotypes of UGT1A4 142T>G, UGT2B7 -161C>T, and UGT2B7 372A>G were identified by polymerase chain reaction analyses. RESULTS: There were no significant relationships between these polymorphisms and the Css of lamotrigine in the subjects regardless of valproate comedication. CONCLUSIONS: This study suggests that these genetic polymorphisms do not affect the Css of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotrigine as augmentation therapy.

Attitudes towards Ambiguity in Japanese Healthy Volunteers.

Multi-dimensional structure of the Attitudes Towards Ambiguity Scale (ATAS: original Japanese version) and its relationship with the Acceptance and Action Questionnaire (AAQ) were investigated. We administered the ATAS and the Japanese version of the AAQ to 1019 Japanese healthy volunteers (513 females and 506 males; age range 18-78 years). Trial of exploratory factor analysis extracted four distinct clusters (Enjoyment; α = .83, Anxiety; α = .75, Exclusion; α = .75, and Noninterference; α = .65) from the ATAS item pool, suggestive of diversity in cognitive/ emotional/ behavioral responses to ambiguity. Confirmative factor analysis showed similar goodness in fit indices between the new four-factor model in the present study and the original five-factor model in our previous study (Nishimura 2007). Considering interpretability by using large number of representative samples with general population in the present study, we adopted the four-factor model. The ATAS Anxiety subscale was negatively correlated with the AAQ willingness subscale (r = -.39, p < .001), while the ATAS Enjoyment subscale was positively correlated with the AAQ Action subscale (r = .40, p < .001). It is thus suggested that one who enjoys ambiguous situations can adopt two distinct attitudes: Excluding ambiguity from active resolution, or not interfering with ambiguity due to good tolerance of this experience, which can lead to positive and flexible commitments in life. In contrast, one who tends to be anxious about ambiguity may be characterized by exclusion-based attitudes due to intolerance of ambiguity, leading to lowered acceptance of their feelings and of the reality of circumstances. Cognitive/emotional attitudes towards ambiguity may affect acceptance of inner experience and active commitment to reality.

Simultaneous resection of endometrial cancer and high-level paraaortic paraganglioma using retroperitoneoscopic surgery.

•Paraganglioma is sometimes suspected as lymph node metastasis or lymph node recurrence of various malignant tumors.•Retroperitoneoscopic surgery is a valid approach to treat the tumor, located above the renal vein.•Resection using retroperitoneoscopic surgery without catecholamine-related complications is possible.