Profiles and the impact of affective temperaments on alcohol use disorder: a cross-sectional study.

AIMS: This study aimed to explore the profiles and impact of affective temperaments, together with social and clinical backgrounds, including affective symptoms, in patients with alcohol use disorder (AUD). METHODS: This study included 314 low-risk drinkers and 257 patients with AUD. To assess affective temperament, we used the short version of the temperament evaluation of Memphis, Pisa, Paris, and San Diego. To evaluate depressive and mixed symptoms, the quick inventory of depressive symptomatology self-report Japanese version and 12-item questionnaire for the quantitative assessment of the depressive mixed state were used. We compared the profiles of affective temperaments as well as social and clinical backgrounds, including affective symptoms, between the two groups and further performed logistic regression analyses to explore the factors contributing to AUD. RESULTS: Our analysis showed higher cyclothymic, hyperthymic, and irritable temperament scores and lower depressive temperament scores in patients with AUD than that in nonclinical drinkers. Regarding other social and clinical backgrounds, patients with AUD were less educated and employed and more experienced depressive and mixed symptoms. Logistic regression analysis identified hyperthymic temperament as a positive contributor and depressive temperament as a negative contributor to AUD. CONCLUSIONS: Our findings indicated potential bipolarity in patients with AUD, as manifested by a more hyperthymic temperament in contrast to less depressive temperament. Despite their self-perceived adaptive temperament profiles, patients showed poorer social outcomes and more affective symptoms. This gap may be partly explained by a lack of insight unique to AUD psychology, which potentially disturbs problem recognition.

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.

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.

Tescalcin is a potential target of class I histone deacetylase inhibitors in neurons.

Class I histone deacetylase (HDAC) inhibitors are believed to have positive effects on neurite outgrowth, synaptic plasticity, and neurogenesis in adult brain. However, the downstream molecular targets of class I HDAC inhibitors in neurons are not clear. Although class I HDAC inhibitors are thought to broadly promote transcription of many neuronal genes through enhancement of histone acetylation, the affected gene set may include unidentified genes that are essential for neuronal survival and function. To identify novel genes that are targets of class I HDAC inhibitors, we used a microarray to screen transcripts from neuronal cultures and evaluated changes in protein and mRNA expression following treatment with four HDAC inhibitors. We identified tescalcin (Tesc) as the most strongly up-regulated gene following treatment with class I HDAC inhibitors in neurons. Moreover, hippocampal neurons overexpressing TESC showed a greater than 5-fold increase in the total length of neurites and number of branch points compared with controls. These findings highlight a potentially important role for TESC in mediating the neuroprotective effect of class I HDAC inhibitors. TESC may also be involved in the development of brain and neurodegenerative diseases through epigenetic mechanisms.

Prediction of an Optimal Dose of Aripiprazole in the Treatment of Schizophrenia From Plasma Concentrations of Aripiprazole Plus Its Active Metabolite Dehydroaripiprazole at Week 1.

BACKGROUND: It has been suggested that a plasma trough concentration of aripiprazole plus its active metabolite, dehydroaripiprazole of 225 ng/mL is a threshold for a good therapeutic response in the treatment of acutely exacerbated patients with schizophrenia. The present study investigated whether or not an optimal dose of aripiprazole could be predicted from these concentrations at week 1. METHODS: The subjects were 26 inpatients with schizophrenia, who received aripiprazole once a day for 3 weeks. The daily doses were 12 mg for the first week and 24 mg for the next 2 weeks. No other drugs except biperiden and flunitrazepam were coadministered. Blood samples were taken at weeks 1 and 3 after the treatment. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass-spectrometric detection. RESULTS: There was a significant linear relationship between the plasma concentrations of aripiprazole plus dehydroaripiprazole at weeks 1 (x) and 3 (y) (P < 0.001). Regression equation was y = 2.580x + 34.86 (R = 0.698). Based on the equation, a nomogram to estimate an optimal dose of aripiprazole could be constructed. CONCLUSIONS: The present study suggests that an optimal dose of aripiprazole for the treatment of patients with schizophrenia can be predicted from the plasma concentrations of the sum of the 2 compounds at week 1.

A Partial Response at Week 4 Can Predict Subsequent Outcome during Lamotrigine Augmentation Therapy in Treatment-Resistant Depressive Disorder: A Preliminary Study.

BACKGROUND/AIMS: The present study prospectively examined whether or not a partial response at week 4 predicts subsequent response at week 8 during lamotrigine augmentation therapy in 51 (16 males and 35 females) inpatients with treatment-resistant depressive disorder using an open-study design. METHODS: The subjects were 51 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 = 19), bipolar I disorder (n = 9), and bipolar II disorder (n = 23). The final doses of lamotrigine were 100 mg/day for 29 subjects who were not taking valproate and 75 mg/day for 22 subjects taking valproate. Depressive symptoms were evaluated by the Montgomery-Åsberg Depression Rating Scale (MADRS) before the start of lamotrigine and then at week 4, and finally after the 8th week of treatment. RESULTS: A significant linear relationship was found between percent improvements in MADRS scores at weeks 4 and 8 (r = 0.492, y = 0.438x + 30.223, R2 = 0.226, p < 0.001). The receiver operating characteristics analysis indicated that a percent improvement of 16% or greater at week 4 was significantly (p < 0.01) predictive of response (50% or more reduction in the MADRS score). The patients were significantly divided by the cut-off point into the responders and the nonresponders (18/26 vs. 1/25, p < 0.001). CONCLUSION: The present study suggests that a partial response at week 4 can predict subsequent outcome at week 8 during lamotrigine augmentation therapy in patients with treatment-resistant depressive disorder, and that the absence of a partial improvement at week 4 is highly predictive of nonresponse.

Both Serum Brain-Derived Neurotrophic Factor and Interleukin-6 Levels Are Not Associated with Therapeutic Response to Lamotrigine Augmentation Therapy in Treatment-Resistant Depressive Disorder.

BACKGROUND/AIMS: Serum levels of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) were prospectively monitored in relation with therapeutic response to lamotrigine augmentation therapy in 46 (15 males and 31 females) inpatients with treatment-resistant depressive disorder during an 8-week treatment with lamotrigine using an open-study design. METHODS: The subjects were 46 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 = 19), bipolar I disorder (n = 6), and bipolar II disorder (n = 22). The final doses of lamotrigine were 100 mg/day for 26 subjects who were not taking valproate and 75 mg/day for 20 subjects taking valproate, respectively. Depressive symptoms were evaluated by the Montgomery-Åsberg Depression Rating Scale (MADRS) before and after the 8-week treatment. Blood sampling was performed before the start of lamotrigine treatment and at week 8. Serum BDNF and IL-6 levels were measured using quantitative sandwich enzyme immunoassays. RESULTS: No significant changes in serum BDNF or IL-6 levels during the 8-week lamotrigine treatment were observed in the total of subjects, responders or nonresponders. There was no significant correlation between the changes in serum BDNF or IL-6 levels and the percent improvement in MADRS scores in the overall subjects. CONCLUSION: The present study suggests that the acute effect of lamotrigine augmentation therapy for a major depressive episode is not related to either BDNF or IL-6, at least in patients with treatment-resistant depressive disorder.

Usefulness of an educational lecture focusing on improvement in public awareness of and attitudes toward depression and its treatments.

BACKGROUND: There is an urgent need to establish effective strategies for suicide prevention. Stigma against depression may be a potential anti-protective factor for suicide. Thus, we investigated baseline levels of awareness and attitudes toward depression and its treatment among the general population by our original 18-item questionnaire, which we aimed to validate in the present study. Next, we conducted two types of educational interventions and examined the results to clarify the difference in the quality of these lectures. METHODS: Subjects were 834 citizens (245 males and 589 females) who received an anti-stigma-targeted (n = 467) or non-targeted lecture (n = 367). An 18-item questionnaire assessing levels of awareness and attitudes toward depression and its treatments was administered to each participant before and after the lecture. A chi-square test was used to investigate categorical variables for background data on the participants. Factor analysis of baseline scores was conducted on the 18 questionnaire items. Student's t-test was used for analysis of the gender effect. A two-way analysis of variance (ANOVA) was used for comparison among the 5 age groups and comparison of the effect of the two lectures. Multiple regression analysis was applied to examine the determinants of improved attitudes after intervention. RESULTS: Public attitudes toward depression consisted of 4 distinct elements, which were disease-model attitudes, help-seeking behavior, negative affect toward depression, and non-medication solutions. Older participants had poorer disease-model attitudes and more negative affect toward depression, whereas younger participants showed poorer help-seeking behavior (p < 0.05). The anti-stigma-targeted lecture was superior to the non-targeted lecture in improving disease-model attitudes and non-medication solutions (p < 0.05). Multiple regression analyses revealed that each subscale score at post-lecture was strongly dependent on its own baseline subscale score (p < 0.01), and that baseline disease-model attitudes also affected post-lecture scores on negative affect toward depression and non-medication solutions (p < 0.01). CONCLUSIONS: The educational intervention appears useful for acquiring accurate attitudes toward depression in a medical model. However, other strategies should be considered to enhance help-seeking behavior, especially in younger people.

Prediction of an Optimal Dose of Lamotrigine for Augmentation Therapy in Treatment-Resistant Depressive Disorder From Plasma Lamotrigine Concentration at Week 2.

BACKGROUND: The authors have previously shown that an early therapeutic response to lamotrigine augmentation therapy is dependent on its plasma concentration and that a plasma lamotrigine concentration of 12.7 µmol/L may be a threshold for a good therapeutic response in treatment-resistant depressive disorder. The present study investigated whether or not an optimal dose of lamotrigine could be predicted from plasma lamotrigine concentration at week 2. METHODS: The subjects were 37 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 = 15), bipolar I disorder (n = 6), and bipolar II disorder (n = 16). They received augmentation therapy with lamotrigine for 8 weeks. The final doses of lamotrigine were 100 mg/d for 16 subjects who were not taking valproate and 75 mg/d for 21 subjects taking valproate, respectively. Blood sampling was performed at weeks 2 and 8. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography. RESULTS: There were significant linear relationships between the plasma lamotrigine concentrations at week 2 (x) and those at week 8 (y) for subjects who were not taking valproate (P < 0.01) and those taking valproate (P < 0.01). Regression equations were y = 2.032x + 2.549 for the former and y = 3.599x + 5.752 for the latter, respectively. Based on the equations, a nomogram to estimate an optimal dose of lamotrigine could be calculated. CONCLUSIONS: The present study suggests that an optimal dose of lamotrigine for augmentation therapy in treatment-resistant depressive disorder can be predicted from a plasma lamotrigine concentration at week 2.

Relationship between plasma concentrations of lamotrigine and its early therapeutic effect of lamotrigine augmentation therapy in treatment-resistant depressive disorder.

BACKGROUND: The relationship between plasma concentrations of lamotrigine and its therapeutic effects was prospectively studied on 34 (9 men and 25 women) inpatients with treatment-resistant depressive disorder during an 8-week treatment of lamotrigine augmentation using an open-study design. METHODS: The subjects were 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 = 12), bipolar I disorder (n = 7), and bipolar II disorder (n = 15). The final doses of lamotrigine were 100 mg/d for 18 subjects who were not taking valproate and 75 mg/d for 16 subjects taking valproate. Depressive symptoms were evaluated by the Montgomery Åsberg Depression Rating Scale (MADRS) before and after the 8-week treatment. Blood sampling was performed at week 8. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography. RESULTS: There was a significant linear relationship between the plasma concentrations of lamotrigine and percentage improvements at week 8 (r = 0.418, P < 0.05). A stepwise multiple regression analysis showed that plasma lamotrigine concentrations alone had a significant effect on the percentage improvements at week 8 (standardized partial correlation coefficients = 0.454, P < 0.001). The receiver operating characteristics analysis indicated that a plasma lamotrigine concentration of 12.7 µmol/L or greater was significantly (P < 0.001) predictive of response (50% or more reduction in the MADRS score). The proportion of the responders was significantly higher in the groups with a lamotrigine concentration >12.7 µmol/L (11/15 versus 4/19, P < 0.01). CONCLUSIONS: The present study suggests that an early therapeutic response to lamotrigine is dependent on its plasma concentration and that a plasma lamotrigine concentration of 12.7 µmol/L may be a threshold for a good therapeutic response in treatment-resistant depressive disorder.

Effects of genetic polymorphisms of CYP2D6, CYP3A5, and ABCB1 on the steady-state plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients with schizophrenia.

BACKGROUND: We studied the effects of various factors, including genetic polymorphisms of the cytochrome P450 (CYP) 2D6, CYP3A5, and ABCB1, age, gender, and smoking habit on the steady-state plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in 89 patients with schizophrenia (46 males, 43 females). METHODS: All patients had been receiving fixed doses of aripiprazole for at least 2 weeks. The daily doses were 24 mg (n = 56) and 12 mg (n = 33). No other drugs except biperiden and flunitrazepam were coadministered. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass-spectrometric detection. The CYP2D6 (CYP2D6*5, CYP2D6*10, and CYP2D6*14), CYP3A5 (CYP3A5*3), and ABCB1 (C3435T and G2677T/A) genotypes were identified by PCR analyses. RESULTS: The mean concentration/dose ratios of aripiprazole and the sum of aripiprazole and dehydroaripiprazole were significantly higher in patients with 1 (P < 0.01 and P < 0.01) or 2 (P < 0.001 and P < 0.05) mutated alleles for CYP2D6 than in those without mutated alleles. No differences were found in the values of dehydroaripiprazole among CYP2D6 genotypes. There were no differences in the values of aripiprazole, dehydroaripiprazole, and the sum of the 2 compounds among CYP3A5 or the 2 ABCB1 variants. Multiple regression analyses including these polymorphisms, age, gender, and smoking habit showed that only the number of mutated alleles for CYP2D6 was correlated with mean concentration/dose ratios of aripiprazole [standardized partial correlation coefficients (beta) = 0.420, P < 0.001] and the sum of the 2 compounds (standardized beta = 0.335, P < 0.01). CONCLUSIONS: The findings of this study suggest that CYP2D6 genotypes play an important role in controlling steady-state plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole in Asian subjects, whereas CYP3A5 and ABCB1 genotypes seemed unlikely to have an impact.

Lack of correlation between the steady-state plasma concentrations of aripiprazole and haloperidol in Japanese patients with schizophrenia.

BACKGROUND: Both aripiprazole and haloperidol have been used in the treatment of schizophrenia, and are metabolized by the cytochrome P450 (CYP) 2D6 and CYP3A4. The authors studied the correlations between the steady-state plasma concentrations (Css) of aripiprazole and its active metabolite, dehydroaripiprazole, and those of haloperidol in 19 Japanese patients with schizophrenia, together with the effects of CYP2D6 genotypes on the steady-state kinetics of these compounds. METHODS: All the patients received first 24 mg/d of aripiprazole for 3 weeks and later received 6 mg/d of haloperidol for 2 weeks. Blood samplings were performed at least 2 weeks after the initiation of each treatment. The Css values of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection, and those of haloperidol were measured by using an enzyme immunoassay. CYP2D6 genotypes were determined by using polymerase chain reaction analysis. RESULTS: None of the correlations between the Css of aripiprazole (r = 0.286) or the sum of aripiprazole plus dehydroaripiprazole (r = 0.344) and those of haloperidol were significant. The mean Css of aripiprazole was significantly higher (P < 0.05) in the subjects with 1 *10 allele of CYP2D6 (n = 6) than in those with no mutated alleles (n = 13), whereas there were no significant differences in those of haloperidol between the 2 groups. CONCLUSIONS: This study suggests that the Css of aripiprazole and that of aripiprazole plus dehydroaripiprazole do not correlate with that of haloperidol in the same individual, because of the greater involvement of CYP2D6 in the metabolism of aripiprazole than in that of haloperidol.

Comorbid atypical autistic traits as a potential risk factor for suicide attempts among adult depressed patients: a case-control study.

BACKGROUND: The present study aims to examine if autism spectrum disorder (ASD) is a risk factor for suicide attempts among adult depressed patients and to elucidate the characteristics of suicide attempts in adult depressed patients with ASD. METHODS: We conducted a case-control study. Subjects consisted of 336 retrospectively recruited first-time visit patients to our outpatient clinic with a current major depressive episode; 31 of the 336 patients had attempted suicide. The demographic backgrounds (i.e., age, gender, personal/family history of suicidality); specific psychopathology like bipolarity, agitation, and psychotic features; and comorbidity such as physical diseases, alcohol abuse, cluster B personality disorder, and ASD including pervasive developmental disorder not otherwise specified (PDD-NOS) were examined as potential risk factors for suicide attempts. We compared these variables between the suicide attempters and non-attempters. In addition, we compared suicide attempters to non-attempters within the ASD group and non-ASD group. Binary logistic regression analysis was performed using the significant independent variables from the comparisons between the suicide attempters and non-attempters, and the odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Logistic regression analysis demonstrated that agitation during a depressive episode (OR = 7.15, 95% CI = 2.88-17.74), past suicidal behaviors (OR = 4.32, 95% CI =1.70-10.98), and comorbid PDD-NOS (OR = 4.04, 95% CI = 1.20-13.54) were significantly associated with suicide attempts. The most prevalent suicidal method was drug overdose (59.1%) among non-ASD attempters while hanging was the most prevalent (44.4%) in ASD attempters. CONCLUSIONS: Depressed adults with comorbid atypical autistic traits are at higher risk for suicide attempts and may engage in methods that are more lethal.

Depressive rumination and past depression in Japanese university students: comparison of brooding and reflection.

The Ruminative Responses Scale, a measure of depressive rumination, contains two subscales: Brooding and Reflection. Treynor, Gonzalez, and Nolen-Hoeksema (2003) proposed that Brooding is maladaptive and Reflection is adaptive. This article examined the relationships among Brooding, Reflection, and previous depression in two samples of Japanese undergraduates, who were non-depressed at the time of their participation. Based on answers to a self-report measure, participants were divided into a formerly depressed group, who had experienced an episode that met the criteria for major depression, and a never-depressed group. Logistic regression analyses were conducted with Brooding, Reflection, and current depression as the independent variables and past depression as the dependent variable. Brooding had consistent positive associations with past depression. The relationship between Reflection and past depression was not significant for one sample, but was statistically significant and positive in the second sample. In the second sample, Brooding and Reflection both were related with past depression after controlling for worry.

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.

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.

Successful treatment with guanfacine in a long-COVID case manifesting marked cognitive impairment.

BACKGROUND: Persistent cognitive impairment is a serious consequence of the post-COVID condition. However, there have been no established effective treatments for this pathophysiology supported by sufficient evidence. CASE PRESENTATION: A 32-year-old woman became aware of difficulty in word recalling, reading, and writing as well as difficulty in completing various household multitasks 3 weeks after the COVID-19 infection. Although blood tests, magnetic resonance imaging, electroencephalography, and Kohs block design test were all within normal limits, completion time by trail making test (TMT) A or B was markedly delayed. Finally, she was referred to our hospital 3 months after the infection. At baseline, the THINC integrated tool (THINC-it), a digital battery consisting of the five-item version of the perceived deficit questionnaire (PDQ-5), choice reaction time (CRT), 1-back test, digit symbol substitution test (DSST), and TMT-B, revealed poor capability in attention, working memory, and executive function. Also, near-infrared spectroscopy (NIRS) demonstrated no activation in frontal or temporal regions during verbal fluency task. Extended-release guanfacine (GXR) 2 mg/day was initiated and a month later was elevated up to 4 mg/day as a maintenance dose. The PDQ-5, CRT, 1-back test, DSST, and TMT-B were dramatically improved 1 month after GXR treatment. NIRS finding was also normalized after 2 months of treatment. These effects were successfully maintained throughout the 6-month follow-up period. CONCLUSION: GXR may be helpful in improving subjective/objective cognitive functioning and frontotemporal brain activity in long-COVID patients manifesting apparent cognitive impairment.

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.