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.

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.

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.

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.

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.

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.

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.

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.

Appendiceal cancer leading to intussusception detected incidentally during follow-up for Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is an autosomal dominant disorder characterized by hamartomatous polyposis, pigmentation, and malignant tumors. We report a case of ileocecal carcinoma that was incidentally detected during follow-up for Peutz-Jeghers syndrome. A 39-year-old man with solitary Peutz-Jeghers syndrome had undergone three abdominal surgeries. He had been followed up via upper and lower gastrointestinal endoscopy and small intestinal endoscopy. In the endoscopic examination of the lower gastrointestinal tract, a 35 mm large, bumpy, elevated lesion was observed in the cecum. This lesion was not observed 9 months earlier during lower endoscopy. Biopsy of the specimen confirmed tubulovillous adenoma and carcinoma. This lesion was judged to be an indication for operation, and we performed ileocecectomy + D3 lymph node dissection. From the excised specimen, poorly differentiated carcinoma and adenoma components in contact with Peutz-Jeghers-type polyps in the appendix were recognized. A review of the computed tomography image obtained 2 years ago confirmed appendiceal swelling. We suspect that the ileocecal carcinoma in the appendix may have rapidly developed within the 9 months, and was incidentally detected on lower endoscopic examination during follow-up. For the prevention of appendicular tumorigenesis, prophylactic appendectomy may be considered in certain cases during follow-up for Peutz-Jeghers syndrome.

Distribution of tenascin-C and -X, and soft X-ray analysis of the mandibular symphysis during mandible formation in the human fetus.

In the development of the human mandible, the process of bone calcification, distribution and expression of tenascin-C and -X in the mental symphyseal region are unknown. The purpose of this study was to determine the distribution of these extracellular matrices in the connective tissue around calcified tissues located on the mental symphyseal region of the human fetus during development through histological and radiographical studies. The radiographic density increased from 16 weeks to 24 weeks gestation in all examined regions; in contrast, the diameter of muscle fiber in the suprahyoid muscles (digastric anterior and geniohyoid muscles) inserted into the inner mental symphyseal region increased from 24 weeks gestation. The extracellular matrices (tenascin) were shown to have a different distribution in the mental symphyseal region of the human fetus at each stage. These different distributions of tenascin-C and -X were found around the epithelium and the endomysium of the mental symphyseal region, and affect the specific formation of the mandible during ossification with hyoid muscle development in human fetus.

Ultrastructure of vascular capillary of lingual filiform papillae in the mole (Mogella wogura wogura).

Detailed observation of the structure of filiform papillae (FP) and microvasculature of those papillae in Japanese Azuma mole were described. In the anterior and medial regions, FP was cylinder in shape with two processes. In the posterior region, it had a long, sharp conical shape. The microvascular casts showed two types of hairpin-shaped capillary loops on three regions of the tongue. In the anterior and medial regions, the end of the capillary loops were shaped like a spoon. In contrast, in the posterior region, it was knot-like end of capillary loop. Since the shape of capillary loop was more complex in the anterior and medial regions than that in the posterior region, it was speculated that the spoon-like end of capillary loops of the FP in the anterior and medial regions supply nutrients to the filiform papillary cells and may be related to the movement of the tongue during mastication in Japanese Azuma mole.