Association between disease severity according to "MN criteria" and 30-day mortality in patients with Clostridioides difficile infection.

INTRODUCTION: A rapid membrane enzyme immunoassays (EIA) are frequently used to diagnose Clostridioides difficile infection (CDI). If EIA does not provide a definitive CDI diagnosis, whether treatment with anti-CD agents is to be performed depends on the pathogenesis and severity of the disease. In Japan, "MN criteria" have been proposed for the classification of disease severity. In this study, we investigated the association between disease severity and CDI prognosis when MN criteria are used. METHODS: This study included 102 patients diagnosed with CDI between April 2015 and March 2020. The disease serverity classification accorditng to MN criteria was divided into two groups: non-severely ill (mild to moderate) and severely ill (severe to critical) group. RESULTS: Mortality was significantly higher in severely ill patients than non-severely ill patients (46.7% vs. 13.8%, p = 0.0025). Multivariable analysis showed that the mortality of patients with CDI was significantly associated with advanced age (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 1.0-1.2; p = 0.019) and disease severity (OR = 4.2; 95% CI = 1.2-14.8; p = 0.023). DISCUSSION: The classification of disease severity according to the MN criteria would be particularly useful in predicting the patients' prognoses.

Bcl1 polymorphism of the glucocorticoid receptor gene and treatment response to milnacipran and fluvoxamine in Japanese patients with depression.

BACKGROUND: Polymorphisms in the glucocorticoid receptors (GRs) have been widely studied with rather less emphasis on relating their differences with possible pharmacological treatment outcomes. The purpose of this study was to investigate whether Bcl1 polymorphisms of GRs are associated with the antidepressant effect of milnacipran, a serotonin noradrenaline reuptake inhibitor (SNRI), and fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), in Japanese patients with depression. METHODS: Patients were prescribed either milnacipran (n = 98) or fluvoxamine (n = 95). The severity of depression was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) at 0, 1, 2, 4 and 6 weeks of treatment. RESULTS: Both agents were similarly effective in reducing MADRS scores in 6 weeks. In all subjects receiving milnacipran or fluvoxamine, our data showed no significant interaction between Bcl1 polymorphisms and therapeutic effects. However, when milnacipran- and fluvoxamine-treated subjects were analyzed independently, patients with G allele in Bcl1 polymorphism had a significantly better response to fluvoxamine than those with C/C genotype. On the other hand, no significant relationship was found between treatment response to milnacipran and Bcl1 polymorphism. CONCLUSION: Bcl1 polymorphism may be one of the genetic factors in predicting treatment response to SSRI but not SNRI in Japanese patients with depression.

Relationship of the 24-item dysfunctional attitude scale with the temperament and character inventory in healthy subjects.

BACKGROUND: 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. AIM: The purpose of the present investigation was to characterize the three subscales in relation to broad dimensions of personality. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 correlated with sociotropy but not with autonomy in healthy subjects.

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 (ß = 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 (ß = 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.

Relationships of sociotropy and autonomy with dimensions of the Temperament and Character Inventory in healthy subjects.

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 (ß = 0.27) and second strongest with lower self-directedness (ß = -0.25). Meanwhile, autonomy was significantly correlated with higher persistence and ST, and lower RD; and the correlations were especially strong with higher ST (ß = 0.37) and lower RD (ß = -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.

Parental overprotection increases interpersonal sensitivity in healthy subjects.

The effect of parental rearing on interpersonal sensitivity was studied in 469 Japanese volunteers. Perceived parental rearing was assessed by the Parental Bonding Instrument, which consists of the factors of care and protection, and interpersonal sensitivity was measured by the Interpersonal Sensitivity Measure (IPSM). In male subjects, higher IPSM scores were related to higher scores of paternal protection (P < .01) and maternal protection (P < .05). In female subjects, higher IPSM scores were related to higher scores of maternal protection (P < .001). The present study suggests that in both males and females, interpersonal sensitivity is increased by high protection of the same-sex parents and that in males there is an additional effect of high maternal protection.

Increased body mass index associated with increased harm avoidance and decreased self-directedness in Japanese women.

Previous studies have suggested that body mass index (BMI) is related to personality traits, and that there may be gender specificity in this relationship. In the present study, the association between BMI and the 7 dimensions of the Temperament and Character Inventory was investigated in 567 Japanese healthy volunteers, with special attention on gender effects. Height and weight were self-reported, and BMI was calculated from these values. In the multiple regression analyses, higher BMI was related to higher scores of harm avoidance (p < 0.05) and lower scores of self-directedness (p < 0.01) in women, whereas BMI was not related to any Temperament and Character Inventory dimension in men. The present study suggests that increasing BMI is associated with increased harm avoidance and decreased self-directedness in women but not in men in healthy subjects.

Dysfunctional parenting styles increase interpersonal sensitivity in healthy subjects.

The effects of dysfunctional parenting styles on interpersonal sensitivity were studied in 640 Japanese volunteers. Interpersonal sensitivity was assessed by the Interpersonal Sensitivity Measure (IPSM), and perceived parental rearing was evaluated by the Parental Bonding Instrument (PBI), which is consisted of care and protection factors. Parental rearing was classified into 4 types, i.e., optimal parenting (high care/low protection), affectionate constraint (high care/high protection), neglectful parenting (low care/low protection), and affectionless control (low care/high protection). Males with paternal affectionless control showed higher total IPSM scores than those with paternal optimal parenting (p = 0.022). Females with maternal affectionate constraint (p = 0.001), neglectful parenting (p = 0.022), and affectionless control (p = 0.003) showed higher total IPSM scores than those with maternal optimal parenting. In males and females, dysfunctional parenting styles by the opposite-sex parents did not affected total IPSM scores. The present study suggests that in both males and females interpersonal sensitivity is increased by dysfunctional parenting styles by the same-sex parents.

Effect of month of birth on personality traits of healthy Japanese.

The effect of month of birth on personality traits was investigated in 595 healthy Japanese. Personality traits were evaluated by the Temperament and Character Inventory (TCI). Statistical analyses were conducted in two steps. Firstly, months of the year were divided according to ambient temperature or photoperiod, and TCI scores were compared between month groups by analysis of covariance (ANCOVA) with age as a covariate. Secondly, multiple regression analysis was performed with TCI scores as dependent variables and ambient temperature and photoperiod at birth month and age as independent variables. Both analyses showed that higher ambient temperature at birth month was related to higher scores of self-directedness and persistence in females. Also, higher ambient temperature at birth month was related to lower body mass index (BMI) in females. These results suggest that month of birth affects self-directedness and persistence in healthy Japanese females, and these effects may be mediated by BMI changes associated with ambient temperature at birth month.

Association study of the cytochrome P450 17 gene polymorphism with personality traits in healthy subjects.

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

Combination of the serotonin transporter and norepinephrine transporter gene promoter polymorphisms might influence harm avoidance and novelty seeking in healthy females.

It has been demonstrated that the interaction between serotonin transporter (5HTT) and norepinephrine transporter (NET) functions affects each transporter function and behavior in studies using knockout mice model. In the present study, we examined the effects of the 5HTT and NET gene promoter polymorphisms on personality traits in 575 Japanese healthy subjects. The 5HTT (long/short, L/S) and NET (-3081 A/T) genotypes were identified by PCR methods, and personality traits were assessed by the Temperament and Character Inventory (TCI). Neither of the two polymorphisms affected any TCI dimension, but the interaction between them had significant effects on harm avoidance and novelty seeking in females. Subsequent analyses showed that the females with the combination of the SS genotype reducing 5HTT function and the TT genotype reducing NET function had higher harm avoidance and lower novelty seeking. The present study suggests that the combination of 5HTT and NET polymorphisms influences harm avoidance and novelty seeking in females.

Augmentation with olanzapine in TCA-refractory depression with melancholic features: a consecutive case series.

Using an 8-week, open label study design, we report the effect of augmentation strategy with olanzapine in hospitalized depressive patients with melancholic features who had insufficient response to a tricyclic antidepressant (TCA), amitriptyline. Subjects were hospitalized patients meeting the criteria of DSM-IV major depressive disorder with melancholic features who had been suffering from residual symptoms after treatment of amitriptyline. After study entry, olanzapine was added to amitriptyline and the dose was adjusted according to patients' clinical condition. Data were analyzed using an intent-to-treat methodology, with last observation carried forward. Paired t-test was adopted to assess the data from baseline to endpoint. Of 26 patients who enrolled in this study, 23 patients completed the trial and 3 patients dropped out. The mean dose of olanzapine was 6.5 (SD = 2.4) mg/day. The mean score of Montgomery-Asberg Depression Rating Scale (MADRS) was significantly decreased from 33.6 (SD = 3.5) to 20.8 (SD = 9.1) during this study (37.9% from baseline) (p < 0.001). Ten patients (38.5%) were considered as responders (50% or greater reduction in MADRS scores from baseline). These results suggest that augmentation with olanzapine in TCAs-resistant melancholia may be effective and well tolerated. We cannot draw any conclusion with certainty from the open-label, uncontrolled clinical trial. Double blind, controlled trial is needed to confirm this preliminary finding.

Influence of the tyrosine hydroxylase val81met polymorphism and catechol-O-methyltransferase val158met polymorphism on the antidepressant effect of milnacipran.

OBJECTIVE: Genetic polymorphisms of the noradrenergic pathway can be factors to predict the effect of antidepressants when their pharmacological mechanisms of action include the noradrenergic system. The purpose of the present study was to determine whether the tyrosine hydroxylase (TH) val81met and catechol-O-methyltransferase (COMT) val158met polymorphisms are associated with the antidepressant effect of milnacipran, a serotonin/noradrenaline reuptake inhibitor. METHOD: Eighty-one Japanese patients with major depressive disorder were treated with milnacipran for 6 weeks. Severity of depression was assessed with the Montgomery and Asberg Depression Rating Scale (MADRS). Assessments were carried out at baseline and at 1, 2, 4 and 6 weeks of treatment. The method of polymerase chain reaction was used to determine allelic variants. RESULTS: The met/met genotype of the COMT val158met polymorphism was associated with a significantly faster therapeutic effect of milnacipran in the MADRS score during this study. No influence of the TH val81met polymorphism on the antidepressant effect of milnacipran was detected. CONCLUSION: These results suggest that the COMT val158met polymorphism in part determines the antidepressant effect of milnacipran.

Predictors of antidepressant response to fluvoxamine obtained using the three-factor structures of the Montgomery and Asberg Depression Rating Scale for major depressive disorders in Japanese patients.

AIMS: Fluvoxamine, a selective serotonin reuptake inhibitor, is widely used to treat major depression. However, the symptomatological predictors of the response to fluvoxamine have not been studied. METHODS: This study included 100 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery and Asberg Depression Rating Scale (MADRS) was 21 or higher. Eighty-one patients were included. Patients with a pretreatment MADRS score of >or=31 were defined as 'severe' (n = 32) and the rest were defined as 'non-severe' (n = 49). The three-factor model of MADRS was used for analysis: the first factor was defined by three items, the second factor was defined by four items, and the third factor was defined by three items representing dysphoria, retardation, and vegetative symptoms, respectively. Fluvoxamine (100-200 mg/day) was administered twice daily for 6 weeks. RESULTS: In the non-severe patients, the mean factor 3 score of the non-responders at pretreatment was significantly higher than that of the responders. However, a significant difference was observed in the mean factor 3 scores from 1 week onwards between the non-severe responders and non-responders. Furthermore, the fluvoxamine response rate in the severe patients was 75% and higher than that of the non-severe patients (65.3%). CONCLUSIONS: This study suggested that a low factor 3 score at pretreatment was a good predictor of the response to fluvoxamine in non-severe patients. The marked efficacy of fluvoxamine in the treatment of severe patients was also confirmed.

No predictors of antidepressant patient response to milnacipran were obtained using the three-factor structures of the Montgomery and Asberg Depression Rating Scale in Japanese patients with major depressive disorders.

AIMS: Milnacipran, a new specific serotonin and norepinephrine re-uptake inhibitor, is as effective as tricyclic antidepressants. Symptomatological predictors of antidepressant response to milnacipran have not been studied until now. METHODS: This study included 101 Japanese patients who fulfilled the DSM-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery and Asberg Depression Rating Scale (MADRS) was > or =21. Eighty-three patients were finally included. Patients with a pretreatment MADRS score > or =31 points were defined as severe (n = 28), and the rest as non-severe (n = 55). The three-factor model of MADRS was used for analysis; the first factor was defined by three items, the second factor was defined by four items and the third factor was defined by three items representing dysphoria, retardation, and vegetative symptoms, respectively. Milnacipran was administered twice daily for 6 weeks. The initial dose was 50 mg/day; after a week it was increased to 100 mg/day. RESULTS: No significant difference was observed in the mean score of first factor, second factor and third factor at pretreatment time between responders and non-responders in both severe and non-severe patients. CONCLUSIONS: No predictor of antidepressant response to milnacipran was obtained using the three-factor structures of the MADRS in Japanese patients with major depressive disorders.

The G196A polymorphism of the brain-derived neurotrophic factor gene and the antidepressant effect of milnacipran and fluvoxamine.

Prediction of the response to different classes of antidepressants has been an important matter of concern in the field of psychopharmacology. The purpose of the present study was to investigate whether the G196A polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with the antidepressant effect of milnacipran, a serotonin norepinephrine reuptake inhibitor, and fluvoxamine, a selective serotonin reuptake inhibitor. The subjects of our previous study of milnacipran (n = 80) and fluvoxamine (n = 54) were included in the present study. Severity of depression was assessed with the Montgomery Asberg depression rating scale (MADRS). Assessments were carried out at baseline and at 1, 2, 4 and 6 weeks of treatment. Polymerase chain reaction was used to determine allelic variants. In all subjects receiving milnacipran or fluvoxamine, the G/A genotype of the BDNF G196A polymorphism was associated with a significantly better therapeutic effect in the MADRS scores during this study. When milnacipran and fluvoxamine-treated subjects were analysed independently, the G/A genotype group showed greater reduction of MADRS scores than other genotype groups, irrespective of which antidepressant was administered. These results suggest that the BDNF G196A polymorphism in part determines the antidepressant effect of both milnacipran and fluvoxamine.

Association between serotonin transporter polymorphisms (5-HTTLPR) and the MADRS Dysphoria, Retardation, and Vegetative Subscale scores in the treatment of depression.

OBJECTIVE: We investigated the association between serotonin- or 5-hydroxytryptamine (5-HT)-related gene polymorphisms and response to antidepressant treatment in a specific symptom cluster of major depression by using the three-factor model of the Montgomery-Åsberg Depression Rating Scale (MADRS), ie, dysphoria (items of sadness, pessimistic thoughts, and suicidal thoughts), retardation (items of lassitude, inability to feel, apparent sadness, and concentration difficulties), and vegetative symptoms (items of reduced sleep, reduced appetite, and inner tension). METHODS: This study was an open-label and nonrandomized trial. A total of 160 patients with baseline MADRS scores of ≥21, who were treated with fluvoxamine or milnacipran for 6 weeks, were included in the statistical analysis. Polymorphisms within a 5-HT transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the second intron of the 5-HTT gene (5-HTTVNTR), and 5HT2A receptor (1438G/A) were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The 5-HTTLPR polymorphisms affected the MADRS score change in dysphoria, but not in retardation, vegetative, or total symptoms. Dysphoria scores significantly decreased in patients with the S/S genotype compared to those in patients with the short (S)/long (L) + L/L genotype. However, 5-HTTVNTR and 1438G/A polymorphisms were not significantly associated with the treatment response to any cluster of depressive symptoms. When a Bonferroni correction was made, however, our results did not reach the criteria for statistical significance. CONCLUSION: The use of a single total depression rating scale may not be sufficient to accurately estimate the clinical response to antidepressants. Analyzing a subset of symptoms in psychological scales could be important when performing pharmacogenetic studies.

Response rate obtained using milnacipran depending on the severity of depression in the treatment of major depressive patients.

Milnacipran--a new specific serotonin and noradrenaline reuptake inhibitor--is as effective as tricyclic antidepressants and exhibits a higher remission rate for major depressive patients than selective serotonin reuptake inhibitors. However, the effectiveness of milnacipran for severe major depressive patients had not been studied adequately. The study included 96 Japanese patients who fulfilled the DSM-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery-Asberg Depression Rating Scale (MADRS) was 21 or higher. Of these, 16 patients were excluded because 10 did not complete the study, and 6 showed poor compliance. Finally, 80 patients were included. We defined patients with a baseline MADRS score of > or = 31 points as "severe" (n = 25). The remaining patients were classified as "moderate" (31 > MADRS score > or = 25, n = 30) and "mild" (MADRS score < 25, n = 25) using the median score of those patients as the cutoff. Milnacipran was administered twice daily for 6 weeks. The initial total dose was 50 mg/d; after a week it was increased to 100 mg/d. The response rates were 72%, 70%, and 44% in the "severe," "moderate," and "mild," respectively. No significant differences were found between "severe" and the "moderate"; however, significant differences were observed between "severe" and "mild" and "moderate" and "mild." These results demonstrated that milnacipran is almost equally effective in "severe" and "moderate." This study suggested that milnacipran has a reliable antidepressant effect in treating severe and moderate major depressive patients.

Remarkable effect of milnacipran, a serotonin-noradrenalin reuptake inhibitor (SNRI), on depressive symptoms in patients with Parkinson's disease who have insufficient response to selective serotonin reuptake inhibitors (SSRIs): two case reports.

The authors present here two cases of Parkinson's disease with depression refractory to SSRIs treatment, who experienced a complete remission after replacing the ongoing SSRIs with a serotonin-noradrenalin reuptake inhibitor (SNRI), milnacipran. The case reports suggest that milnacipran may be one of the treatment options for depression in patients with Parkinson's disease who had inadequate response to SSRIs. Further studies are warranted to confirm this observation.

Remarkable effect of selegiline (L-deprenyl), a selective monoamine oxidase type-B inhibitor, in a patient with severe refractory depression: a case report.

A 34-year-old man presented with severe refractory depression. He had failed to respond to various antidepressants, augmentation therapy with lithium carbonate, and modified electroconvulsive therapy. Switching from amoxapine 150 mg/day to selegiline 7.5 mg/day, a selective monoamine oxidase type-B inhibitor, produced a dramatic reduction in hypobulia and lassitude, leading to a complete remission of all depressive symptoms. The patient reverted to his former position at work after an interval of approximately 3 years. Although the biologic basis of the antidepressant effect of selegiline in this patient is unknown, it is suggested that the enhancement of dopaminergic neurotransmission or elevation of brain-derived neurotrophic factor levels in the brain by administration of selegiline is involved in the recovery of this patient from severe refractory depression. This report indicates the antidepressant effect of selegiline in a refractory depressed patient.