Genetic risks of schizophrenia identified in a matched case-control study.

It has been suggested that dopaminergic neurotransmission plays important roles for the psychotic symptoms and probably etiology of schizophrenia. In our recent preliminary study, we demonstrated that the specific allele combinations of dopamine-related functional single nucleotide polymorphisms (SNPs), rs10770141, rs4680, and rs1800497 could indicate risks for schizophrenia. The present validation study involved a total of 2542 individuals who were age- and sex-matched in a propensity score matching analysis, and the results supported the statistical significances of the proposed genetic risks described in our previous reports. The estimated odds ratios were 1.24 (95% CI 1.06-1.45, p < 0.001) for rs4680, 1.73 (95% CI 1.47-2.02, p < 0.0001) for rs1800497, and 1.79 (95% CI 1.35-2.36, p < 0.0001) for rs10770141. A significant relationship was also revealed among these three polymorphisms and schizophrenia, with corresponding coefficients (p < 0.0001). In this study, we also present a new scoring model for the identification of individuals with the disease risks. Using the cut-off value of 2, our model exhibited sensitivity for almost two-thirds of all of the schizophrenia patients: odds ratio 1.87, 95% CI 1.59-2.19, p < 0.0001. In conclusion, we identified significant associations of dopamine-related genetic combinations with schizophrenia. These findings suggest that some types of dopaminergic neurotransmission play important roles for development of schizophrenia, and this type of approach may also be applicable for other multifactorial diseases, providing a potent new risk predictor.

Perception of and anxiety about COVID-19 infection and risk behaviors for spreading infection: an international comparison.

BACKGROUND: To control the spread of the new SARS-CoV-2 infection's disease (COVID-19), appropriate precautionary behaviors by the public should be promoted. There are international differences in public cognitive and behavioral pattern, attitudes toward information sources, and anxiety about COVID-19. Information about these differences could increase understanding of the patterns of epidemic-related anxiety and behavior, and would help optimize future policies for preventing the next wave of the epidemic. METHODS: To examine between-country differences in perception, attitude, and precautionary behaviors toward COVID-19, we conducted a cross-sectional study using an online questionnaire survey. Participants were adults who had been registered in Cross Marketing Group Inc. and living in the UK, Spain, or Japan. A total of 8,000 people stratified by age were recruited on a first-come, first-serve basis. Knowledge of and anxiety about COVID-19, the frequency of access and perceived credibility of several information sources, and the frequency of each precautionary behavior were examined on March 27-28, 2020, in Japan and April 17-21, 2020, in the UK and Spain. RESULTS: Knowledge, anxiety, and the frequency of precautionary behaviors were higher in the UK and Spain than in Japan. Participants with infected acquaintances were more concerned about COVID-19. However, participants in the UK rarely wore a medical mask. Participants in the UK and Spain were more eager to obtain information about COVID-19 than those in Japan. Participants in Spain tended not to trust official information and to believe specialists' comments instead. CONCLUSION: The rapidity of the spread of COVID-19, cultural background, and recent political situations seemed to contribute to the international differences here.

Altered serum level of matrix metalloproteinase-9 and its association with decision-making in eating disorders.

AIM: The aims of this study were to determine whether the serum levels of precursor brain-derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and matrix metalloproteinase-9 (MMP-9) are altered in patients with eating disorders (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore whether those levels are associated with decision-making abilities. METHODS: Nineteen women with AN, 28 women with BN, and 22 age-matched healthy control women (HC) were enrolled in the current study. All participants had their decision-making abilities assessed using the Iowa Gambling Task (IGT). Their eating-related pathophysiology and depressive/anxiety symptoms were also evaluated. RESULTS: The MMP-9 level in AN was significantly lower than that in either BN or HC, but the serum levels of proBDNF and mBDNF did not differ among the three groups. Investigation of the serum levels of proBDNF and MMP-9 in patients with ED and controls revealed a significant correlation between them. In the BN, there were positive correlations between mBDNF level and IGT performance and also between MMP-9 level and IGT performance, but these correlations did not occur in AN. The MMP-9 level was positively associated with the Symptom Scale, one of the subscales of the Bulimic Investigatory Test, Edinburgh, only in AN. CONCLUSION: These results suggest that the serum level of MMP-9 plays a role in the pathophysiology of AN, and both the serum levels of mBDNF and MMP-9 may be associated with decision-making abilities in patients with BN.

Genetic and molecular risk factors within the newly identified primate-specific exon of the SAP97/DLG1 gene in the 3q29 schizophrenia-associated locus.

The synapse-associated protein 97/discs, large homolog 1 of Drosophila (DLG1) gene encodes synaptic scaffold PDZ proteins interacting with ionotropic glutamate receptors including the N-methyl-D-aspartate type glutamate receptor (NMDAR) that is presumed to be hypoactive in brains of patients with schizophrenia. The DLG1 gene resides in the chromosomal position 3q29, the microdeletion of which confers a 40-fold increase in the risk for schizophrenia. In the present study, we performed genetic association analyses for DLG1 gene using a Japanese cohort with 1808 schizophrenia patients and 2170 controls. We detected an association which remained significant after multiple comparison testing between schizophrenia and the single nucleotide polymorphism (SNP) rs3915512 that is located within the newly identified primate-specific exon (exon 3b) of the DLG1 gene and constitutes the exonic splicing enhancer sequence. When stratified by onset age, although it did not survive multiple comparisons, the association was observed in non-early onset schizophrenia, whose onset-age selectivity is consistent with our recent postmortem study demonstrating a decrease in the expression of the DLG1 variant in early-onset schizophrenia. Although the present study did not demonstrate the previously reported association of the SNP rs9843659 by itself, a meta-analysis revealed a significant association between DLG1 gene and schizophrenia. These findings provide a valuable clue for molecular mechanisms on how genetic variations in the primate-specific exon of the gene in the schizophrenia-associated 3q29 locus affect its regulation in the glutamate system and lead to the disease onset around a specific stage of brain development.

Effect of mirtazapine versus selective serotonin reuptake inhibitors on benzodiazepine use in patients with major depressive disorder: a pragmatic, multicenter, open-label, randomized, active-controlled, 24-week trial.

BACKGROUND: This study aimed to evaluate whether selecting mirtazapine as the first choice for current depressive episode instead of selective serotonin reuptake inhibitors (SSRIs) reduces benzodiazepine use in patients with major depressive disorder (MDD). We concurrently examined the relationship between clinical responses and serum mature brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF. METHODS: We conducted an open-label randomized trial in routine psychiatric practice settings. Seventy-seven MDD outpatients were randomly assigned to the mirtazapine or predetermined SSRIs groups, and investigators arbitrarily selected sertraline or paroxetine. The primary outcome was the proportion of benzodiazepine users at weeks 6, 12, and 24 between the groups. We defined patients showing a ≥50 % reduction in Hamilton depression rating scale (HDRS) scores from baseline as responders. Blood samples were collected at baseline, weeks 6, 12, and 24. RESULTS: Sixty-five patients prescribed benzodiazepines from prescription day 1 were analyzed for the primary outcome. The percentage of benzodiazepine users was significantly lower in the mirtazapine than in the SSRIs group at weeks 6, 12, and 24 (21.4 vs. 81.8 %; 11.1 vs. 85.7 %, both P < 0.001; and 12.5 vs. 81.8 %, P = 0.0011, respectively). No between-group difference was observed in HDRS score changes. Serum proBDNF levels were significantly decreased (χ2 = 8.5, df = 3, P = 0.036) and serum mature BDNF levels were temporarily significantly decreased (F = 3.5, df = 2.4, P = 0.027) in the responders of both groups at week 24. CONCLUSION: This study demonstrated mirtazapine as the first-choice antidepressant for current depressive episodes may reduce benzodiazepine use in patients with MDD. Trial registration UMIN000004144. Registered 2nd September 2010. The date of enrolment of the first participant to the trial was 24th August 2010. This study was retrospectively registered 9 days after the first participant was enrolled.

Increased serum levels of serine enantiomers in patients with depression.

OBJECTIVE: Glutamatergic neurotransmission via the N-methyl-d-aspartate (NMDA) receptor is integral to the pathophysiology of depression. This study was performed to examine whether amino acids related to NMDA receptor neurotransmission are altered in the serum of patients with depression. METHOD: We measured the serum levels of d-serine, l-serine, glycine, glutamate and glutamine in patients with depression (n=70), and age-matched healthy subjects (n=78). RESULTS: Serum levels of d-serine and l-serine in patients with depression were significantly higher than those of healthy controls (p<0.001). In contrast, serum levels of glycine, glutamate and glutamine did not differ between the two groups. Interestingly, the ratio of l-serine to glycine in patients was significantly higher than that of healthy controls (p<0.001). CONCLUSION: This study suggests that serine enantiomers may be peripheral biomarkers for depression, and that abnormality in the d-serine-l-serine-glycine cycle plays a role in the pathophysiology of depression.

Association study of H2AFZ with schizophrenia in a Japanese case-control sample.

It is widely accepted that malfunction of the N-methyl-D-aspartate (NMDA)-type glutamate receptor may be involved in the pathophysiology of schizophrenia. Several recent microRNA (miRNA) studies have demonstrated that the expression of the glutamate system-related miR-132 and miR-212 is changed in postmortem schizophrenic brains. Here we attempted to obtain further insight into the relationships among schizophrenia, the NMDA receptor, the molecular cascades controlled by these miRNAs and commonly predicted target genes of the two miRNAs. We focused on the H2AFZ (encoding H2A histone family, member Z) gene, whose expression was shown in our screening study to be modified by a schizophrenomimetic NMDA antagonist, phencyclidine. By performing polymerase chain reaction with fluorescent signal detention using the TaqMan system, we examined four tag single nucleotide polymorphisms (SNPs; SNP01-04) located around and within the H2AFZ gene for their genetic association with schizophrenia. The subjects were a Japanese cohort (2,012 patients with schizophrenia and 2,170 control subjects). We did not detect any significant genetic association of these SNPs with schizophrenia in this cohort. However, we observed a significant association of SNP02 (rs2276939) in the male patients with schizophrenia (allelic P = 0.003, genotypic P = 0.008). A haplotype analysis revealed that haplotypes consisting of SNP02-SNP03 (rs10014424)-SNP04 (rs6854536) also showed a significant association in the male patients with schizophrenia (P = 0.018). These associations remained significant even after correction for multiple testing. The present findings suggest that the H2AFZ gene may be a susceptibility factor in male subjects with schizophrenia, and that modification of the H2AFZ signaling pathway warrants further study in terms of the pathophysiology of schizophrenia.

Erratum to: Association study of H2AFZ with schizophrenia in a Japanese case-control sample.

Table 1 contains several errors as originally published. Table 1 should read as follows; the corrected values are shown in italics.

Sequencing and expression analyses of the synaptic lipid raft adapter gene PAG1 in schizophrenia.

Disruption of synaptic networks has been advocated in the pathogenesis of psychiatric diseases like schizophrenia. The majority of synaptic proteins involved in neuronal communications are localized in lipid rafts. These rafts form the platform for coordinating neuronal signal transduction, by clustering interacting partners. The PAG1 protein is a transmembrane adaptor protein in the lipid raft signaling cluster that regulates Src family kinases (SFKs), a convergent point for multiple pathways regulating N-methyl-D-aspartate (NMDA) receptors. Reports of de novo missense mutations in PAG1 and SFK mediated reductions in tyrosine phosphorylation of NMDA receptor subunit proteins in schizophrenia patients, point to a putative role in schizophrenia pathogenesis. To evaluate this, we resequenced the entire coding region of PAG1 in Japanese schizophrenia patients (n = 1,140) and controls (n = 1,140). We identified eight missense variants, of which four were previously unreported. Case-control genetic association analysis of these variants in a larger cohort (n = 4,182) showed neither a statistically significant association of the individual variants with schizophrenia, nor any increased burden of the rare alleles in the patient group. Expression levels of PAG1 in post-mortem brain samples from schizophrenia patients and controls also showed no significant differences. To assess the precise role of PAG1 in schizophrenia, future studies with larger sample sizes are needed.

Optimal extent of dopamine D2 receptor occupancy by antipsychotics for treatment of dopamine supersensitivity psychosis and late-onset psychosis.

Several studies have proposed an optimal dopamine D2 receptor occupancy by antipsychotics (OOc) to establish optimal pharmacological treatment of schizophrenia. However, there are limitations to the use of the OOc, especially in application to patients with treatment-resistant schizophrenia, including dopamine supersensitivity psychosis (DSP) or late-onset psychosis (LOP). It has been suggested that D2 receptor density is up-regulated by chronic treatment of antipsychotics in DSP, whereas it may be low in LOP owing to age-related reduction. In estimation of the proposed OOc, these alterations have not been taken into account, which may be one of the factors contributing to the limited application of this index. We here hypothesize that there is an optimal range in the number of D2 receptors available for dopamine binding to elicit adequate neurotransmission in the treatment of patients with schizophrenia. We then estimated the OOc under the assumption that the range is constant while D2 density is variable. The results showed that the OOc and plasma level of antipsychotics increase with an increase in the D2 density but decrease with a decrease in the D2 density. That is, if the range of OOc is 65% to 78% in a standard D2 density, it becomes 82% to 89% under 2-fold up-regulated density and 42% to 63% under a 40% reduced density. The results also indicated that the reduction of the plasma antipsychotic level is greater during a given time period in patients with higher D2 density, as they need a higher antipsychotic dose to achieve the raised OOc, which would account for the clinical features of DSP, for example, acute exacerbation after a discontinuation of antipsychotics. On the other hand, in patients with lower D2 density, only a lower antipsychotic dose will achieve the OOc, and a small increase in the dose will result in a greater increase in occupancy and induce extrapyramidal adverse effects more easily. Furthermore, the reduction of the plasma antipsychotic level during the time period is smaller, which prolongs extrapyramidal adverse effects after discontinuation of antipsychotics in LOP. We also attempted to develop a strategy for the prevention and treatment of patients with DSP or LOP by focusing on D2 density.

Effect of a multidisciplinary approach on hospital visit continuation in the treatment of patients with alcohol dependence.

AIMS: Given the high dropout rates from initial treatment for alcoholism among patients with alcohol dependence, it is highly essential to prevent alcohol-dependent patients from early dropout. This study aims to investigate whether a multidisciplinary approach can help achieve continuous hospital visits for this patient population for initial treatment. METHODS: This is a retrospective cohort study based on the medical records of all sequential alcohol-dependent outpatients who visited Sodegaura Satsukidai Hospital for alcoholism at least once between October 2017 and March 2019. The primary outcome was the difference in the rates of patients who achieved 6 and 12 months of continuous hospital visits following the first visit with and without the multidisciplinary approach. RESULTS: Of all the participants (n = 67), the female-to-male ratios for patients supported with and without the multidisciplinary approach were 6:30 and 5:26, respectively. It was found that the rate of alcoholic patients treated with the multidisciplinary approach (n = 33, 91.7%), who had continuous hospital visits, was significantly higher than that of those without (n = 12, 38.7%) (χ2 = 21.2, p < 0.0001) during the first 6 months of treatment. Similarly, the rate of alcoholic patients treated with the multidisciplinary approach (n = 29, 90.6%) having continuous visits was significantly higher than that of those who did not receive such support (n = 8, 25.8%) (χ2 = 27.3, p < 0.0001) during the first 12 months. CONCLUSION: A multidisciplinary approach can be used to reduce dropout from initial treatment among outpatients with alcohol dependence.

A pilot trial of an online guided self-help cognitive behavioral therapy program for bulimia nervosa and binge eating disorder in Japanese patients.

BACKGROUND: The purpose of this study was to develop an internet-based Guided Self-Help CBT (iGSH-CBT) for Bulimia Nervosa (BN) / Binge Eating Disorder (BED) for Japanese patients and to test its feasibility. METHODS: A single-arm feasibility study. After baseline assessment, patients underwent a 16-week iGSH-CBT program, our Japanese adaption of the European-based Salut BN program. During the treatment period, weekly email support from trained counselors was provided. Evaluations were performed at baseline, after 8 weeks, at the end of the 16-week intervention, and at 2 months after treatment had ended. The primary outcome measure was the change in the weekly frequency of objective binging. Secondary outcomes were the change in the weekly frequency of objective purge episodes, responses on self-report questionnaires of the frequencies of binging and purging, psychopathological characteristics of eating disorders found on BITE, EDE-Q, EDI-2, HADS and EQ-5D, measurements of motivation, and completion of intervention (vs. dropout). RESULTS: Participants were 9 female outpatients with BN (n = 5) or BED (n = 4), of whom 8 (88.9%) attended the assessment at the end of the 16-week intervention. Mean age was 28 years (SD = 7.9). Percent change of the weekly frequency of objective binging was -4.40%, and at the end of the 16-week intervention 25% of the participants had achieved symptom abstinence. CONCLUSIONS: No adverse events were observed during the treatment period and follow-up, and the implementation and operation of the program could be performed without any major problems, confirming the feasibility of iGSH-CBT for BN and BED for Japanese patients. Although no significant change was observed in the weekly frequency of objective binging, the abstinence rate from bulimic behaviors of those who completed the assessments was 25.0% at the end of treatment, and the drop-out rate was 11.1%. iGSH-CBT may be an acceptable and possibly even a preferred method of CBT delivery for Japanese patients with BN or BED, and our Japanese adaptation of Salut BN seems feasible. TRIAL REGISTRATION: UMIN, UMIN000031962. Registered 1 April 2018 - Retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000036334.

Association between precautionary behaviors against coronavirus disease and psychosocial factors in outpatients with a pre-existing disease and their attendants.

Aim: The spread of the novel coronavirus infection (coronavirus disease 2019 [COVID-19]) has caused behavioral changes and mental illness in patients and their attendants during its early phase. The present study aimed to examine the association between precautionary behaviors against COVID-19 and psychosocial factors in outpatients with pre-existing disease and their attendants. Methods: We conducted a cross-sectional paper-based questionnaire survey in Chiba University Hospital on 1019 patients and 513 attendants, and a web-based questionnaire survey in Japan on 3981 individuals from the general population. We evaluated the participants' anxiety about COVID-19, depression, health anxiety, and precautionary behaviors. Results: Regarding knowledge and anxiety about COVID-19, the protective factors for the high precautionary behaviors group were knowledge of COVID-19 (odds ratio [OR] = 1.178, 95% confidence interval [CI]: 1.099-1.263), anxiety about the spread of COVID-19 (OR = 1.348, 95% CI: 1.243-1.461), and anxiety about infecting someone with COVID-19 (OR = 1.135, 95% CI: 1.039-0.239). Regarding psychosocial factors, the protective factors for the high precautionary behaviors group were patients (OR = 1.759, 95% CI: 1.056-2.929), their attendants (OR = 3.892, 95% CI: 1.416-10.700), health anxiety (OR = 2.005, 95% CI: 1.451-2.772), and nondepression states (OR = 1.368, 95% CI: 1.004-1.864). Conclusion: Our findings suggest that patients and their attendants may perform high precautionary behaviors. Health anxiety and nondepression states may be associated with high precautionary behaviors.

A randomized, double-blind, placebo-controlled trial of fluvoxamine in patients with schizophrenia: a preliminary study.

Cognitive impairments in schizophrenia are associated with suboptimal psychosocial performance. Several lines of evidence have suggested that endoplasmic reticulum protein sigma-1 receptors were involved in cognitive impairments in patients with schizophrenia and that the sigma-1 receptor agonist fluvoxamine was effective in treating cognitive impairments in animal models of schizophrenia and in some patients with schizophrenia. A randomized, double-blind, placebo-controlled, parallel trial of fluvoxamine adjunctive therapy in patients with schizophrenia was performed. A total of 48 patients with chronic schizophrenia were enrolled. Subjects were randomly assigned to an 8-week administration of add-on fluvoxamine (n = 24, titrated up to 150 mg/d) or placebo (n =24) in a total 12-week double-blind trial. The primary outcome measure was the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing visual memory, working memory, attention, and executive function. The secondary outcome measures were the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Quality of Life Scale, and the Montgomery-Åsberg Depression Rating Scale. Fluvoxamine was well tolerated. No significant time × group interaction effects were observed in the scores of the CANTAB, Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, or the Montgomery-Åsberg Depression Rating Scale. However, in secondary analyses, the change from baseline to end point on the Spatial Working Memory strategy score (executive function) of CANTAB improved in the fluvoxamine group. This study suggests no major benefit of fluvoxamine adjunctive therapy to improve cognitive impairments in patients with schizophrenia. Nevertheless, a further study using a large sample size will be needed to confirm the secondary analyses findings.

Treatment of refractory catatonic schizophrenia with low dose aripiprazole.

This case is of 54-year-old female with catatonic schizophrenia, characterized by treatment resistance to the pharmacotherapy with olanzapine, risperidone, flunitrazepam, and ECT. Olanzapine and risperidone and flunitrazepam did not improve her catatonic and psychotic symptoms, and induced the extrapyramidal symptoms. The effects of ECT did not continue even for a month. However, the treatment with low-dose aripiprazole dramatically improved the patient's psychotic symptoms and extrapyramidal symptoms. The mechanisms underlying the effects of low-dose aripiprazole in this case remain unclear, but unlike other antipsychotics, aripiprazole is a dopamine D2 partial agonist. In this regard, our results suggest that aripiprazole has numerous advantages, especially in cases of stuporous catatonia and a defective general status.

Delayed sleep-wake rhythm is associated with cognitive dysfunction, social dysfunction, and deteriorated quality of life in patients with major depressive disorder.

Background: The delayed sleep-wake phase is commonly observed in major depressive disorder (MDD) and thought to be associated with functional impairments. This study aimed to evaluate the relationship between the delayed sleep-wake phase, cognitive dysfunction, social dysfunction, and quality of life in patients with MDD. Methods: This cross-sectional design included 33 outpatients with MDD. Objective sleep-wake rhythm was assessed by actigraphy. Functional impairments were evaluated by the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J), World Health Organization Disability Assessment Schedule (WHO-DAS), and Euro QOL 5 dimensions (EQ5D). Results: Actigraphic assessment of the delayed sleep-wake phase (midpoint of sleep) was significantly correlated with the composite score of the BACS-J (r = -0.489, p = 0.010), WHO-DAS score (r = 0.466, p = 0.014), and EQ5D score (r = 0.472, p = 0.013). No significant correlation was found between the other actigraphic sleep parameters (sleep latency, total sleep time, and sleep efficiency) and functional impairments. Conclusion: Our study's results suggested that the delayed sleep-wake phase is associated with cognitive dysfunction, social dysfunction, and deteriorated quality of life in patients with MDD. Clinicians should pay attention to the sleep-wake rhythm in patients with MDD in clinical settings.

Pharmacotherapy for elderly patients with delirium in a general ward setting: A retrospective study.

Antipsychotic medications are widely used in patients with delirium. However, antipsychotics may lead to various adverse events including cardiac arrythmias, extrapyramidal side effects, and oversedation. This study aimed to investigate whether non-antipsychotic medications including ramelteon, suvorexant, and trazodone are useful for the treatment of elderly inpatients with delirium in a general ward setting. This was a retrospective cohort study using medical chart reviews of all consecutive inpatients with hyperactive forms of delirium who were admitted to a regional general hospital. The primary outcome of this study was to evaluate whether non-antipsychotic medication (ramelteon, suvorexant, and trazodone) is inferior, in terms of efficacy and safety, to antipsychotic medication in delirium treatment. Of 154 patients who consulted psychiatrists during the study period, 33 patients were diagnosed with hyperactive delirium. Of these patients, 21 were categorized into the antipsychotic medication group, and 12 were categorized into the non-antipsychotic medication group. The duration of delirium after pharmacological treatments was not statistically different between the two groups. However, the rates of adverse events related to psychotropic medications in the antipsychotic medication group were significantly higher than that in the non-antipsychotic medication group. This study demonstrated that, in the treatment of elderly patients with delirium, non-antipsychotic drugs, such as suvorexant, ramelteon, and trazodone, could be more useful than antipsychotics in terms of efficacy and safety.

Ifenprodil tartrate treatment of adolescents with post-traumatic stress disorder: A double-blind, placebo-controlled trial.

BACKGROUND: Several lines of evidence suggest that glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptor plays a role in certain behavioral manifestations common to Post-Traumatic Stress Disorder (PTSD). Ifenprodil tartrate is a neuroprotective agent that binds to the GluN2B subunit of the NMDA receptor. The aim of this study is to confirm whether ifenprodil tartrate is effective in the adolescent PTSD patients. METHODS: This is a randomized, double-blind, placebo-controlled trial. Ten adolescent (13 to 18 years old) PTSD patients were randomized into two arms: placebo (n = 4), 40 mg/day ifenprodil tartrate (n = 6) for 4 weeks. All of the patients were assessed by IES-R-J (Primary outcome measure), TSCC-J, CDRS-R, DSRS-C-J and CGI-I. RESULTS: A comparison of baseline IES-R-J total scores and 4-week end-point scores showed a mild trend of improvement (p = 0.0895) and the difference score was -9.314. A comparison of baseline scores and 2-week intermediate-point scores showed that IES-R-J hyperarousal subscores and TSCC-J subscores (dissociation subscores, sexual concerns subscores) improved significantly. A comparison of baseline TSCC-J sexual concerns subscores and 4-week end-point scores improved significantly. CONCLUSIONS: Our study may prove to be an short-term effective alternative safe treatment for adolescent patients with PTSD.

Establishment of a Japanese version of the Sick, Control, One Stone, Fat, and Food (SCOFF) questionnaire for screening eating disorders in university students.

OBJECTIVE: This study aimed to validate the Sick, Control, One stone, Fat, and Food (SCOFF) questionnaire in relation to the Eating Disorders Examination Questionnaire (EDE-Q) and to examine the appropriateness of a question concerning weight loss among Japanese university students. The psychometric properties of the two Japanese versions were determined among 649 Japanese college students. The original version (SCOFF-O) employed the original item 3, whereas the revised version (SCOFF-2.5) modified the item to "Have you recently lost more than 2.5 kg within three months?" Validity was tested relative to EDE-Q. RESULTS: The test-retest reliabilities of SCOFF-O and SCOFF-2.5 were 0.52 and 0.57, while the correlations of SCOFF-O and SCOFF-2.5 with EDE-Q were r = 0.53 and r = 0.56. The sensitivity and specificity of SCOFF-O were 65.2 and 89.7, and those of SCOFF-2.5 were 69.5 and 86.5, respectively. There were significant correlations between the question concerning losing 2.5 kg and the EDE-Q subscales. The Japanese version of SCOFF-2.5 is an appropriate tool for the early screening of eating disorders among Japanese university students.

Identification of psychological features and development of an assessment tool for event-related psychological distress after experiencing non-traumatic stressful events.

Stressful events in daily life that are non-traumatic (e.g., family-, school-, work-, interpersonal-, and health-related problems) frequently cause various mood disturbances. For some people, being exposed to non-traumatic but stressful events could trigger the onset and relapse of mood disorders. Furthermore, non-traumatic stressful events also cause event-related psychological distress (ERPD), similar to that of post-traumatic stress disorder (PTSD; i.e., intense intrusive imagery or memory recall, avoidance, and hyperarousal) in the general population and individuals with mood disorders. However, previous ERPD studies only showed that people with ERPD display PTSD-like symptoms after non-traumatic experiences; they failed to get to the crux of the matter by only utilizing trauma- or PTSD-related assessment tools. We thus aimed to identify the psychological phenomena and features of ERPD after individuals experienced non-traumatic stressful events, and to develop and validate an appropriate ERPD assessment tool. First, we conducted a qualitative study to obtain the psychological features through interviews with 22 individuals (mean age = 41.50 years old, SD = 12.24) with major depressive disorder or bipolar disorder. Second, in the quantitative component, we implemented a web-based survey with 747 participants of the general population (mean age = 41.96 years old, SD = 12.64) by using ERPD-related questionnaires created based on the qualitative study; then, we examined the reliability and validity of the ERPD assessment tool. Results yielded that the psychological features of ERPD comprised four factors: feelings of revenge, rumination, self-denial, and mental paralysis. These were utilized in the developed 24-item measure of ERPD-a novel self-report assessment tool. For various professionals involved in mental healthcare, this tool can be used to clarify and assess psychological phenomena in people with ERPD.