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Background Guideline for Pharmacological Therapy for Schizophrenia was published by the Japanese Society of Neuropsychopharmacology in 2015. “Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)” project aimed to standardize medical practice using quality indicators (QIs) as indices to evaluate the quality of medical practice. In this study, we have reported the quality indicator values of prescription before the beginning of the guideline lectures in the EGUIDE project to ascertain the baseline status of treating patients with schizophrenia. Methods A cross‐sectional, retrospective case record survey was conducted, involving 1164 patients with schizophrenia at the time of discharge. We checked all types and dosage of psychotropic drugs. Results Forty‐three percent of patients had antipsychotic polypharmacy, and substantial concomitant medication was observed (antidepressants; 8%, mood stabilizers: 37%, anxiolytics or hypnotics: 68%). Conclusions In the results obtained in this study, we plant to report changes in the effectiveness of education in the EGUIDE project near the future. This study reports the prescription pattern in schizophrenia in Japan from EGUIDE (Effectiveness of Guideline for Dissemination and Education in psychiatric treatment) project. A cross‐sectional, case record survey conducted, involving 1164 patients with schizophrenia at the time of discharge. Forty‐three percent of patients received antipsychotic polypharmacy. Based on the results, we plan to report changes in the effectiveness of education in the EGUIDE project in the future.

Aim Bee honey is widely used as a bioactive food to improve general health and produce therapeutic benefits in various physical disorders. It also improves cognitive and mood‐related behaviors and symptoms in mice and humans. Still, its direct effect on brain cells is unclear. Here, we examined the effect of whole honey on the survival of astrocytes exposed to oxidative stress. Methods Cultured cortical astrocytes were treated with honey (0.1%, 0.3%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 3%, and 5% [v/v]) for 24 hours followed by H2O2 (100 μmol/L) for 3 hours. Cellular viability was assessed with MTT assay. Results Honey prevented cellular death in a dose‐dependent manner compared with H2O2‐treated cells. Honey at 1% concentration had the most significant effect (P = .015). Conclusion Bee honey exerts a neuroprotective effect through its antioxidant activity. This study tested the effect of bee honey on the survival of astrocytes exposed to H2O2‐induced oxidative stress. Honey prevented cellular death in a dose‐dependent manner compared with H2O2‐treated cells. Honey at 1% concentration had the most significant effect (P = .015).

Aims Chronic stress and glucocorticoid exposure are risk factors for depression. Oxytocin (OT) has been shown to have antistress and antidepressant‐like effects in male rodents. However, depression is twice as common in women than in men, and it remains unclear whether OT exerts antidepressant‐like effects in women with depression. Therefore, in this study, we investigated the therapeutic effect of chronic OT administration in a female mouse model of dexamethasone (DEX)‐induced depression. Methods Female C57BL/6J mice were administered saline (vehicle, s.c.), DEX (s.c.), or OT (i.p.) + DEX (s.c.) daily for 8 weeks, and then assessed for anxiety‐ and depression‐like behaviors. We also examined the hippocampal levels of phosphorylated cAMP response element‐binding protein (p‐CREB) and brain‐derived neurotrophic factor (BDNF), which are important mediators of the response to antidepressants. Results Simultaneous OT treatment blocked the adverse effects of DEX on emotional behaviors. Furthermore, it upregulated p‐CREB and BDNF in the hippocampus. Conclusion OT may exert antidepressant‐like effects by activating hippocampal CREB‐BDNF signaling in a female mouse model of depression.

Aim Patients with autism spectrum disorder (ASD) are prone to develop overt psychosis and share symptom presentations with those with schizophrenia (SZ). This study aimed to explore differences in the distributions of psychotic symptoms among first‐visit patients with ASD, SZ, or a nonpsychiatric diagnosis (N‐PD). Methods Data from first‐visit patients were retrospectively collected from medical records from the Department of Psychiatry, Dokkyo Medical University Hospital between June 2019 and May 2021. A total of 254 patients with data on the PRIME Screen‐Revised (PS‐R) assessments were included in our analysis. In the hospital, all psychiatric diagnoses were based on the DSM‐5 diagnostic criteria. Results In the ASD, SZ, and N‐PD groups, endorsements of perplexity and delusional mood were 15.6% (7/45), 41.5% (44/106), and 1.1% (1/88), and those of perceptual abnormalities were 11.1% (5/45), 40.6% (43/106), and 2.3% (2/88), respectively. Trend analysis clarified that the endorsement of these psychotic symptoms increased from N‐PD to ASD and SZ. In the multivariate‐adjusted multinomial logistic regression analysis, the ASD and N‐PD groups were compared with the SZ group. Higher age and the presence of perceptual abnormalities were associated with lack of an ASD diagnosis, whereas male sex, lack of perplexity and delusional mood, and lack of perceptual abnormalities were associated with N‐PD. Conclusion Our results are preliminary; however, a detailed assessment of positive symptoms might facilitate differentiation between ASD and SZ. In the multivariate‐adjusted multinomial logistic regression analysis, the autism spectrum disorder (ASD) and nonpsychiatric diagnosis groups were compared with the schizophrenia group. Higher age and the presence of perceptual abnormalities were associated with lack of an ASD diagnosis, whereas male sex, lack of perplexity and delusional mood, and lack of perceptual abnormalities were associated with N‐PD.

Aims The purpose of this study was to retrospectively investigate care difficulties experienced by caregivers of people with schizophrenia during COVID‐19 pandemic lockdowns in Japan (April 7‐May 25, 2020) and examine associations between these care difficulties during lockdowns and daily caregiver burden. Methods Data were collected from 132 participants of the LINE Schizophrenia Family Association using an online survey. Results Caregivers were mostly concerned about who would care for people with schizophrenia if caregivers become infected with COVID‐19. A significant association was found between higher daily caregiver burden and more difficult care experiences during COVID‐19 pandemic lockdowns (B = 0.58, 95% confidence interval, 0.40‐0.75, P < .01, adjusted R‐squared = .34). Conclusions Further studies and supports for caregivers of people with schizophrenia are needed. This study showed care difficulties experienced by caregivers of people with schizophrenia during COVID‐19 pandemic lockdowns in Japan and its association with daily caregiver burden.

Aim Excitatory projections from the prelimbic cortex (PL) to the basolateral nucleus of the amygdala (BLA) are implicated in the regulation of anxiety‐like behaviors, and we previously demonstrated that anxiolytic‐like effects of the selective delta‐opioid receptor (DOP) agonist KNT‐127 is involved in suppressing glutamate neurotransmission in the PL. Here, we investigated the mechanisms underlying the anxiolytic‐like effect of KNT‐127 in mice by combining optogenetic stimulation of the PL–BLA pathway with behavioral analyses. Methods Four‐week‐old male C57BL/6J mice received bilateral administration of adeno‐associated virus (AAV)2‐CaMKIIa‐hChR2(H134R)‐enhanced yellow fluorescent protein (EYFP) into the PL to induce expression of the light‐activated excitatory ionic channel ChR2. Subsequently, an optic fiber cannula connected to a wireless photo‐stimulator was implanted into the BLA for optogenetic PL–BLA pathway stimulation. We evaluated innate anxiety using the elevated plus maze (EPM) and open field (OF) tests as well as learned anxiety using the contextual fear conditioning (CFC) test. Results Optogenetic activation of the PL–BLA pathway enhanced anxiety‐like behaviors in the EPM and OF, while prior subcutaneous administration of KNT‐127 (10 mg/kg) reduced this anxiogenic effect. In contrast, optogenetic activation of the PL–BLA pathway had no significant effect on conditioned fear. Conclusion Our findings indicate that the PL–BLA circuit contributes to innate anxiety and that the anxiolytic‐like effects of KNT‐127 are mediated at least in part by suppression of PL–BLA transmission. The PL delta‐opioid receptor may thus be an effective therapeutic target for anxiety disorders. Our findings indicate that the PL–BLA circuit contributes to innate anxiety. In Addition, the anxiolytic‐like effects of KNT‐127 are mediated PL–BLA circuit.

The Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) project, which is a nationwide dissemination and implementation program for clinical practice guidelines (CPGs) in the field of psychiatry, is currently ongoing. In the current study, a subjective assessment of the participants in the EGUIDE programs was assessed using a questionnaire. Then, the relationships between the subjective assessment, the characteristics of the participants, and the clinical knowledge of the CPGs were evaluated. More than 90% of the participants gave a high rating for the components of content, recommendation, knowledge, skill, and adherence, but not for the component of confidence. A positive correlation was found between years of professional experience and the score of confidence. These results suggest that it may be necessary to apply the knowledge and skills of CPGs obtained in the education programs into practice to increase confidence in the proper use of psychiatric therapies based on CPGs. Through the educational program of clinical practice guidelines (CPGs; major depressive disorder:MDD and schizophrenia: SC) \"EGUIDE,\" we found that participants gave a high rating for the components of content, recommendation, knowledge, skill, and adherence, but not for the component of confidence. A positive correlation was found between years of professional experience and the score of confidence. These results suggest that it may be necessary to apply the knowledge and skills of CPGs obtained in the education programs into daily practice to increase confidence in the proper use of psychiatric therapies based on CPGs.

Aim Selective serotonin reuptake inhibitors (SSRIs) are used to treat major depressive disorder (MDD) and other psychiatric disorders (e.g., obsessive compulsive disorder, social anxiety disorder, and panic disorder). In MDD treatment, SSRIs do not show remission in approximately 30% of patients, indicating a need for a better treatment option. Forced swimming test (FST) is a behavioral assay to evaluate depression‐like behavior and antidepressant efficacy in rodents. In the present study, we evaluated the combination effect of brexpiprazole with SSRIs on FST in mice, in order to investigate their synergistic effect. Methods Brexpiprazole (0.003 mg/kg) was intraperitoneally injected to mice 15 min before testing. Escitalopram (10 mg/kg), fluoxetine (75 mg/kg), paroxetine (10 mg/kg), or sertraline (15 mg/kg) were orally administered to mice 60 min before testing. Then, the mice were placed in water and immobility time was measured. Data from animals treated with escitalopram, fluoxetine, paroxetine, and sertraline were pooled as SSRI‐treated group data. Results Combination treatment of brexpiprazole with SSRIs reduced immobility time in FST more than vehicle or each single treatment. A significant interaction effect was confirmed in the combination of brexpiprazole and SSRIs (p = 0.0411). Conclusion Efficacy of adjunctive brexpiprazole has already been demonstrated in clinical trials in MDD patients not adequately responding to antidepressants including escitalopram, fluoxetine, paroxetine, and sertraline. The synergistic antidepressant‐like effect of brexpiprazole with SSRIs found in this study supports the already known clinical findings. Synergistic antidepressant‐like effect of brexpiprazole with selective serotonin reuptake inhibitors was confirmed on the forced swimming test in mice. The combination treatment reduced immobility time in the forced swimming test more than vehicle or each single treatment.

Gamma oscillations, thought to arise from the activity of ɣ‐aminobutyric acid (GABA)ergic interneurons, have potential as a biomarker for schizophrenia. Gamma‐band auditory steady‐state responses (ASSRs) are notably reduced in both chronic and early‐stage schizophrenia patients. Furthermore, alterations in gamma‐band ASSRs have been demonstrated in animal models through translational research. However, the 40‐Hz harmonic responses of the 20‐Hz ASSR are not as well‐characterized, despite the possibility that these harmonic oscillatory responses may reflect resonant activity in neural circuits. In this study, we investigated the 40‐Hz harmonic response to the 20‐Hz ASSR in the early stages of schizophrenia. The study recruited 49 participants, including 15 individuals at ultra‐high‐risk (UHR) for psychosis, 13 patients with first‐episode schizophrenia (FES), and 21 healthy controls (HCs). The 40‐Hz harmonic responses of the 20‐Hz ASSR were evident in all groups. Interestingly, while previous report observed reduced 40‐Hz ASSRs, the 40‐Hz harmonic responses of the 20‐Hz ASSR were not reduced in the UHR or FES groups. These findings suggest that the gamma‐band ASSR and its harmonic responses may represent distinct aspects of pathophysiology in the early stages of schizophrenia. We investigated the 40‐Hz harmonic response to the 20‐Hz ASSR in the early stages of schizophrenia and found intact 40‐Hz harmonic responses of the 20‐Hz ASSR in the UHR or FES groups.

Background More than 800 000 people die by suicide annually. The heritability of suicide is 30%–50%. We focused on the hypoxia response element (HRE), which promotes the expression of macrophage migration inhibitory factor (MIF) via the hypoxia‐inducible factor (HIF) pathway, important in neurogenesis and neuroprotection. We examined a genetic polymorphism of rs17004038, a single‐nucleotide polymorphism (SNP), in suicide completers and controls. Methods The study population included 1336 suicide completers and 814 unrelated healthy controls. All participants were Japanese. We obtained peripheral blood, extracted DNA, and genotyped the patients for SNP rs17004038 (C > A). Results No significant differences were observed between the two groups in either the allele or genotype analyses. Subgroup analyses by sex, age (<40 or ≥40), and suicide method (violent or nonviolent suicide) were performed with similar results. Conclusion No association was observed between SNP rs17004038 and suicide completion. Although it is challenging to collect a large number of samples from suicide completers, further MIF‐related genetic studies, including those of rs17004038, are necessary with larger sample sizes. This study examined SNP rs17004038 at the HRE on the MIF gene between 1336 suicide completers and 814 controls. No significant differences were observed between the two groups in either the allele or genotype analyses. No association was observed between SNP rs17004038 and suicide completion.