Improvement of psychiatrists' clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' project: A nationwide dissemination, education, and evaluation study.

AIM: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. METHODS: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants' clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants' demographics and their clinical knowledge scores. RESULTS: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. CONCLUSION: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants' clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.

Chronic exposure to carbon monoxide in two elderly patients using a kotatsu, a traditional Japanese charcoal-based heater.

We report on two elderly patients with cognitive impairments, for whom chronic carbon monoxide (CO) exposure was suspected based on elevated carboxyhaemoglobin levels in their serum. On their initial visits, cognitive impairment and brain magnetic resonance imaging findings in both patients were compatible with the diagnosis of Alzheimer's-type dementia. However, after discontinuation of the use of a kotatsu, a charcoal-based heater, their serum carboxyhaemoglobin levels normalized and their physical symptoms resolved. Their cognitive function also slightly improved. The causal relationship between physical symptoms and cognitive impairment after chronic CO poisoning is uncertain; however, it is possible that chronic exposure to low CO levels exacerbated the clinical manifestation in our patients.

Patterns of hippocampal atrophy differ among Alzheimer's disease, amnestic mild cognitive impairment, and late-life depression.

AIM: This study investigated whether the characteristic changes in hippocampal atrophy seen in coronal scans are useful for differentiating Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), and major depressive disorder (MDD). METHODS: Subjects included 58 patients with AD, 33 with aMCI, 20 with MDD, and 22 normal controls, all aged 60 years or older. For each subject, eight coronal short TI inversion recovery images perpendicular to the hippocampal longitudinal axis were obtained. Images were manually measured using the conventional region of interest method of quantitative analysis. RESULTS: The overall trend in the corrected volumes of the hippocampus was AD < aMCI < MDD < normal controls. We found atrophy in all slices in AD, atrophy centred on the hippocampal head in aMCI, and atrophy in the slice of the hippocampal body 12 mm from the amygdala in MDD. CONCLUSIONS: The present study suggested that our method of comparing hippocampal atrophy by region may be useful in distinguishing AD, aMCI, MDD, and normal controls.

Comparison of alterations in cerebral hemoglobin oxygenation in late life depression and Alzheimer's disease as assessed by near-infrared spectroscopy.

BACKGROUND: Patients with Alzheimer's disease (AD) often present with apathy symptoms resembling the decreased motivation observed in depressed patients. Therefore, differentiating the initial phase of AD from late life depression may be difficult in some cases. Near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that uses near-infrared light to measure changes in hemoglobin concentration on the cortical surface during activation tasks. The objective of this study was to investigate differences in brain activation associated with late life depression and with AD by means of NIRS. METHODS: NIRS was performed in 30 patients with depression, 28 patients with AD, and 33 healthy controls, all aged 60 years or older. During two tasks, a verbal fluency task and a visuospatial task, changes in oxygenated hemoglobin concentration in the frontal and parietal cortices were investigated. RESULTS: In the visuospatial task, cortical activation was lower in the depressed group than in the AD group, and significant differences were observed in the parietal cortex. CONCLUSIONS: NIRS can detect differences in brain activation between patients with late life depression and those with AD. NIRS is a promising tool for the differential diagnosis of late life depression and AD.

Outcomes of an interdisciplinary return to work intervention including occupational therapy for mood and adjustment disorders: A single-arm clinical trial.

BACKGROUND: Mood and adjustment disorders are two major causes of long-term sick leave among employees, leading to large social losses. Therefore, a return to work (RTW) intervention was attempted, targeting patients with mood and adjustment disorders. OBJECTIVE: This study aimed to investigate the outcome of an interdisciplinary RTW intervention including occupational therapy implemented within the Japanese healthcare framework. METHODS: An interdisciplinary RTW intervention including occupational therapy was conducted five times a week for approximately three months, targeting individuals with mood and adjustment disorders who took a leave of absence. Their mental symptoms, cognitive functioning, job performance, temperament, social adaptation, psychosocial state, and readiness to RTW before and after the intervention were evaluated. Full-time RTW ratios at 3, 6, 12, 18, and 24 months from baseline were followed up and compared with those of prior studies. RESULTS: A total of 30 individuals completed the intervention. After the intervention, participants' psychological symptoms, cognitive function, vocational aptitude, temperament, social adaptation, psychosocial state, and readiness to RTW improved (p≤0.001-0.0279). The ratios of RTW at 3, 6, 12, 18, and 24 months from the baseline were 6.7%, 46.7%, 73.3%, 77.8%, and 82.6%, respectively, reflecting a higher pattern than prior reports. CONCLUSIONS: The interdisciplinary RTW intervention including occupational therapy has the potential to improve not only depressive symptoms but also cognitive functioning, job performance, social adaptation, and readiness to RTW. They can also raise RTW ratios.

A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is usually described as a pathological proliferation of prostatic fibroblasts/myofibroblasts and epithelial cells. In the present study of BPH samples, we have made a morphological and immunohistochemical study of BPH prostatic sections using markers of proliferation, apoptosis, hormone receptors, and TGF-beta signaling. We found no evidence of proliferation in the stroma but in the epithelium of some ducts; 0.7% of the basal and 0.4% of luminal cells were positive for Ki67 and PCNA. Androgen receptor and estrogen receptor beta (ERbeta)1 and ERbetacx were abundant in both stromal and epithelial compartments but cells expressing ERalpha were very rare. What was very common in all BPH samples was the following: (i) regions of the ductal epithelium where the epithelial cells did not express E-cadherin, had lost their polarization, and become spindle shaped (the nuclei of these cells were strongly positive for pSmad 3 and Snail); and (ii) regions where the walls of the blood vessels were extremely thick and there was loss of endothelial layer. Loss of E-cadherin, increased pSmad 3, and high expression of Snail are all characteristic of epithelial-mesenchymal transition (EMT). We conclude that BPH is not a disease of prostatic stromal proliferation but rather of accumulation of mesenchymal-like cells derived from the prostatic epithelium and the endothelium. TGF-beta is thought to play a key role in EMT. Our data suggests that TGF-beta/Smad should be considered as targets for treatment of BPH.

Poor performance on the Iowa gambling task in children with obsessive-compulsive disorder.

BACKGROUND: Several lines of evidence implicate orbitofrontal cortex dysfunction in the pathophysiology of obsessive-compulsive disorder (OCD). The purpose of this study was to investigate neuropsychological dysfunction of the orbitofrontal cortex in children with OCD. METHODS: The Iowa Gambling Task (IGT), which reflects orbitofrontal cortex function, and the Wisconsin Card Sorting Test (WCST), which is associated with functioning of the dorsolateral prefrontal cortex, were administered to 22 children with OCD and 22 healthy controls matched for gender, age, and intelligence. RESULTS: OCD patients displayed poor performance on the IGT. In contrast, performance on the WCST was not impaired in OCD patients compared to controls. CONCLUSIONS: These findings are in line with previous studies demonstrating that OCD in childhood is associated with a dysfunction of orbitofrontal-striatal-thalamic circuitry.

A dissemination and education programme to improve the clinical behaviours of psychiatrists in accordance with treatment guidelines for schizophrenia and major depressive disorders: the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project.

BACKGROUND: Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists. AIMS: The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes. METHOD: A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme. RESULTS: All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending. CONCLUSIONS: All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists.

Subjective assessment of participants in education programs on clinical practice guidelines in the field of psychiatry.

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.

Sex differences in serum levels of 5α-androstane-3ß, 17ß-diol, and androstenediol in the young adults: A liquid chromatography-tandem mass spectrometry study.

Animal experiments have consistently shown that estrogen receptor ß (ERß)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands for ERß include 5α-androstane-3ß, 17ß-diol (3ßAdiol) and androstenediol (Δ5-diol). We determined, for the first time, the exact serum levels of 3ßAdiol and Δ5-diol in young healthy volunteers using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We investigated the effect of the menstrual cycle on the levels of these steroids in women; then, we performed a gender comparison. Blood samples were collected from 48 subjects: 23 women (mean age = 28.4±7.8 years) and 25 men (mean age = 31.4±7.8 years). We collected the blood samples of women at three time-points in the menstrual cycle: the early follicular phase, ovulatory or mid-cycle phase, and mid-luteal phase. A total of 92 blood samples were analyzed using LC-MS/MS. The levels of two well-studied steroids, namely dehydroepiandrosterone (DHEA) and 17ß-estradiol (E2), were simultaneously measured. Depression rating scale (Hamilton Rating Scale for Depression, Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology) scores were also recorded at the time of blood sampling. Significant differences in the levels of 3ßAdiol and E2 and in the depression rating scale scores were observed over the duration of the menstrual cycle of the women. The levels of 3ßAdiol and Δ5-diol were significantly lower in women than in men. E2 levels were higher in women than in men, and DHEA levels did not differ significantly between men and women. Further, women had higher scores than men on the Hamilton Rating Scale for Depression. Sex differences in depressive symptoms can be explained by 3ßAdiol and Δ5-diol levels, and the effect of the menstrual cycle on mood can be explained by 3ßAdiol and E2 levels, not by Δ5-diol level.

Possible utilization of salivary IFN-γ/IL-4 ratio as a marker of chronic stress in healthy individuals.

INTRODUCTION: Several studies show that psychological stress reduces Th1/Th2 ratio in blood samples. However, evidence is scarce regarding the cytokine alterations during stress in saliva. We investigated the influence of chronic stress on Th1/Th2 ratio and cytokine profiles in the saliva of healthy individuals. Further, we examined the associations of the salivary cytokine levels with sleep and attention problems, which are closely related with psychological stress. METHODS: Salivary levels of 27 cytokines were measured by multiplex bead array assays in 31 healthy young individuals (health science students and hospital staff consisting of 11 men and 20 women, mean age [standard deviation] =21.5 [0.8] years). The Kessler Psychological Distress scale (K10) and Athens Insomnia Scale (AIS) were administered to assess subjective chronic psychological stress and sleep problems. Further, participants were asked to wear Actigraph GT3X accelerometers for 3 days to assess the total sleep time. Attention problems were assessed by administering the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT). RESULTS: Thirteen cytokines with >80% detectable results were included in the main analyses. The IFN-γ/IL-4 ratio, which is a commonly used index for Th1/Th2 ratio, showed significant negative correlations with the K10 and AIS scores. None of the cytokines were significantly associated with sex, body mass index, sleep index measured by Actigraph, or IVA-CPT scores. CONCLUSION: Chronic stress may be associated with alterations of the Th1/Th2 balance in salivary cytokine production. IFN-γ/IL-4 ratio in saliva may serve as a potential biomarker of chronic stress in healthy individuals.

Psychotic symptoms complicate the clinical differentiation of Parkinson's disease with major depressive disorder from dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is diagnosed clinically according to the diagnostic criteria in the Third Report of the DLB Consortium. However, psychotic symptoms, such as visual hallucinations, delusions, and stupor, may complicate the clinical diagnosis of DLB. The present study reports on a patient with Parkinson's disease that was difficult to distinguish from DLB because of the presence of various psychotic symptoms. In making a diagnosis of DLB, it is important to assess essential psychiatric features and to observe patients for any changes in these features.

Prescription patterns in patients with schizophrenia in Japan: First-quality indicator data from the survey of "Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)" project.

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.

Prion disease causes less severe lesions in human hippocampus than other parts of brain.

AIM: The hippocampus can be very sensitive to damage in the scrapie-infected mouse, a well-established animal model of prion diseases. Terminally ill scrapie-infected animals exhibit nearly complete loss of cornu ammonis (CA) 1 pyramidal neurons, but few studies have focused on the neuropathological lesions of the human hippocampus in autopsied brain tissue; in particular, few findings on differences in severity of pathology between the hippocampal and parahippocampal formations have been obtained. The aim of the present paper is to evaluate the human hippocampus of prion disease through neuropathological examination. METHODS: A systemic, detailed neuropathological study throughout the subdivisions of the hippocampus was carried out in 23 autopsied cases of prion diseases. Prion protein immunohistochemistry was performed in serial brain sections to determine the topography of prion deposits. RESULTS: Compared to lesions in other brain regions, hippocampal lesions were mild, despite numerous prion deposits. The distribution of prion deposits did not appear to be correlated with neuropathological changes. The present findings differed from the hippocampal pathology observed in scrapie-infected mice. In addition, differences in neuropathological severity were observed within the hippocampal formation. CONCLUSION: The human hippocampus may be protected from the neurotoxic effects of prion deposits.

Jitteriness/Anxiety Syndrome Developing Immediately following Initiation of Oral Administration of Sertraline.

Here, we report our experience with patients in whom jitteriness/anxiety syndrome developed immediately following the start of oral sertraline administration. Administration was discontinued in these patients on day 2, and the jitteriness/anxiety syndrome improved the following day. Jitteriness/anxiety syndrome may develop immediately following oral administration of even low doses of sertraline, and improvement can be expected if sertraline is promptly discontinued.