Search

Anti-NMDAR encephalitis has a psychotic presentation that is difficult to distinguish from primary psychosis. An atypical psychosis that is similar to schizophrenia, mood disorder, and epilepsy is unique, and the original diagnostic criteria exist only in Japan. The clinical symptoms and courses of anti-NMDAR encephalitis and atypical psychosis are very similar. We investigated whether the diagnostic criteria of atypical psychosis are useful to increase the detection rate of anti-NMDAR encephalitis with psychiatric symptoms. The presence of anti-NR1/NR2B IgG antibodies in the cerebrospinal fluid of 218 newly admitted inpatients initially diagnosed with schizophrenia (n = 151), mood disorder (n = 47), or epilepsy with psychiatric symptoms (n = 20) was assessed by cell-based assay. Of 218 patients, 123 (36.3 years ± SD 17.2, 69.9 % females) fulfilled the diagnostic criteria of category B for atypical psychosis. All 12 patients (9.8 %, 12/123) with anti-NR1/NR2B IgG antibodies fulfilled category B of atypical psychosis statistically better than the patients without anti-NR1/NR2B IgG antibodies (P = 0.0009). Of the 12 patients with anti-NMDAR antibodies, two did not fulfill either criteria of catatonia (DSM-5) or Graus' diagnostic criteria of anti-NMDAR encephalitis during the time course, and 11 patients showed good prognosis with early immunotherapies. In ROC analysis, abnormal electroencephalogram findings showed the highest sensitivity (0.833) for detection of anti-NR1/NR2B IgG antibodies, and 31.3 % of patients with category B atypical psychosis and abnormal electroencephalogram findings had anti-NMDAR antibodies. Lumbar puncture and detection of anti-NMDAR antibodies should be considered for patients who fulfill atypical psychosis diagnosis criteria with an abnormal electroencephalogram.

To reduce cancer care disparities, this study aimed to clarify the difficulties in cancer care for people with mental disorders as perceived by cancer care providers.Cancer care providers at 17 designated cancer hospitals in Japan were surveyed using mail questionnaires. Respondents were asked to rate 29 items related to difficulties or insufficiencies in cancer care for patients with mental disorders on a five-point Likert scale. We analyzed the proportion of respondents who answered "difficult/insufficient" in each item. We also calculated the proportions of responders stratified according to the presence of psychiatric support systems within their hospitals.A total of 388 (58.4%) cancer care providers responded. Among the issues related to "difficulties in diagnosing and treating cancer," support for decision-making, assessment of treatment adherence, and assessment of physical symptoms were perceived as most difficult (73.5%-81.5% of respondents). Among the issues related to 'difficulties or insufficiencies in collaboration among multidisciplinary health care providers,' the issue of advance consultation and sharing information with the patient's primary psychiatric care provider was perceived as most difficult (52.2%). Among the issues related to "insufficiencies of in-hospital and community medical systems," education to provide reasonable accommodation was perceived as most insufficient (47.4%). The perceived difficulties of over half of the issues varied significantly between hospitals depending on the level of psychiatric support systems.This study clarified the difficulties of cancer care in patients with mental disorders as perceived by cancer care providers. Some issues may be resolved by psychiatric liaison teams.

Although reported for Caucasians, changes in plasma clozapine levels after smoking cessation in East Asians remain unclear. We here investigated plasma clozapine levels before and after smoking cessation in Japanese inpatients with schizophrenia. We conducted a retrospective chart review of 14 inpatients with schizophrenia who were being treated with clozapine between June 1, 2019, and July 31, 2019 and who were smokers as of July 1, 2019, the day on which a smoking ban was instituted in the tertiary public psychiatric hospital. The primary outcome was individual differences in plasma clozapine levels between before and after the smoking ban, which were compared using paired t-tests. The mean plasma clozapine level was significantly increased, by 213.4 ng/mL (95% CI 119.9-306.8; p

It is necessary to assess functional impairment when treating schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) has been adopted as a measure of functional disability in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This study was a secondary analysis from a cross-sectional study of health-related behaviors among patients with schizophrenia. We examined the validity and reliability of the Japanese version of the 12-item WHODAS 2.0 when self-administered by such patients. Participants were 350 outpatients with schizophrenia from a psychiatric hospital. The standard six-factor structure of the WHODAS 2.0 showed a good fit for these participants. The Cronbach's alpha coefficient was 0.858, showing good internal consistency. The WHODAS 2.0 showed moderate correlations with the modified Global Assessment of Functioning and Kessler 6 scales (r=-0.434 and 0.555, respectively). The results of this study show that the Japanese version of the 12-item self-administered WHODAS 2.0 has good internal consistency and convergent validity among patients with schizophrenia. Further exploration of the usefulness of WHODAS 2.0 in clinical settings is needed.

Argyrophilic grain disease (AGD), progressive supranuclear palsy (PSP) and corticobasal degeneration are four-repeat (4R) tauopathies that develop in the presenium or later. Whether these diseases are associated with the occurrence of late-onset psychiatric disorders remains unclear. To facilitate the accumulation of clinicopathological findings regarding this issue, we here present a selected series of 11 cases that clinically developed psychotic disorder (n = 7; age at onset: 41-75 years), depressive disorder (n = 1; 49 years), bipolar disorder (n = 2; 32 and 37 years) and somatoform disorder (n = 1; 88 years), and had at least one pathological hallmark of these tauopathies. The mean age at death was 74.3 years. No case showed dementia, at least in the early stage of the course. Nine cases had AGD. Granular fuzzy astrocytes in the amygdala were noted in all AGD cases and one non-AGD case. Two AGD cases had tufted astrocytes (TAs) in the amygdala but not in the frontal cortex and striatum. Three AGD and two non-AGD cases had TAs in the frontal cortex and/or striatum but not in the amygdala. One AGD case had a small number of astrocytic plaques in the frontal cortex, striatum and globus pallidus. Only one case was diagnosed as atypical PSP according to the NINDS-PSP neuropathological criteria. No case had high-level Alzheimer's disease pathology, Lewy body disease or limbic-predominant age-related TDP-43 encephalopathy. Two cases had mild neuronal loss in the hippocampus and substantia nigra, respectively. Clinicopathological studies focusing especially on early changes of 4R tauopathies, as well as the development of surrogate markers of these diseases, may be necessary for better understanding of the pathogenic backgrounds of late-onset psychiatric disorders.

Granular/fuzzy astrocytes (GFAs), a subtype of “aging‐related tau astrogliopathy,” are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N = 26), and progressive supranuclear palsy (PSP, N = 10), Alzheimer’s disease (AD, N = 20) and primary age‐related tauopathy cases (PART, N = 18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation and (iii) immunohistochemical features useful to understand the formation process of GFAs. In AGD cases, GFAs consistently occurred in the amygdala (100%), followed by the putamen (69.2%) and caudate nucleus and frontal cortex (57.7%, respectively). In PSP cases without AGD, GFAs were almost consistently noted in all regions examined (90–100%). In AD cases without AGD, GFAs were less frequent, developing preferably in the putamen (35.0%) and caudate nucleus (30.0%). PART cases without AGD had GFAs most frequently in the amygdala (35.3%), being more similar to AGD than to AD cases. Ordered logistic regression analyses using all cases demonstrated that the strongest independent factor of GFA formation in the frontal cortex and striatum was the diagnosis of PSP, while that in the amygdala was AGD. The age was not significantly associated with GFA formation in any region. In GFAs in AGD cases, phosphorylation and conformational change of tau, Gallyas‐positive glial threads indistinguishable from those in tufted astrocytes, and the activation of autophagy occurred sequentially. Given these findings, AGD, PSP, AD and PART cases may show distinct distributions of GFAs, which may provide clues to predict the underlying processes of primary tauopathies.

Background There are only a few studies of the prevalence of dementia in people with intellectual disability (ID) without Down syndrome (DS), and there is a large difference in the prevalences between reported studies. Moreover, the prevalence of mild cognitive impairment (MCI) in ID has not been reported. We aimed to evaluate the prevalence of dementia in adults of all ages and the prevalence of MCI in people with ID. Furthermore, we tried to clarify the differences depending on the various diagnostic criteria. Methods The survey included 493 adults with ID at 28 facilities in Japan. The caregivers answered a questionnaire, and physicians directly examined the participants who were suspected of cognitive decline. Dementia and MCI were diagnosed according to ICD‐10, DC‐LD, and DSM‐5 criteria. Results The prevalence of dementia was 0.8% for the 45 to 54 years old group, 3.5% for the 55 to 64 years old group, and 13.9% for the 65 to 74 years old group in people with ID without DS. The prevalence of MCI was 3.1% for patients 45 to 54, 3.5% for patients 55 to 64, and 2.8% for patients 65 to 74 with ID without DS. DSM‐5 was the most inclusive in diagnosing dementia and MCI in people with ID. Conclusions People with ID without DS may develop dementia and MCI at an earlier age and higher rate than the general population. Among the diagnostic criteria, DSM‐5 was the most useful for diagnosing their cognitive impairment.

BACKGROUND: Numerous studies focusing on the burden of caregivers of dementia patients have been published. However, there have been few studies focusing on positive affect as an important factor affecting the caregiver burden, and only a few studies comparing the caregiver burden between different dementia diseases have been reported. METHODS: Three hundred and thirty-seven consecutive caregivers of people with dementia participated in this study. The caregiver burden was evaluated by the short version of the Japanese version of the Zarit Burden Interview. RESULTS: Positive affect scores had a significant relationship with the scores of the short version of the Zarit Burden Interview. Caregivers for patients with dementia with Lewy bodies or frontotemporal dementia suffered from a greater burden than those for patients with Alzheimer's disease dementia. CONCLUSIONS: The caregiver burden differed between people caring for patients with different dementia diseases. Positive affect of dementia patients has a significant relationship with caregiver burden, independently from neuropsychiatric symptoms of patients.

Background We performed a follow up study about willingness and behaviors to quit smoking among smokers with schizophrenia in Japan. Methods Participants were outpatients with schizophrenia aged 20–69 years who had been visiting the hospital for ≥1 year as of April 1, 2016, and had visited the hospital more than once in the previous 6 months. A baseline survey on smoking behaviors including current smoking status and smoking cessation stage, was administered in 420 participants that were randomly extracted from a patient pool (n = 680) in 2016, and a follow-up survey was administered in 2017. We calculated the distribution and change in smoking cessation stage, number of smokers and nonsmokers after 1 year, and quitting rate from a naturalistic 1-year smoking-cessation follow up. Results The number of baseline respondents was 350; 113 current smokers and 68 former smokers. Among the 113 current smokers, 104 (92.0%) were followed for 1 year, 79 (70.0%) were interested in smoking cessation, and only 7 had received smoking cessation treatments at baseline. Among the tracked 104 participants, only 6 (5.8%) stopped smoking after 1 year. Among the 25 participants who had intentions to quit smoking within 6 months at baseline, 6 (24.0%) maintained their intention to quit smoking for 1 year, and 16 (64.0%) did not maintain their intention to quit smoking. Conclusions Our findings showed that many smokers with schizophrenia were interested in quitting smoking, but few patients received treatment and actually quit smoking. Timely intervention, including the option to receive smoking cessation treatment, is necessary for those patients with schizophrenia who smoke. Trial registration UMIN Clinical Trials Registry (UMIN000023874, registered on August 31, 2016).

Benzodiazepine (BZD) dependence has become a social problem and results in poor outcomes. Only a few evidence-based treatments for pharmacotherapy, including antidepressants, are recommended.We reported about a 71-year-old man with onset of blindness at 50 years of age due to pigmentary degeneration of the retina developed insomnia at age 59 years, characterized by nocturnal and early morning awakenings.Mirtazapine was effective to not only treat sleep disturbance but also a craving for BZD.The increases of dopamine, norepinephrine, and serotonin signaling by mirtazapine may be related to the effectiveness in reducing BZD dependence.

Background Several studies have attempted to estimate the prevalence of gender dysphoria (GD) from a general population sample. However, no previous studies used reliable questionnaires. Aim To estimate the prevalence of GD in Japan by gender and age using the Utrecht Gender Dysphoria Scale (UGDS). Methods A cross-sectional observational study was conducted with 20,000 respondents between the ages of 20 and 69 who were registered with an internet research company. The study consisted of two phases. First, the participants were asked to self-identify their gender on two 5-point Likert scales. Second, the screened participants completed the UGDS. Outcomes Self-identified gender and GD were defined as follows: ambivalent gender (equally feeling like the birth gender and another gender), incongruent gender (a stronger sense of the latter vs the former), narrow GD (incongruent gender + UGDS score ≥ 41), and broad GD (ambivalent or incongruent gender + UGDS score ≥ 41). Results Among the eligible participants, the age-adjusted proportions of those classified as male (n = 7827) and female (n = 8903) at birth were 6.0% and 5.9%, respectively, for ambivalent gender, and 0.93% and 1.0%, respectively, for incongruent gender. The age-adjusted prevalence of GD was 0.27% (95% confidence interval, 0.18–0.42) and 0.35% (95% confidence interval, 0.25–0.50) for narrow GD and 0.87% (95% confidence interval, 0.69–1.1) and 1.1% (95% confidence interval, 0.86–1.3) for broad GD, respectively. No significant gender differences were found within the age groups, except for broad GD in respondents in their 50s (P = .016). However, for both genders, significant differences were found between age groups such that GD was more prevalent in younger vs older respondents, except for broad GD in respondents classified as female at birth (P = .063). Clinical Implications Clinicians should be aware that the prevalence of GD is not negligible and that it varies with age. GD should be assessed in detail from various perspectives in addition to self-identified gender. Strengths & Limitations This study used a reliable questionnaire to examine the prevalence of GD in a large population. However, the participants did not represent the general population because this was an internet survey. Conclusion The prevalence of GD was much higher than previously estimated by clinic-based studies, and was more frequently associated with participant age vs gender.

RATIONALE Adequate immunotherapies for anti-NMDAR encephalitis during pregnancy produce a relatively good clinical outcome for pregnant mothers and their infants, but there are no reports about the future growth of their babies. The damage of anti-NMDAR antibodies to early neuronal development is still unknown. OBJECTIVES Serum or cerebrospinal fluid from one patient with anti-NMDAR encephalitis (the index patient) and one patient with schizophrenia (the control patient) was administered to primary cultures of dissociated rat cortical neurons, and dendritic outgrowth, centrosome elimination, and branching of dendrites were investigated. For rescue experiments, serum of the index patient was replaced with normal culture media after 3 days' administration of the index patient. RESULTS Serum and cerebrospinal fluid of the index patient statistically significantly impaired dendritic outgrowth of cultured rat cortical primary neurons. Serum of the index patient also statistically significantly delayed centrosome elimination. Impaired dendritic outgrowth and delayed centrosome elimination were not perfectly rescued by changing to normal culture media. Serum of the index patient also statistically significantly reduced the branching of dendrites. CONCLUSIONS This is the first demonstration of the damage by anti-NMDAR antibodies on early dendritic development in vitro. As a strategy to protect embryonic neurons, our findings may support the efficacy of early immunotherapy for anti-NMDAR encephalitis in pregnancy.

Depression in schizophrenia is an important symptom. We investigated whether depression and suicidal symptoms in the chronic phase are related to remote future clinical outcomes in patients with schizophrenia and whether psychotropics improved clinical outcomes.The subjects included 462 outpatients of working age (15 to 64 years old) with schizophrenia treated at Okayama University Hospital from January 2010 to December 2011. We investigated the relationship between the Clinical Global Impression-Severity score at the last visit (average 19.2 years) and the existence of previous depression, suicidal ideas, and suicide attempts. We adjusted by several possible confounders including medical history using multiple regression analysis or logistic regression analysis.Of 462 patients, 168 (36.4%) presented with depression 2 years after schizophrenia onset. A history of suicidal ideas and attempts was related to worse clinical outcome. In males, a history of depression was related to worse clinical outcome, but not in females. Lithium carbonate was related to better clinical outcome in all schizophrenia patients with depression, especially in males. Treatment with antidepressants was related to better clinical outcome only in males.A history of depression or suicidal symptoms in the chronic phase predicted the future worse clinical outcome in patients with schizophrenia. The administration of lithium carbonate or antidepressants might be recommended, especially to male schizophrenia patients with depression.

OBJECTIVE We examined the efficacy of a case management approach to improve participation in colorectal cancer screening among people with schizophrenia. METHODS This was a randomized, parallel group trial. We recruited outpatients with schizophrenia aged 40 years or over from two psychiatric hospitals in Japan. Participants were randomly assigned (1:1) to treatment as usual or case management intervention plus treatment as usual using a web-based system. Attending clinicians and participants were unmasked to the allocation. Case management included education and patient navigation for colorectal cancer screening using a fecal occult blood test. Treatment as usual included direct mail government recommendations. The primary endpoint was participation in colorectal cancer screening assessed using municipal records. We also assessed the secondary endpoint of participation in other cancer screenings (lung, gastric, breast, and cervical). RESULTS Between 3 June and 9 September 2019, 172 eligible participants were randomly assigned to the case management plus treatment as usual group (n = 86) or treatment as usual group (n = 86). One participant was ineligible and another withdrew consent; both were excluded from analysis. A significantly higher proportion of participants received colorectal cancer screening in the case management plus treatment as usual group than in the treatment as usual group (40 [47.1%] of 85 participants vs. 10 [11.8%] of 85 participants, p

Anti-NMDAR encephalitis is increasingly recognized as one etiology of psychiatric symptoms, but there is not enough evidence on patients with mood disorder. We assayed anti-NR1/NR2B IgG antibodies in serum and/or cerebrospinal fluid of 62 patients initially diagnosed with mood disorder by a cell-based assay. We also investigated the specific patient characteristics and psychotic symptoms. At first admission, the patients showed only psychiatric symptoms without typical neurological signs or abnormal examination findings. Four of the 62 patients had anti-NR1/NR2B IgG antibodies. The anti-NR1/NR2B IgG antibody-positive patients showed more super- or abnormal sensitivity (P = 0.00088), catatonia (P = 0.049), and more conceptual disorganization (P 0.0001), hostility (P = 0.0010), suspiciousness (P 0.0001), and less emotional withdrawal (P 0.0001) and motor retardation (P 0.0001) on the Brief Psychiatric Rating Scale than the antibody-negative patients. During the clinical course, anti-NR1/NR2B IgG antibody-positive patients showed more catatonia (P = 0.0042) and met Graus's criteria for diagnosis of anti-NMDAR encephalitis, but negative patients did not. Immunotherapy was effective for anti-NR1/NR2B IgG antibody-positive patients, and there was the weak relationship (R² = 0.318) between the anti-NR1/NR2B IgG antibody titer in the cerebrospinal fluid and the Brief Psychiatric Rating Scale score.

BACKGROUND: Recently, depression with Lewy body pathology before the appearance of parkinsonism and cognitive dysfunction has been drawing attention. Low cardiac metaiodobenzylguanidine (MIBG) uptake is helpful for early differentiation of Lewy body disease (LBD) from late-onset psychiatric disorders even before parkinsonism or dementia appears. In this study, we used MIBG uptake as a tool in suspected LBD, and evaluated the relationship of MIBG results to clinical characteristics and depressive symptoms. METHODS: Fifty-two elderly inpatients with depression were included in this study. The Hamilton Depression Rating Scale (HDRS) was administered at admission, and 123 I-MIBG cardiac scintigraphy was performed. Of 52 patients, 38 had normal and 14 had reduced MIBG uptake. RESULTS: Correlation analyses of the late phase heart-to-mediastinum (H/M) ratio on the MIBG test and each item of the HDRS revealed that the H/M ratio was significantly correlated with scores of 'agitation', 'anxiety-somatic', and 'retardation' on the HDRS. Mean HDRS composite scores of 'somatic and psychic anxiety (Marcos)' and 'somatic anxiety/somatization factor (Pancheri)' were higher in the low uptake group than in the normal uptake group. CONCLUSION: Elderly patients with depression who manifested an obvious somatic anxiety tend to show low MIBG uptake, and are more likely to have Lewy body pathology.

ObjectivesWe examined the efficacy of case management (CM) interventions to encourage participation in colorectal cancer screening for patients with schizophrenia. This study aimed to clarify patients’ acceptability of the intervention and the helpful components of the intervention. Simultaneously, the study aimed to determine the acceptability, appropriateness and feasibility of the intervention from the perspective of psychiatric care providers.Study design and settingThis study was a secondary qualitative analysis of a mixed-method randomised controlled trial that evaluated the efficacy of the CM approach to encourage participation in cancer screening for people with schizophrenia. The intervention comprised education and patient navigation for colorectal cancer screening. Interviews were conducted with patients who received the intervention and staff from two psychiatric hospitals in Japan who delivered the intervention.ParticipantsOf the 172 patients with schizophrenia who participated in the trial, 153 were included. In addition, three out of six providers were included.Data collection and analysisUsing a structured interview, the case manager asked participants about patient acceptability and the helpful components of the intervention. Content analysis was conducted for the responses obtained, and the number of responses was tabulated by two researchers. For the interviews with the providers, opinions obtained from verbatim transcripts were extracted and summarised.ResultsForty-three of the 56 patients perceived that the intervention was acceptable. For the intervention component, inperson counselling with an explanation of the screening process by psychiatric care providers was most frequently reported by the patients as helpful (48 of the 68 respondents). Psychiatric care providers evaluated the intervention as acceptable, appropriate and easy to understand and administer. However, providing the intervention to all patients simultaneously was considered difficult with the current human resources.ConclusionsThis study showed that the CM intervention was perceived as acceptable by patients and acceptable and appropriate by psychiatric care providers.Trial registration numberUMIN000036017.

AIM: Most patients with dementia frequently encounter various problems in their daily lives. Those troubles embarrass both the patients and their families, and cause problems for society. However, there have been few scientific reports on the difficulties in the daily life of patients with dementia. Therefore, we tried to clarify the frequency and characteristics of troubles experienced by patients with dementia. METHODS: Seven medical centers treating dementia patients in Okayama Prefecture, Japan, participated in this survey. A total of 737 patients were placed in one of the three groups: a dementia group (n = 478), a mild cognitive impairment group (n = 199) and a control group (n = 60). The frequency of 13 difficulties was scored for each patient. RESULTS: Among normal participants, no person caused these problems once a year or more frequently. "Massive, recurrent buying" and "acts that risk causing a fire" were reported once a year or more for >10% of mild cognitive impairment patients. "Troubles with wealth management" and "troubles with money management" were the most frequent problems of dementia patients. CONCLUSIONS: Several problems are already sometimes encountered in patients with mild cognitive impairment. It would be useful to know which social difficulties are often seen in dementia patients in order to protect the safety of the patients. It is always difficult to balance respecting the autonomy of dementia patients and ensuring their safely.

AIM: Most patients with dementia frequently encounter various problems in their daily lives. Those troubles embarrass both the patients and their families, and cause problems for society. However, there have been few scientific reports on the difficulties in the daily life of patients with dementia. Therefore, we tried to clarify the frequency and characteristics of troubles experienced by patients with dementia. METHODS: Seven medical centers treating dementia patients in Okayama Prefecture, Japan, participated in this survey. A total of 737 patients were placed in one of the three groups: a dementia group (n = 478), a mild cognitive impairment group (n = 199) and a control group (n = 60). The frequency of 13 difficulties was scored for each patient. RESULTS: Among normal participants, no person caused these problems once a year or more frequently. "Massive, recurrent buying" and "acts that risk causing a fire" were reported once a year or more for >10% of mild cognitive impairment patients. "Troubles with wealth management" and "troubles with money management" were the most frequent problems of dementia patients. CONCLUSIONS: Several problems are already sometimes encountered in patients with mild cognitive impairment. It would be useful to know which social difficulties are often seen in dementia patients in order to protect the safety of the patients. It is always difficult to balance respecting the autonomy of dementia patients and ensuring their safely.

Nalmefene is the only medication marketed to reduce the consumption of alcohol in patients with alcohol dependence, but it remains unclear which patients could most benefit from it. This study aimed to identify clinical moderators that affect treatment response to nalmefene in patients with alcohol dependence.In a multicenter, randomized, controlled, double-blind, phase 3 study of nalmefene on Japanese patients with alcohol dependence, the relationship between the reduction of heavy drinking days (HDD) and total alcohol consumption (TAC) at 12 and 24 weeks of treatment and baseline variables of the participants were analyzed in a linear regression and multiple adjusted analysis.Age 65, no family history of problem drinking, age at onset of problem drinking ≥ 25, and not currently smoking were possible positive moderators. Nalmefene showed a significant HDD reduction in patients with age 65 or no family history of problem drinking, and a significant TAC reduction in patients with age at onset of problem drinking ≥ 25 or who were not currently smoking. After multiple adjusted analyses, age 65 (p = .028), no family history of problem drinking (p = .047), and age at onset of problem drinking ≥ 25 (p = .030) were statistically significant. Not currently smoking (p = .071) was marginally significant. In combination, these moderators indicated synergistic effects.Alcohol-dependent patients with favorable prognostic factors such as non-smoking status, no family history of problem drinking, and a late-onset of problem drinking selectively benefit from nalmefene. Further research is needed to validate these exploratory results.

OBJECTIVE There is no report that statistically evaluates the therapeutic reference (350-600 ng/ml) and adverse drug reaction (ADR) range (>1000 ng/ml) of clozapine (CLZ) recommended by the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) consensus guidelines in an isolated and large sampling study. METHODS We administered CLZ to 131 Japanese patients with treatment-resistant schizophrenia in a multicenter cross-sectional study. Plasma CLZ concentrations were assayed by high-performance liquid chromatography using trough sampling. The Brief Psychiatric Rating Scale (BPRS) and severe dose-dependent ADR (sedation, myoclonus, and seizures) were analyzed statistically after adjusting for possible confounders. RESULTS The daily CLZ dosage showed a moderately positive relationship with the plasma concentration (r = 0.49, p

The mortality rate of patients with schizophrenia is high, and life expectancy is shorter by 10 to 20 years. Metabolic abnormalities including type 2 diabetes mellitus (T2DM) are among the main reasons. The prevalence of T2DM in patients with schizophrenia may be epidemiologically frequent because antipsychotics induce weight gain as a side effect and the cognitive dysfunction of patients with schizophrenia relates to a disordered lifestyle, poor diet, and low socioeconomic status. Apart from these common risk factors and risk factors unique to schizophrenia, accumulating evidence suggests the existence of common susceptibility genes between schizophrenia and T2DM. Functional proteins translated from common genetic susceptibility genes are known to regulate neuronal development in the brain and insulin in the pancreas through several common cascades. In this review, we discuss common susceptibility genes, functional cascades, and the relationship between schizophrenia and T2DM. Many genetic and epidemiological studies have reliably associated the comorbidity of schizophrenia and T2DM, and it is probably safe to think that common cascades and mechanisms suspected from common genes’ functions are related to the onset of both schizophrenia and T2DM. On the other hand, even when genetic analyses are performed on a relatively large number of comorbid patients, the results are sometimes inconsistent, and susceptibility genes may carry only a low or moderate risk. We anticipate future directions in this field.

Aim Social cognition encompasses facial expression recognition (FER), theory of mind, and empathy. Although studies examining FER in large numbers of patients with mild cognitive impairment (MCI) or dementia are rare, relative preservation of happiness recognition in dementia was reported in some studies. In this study, we examined performance on FER tests and its relationship to clinical demographics and other cognitive function test scores in patients with cognitive decline. Methods The present study administered an FER test and several cognitive tests to outpatients at a memory clinic. The FER test presents four facial expressions (happiness, surprise, anger, and sadness). A total of 187 patients were placed in one of the three groups based on their cognitive status: dementia group (n = 63), MCI group (n = 92), and normal cognition group (n = 32). Results The total scores on the FER test significantly differed among the three groups (normal > MCI > dementia). In the recognition of happiness and surprise, the dementia group had significantly lower scores than the normal cognition group. There were no significant differences in the recognition of anger and sadness scores among the three groups. The FER scores for happiness and surprise were primarily related to executive function scores, but the FER scores for anger and sadness were primarily related to age. Conclusions We note the difference in recognition of causative factors among the four emotions (happiness, surprise, anger, sadness). Our study raises serious doubts about the preservation of happiness recognition hypothesis in dementia based on FER tests.

Background, Dementia in people with intellectual disabilities (IDs) is difficult to detect because of preexisting cognitive deficits. An effective screening method is required. The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) was developed as an observer rating tool to screen dementia in people with ID. The aim of this study was to verify the screening accuracy of the DSQIID for Japanese people with ID. Methods Four‐hundred ninety‐three subjects with ID participated in this study. Caregivers who had observed the participants for more than 2 years scored the Japanese version of the DSQIID (DSQIID‐J) of the participants. Three doctors examined participants directly and diagnosed dementia using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. To identify the key screening items that predict dementia, the specificities of a single and pairs of items with 100% sensitivity were evaluated relative to the dementia diagnosis. Results Of 493 participants, 34 were people with Down syndrome (DS), and 459 were people without DS. Seventeen participants were diagnosed with dementia. The suitable cut‐off score of the DSQIID‐J was 10/11 (sensitivity 100% and specificity 96.8%) for screening dementia. The inter‐rater reliability, test–retest reliability and internal consistency of the DSQIID‐J were excellent. Regarding key items, there was no single item with 100% sensitivity, and the best two‐item combination was the pair of ‘Cannot dress without help’ and ‘Walks slower’ (sensitivity 100% and specificity 93.5%). Conclusions We identified several important question items of the DSQIID‐J related to the diagnosis of dementia in people with ID. The DSQIID‐J is a useful screening tool for dementia in adults with ID.

Background Smoking behavior among people with serious psychological distress (SPD) has not been fully investigated in Asia, although smoking has become a public health concern worldwide. Many Western population-based studies indicate that people with psychological distress are more likely to smoke. Methods This study used a national representative data set from the 2010 Comprehensive Survey of Living Conditions of Japan. SPD was defined as scores ≥13 or greater on the Kessler Psychological Distress Scale (K6). Multivariate logistic regression analyses were conducted to analyze the association between SPD and current smoking in Japanese adults. Results In both men (n = 27,937) and women (n = 30,786), SPD was significantly associated with current smoking (adjusted odds ratios [95% confidence intervals]: 1.169 [1.030–1.328] for men and 1.677 [1.457–1.931] for women). Among men, SPD was significantly associated with current smoking only in people aged ≥50 years (1.519 [1.232–1.874]) and married (1.456 [1.228–1.728]). SPD was significantly associated with current smoking in women of all ages. SPD had a greater impact on current smoking for women aged 20–49 years than for those aged ≥50 years (1.832 [1.552–2.162] and 1.445 [1.099–1.900], respectively). Limitations The cross-sectional design precludes assumptions about the direction of causality. In addition, smoking status was self-reported. Conclusions SPD was significantly associated with current smoking in Japan and the association was much stronger for younger women. Clinical strategies are needed to reduce the prevalence of smoking among people with SPD to reduce excess mortality in this population.

IntroductionOne of the reasons for the high mortality rate from cancer in people with schizophrenia is delay in diagnosis. Many studies have shown lower cancer screening rates in people with schizophrenia; however, there are no interventions for people with schizophrenia to increase cancer screening. Therefore, we developed a case management (CM) intervention to encourage participation in cancer screening. The purpose of this study was to examine the efficacy of CM to encourage participation in cancer screening for people with schizophrenia, with particular focus on colorectal cancer screening by faecal occult blood testing, compared with usual intervention (UI), namely, municipal public education.Methods and analysisThis is an individually randomised, parallel group trial with blinded outcome assessments. The participants will be randomly allocated to either the CM plus UI group or UI alone group in a 1:1 ratio using a web-based program at a data management centre. The primary end point of the study is participation in colorectal cancer screening in the year of intervention, which will be assessed based on municipal records.Ethics and disseminationThis study is performed in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects published by Japan’s Ministry of Education, Science, and Technology and the Ministry of Health, Labour, and Welfare and the modified Act on the Protection of Personal Information as well as the Declaration of Helsinki. This study was approved by the institutional ethics committee at the Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital on 23 April 2019 (approval number: RIN1904-003). The findings of this trial will be submitted to an international peer-reviewed journal.Trial registration numberUMIN000036017.

Background Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease. Common first symptoms are dementia, cerebellar ataxia, visual disturbance, and psychiatric symptoms. Seizure as the first symptom of CJD is a very rare finding. Case presentation We experienced an elderly woman who presented initially with status epilepticus following repeated partial seizures in the course of Alzheimer disease (AD) dementia. Anti-convulsive therapy had no effect. Autopsy revealed definite CJD with AD pathology. Coclusions This is the first reported CJD case presenting with status epilepticus in the course of AD dementia.

Background: Clozapine is the most efficacious among antipsychotics for patients with schizophrenia. Nevertheless, clozapine is not effective in more than about 50% of treatment refractory schizophrenia patients, and several pharmacological strategies are used to augment it. Several reviews including meta-analyses have been published, but the efficacy of augmentation therapy for clozapine-resistant patients is not adequately supported. Though there is a weak connection between the oral dose and plasma concentration of clozapine, there is no report of augmentation therapy considering the plasma concentration of clozapine. Blonanserin is reported to be effective in treatment of both positive and negative symptoms of schizophrenia and well tolerated. Methods: We obtained consent to evaluate clinical presentations and clozapine plasma concentrations at the Okayama Psychiatric Medical Center and had not identified the individual for ethical reasons. This is a case report. Results: This case fulfilled the diagnostic criteria of neuroleptic-induced dopamine supersensitivity psychosis. Monotherapy with blonanserin was not effective, but augmentation of blonanserin with clozapine was effective and well tolerated by a clozapine-resistant schizophrenia patient. Conclusion: Because clozapine may ameliorate dopamine supersensitivity psychosis, the addition of blonanserin to clozapine may be effective even if monotherapy with blonanserin was not.

Objective: Among many cognitive function deficits, memory impairment is an initial and cardinal symptom in Alzheimer disease (AD). In most cases, verbal and visual memory scores correlate highly, but in some cases the deficit of verbal or visual memory is very different from that of the other memory. In this study, we examined the neural substrates of verbal and visual memory in patients with AD. Methods: One hundred eighty-eight consecutive patients with AD were recruited from outpatient units. Verbal and visual memory scores were evaluated using the Wechsler Memory Scale – revised. The patients underwent brain SPECT with 99mTc-ethylcysteinate dimer. Results: After removing the effects of age, sex, education, and Mini-Mental State Examination scores, correlation analysis showed a significant correlation of verbal memory scores to regional cerebral blood flow (rCBF) in the bilateral cingulate gyrus and left precuneus. Similarly, a significant correlation of visual memory scores to rCBF was found in the right precuneus and right cingulate gyrus. Conclusion: The posterior medial cortices (PMC) are very important areas in episodic memory among patients with mild AD. Verbal memory is more closely related to the both sides of the PMC, while visual memory is more closely related to the right PMC.

Aim Early clinical response predicts symptomatic remission and recovery in the maintenance treatment phase of first-episode schizophrenia (FES). However, little is known about predictors of symptomatic remission during acute treatment of severely ill patients with FES. Here, we conducted a secondary analysis of our retrospective observational study, which examined response, remission and treatment-resistance rates in seriously ill patients with FES spectrum disorders involuntarily hospitalized and treated with algorithm-based pharmacotherapy. Methods We performed a retrospective chart review of 131 involuntarily admitted patients with schizophrenia or schizoaffective disorder. Our algorithm aimed to delay olanzapine treatment, standardize medications and suggest initiation of clozapine after failure of third-line antipsychotic treatment. The duration of each adequate antipsychotic treatment at an optimal dosage was 4 weeks or more. Remission was defined using the symptom-severity component of consensus remission criteria. A logistic regression model was applied to identify significant predictors of remission at discharge. Results Overall, 74 patients (56%) were in remission at discharge. Non-remitters were hampered from becoming remitters mainly by the presence of negative symptoms. There were no differences in first-line antipsychotics, dosage of antipsychotics at time of response and adherence rates to algorithm-based pharmacotherapy between remitters and non-remitters. Shorter duration of untreated psychosis, favourable early response and less negative symptoms at baseline were identified as independent predictors of remission at discharge. Conclusions The importance of early intervention and specific and adequate treatments of negative symptoms is highlighted.