Effect of lemborexant on pharmacokinetics of clozapine: A potential drug-drug interaction mediated by time-dependent inhibition of CYP3A4.

Clozapine (CLZ) is extensively used for treatment-resistant schizophrenia (TRS) with caution to avoid serious adverse events such as agranulocytosis and drug-drug interactions (DDIs). In the current report, we present a case of a 35-year-old male non-smoking TRS patient whose steady-state plasma trough concentrations (Ctrough ) of CLZ and its active metabolite, N-desmethylclozapine (NDMC), were significantly increased after initiating oral administration of lemborexant (LEM), a dual orexin receptor antagonist, for the treatment of insomnia. The patient experienced oversedation with sleepiness and fatigue while maintaining high levels of Ctrough of CLZ. The increased concentrations of CLZ returned to normal ranges after the discontinuation of LEM dosing, implying a pharmacokinetic DDI between CLZ and LEM. To gain insight into possible mechanisms, we performed in vitro assays of CYP1A2- and CYP3A4-mediated CLZ metabolism by measuring the formations of NDMC and clozapine N-oxide (CNO). In accordance with previous studies, the incubation of CLZ with each enzyme resulted in the production of both metabolites. LEM had only a weak inhibitory effect on CYP1A2- and CYP3A4-mediated CLZ metabolism. However, the preincubation of LEM with CYP3A4 in the presence of NADPH showed a significant enhancement of inhibitory effects on CLZ metabolism with IC50 values for the formations of CNO and NDMC of 2.8 µM and 4.1 µM, respectively, suggesting that LEM exerts as a potent time-dependent inhibitor for CYP3A4. Taken together, the results of the current study indicate that co-medication of CLZ with LEM may lead to increase in exposure to CLZ and risks of CLZ-related adverse events.

Post-Disaster Community Transition of Psychiatric Inpatients: Lessons from the Fukushima Nuclear Accident.

This study sought to explore factors related to community transition after the mandatory evacuation of psychiatric inpatients to other hospitals owing to the Fukushima Daiichi Nuclear Power Plant accident. A retrospective cohort design was adopted and 391 psychiatric patients were examined. Univariate and multivariate analyses were conducted to confirm the association between the achievement or non-achievement of discharge to community living and their backgrounds (age, gender, evacuation destination, psychiatric diagnoses, and physical complications). Multivariate analysis indicated that patients with psychiatric diagnoses of schizophrenia, schizotypal, and delusional disorders (International Statistical Classification of Diseases and Related Health Problems 10th revision, F20-29), and those with physical diagnoses of the circulatory (I00-95) and digestive (K00-93) systems showed a significant association with the non-attainment of community transition. From these results, we hypothesized that difficulties in the management of medication during and immediately after the extremely chaotic settings of evacuation could have negative effects on the community transitions. Furthermore, another possible concern was that individuals' persistent psychotic status before the accident had been carried over to the destination hospitals. Therefore, pre-disaster daily cooperation across hospitals and challenges for vulnerable psychiatric patients' future community lives are also essential.

Posttraumatic stress response following the loss of significant close others in the Great East Japan Earthquake: Fukushima Health Management Survey.

During the Great East Japan Earthquake, many people experienced the loss of family and friends, among other traumatic events. This study sought to clarify the impact of the loss of significant close others on posttraumatic stress symptoms (PTSS), as well as the factors associated with PTSS, among individuals who experienced the loss of significant close others (i.e., bereaved group). Self-administered questionnaires were mailed to men and women (N = 180,604) aged 16 years and older living in municipalities that included evacuated areas surrounding the Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Station, which was significantly damaged following an earthquake and tsunami in March 2011, causing subsequent radiation leakage; this mailing yielded a 40.7% response rate, with 57,388 valid responses, in 2012. We used the Posttraumatic Stress Disorder Checklist-Specific (PCL-S) to measure PTSS as the outcome variable. Loss of significant close others in the disaster and respondents' relationship with the deceased constituted the explanatory variables. Basic characteristics and disaster-related factors were the confounding variables. Data were analyzed using chi-square tests and logistic regression analyses. The bereaved group showed more severe PTSS than the nonbereaved group, aOR = 1.58, 95% CI [1.50, 1.67]. The risk of developing PTSS increased if the deceased was a respondent's spouse, aOR = 1.67, 95% CI [1.22, 2.29]; child, 1.51 [1.01, 2.25]; or friend, 1.33 [1.16, 1.53]. Individuals who lose significant close others, including both family and friends, in disasters require close mental health care and, if necessary, should be referred for psychiatric treatment.

Second-Generation Antipsychotic Long-Acting Injection Reduced the Time of Restrictive Interventions in Patients With Schizophrenia: Retrospective, A 4-Year Mirror-Image Study.

BACKGROUND: Whether second-generation antipsychotic long-acting injection (SGA-LAI) reduces psychotic symptoms at relapse compared with oral antipsychotics remains unclear. The present study investigated the effects of SGA-LAI on the time (in hours) of restrictive interventions in hospitalization by conducting a retrospective observational 4-year mirror-image study at a single medical center in Japan. METHOD: We performed a retrospective observational mirror-image study conducted between November 2013 and January 2018. Data were initially retrieved from 101 patients. The 38 patients with schizophrenia who met the inclusion criteria were enrolled in the analysis. The primary outcome was the time of restrictive interventions and the secondary outcomes included the number of hospitalizations (total, voluntary, and involuntary) and bed days compared 2 years before and after initiating SGA-LAI. The restrictive interventions were defined as seclusion and physical restraints. RESULTS: The mean time of restrictive interventions significantly decreased from 43.7 to 3.03 ( P = 0.021). The number of admissions and the total number of bed days in post-SGA-LAI fell from 1.03 to 0.61 ( P = 0.011) and 130 to 39.3 ( P = 0.003), respectively, compared with pre-SGA-LAI. In particular, the number of involuntary admissions was significantly reduced (0.50-0.26, P = 0.039). CONCLUSIONS: The findings indicate that SGA-LAI reduced the time of restrictive interventions and the number of involuntary admissions. Moreover, SGA-LAI may contribute to mild psychiatric symptoms during relapse.

Elevation of EGR1/zif268, a Neural Activity Marker, in the Auditory Cortex of Patients with Schizophrenia and its Animal Model.

The family of epidermal growth factor (EGF) including neuregulin-1 are implicated in the neuropathology of schizophrenia. We established a rat model of schizophrenia by exposing perinatal rats to EGF and reported that the auditory pathophysiological traits of this model such as prepulse inhibition, auditory steady-state response, and mismatch negativity are relevant to those of schizophrenia. We assessed the activation status of the auditory cortex in this model, as well as that in patients with schizophrenia, by monitoring the three neural activity-induced proteins: EGR1 (zif268), c-fos, and Arc. Among the activity markers, protein levels of EGR1 were significantly higher at the adult stage in EGF model rats than those in control rats. The group difference was observed despite an EGF model rat and a control rat being housed together, ruling out the contribution of rat vocalization effects. These changes in EGR1 levels were seen to be specific to the auditory cortex of this model. The increase in EGR1 levels were detectable at the juvenile stage and continued until old ages but displayed a peak immediately after puberty, whereas c-fos and Arc levels were nearly indistinguishable between groups at all ages with an exception of Arc decrease at the juvenile stage. A similar increase in EGR1 levels was observed in the postmortem superior temporal cortex of patients with schizophrenia. The commonality of the EGR1 increase indicates that the EGR1 elevation in the auditory cortex might be one of the molecular signatures of this animal model and schizophrenia associating with hallucination.

Associations Between External Radiation Doses and the Risk of Psychological Distress or Post-traumatic Stress After the Fukushima Daiichi Nuclear Power Plant Accident: the Fukushima Health Management Survey.

BACKGROUND: The relationship between radiation levels and mental health status after a nuclear disaster is unknown. We examined the association between individual external radiation doses and psychological distress or post-traumatic stress after the Fukushima Daiichi nuclear power plant accident in March 2011 in Japan. METHODS: The Mental Health and Lifestyle Survey was conducted from January 2012. Based on the estimated external radiation doses for the first 4 months, a total of 64,184 subjects were classified into <1 mSv, 1 to <2 mSv, and ≥2 mSv groups. Odds ratios (ORs) and 95% confidence intervals (CIs) of psychological distress and post-traumatic stress, with the <1 mSv group as the reference, were calculated using logistic regression analysis adjusted for age, sex, evacuation, perception of radiation risk, and subjective health status. RESULTS: The prevalence of psychological distress/post-traumatic stress in the <1 mSv, 1 to <2 mSv, and ≥2 mSv groups was 15.1%/22.1%, 14.0%/20.1%, and 15.0%/21.7%, respectively. In women, although the ≥2 mSv group tended to have a higher risk of psychological distress with the age-adjusted OR of 1.13 (95% CI, 0.99-1.30), the adjusted OR decreased to 1.00 (95% CI, 0.86-1.16) after controlling for all variables. On the other hand, there were no dose-dependent associations between radiation dose and post-traumatic stress. CONCLUSION: Although external radiation doses were not associated with psychological distress, evacuation and perception of radiation risk may increase the risk of psychological distress in women in the higher dose group.

Long-Term, Community-based Approach for Affected People Having Problems With Mental Health and Lifestyle Issues After the 2011 Fukushima Disaster: the Fukushima Health Management Survey.

A Mental Health and Lifestyle Survey (MHLS) has been conducted yearly as part of the Fukushima Health Management Survey since 2012, in order to monitor different health issues related to long-term evacuation of affected people after the 2011 Fukushima disaster. This survey is a mail-based one of nearly 210,000 affected people living in the evacuation zone at the time of the disaster. Another purpose of the MHLS is to provide efficient interventions by telephone based on the results of the survey. Significant findings contributing to understanding of non-radiological health effects caused by long-term evacuation were obtained from the MHLS, directly connecting to telephone-based interventions for over 3,000 respondents per year. In this article, the mental health outcomes of the MHLS, including depressive symptoms and posttraumatic responses, are reviewed, and the usefulness of telephone-based interventions is discussed. The evidence showed that, despite improvement of core mental health outcomes, the prevalence of respondents at high risk of some psychiatric problems remained high compared to that among the general population in Japan. In particular, several mental health consequences of respondents staying outside of Fukushima Prefecture were higher than those staying inside Fukushima. Along with further efforts to increase the response rate, we need to continue and modify the MHLS to meet the requirements of the affected people and communities.

Lessons learned from psychosocial support and mental health surveys during the 10 years since the Great East Japan Earthquake: Establishing evidence-based disaster psychiatry.

Post-disaster mental health and psychosocial support have drawn attention in Japan after the 1995 Great Hanshin-Awaji Earthquake, with mental health care centers for the affected communities being organized. After the catastrophe, a reconstruction budget was allocated to organize mental health care centers to provide psychosocial support for communities affected by the 2007 Chuetsu offshore earthquake, the 2011 Great East Japan Earthquake, and the 2016 Kumamoto Earthquake. There were several major improvements in post-disaster mental health measures after the Great East Japan Earthquake. The Disaster Psychiatric Assistance Team system was organized after the earthquake to orchestrate disaster response related to the psychiatric health system and mental health of the affected communities. Special mental health care efforts were drawn to the communities affected by the nuclear power plant accident through Chemical, Biological, Radiological, Nuclear, and high yield Explosives, being succeeded by measures against the coronavirus pandemic. As another new movement after the Great East Japan Earthquake, the number of surveys involving communities affected by disasters has soared. More than 10 times the number of scientific publications were made in English during the decade following the Great East Japan Earthquake, compared with the previous decades. In this review, we examined the results and issues acquired in the 10 years since the Great East Japan Earthquake, proposing evidence-based disaster psychiatry as the direction of future mental health measures related to emergency preparedness and response.

Antidepressive Effect of Antipsychotics in the Treatment of Schizophrenia: Meta-Regression Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: Antipsychotics improve the positive symptoms of schizophrenia. However, little is known about the extent of antidepressive effects of antipsychotics and their correlation with effects on other symptom domains in schizophrenia. The aim was to investigate whether antidepressive effects of antipsychotics have a significant correlation with the effects on specific symptom domains of schizophrenia. METHODS: Electronic databases were searched to identify eligible studies that reported antidepressive effects of antipsychotics for the treatment of adult patients with schizophrenia in double-blind, randomized placebo-controlled trials (RCTs). Mean change from baseline in depressive symptoms was meta-analyzed, and the correlation with the effects on other symptom domains was examined through meta-regression analysis. RESULTS: Thirty-five RCTs (13 890 patients) were included in this meta-analysis. Overall, antipsychotics showed greater efficacy than placebo in reducing depressive symptoms, with small to medium effect sizes (standardized mean difference = -0.27, 95% confidence interval -0.32 to -0.22, P < .001). All the antipsychotics, except for chlorpromazine, haloperidol, and ziprasidone, were associated with significantly greater decreases in depressive symptoms compared with placebo (standardized mean difference = -0.19 to -0.40). A higher antidepressive effect was significantly correlated with a higher improvement in Positive and Negative Syndrome Scale/Brief Psychiatric Rating Scale total, positive, and negative, and Positive and Negative Syndrome Scale-general psychopathology symptoms (ß = .618, P < .001; ß = .476, P < .001; ß = .689, P < .001; ß = .603, P < .001, respectively). CONCLUSIONS: Second-generation antipsychotics (except for ziprasidone) were associated with small to medium effects sizes on improvement in depressive symptoms among adult patients with schizophrenia. The antidepressive effect of antipsychotics was significantly correlated with improvement in other symptom domains, with the highest correlation observed for improvement in negative symptoms. PROSPERO REGISTRATION NUMBER: CRD42019133015.

Evacuation after the Great East Japan Earthquake is an independent factor associated with hyperuricemia: The Fukushima Health Management Survey.

BACKGROUND AND AIMS: On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. This study assessed the association between evacuation and hyperuricemia based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective. METHODS AND RESULTS: This cross-sectional study included 22,812 residents (9391 men and 13,297 women) who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between hyperuricemia and lifestyle- and disaster-related factors including evacuation were estimated using a logistic and liner regression analysis. With hyperuricemia defined as uric acid levels >7.0 mg/dL for men and >6.0 mg/dL for women, significant associations were observed between evacuation and hyperuricemia in men (the multivariate-adjusted odds ratio 1.20, 95% confidence interval, 1.05-1.36, p = 0.005), but not in women. In the multivariate-adjusted multiple liner regression analysis, evacuation had significant and positive associations with uric acid levels both in men (ß = 0.084, p = 0.002) and women (ß = 0.060, p < 0.001). CONCLUSION: Evacuation after a natural disaster is an independent factor associated with hyperuricemia.

Dietary pattern changes in Fukushima residents after the Great East Japan Earthquake: the Fukushima Health Management Survey 2011-2013.

OBJECTIVE: Dietary patterns more closely resemble actual eating behaviours because multiple food groups, not a single food group or nutrient, are considered. The present study aimed to identify and assess changes of dietary patterns in Fukushima residents. DESIGN: Dietary data were collected using a short-form FFQ in annual Fukushima Health Management Survey between 2011 and 2013 after the Great East Japan Earthquake. Year- and sex-specific dietary patterns were determined by the principal component analysis. SETTING: Evacuation and nonevacuation zones in Fukushima, Japan. PARTICIPANTS: Eligible participants aged ≥16 years answered the FFQ (n 67 358 in 2011, n 48 377 in 2012 and n 40 742 in 2013). RESULTS: Three identified dietary patterns were assessed similarly in men and women and among years: typical, juice and meat. In total participants, the Spearman's correlation coefficients between two survey years were 0·70-0·74 for the typical, 0·58-0·66 for the juice and 0·50-0·54 for the meat pattern scores. Adjusted for sociodemographic factors, evacuees had lower typical pattern scores, higher juice pattern scores and the same meat pattern scores compared with non-evacuees. The means of typical pattern scores in evacuees and it of juice pattern scores in non-evacuees continued declining over years. Similar profiles of dietary patterns and trends of pattern scores were observed in participants (n 22 805) who had provided three dietary assessments. CONCLUSIONS: Changes of dietary patterns have been observed between 2011 and 2013. Careful investigation of those with low intake of typical pattern foods and promotion of them, particularly in evacuees, are needed.

Association between post-traumatic stress disorder symptoms and bone fractures after the Great East Japan Earthquake in older adults: a prospective cohort study from the Fukushima Health Management Survey.

BACKGROUND: It has been reported that psychological stress affects bone metabolism and increases the risk of fracture. However, the relationship between bone fractures and post-traumatic stress disorder (PTSD) is unclear. This study aimed to evaluate the effects of disaster-induced PTSD symptoms on fracture risk in older adults. METHODS: This study evaluated responses from 17,474 individuals aged ≥ 65 years without a history of fractures during the Great East Japan Earthquake who answered the Mental Health and Lifestyle Survey component of the Fukushima Health Management Survey conducted in 2011. The obtained data could determine the presence or absence of fractures until 2016. Age, sex, physical factors, social factors, psychological factors, and lifestyle factors were subsequently analyzed. Survival analysis was then performed to determine the relationship between the fractures and each factor. Thereafter, univariate and multivariate Cox proportional hazard models were constructed to identify fracture risk factors. RESULTS: In total, 2,097 (12.0%) fractures were observed throughout the follow-up period. Accordingly, univariate and multivariate Cox proportional hazard models showed that PTSD symptoms (total PTSD checklists scoring ≥ 44) [hazard ratio (HR): 1.26; 95% confidence interval (CI): 1.10-1.44; P = 0.001], history of cancer (HR: 1.49; 95% CI: 1.24-1.79; P < 0.001), history of stroke (HR: 1.25; 95% CI: 1.03-1.52; P = 0.023), history of heart disease (HR: 1.30; 95% CI: 1.13-1.50; P < 0.001), history of diabetes (HR: 1.23; 95% CI: 1.09-1.39; P < 0.001), current smoking (HR: 1.29; 95% CI: 1.02-1.63; P = 0.036), and high dissatisfaction with sleep or no sleep at all (HR: 1.33; 95% CI: 1.02-1.74; P = 0.035) promoted a significant increase in fracture risk independent of age and sex. CONCLUSIONS: The present study indicates that disaster-induced PTSD symptoms and insomnia contribute to increased fracture risk among older adults residing in evacuation areas within the Fukushima Prefecture.

Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia.

Phosphoinositides (PIs) play important roles in the structure and function of the brain. Associations between PIs and the pathophysiology of schizophrenia have been studied. However, the significance of the PI metabolic pathway in the pathology of schizophrenia is unknown. We examined the expression of PI signaling-associated proteins in the postmortem brain of schizophrenia patients. Protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA, also known as PIK4A), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), protein kinase B (Akt), and glycogen synthase kinase 3ß (GSK3ß) were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays of the prefrontal cortex (PFC) of postmortem samples from 23 schizophrenia patients and 47 normal controls. We also examined the association between PIK4CA expression and its genetic variants in the same brain samples. PIK4CA expression was lower, whereas Akt expression was higher, in the PFC of schizophrenia patients than in that of controls; PIP5K1C, PTEN, and GSK3ß expression was not different. No single-nucleotide polymorphism significantly affected protein expression. We identified molecules involved in the pathology of schizophrenia via this lipid metabolic pathway. These results suggest that PIK4CA is involved in the mechanism underlying the pathogenesis of schizophrenia and is a potential novel therapeutic target.

Effects of the Great East Japan Earthquake and the Fukushima Daiichi Nuclear Power Plant accident on behavioural and psychological symptoms of dementia among patients.

BACKGROUND: The Great East Japan Earthquake triggered accidents at the Fukushima Daiichi Nuclear Power Plant, becoming the first complex disaster that included both a natural and a nuclear power disaster. This study examines how complex disasters affect patients with dementia. METHODS: Participants included the 331 people diagnosed with dementia out of the 2482 new patients (between January 2008 and December 2015) at a psychiatric hospital located in the indoor sheltering zones nearby mandatory evacuation zones. Medical records were retrospectively examined to identify the number of new patients with dementia, the severity, their chief complaints, and the behavioural and psychological symptoms of dementia (BPSD) types. BPSD were classified into the hyperactive BPSD group and the hypoactive BPSD group. The hyperactive BPSD group was further subdivided into the hyperactivity-impulsivity-irritability-disinhibition-aggression-agitation group, which exhibited agitation, disinhibition, and irritability, and the psychosis group, which exhibited delusions and hallucinations. The hypoactive BPSD group included depression, inactivity, apathy, and anxiety. Results were divided into the period before the complex disaster (2008-2010) and after (2012-2015) and were compared. In addition, the post-complex-disaster period was subdivided into the early phase (2012-2013) and the late phase (2014-2015). RESULTS: The proportion of new patients with dementia increased significantly after the disaster. Although there was no change in patients' age and the disease's severity, the proportion of patients whose chief complaint was BPSD increased significantly after the disaster. Furthermore, there was a significant increase in the hyperactivity-impulsivity-irritability-disinhibition-aggression-agitation group in the early post-complex-disaster phase and a significant increase in the psychosis group in the late post-complex-disaster phase. CONCLUSION: This complex disaster caused increased consultations from patients with dementia and increased BPSD. Additionally, it increased participants' symptoms of agitation and irritability in the early post-complex-disaster phase and the proportion of hallucinations and delusions in the late post-complex-disaster phase.

Do tone duration changes that elicit the mismatch negativity also affect the preceding middle latency responses?

The human brain can automatically detect sound changes. Previous studies have reported that rare sounds presented within a sequence of repetitive sounds elicit the mismatch negativity (MMN) in the absence of attention in the latency range of 100-250 ms. On the other hand, a previous study discovered that occasional changes in sound location enhance the middle latency response (MLR) elicited in the latency range of 10-50 ms. Several studies have reported an increase in the amplitude of the MLR within the frame of oddball paradigms such as frequency and location changes. However, few studies have been conducted on paradigms employing a duration change. The purpose of the present study was to examine whether the peak amplitudes of the MLR components are enhanced by a change in duration. Twenty healthy Japanese men (age: 23.9 ± 2.9 years) participated in the present study. We used an oddball paradigm that contained standard stimuli with a duration of 10 ms and deviant stimuli with a duration of 5 ms. The peak amplitudes of the MLR for the deviant stimuli were then compared with those for the standard stimuli. No changes were observed in the peak amplitude of the MLR resulting from a duration change, whereas a definite MMN was elicited. The amplitude of the MLR was increased within the frame of oddball paradigms such as frequency and location changes. By contrast, the amplitude of the MLR was not changed within the duration change oddball paradigm that elicited the MMN.

Does Treatment Response With Antidementia Drugs After 6 Months in Alzheimer's Disease Predict Long-term Treatment Outcome?

BACKGROUND: Alzheimer's disease (AD) is a chronic, progressive disorder that causes declines in cognitive and physical functions. This condition places severe burdens on families and caregivers. Delaying progressive declines in cognitive function and reducing their burden are thus important. Relationships between early treatment response and subsequent outcomes of schizophrenia and major depressive disorder have been reported. We thus aimed to investigate the relationships between treatment response to antidementia drugs in AD after 6 months (M) and subsequent outcomes. METHODS: Eligible individuals comprised 194 patients diagnosed with presumed AD. Of these, 110 patients who received antidementia drugs for the first time and were assessed using the Mini-Mental State Examination (MMSE) at 6 M, 12 M, and 24 M were categorized as responders (n = 84) or nonresponders (n = 26). Responders were defined as showing a change in MMSE after 6 M the same as or lower than that in the natural course according to previously reported data. RESULTS: No significant differences in baseline characteristics (age, sex, education, or comorbidities) were seen between groups. Mean MMSE score at baseline was significantly lower in responders (18.0) than in nonresponders (20.7; P = 0.008). Mean change from baseline MMSE was significantly smaller in responders than in nonresponders at both 12 M (-0.46 vs -2.5; P = 0.04) and 24 M (-0.78 vs -4.4; P = 0.001). CONCLUSIONS: Treatment response with antidementia drugs after 6 M predicted better outcomes at 12 M and 24 M. Treatment response should be assessed every 6 M, and treatment should be reconsidered accordingly.

Effects of single green tea ingestion on pharmacokinetics of nadolol in healthy volunteers.

AIMS: The aim of this study was to investigate the effects of a single green tea (GT), administered concomitantly or 1 hour before nadolol intake on nadolol pharmacokinetics. METHODS: In a randomized 3-phase crossover study, 11 healthy volunteers received an oral administration of nadolol with, or 1 hour after preingestion of brewed GT, or with water in a volume of 150 mL. RESULTS: Geometric mean ratio with 90% confidence interval for nadolol AUC0-48 was 0.371 (0.303-0.439) with concomitant GT. In addition, ingestion of GT 1 hour before nadolol administration resulted in a significant reduction of nadolol AUC0-48 with geometric mean ratio of 0.536 (0.406-0.665). There were no differences in time to maximal plasma concentration and renal clearance of nadolol among groups. CONCLUSION: These results suggest that single concomitant ingestion of GT substantially decreases plasma concentrations of nadolol. Moreover, the reduction in nadolol bioavailability could persist for at least 1 hour after drinking a cup of GT.

Onset and remission of common mental disorders among adults living in temporary housing for three years after the triple disaster in Northeast Japan: comparisons with the general population.

BACKGROUND: People living in temporary housing for long periods after a disaster are at risk of poor mental health. This study investigated the post-disaster incidence and remission of common mental disorders among adults living in temporary housing for the 3 years following the 2011 Great East Japan Earthquake. METHODS: Three years after the disaster, face-to-face interviews were conducted with 1089 adult residents living in temporary housing in the disaster area, i.e., the shelter group, and a random sample of 852 community residents from non-disaster areas of East Japan. The World Health Organization Composite International Diagnostic Interview was used to diagnose DSM-IV mood, anxiety, and alcohol use disorders. Information on demographic variables and disaster experiences was also collected. RESULTS: Response rates were 49 and 46% for the shelter group and the community residents, respectively. The incidence of mood/anxiety disorder in the shelter group was elevated only in the first year post-disaster compared to that of the general population. The rate of remission for mood and anxiety disorders was significantly lower in the shelter group than in the community residents. The proportion seeking medical treatment was higher in the shelter group. CONCLUSIONS: The onset of common mental disorders increased in the first year, but then levelled off in the following years among residents in temporary housing after the disaster. Remission from incident post-disaster mental disorders was slower in the shelter group than in the general population. Post-disaster mental health service could consider the greater incidence in the first year and prolonged remission of mental disorders among survivors with a long-term stay in temporary housing after a disaster.

Lifestyle factors associated with prevalent and exacerbated musculoskeletal pain after the Great East Japan Earthquake: a cross-sectional study from the Fukushima Health Management Survey.

BACKGROUND: While the prevalence of post-disaster musculoskeletal pain has been documented, its associated disaster-related factors have not been investigated. This study was to investigate the association of lifestyle factors associated with musculoskeletal pain after the Great East Japan Earthquake. METHODS: We conducted a cross-sectional study of 34,919 participants, aged 40-89 years, without any major disabilities at about 1 year after the disaster. The participants were asked about their musculoskeletal pain (low back and limb pain) and lifestyle factors: use of evacuation shelters or temporary housing at any point of time, job loss after the disaster, decreased income after the disaster, current smoking status, current drinking status, lack of sleep, regular exercise, and participation in recreational or community activities. Furthermore, psychological factors, such as traumatic reactions, psychological distress, and uncomfortable symptoms, affecting musculoskeletal pain were assessed. We used multinomial logistic regression analysis to calculate odds ratios of each lifestyle factor for prevalent and prevalent plus exacerbated musculoskeletal pain. RESULTS: Musculoskeletal pain prevalence was 32.8%: 27.6% for prevalent and 5.2% for prevalent plus exacerbated musculoskeletal pain. Multivariable adjusted odds ratios and 95% confidence intervals of lifestyle factors associated with prevalent and prevalent plus exacerbated musculoskeletal pain were as follows: shelter use (prevalent: 1.02, 0.96-1.08; exacerbated: 1.44, 1.29-1.60), job loss (prevalent: 1.03, 0.96-1.10; exacerbated: 1.30, 1.16-1.47), decreased income (prevalent: 1.13, 1.05-1.21; exacerbated: 1.29, 1.14-1.45), current heavy drinking (prevalent: 1.33, 1.21-1.47; exacerbated: 1.38, 1.14-1.68), insomnia (prevalent: 1.22, 1.15-1.29; exacerbated: 1.50, 1.36-1.65), exercising almost daily (prevalent: 0.83, 0.77-0.91; exacerbated: 0.80, 0.68-0.95), and participating in community activities often (prevalent: 0.83, 0.75-0.92; exacerbated: 0.76, 0.61-0.95). CONCLUSIONS: Prevalent and exacerbated musculoskeletal pain were inversely associated with exercising almost daily and participating in recreational or community activities sometimes or often, and positively associated with decreased income, current heavy drinking, and insomnia. Besides, the use of evacuation shelters or temporary housing/job loss was positively associated only with exacerbated musculoskeletal pain. These results suggest that post-disaster lifestyle factors are potentially associated with musculoskeletal pain. To achieve better post-disaster pain management, further studies are needed to confirm the consistency of these results in other disasters and to highlight the underlying causative mechanisms.

Plasma levels of dopamine metabolite correlate with mismatch negativity in patients with schizophrenia.

AIM: Mismatch negativity (MMN) deficit is one of the most robust and replicable findings in schizophrenia, and primarily reflects deficient functioning of the N-methyl-D-aspartate (NMDA) receptor system. Although the dopamine receptor is known not to modulate MMN over the short term, it is unclear whether the dopamine system affects MMN in the long term. METHODS: We explored correlations between MMN and levels of plasma dopamine and serotonin metabolites in 18 patients with schizophrenia psychiatrically evaluated with the Positive and Negative Syndrome Scale (PANSS). RESULTS: A significant negative correlation exists between MMN amplitude and plasma levels of dopamine metabolites. Plasma serotonin metabolite levels were not correlated with MMN. The PANSS total score and Negative score also showed negative correlations with MMN amplitude. CONCLUSION: The usual strong therapeutic blockade of dopamine receptors applied in cases of schizophrenia may reduce MMN over the long term.