Published papers

© 2020 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology With recent rapid advances in technology, human-like robots have begun functioning in a variety of ways. As increasing anecdotal evidence suggests, robots may offer many unique opportunities for helping individuals with autism spectrum disorders (ASD). Individuals with ASD often achieve a higher degree of task engagement through the interaction with robots than through interactions with human trainees. The type and form of robots to be used for individuals with ASD have been meticulously considered. Simple robots and animal robots are acceptable because of their simplicity and the ease of interesting and engaging interactions. Android robots have the benefit of the potential of generalization into daily life to some extent. Considering the affinity between robots and users is important to draw out the potential capabilities of robotic intervention to the fullest extent. In the robotic condition, factors such as the appearance, biological motion, clothes, hairstyle, and disposition are important. Many factors of a user, such as age, sex, and IQ, may also affect the affinity of individuals with ASD toward a robot. The potential end-users of this technology may be unaware or unconvinced of the potential roles of robots in ASD interventions. If trainers have extensive experience in using robots, they can identify many potential roles of robots based on their experience. To date, only a few studies have been conducted in the field of robotics for providing assistance to individuals with ASD, and future studies are needed to realize an optimal robot for this purpose.

© 2019 Japanese Psychogeriatric Society Background: Subjective cognitive decline (SCD) may herald the first symptoms of Alzheimer's disease (AD) whereas individuals with beta-amyloid (Aβ) deposition are regarded as a high-risk group for AD. Recently, amyloid positron emission tomography (PET) studies have demonstrated clinical and cognitive feature differences between Aβ-positive and negative SCD, but details of their differences remain unclear. We aimed to investigate the relationships among Aβ deposition, clinical, and cognitive features in patients with SCD. Methods: Forty-two patients with SCD (22 women, 74.5 ± 4.7 years) were examined using fluorine-18 florbetaben PET and were divided into Aβ-positive (n = 10) and negative (n = 32) groups. We compared cognitive and psychological outcomes, and single photon emission computed tomography (SPECT) imaging data between the two groups. In addition, a linear regression analysis was performed to assess relationships between the severity of SCD and neuropsychological tests, affective scores, and demographic factors. Results: The rate of score changes from the immediate recall to delayed recall in the logical memory subtest of the Wechsler's Memory Scale Revised were different between the groups (P = 0.04). However, the binary logistic regression analysis showed no significant differences between the two. In addition, the severity of SCD was significantly strong in women (P = 0.002). Furthermore, within the Aβ-negative group, subjective memory loss correlated with word fluency category score (P = 0.023) and apathy scale (P = 0.037). Conclusions: No significant differences were observed between Aβ-positive and -negative SCD on any of the neuropsychological measures, clinical measures, or SPECT imaging. Further, the severity of SCD was not predicted by the symptoms of anxiety, depression, or neuropsychological examination.

© 2018 The Author(s). Objective Although catatonia can occur secondary to a general medical condition, catatonia itself has been known to lead to various medical compolications. Although case reports on the association of catatonia with subsequent medical complications have been documented, no comprehensive large-scale study has been performed. To investigate specific medical complications after catatonia, we conducted a retrospective cohort study of specific medical complications of schizophrenia patients with catatonia. Methods The 1719 schizophrenia inpatients in our study were categorized into two groups: the catatonia group, i.e., those who exhibited catatonic stupor while they were hospitalized, and the noncatatonia group, i.e., those who never exhibited catatonic stupor. Differences between the two groups in the occurrence of subsequent medical complications were examined using linear and logistic regression analyses, and models were adjusted for potentially confounding factors. Results The catatonia group had an increased risk for mortality (odds ratio = 4.8, 95% confidence interval = 2.0-10.6, p <.01) and certain specific medical complications, i.e., pneumonia, urinary tract infection, sepsis, disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep venous thrombosis, pulmonary embolism, urinary retention, decubitus, arrhythmia, renal failure, neuroleptic malignant syndrome, hypernatremia, and liver dysfunction (all p values <.01, except for deep venous thrombosis, p =.04 in the multiple linear regression analysis). Conclusions Catatonic stupor in schizophrenia substantially raises the risk for specific medical complications and mortality. Hyperactivity of the sympathetic nervous system, dehydration, and immobility, which are frequently involved in catatonia, might contribute to these specific medical complications. In catatonia, meticulous care for both mental and medical conditions should be taken to reduce the risk of adverse medical consequences.

© 2019 Elsevier Ltd The objective of this study was to investigate possible circadian pattern of psychotic symptoms in patients with schizophrenia, which could be reflected on the dosing schedule/regimen, i.e. chrono-pharmacology. Patients with schizophrenia (ICD-10) who reported having auditory hallucination, receiving monotherapy with risperidone, olanzapine or paliperidone for at least two weeks were included. The subjects were provided a diary and asked to record the time and duration of auditory hallucinations during the eight time periods (i.e. 00:00–03:00, 03:00–06:00, 06:00–09:00, 09:00–12:00, 12:00–15:00, 15:00–18:00, 18:00–21:00, and 21:00–24:00). In the diary, times of medication doses and sleep were also recorded. Time and degree of peak and trough dopamine D2 receptor blockade with antipsychotics were estimated from 2 sparsely collected plasma drug concentrations. The prevalence and duration of auditory hallucinations were statistically examined among the eight time periods, respectively. Forty-nine patients participated in this study (mean ± SD age, 50.7 ± 14.8 years; 36 men (73.5%); 34 inpatients (69.4%)). Auditory hallucinations occurred most frequently and lasted for the longest duration in the period of 18:00–21:00 (75.5% (37/49) and 1.37 ± 1.67 h). This happened despite the fact that the difference in D2 receptor occupancy between the peak and trough was less than 2%, indicating a stable drug delivery. Since the dopamine D2 receptor blockade by antipsychotics was stable, the nocturnal circadian pattern found in this study may reflect intrinsic dopaminergic fluctuation or generally quieter environments at night. These circadian patterns may be considered to devise individualized treatment approach in the context of “chrono-pharmacology” for patients with schizophrenia.

© Wolters Kluwer Health, Inc. All rights reserved. Purpose/Background Although discontinuing antipsychotics clearly increases the risk of relapse in schizophrenia, some patients remain clinically well without continuous antipsychotic treatment. However, data on the characteristics of such patients are still scarce. Methods/Procedures A systematic literature review was conducted to identify predictive factors for successful antipsychotic discontinuation in schizophrenia using PubMed (last search; June 2018) with the following search terms: (antipsychotic∗ or neuroleptic) AND (withdraw∗ or cessat∗ or terminat∗ or discontinu∗) AND (schizophreni∗ or psychosis). The search was filtered with humans and English. Factors associated with a lower risk of relapse, when replicated in 2 or more studies with a follow-up period of 3 months or longer, were considered successful. Findings/Results Systematic literature search identified 37 relevant articles. Mean relapse rate after antipsychotic discontinuation was 38.3% (95% confidence interval = 16.0%-60.6%) per year. Factors associated with a lower risk of relapse were being maintained on a lower antipsychotic dose before discontinuation, older age, shorter duration of untreated psychosis, older age at the onset of illness, a lower severity of positive symptoms at baseline, better social functioning, and a lower number of previous relapses. Implications/Conclusions Although this literature review suggests some predictors for successful antipsychotic withdrawal in patients with schizophrenia, the very limited evidence base and unequivocally high relapse rates after discontinuation must remain a matter of serious debate for risk/benefit considerations.

© The Author(s) 2019. Neurodevelopmental disorders, including autism spectrum disorder, are common in children and adolescents, but treatment strategies remain limited. Although repetitive transcranial magnetic stimulation has been studied for neurodevelopmental disorders, there is no clear consensus on its therapeutic effects. This systematic review examined literature on repetitive transcranial magnetic stimulation for children and adolescents with neurodevelopmental disorders published up to 2018 using the PubMed database. The search identified 264 articles and 14 articles met eligibility criteria. Twelve of these studies used conventional repetitive transcranial magnetic stimulation and two studies used theta burst stimulation. No severe adverse effects were reported in these studies. In patients with autism spectrum disorder, low-frequency repetitive transcranial magnetic stimulation and intermittent theta burst stimulation applied to the dorsolateral prefrontal cortex may have therapeutic effects on social functioning and repetitive behaviors. In patients with attention deficit/hyperactivity disorder, low-frequency repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex and high-frequency repetitive transcranial magnetic stimulation applied to the right dorsolateral prefrontal cortex may target inattention, hyperactivity, and impulsivity. In patients with tic disorders, low-frequency repetitive transcranial magnetic stimulation applied to the bilateral supplementary motor area improved tic symptom severity. This systematic review suggests that repetitive transcranial magnetic stimulation may be a promising intervention for children and adolescents with neurodevelopmental disorders. The results warrant further large randomized controlled trials of repetitive transcranial magnetic stimulation in children with neurodevelopmental disorders.

© 2019 The Authors. Psychiatry and Clinical Neurosciences © 2019 Japanese Society of Psychiatry and Neurology Aim: Cognitive dysfunction is a core symptom of schizophrenia spectrum disorder, but the reported long-term cognitive outcomes are heterogeneous. This study aimed to elucidate the long-term trajectories of patients with schizophrenia spectrum disorder who transitioned to community dwelling with integrated care, and to identify predictors of successful community reintegration. Methods: After the closure of a psychiatric hospital, 78 patients with schizophrenia spectrum disorder (mean age: 54.6 years) were transferred to the community. We assessed patients' cognitive function over 15 years with the Mini-Mental State Examination (MMSE) and analyzed the scores every 3 years. Forty-four patients completed all assessments. Results: The mean MMSE score at discharge was 25.8, which changed to 26.8 after 3 years and 25.3 after 6 years. After 12 and 15 years, it had decreased significantly to 23.3 and 23.0, respectively. Group-based trajectory modeling identified two groups of patients: a ‘poor-outcome’ group (63.4%), showing a decline in scores after maintaining post-discharge levels for several years, and a ‘good-outcome’ group (36.6%), maintaining post-discharge scores after showing improved scores. Conclusion: Considering the significant difference in age between the aforementioned groups (P = 0.040), we suggest that community transitions at younger ages contribute to better cognitive function and adaptation to community life. Even middle-aged and elderly patients with chronic schizophrenia spectrum disorder showed improved or maintained cognitive function at least 3 years after discharge, and the good-outcome group maintained cognitive function over 15 years. Improvements were dominated primarily by age at discharge, with cognitive function being maintained longer in patients in the good-outcome group.

© 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology Aim: While emotional processing is implicated in various psychiatric illnesses, its differences among diagnoses are unclear. We compared associative learning of social values in patients with depression and schizophrenia by measuring skin conductance response to interpersonal stimuli. Methods: We included 20 female outpatients each with depression and schizophrenia. They underwent Pavlovian conditioning experiments in response to a classical aversive sound, and an interpersonal stimulus that was designed to cause aversive social conditioning with actors’ faces coupled with negative verbal messages. Multiple regression analysis was performed to examine the associations between the degree of conditioned response and the clinical characteristics of the participants. Results: Conditioned responses during the acquisition phase in both conditions were higher in depression compared to schizophrenia. Patients with depression successfully showed fear conditioning in both conditions, and they exhibited slower extinction in the interpersonal condition. The conditioned response during the extinction phase showed a positive association with Emotion Regulation Questionnaire Expressive Suppression score, and a negative association with the Emotion Regulation Questionnaire Cognitive Reappraisal score and the use of antidepressants. Patients with schizophrenia did not become conditioned in either of the conditions. The Positive and Negative Syndrome Scale Negative Syndrome score was negatively associated with the degree of conditioned response during the acquisition phase in the interpersonal condition. Conclusion: Female patients with schizophrenia, especially those who prominently demonstrated negative symptoms, suggested their intrinsic impairments in the associative learning of social context. Antidepressants and adaptive emotional regulation strategy may enhance the extinction learning of aversive social conditioning in depression.

© 2019 The Author(s). Published by Wolters Kluwer Health, Inc. Concomitant use of benzodiazepines and alcohol appears prevalent in a clinical setting. The objectives of this study were as follows: (1) to investigate the prevalence of concomitant use of benzodiazepine hypnotics and alcohol in psychiatric outpatients, (2) to examine the clinical characteristics and factors associated with the concomitant use, and (3) to investigate the awareness of the psychiatrists-in-charge about the concomitant use. Outpatients with schizophrenia, depression, and insomnia who were receiving benzodiazepine hypnotics were asked to fill in a sleeping diary for seven consecutive days in which use of hypnotics and alcohol was also recorded. Clinical characteristics were assessed, and logistic analysis was performed to examine factors associated with the concomitant use. In addition, psychiatrists-in-charge were asked as to whether they thought their patients were concomitantly using them. The prevalence rate of the concomitant use was 39.8% (37/93). The CAGE score showed significant positive association with the concomitant use (odds ratio = 2.40, 95% confidence interval = 1.39-4.16, P = 0.002). Only in 32.4% of the concomitant users were suspected by their psychiatrists. The results suggest that concomitantly used benzodiazepine hypnotics and alcohol appears prevalent, and has been frequently overlooked by treating psychiatrists. The CAGE questionnaire may be helpful to screen such potentially hazardous users.

© 2019 The Authors. Psychiatry and Clinical Neurosciences © 2019 Japanese Society of Psychiatry and Neurology Aim: Prior structural magnetic resonance imaging studies demonstrated atypical gray matter characteristics in siblings of individuals with autism spectrum disorder (ASD). However, they did not clarify which aspect of gray matter is related to the endophenotype (i.e., genetic vulnerability) of ASD. Further, because they did not enroll siblings of typically developing (TD) people, they may have underestimated the difference between individuals with ASD and their unaffected siblings. The current study aimed to address these gaps. Methods: We recruited 30 pairs of adult male siblings (15 pairs with an ASD endophenotype and 15 pairs without) and focused on four gray matter parameters: cortical volume and three surface-based parameters (cortical thickness, fractal dimension, and sulcal depth [SD]). First, we sought to identify a pattern of an ASD endophenotype, comparing the four parameters. Then, we compared individuals with ASD and their unaffected siblings in the cortical parameters to identify neural correlates for the clinical diagnosis accounting for the difference between TD siblings. Results: A sparse logistic regression with a leave-one-pair-out cross-validation showed the SD as having the highest accuracy for the identification of an ASD endophenotype (73.3%) compared with the other three parameters. A bootstrapping analysis accounting for the difference in the SD between TD siblings showed a significantly large difference between individuals with ASD and their unaffected siblings in six out of 68 regions of interest. Conclusion: This proof-of-concept study suggests that an ASD endophenotype emerges in the SD and that neural bases for ASD diagnosis can be discerned from the endophenotype when accounting for the difference between TD siblings.

© 2020 - IOS Press and the authors. All rights reserved. Background: As the Japanese population ages, caring for people with Alzheimer's disease (AD) dementia is becoming a major socioeconomic issue. Objective: To determine the contribution of patient and caregiver costs to total societal costs associated with AD dementia. Methods: Baseline data was used from the longitudinal, observational GERAS-J study. Using the Mini-Mental State Examination (MMSE) score, patients routinely visiting memory clinics were stratified into three groups based on AD severity. Health care resource utilizationwas recorded using the Resource Utilization in Dementia questionnaire. Total monthly societal costs were estimated using Japan-specific unit costs of services and products (patient direct health care use, patient social care use, and informal caregiving time). Uncertainty around mean costs was estimated using bootstrapping methods. Results: Overall, 553 community-dwelling patients withADdementia (28.3% mild[MMSE21-26], 37.8% moderate[MMSE 15-20], and 34.0% moderately severe/severe [MMSE < 14]) and their caregivers were enrolled. Patient characteristics were: mean age 80.3 years, 72.7% female, and 13.6% living alone. Caregiver characteristics were: mean age 62.1 years, 70.7% female, 78.8% living with patient, 49.0% child of patient, and 39.2% sole caregiver. Total monthly societal costs of AD dementia (Japanese yen) were: 158,454 (mild), 211,301 (moderate), and 294,224 (moderately severe/severe). Informal caregiving costs comprised over 50% of total costs. Conclusion: Baseline results of GERAS-J showed that total monthly societal costs associated with AD dementia increased with AD severity. Caregiver-related costs were the largest cost component. Interventions are needed to decrease informal costs and decrease caregiver burden.

© 2020 The Author(s). Published by Cambridge University Press. Background: The stigma associated with cancer has negative impacts on cancer patients as well as the general public, who have a potential risk of cancer. To the best of our knowledge, a validated measure to assess cancer stigma among the general Japanese population does not exist. Method: We translated the Cancer Stigma Scale (CASS) - a 25-item self-administered scale to evaluate stigma related to cancer - into Japanese and examined its psychometric properties. The Japanese version of CASS (J-CASS) was validated among a sample of the general Japanese population through an online survey to validate its test-retest reliability, internal consistency, and concurrent validity. Results: A total of 319 responses were included in the analysis. An exploratory factor analysis eliminated two original items but showed a six-factor model (Awkwardness, Severity, Avoidance, Policy Opposition, Personal Responsibility, and Financial Discrimination), which was similar to the original scale. Cronbach's alpha for each factor was satisfactory, ranging from 0.81 to 0.91. The internal correlation coefficients were above 0.70, except for Policy Opposition. The total and subtotal scores of each factor of the J-CASS were significantly associated with respondents' age, gender, familiarity with cancer patients, and social desirability, demonstrating the scales' good concurrent validity. A substantial proportion of the participants selected "unsure"for some items of the scale, suggesting a further need for refining the scale. Significance of results. This study demonstrated that J-CASS is a reliable and valid measure for evaluating misconceptions and stigma toward cancer in the general Japanese population.

© 2018 Komeda, Eguchi, Kusumi, Kato, Narumoto and Mimura. Information used by older adults engaging in a social decision making task of judging a protagonist as a good or a bad person was investigated. Older (n = 100, 50 women, mean age = 63.6 years) and younger (n = 100, 50 women, mean age = 25.7 years) adults participated in a web-based survey. In Experiment 1, we assessed participants' rapid decision-making processes when making good or bad judgments after reading consecutive sentences without reviewing previously read sentences. The percentages of good judgments were analyzed. In Experiment 2, two protagonists engaging in a deliberate decision-making process were presented, and participants were asked to judge better and worse protagonists. The percentages of behavior-based judgments were analyzed. Results of Experiment 1 indicated that older adults judged protagonists as "good" more often than younger adults. Especially, older adults judged protagonists with good behavior as being "good." In Experiment 2, older adults made behavior-based judgments more than younger people. Additionally, older and younger adults used information on personalities of protagonists for making judgments in situations with bad outcomes, or incongruent. Moreover, multiple regression analysis suggested that people with more general trust engaged more, whereas people with more caution engaged less in making behavior-based judgments.

© 2019, Fondazione Società Italiana di Neurologia. Background: The timing of progression of logopenic variant primary progressive aphasia (lvPPA) to severe dementia has not been elucidated. To address this shortcoming, 10 patients with lvPPA were continuously followed. Methods: Patients were assessed with the annual rate of change in the Clinical Dementia Rating (CDR) sum of boxes and period from lvPPA onset to the onset of benchmark signs, including mild, moderate, or severe dementia, episodic memory deficits, topographical disorientation, difficulties with using controls for electronic appliances, and conceptual apraxia. When severe dementia was evident, we also investigated the incidence of severe cognitive and behavioral signs such as neologistic jargon, difficulties in recognizing family members, pica, and mirror sign. Results: The mean time for patients to reach a particular CDR was as follows: CDR of 1, 4.1 ± 1.3 years post-onset; CDR 2, 5.7 ± 1.6 years; CDR 3, 7.3 ± 1.6 years. The annual rate of change in the CDR sum of boxes was 3.4 ± 1.1, corresponding to 1.7 years for the CDR to increase by 1.0. Difficulties with using electronic controls began at 3.3 ± 1.6 years, episodic memory deficits at 4.0 ± 2.0 years, topographical disorientation at 5.2 ± 2.1 years, and conceptual apraxia at 5.5 ± 2.1 years. For patients who progressed to severe dementia, six could not recognize family members, five exhibited pica, three experienced mirror sign, and one developed neologistic jargon. Conclusions: Our results suggest that patients with lvPPA progress rapidly to dementia and develop conceptual apraxia, episodic memory deficits, visuospatial deficits, and semantic memory deficits.

© 2018 Japanese Psychogeriatric Society Aim: The number-transcoding task on the Japanese version of the Rapid Dementia Screening Test (RDST-J) requires conversion between Arabic and Chinese numerals (209 to 二百九, 4054 to 四千五十四, 六百八十一 to 681, 二千二十七 to 2027). In this task, questions and answers are written for Chinese-Arabic conversion. We reported that the RDST-J could distinguish subjects with Alzheimer's disease with a Clinical Dementia Rating Scale score of 0.5 from controls. In this study, we investigated the impact of changing the task to a hiragana-Arabic conversion. Methods: Participants consisted of 45 patients with a Clinical Dementia Rating Scale score of 0.5 and 52 normal controls. Results: The sensitivity and specificity of total scores ≥9 on the two RDST-J versions for discriminating subjects with a Clinical Dementia Rating Scale score of 0.5 from controls were 73.1% and 75.5%, respectively, on the original version, and 71.8% and 73.0%, respectively, on the revised version. Conclusions: The sensitivity and specificity of the revised version of the RDST-J was equivalent to those of the original version.

© 2019, The Author(s). The association of overall diet quality based on the Japanese Food Guide Spinning Top with risk of depression is not known. This prospective cohort study aimed to determine whether higher adherence to the Japanese food guide reduced the risk of depression. Of 12,219 residents enrolled at baseline, we extracted 1,112 participants who completed a 5-year follow-up (1995) and participated in a mental health screening (2014–2015). Diet quality was scored based on adherence to the Japanese food guide and the ratio of white to red meat according to the Alternative Healthy Index and ranged from 0 (worst) to 80 (best). We calculated odds ratios and 95% confidence intervals for current psychiatrist-diagnosed depression per quartile of total score and of eight component scores with the lowest quartile as reference. Mean age of the participants was 73 years and 59% were women. Total diet quality score was not significantly associated with risk of depression 20 years after the baseline assessment. Among the eight components on the diet quality score, there was a significantly reduced risk for the highest quartile of the white to red meat ratio score. In conclusion, our results do not indicate that higher adherence to the Japanese food guide prevents depression.

This study aimed to investigate the long-term impacts of disclosing amyloid status for a risk of Alzheimer disease (AD) to cognitively normal research participants with subjective cognitive decline (SCD), which represents an initial manifestation of AD. Forty-two participants were classified as the amyloid-positive (n = 10) or amyloid-negative (n = 32) groups. We assessed symptoms of anxiety, depression, and test-related distress at 6, 24, and 52 weeks after results disclosure. No difference was found over time in anxiety, depression, and test-related distress in either group. Although no significant differences were observed between groups in anxiety or depression, the amyloid-negative group had a significantly higher level of test-related distress than the amyloid-positive group at 52 weeks. Disclosing amyloid status to cognitively healthy research participants with SCD did not cause significant long-term psychological risks. However, a theoretical spectrum of subjective concern may exist about cognitive decline in amyloid-negative individuals.

© Georg Thieme Verlag KG Stuttgart · New York. Introduction While the current nomenclature of psychotropic drugs is disease-based, their approved indications do not always match their classifications. Methods Information on approved indications of second-generation antipsychotics and newer antidepressants that are available in the United States (US), the United Kingdom (UK), France, Germany, and Japan were extracted from their packet inserts. Results A significant proportion of atypical antipsychotics were approved for psychiatric conditions other than psychotic disorders (i. e., bipolar disorder, major depressive disorder, and autistic disorder) as follows: 76.9% in the US, 66.7% in the UK, 66.7% in France, 60.0% in Germany, and 44.4% in Japan. Likewise, more than half of newer antidepressants had approved indications for psychiatric conditions other than depression (e. g., panic disorder, obsessive compulsive disorder, social anxiety disorder, general anxiety disorder, and post-traumatic stress disorder): 56.3% in the US, 69.2% in the UK, 69.2% in France, 50.0% in Germany, and 62.5% in Japan. Conclusions Our results raise concerns regarding generic terminologies of antipsychotics and antidepressants since the conventional indication-based nomenclature does not fit well with the official indication.

© 2020 Elsevier Ltd Objective: The purpose of this study was to extract important patient questionnaire items by creating random forest models for predicting pattern diagnosis considering an interaction between deficiency-excess and cold-heat patterns. Design: A multi-centre prospective observational study. Setting: Participants visiting six Kampo speciality clinics in Japan from 2012 to 2015. Main outcome measure: Deficiency–excess pattern diagnosis made by board-certified Kampo experts. Methods: We used 153 items as independent variables including, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We sampled training data with an equal number of the different patterns from a 2 × 2 factorial combination of deficiency–excess and cold–heat patterns. We constructed the prediction models of deficiency–excess and cold–heat patterns using the random forest algorithm, extracted the top 10 essential items, and calculated the discriminant ratio using this prediction model. Results: BMI and blood pressure, and subjective symptoms of cold or heat sensations were the most important items in the prediction models of deficiency–excess pattern and of cold–heat patterns, respectively. The discriminant ratio was not inferior compared with the result ignoring the interaction between the diagnoses. Conclusions: We revised deficiency–excess and cold–heat pattern prediction models, based on balanced training sample data obtained from six Kampo speciality clinics in Japan. The revised important items for diagnosing a deficiency–excess pattern and cold–heat pattern were compatible with the definition in the 11th version of international classification of diseases.

© Copyright 2020 Physicians Postgraduate Press, Inc. OBJECTIVE: The objective of this study was to examine the extent of possible dissociation in pharmacokinetic decay between central dopamine D₂ receptor occupancy with antipsychotics and their peripheral blood concentrations. DATA SOURCES: MEDLINE and Embase were searched using the following keywords: (positron emission tomography OR PET OR single-photon emission computed tomography OR SPECT) AND (dopamine OR D2) AND (receptor* OR occupanc*) AND antipsychotic*, with a limitation of English language (last search: December 14, 2019). STUDY SELECTION: The search identified 18 studies that met the following criteria: (1) including patients with schizophrenia spectrum disorders and/or healthy subjects, (2) using positron emission tomography or single-photon emission computed tomography, and (3) examining the time courses of D₂ occupancy with antipsychotics and their blood concentrations. DATA EXTRACTION: The ratios of D₂ occupancy reduction rate (%) from peak to blood concentration reduction rate (%) from peak (relative attenuation ratio) were calculated. RESULTS: Among the studies, oral risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perospirone, haloperidol, sulpiride, and clozapine and long-acting injectable risperidone and haloperidol were included. Relative attenuation ratios were less than 1, indicating a slower central versus peripheral attenuation, across the time points for all antipsychotic types and doses with only a few exceptions. The ratio decreased in a dose-dependent as well as a peak D₂ occupancy-dependent fashion. It contrarily increased in a time-dependent manner. CONCLUSIONS: The findings indicate pharmacokinetic attenuation of antipsychotics was generally slower at the central versus the peripheral level and pose a critical challenge to the current dosing strategy that primarily relies on peripheral pharmacokinetics of antipsychotics.