No adverse events were observed in clozapine-treated patients on extended hematologic monitoring intervals during the coronavirus pandemic in four psychiatric centers in Japan.

AIM: As an emergency measure during the coronavirus disease pandemic, the monitoring interval for clozapine use was temporarily extended beyond the regulatory requirement in Japan, which is the safest monitoring interval worldwide. In this study, we aimed to explore the effect of this measure on patients undergoing clozapine treatment. METHODS: This retrospective chart review study included patients with treatment-resistant schizophrenia (TRS) who were undergoing clozapine treatment at four psychiatric institutions in Japan. Demographic characteristics and clinical information of these patients were collected on April 27, 2020, when Japanese psychiatrists were virtually allowed to prescribe clozapine beyond the regulatory requirement. Furthermore, information of adverse events related to the emergency measure was collected and analyzed. RESULTS: Of the 41 patients with TRS included in this study, 19 patients underwent extended hematological monitoring during clozapine treatment. No psychiatric or hematological adverse events were observed in the patients during the extended monitoring interval. CONCLUSION: This study suggested that there were few adverse events of clozapine-treated patients related to emergency measures in Japan. However, hematological monitoring intervals during clozapine treatment have been emergently extended worldwide; hence, it is necessary to verify the results of these measures.

The Feasibility and Efficacy of Social Cognition and Interaction Training for Outpatients With Schizophrenia in Japan: A Multicenter Randomized Clinical Trial.

Background: Schizophrenia is a disabling illness. Social cognition and interaction training (SCIT) seeks to improve patients' social functioning by alleviating deficits in social cognition. SCIT has shown promise in improving social cognition in patients with schizophrenia, but has not yet been studied in Japan. Design: An assessor-masked, randomized, parallel-group clinical trial was conducted to compare the feasibility and efficacy of SCIT with treatment as usual (TAU). Setting: Participants were recruited from outpatient clinics at the National Center of Neurology and Psychiatry and four other hospitals in Japan. Participants: Seventy-two patients diagnosed with schizophrenia or schizoaffective disorder consented to participate in the trial. Procedure: Participants were randomly allocated to either a SCIT subgroup or a TAU subgroup. SCIT is a manual-based group intervention that is delivered in 20-24-h-long weekly sessions. Groups include two to three clinicians and four to eight patients. Hypotheses: We hypothesized that SCIT would be found to be feasible and that patients who were randomized to receive SCIT would exhibit improvements in social cognition. Results: Data from 32 participants in each subgroup were entered into analyses. The persistence rate in the SCIT subgroup was 88.9%, and the average attendance rate was 87.0%. Intrinsic motivation was significantly higher in the SCIT subgroup than the TAU group during the first half of the program. Mixed effects modeling of various outcome measures revealed no significant interaction between measurement timepoint and group in any measures, including social cognition, neurocognition, symptom severity, and social functioning. In the case of the social cognition measure, significant change was observed only in the SCIT subgroup; however, the interaction between timepoint and group failed to reach significance. In an exploratory subgroup analysis, a shorter duration of illness was found to be associated with significantly better improvement on the social cognition measure in the SCIT subgroup compared with the TAU subgroup. Conclusions: In terms of the primary objective, the relatively low dropout rate observed in the present study suggests that SCIT is feasible and well tolerated by patients with schizophrenia in Japan. This view is also supported by participants' relatively high attendance and intrinsic motivation.

Feasibility and effectiveness of a cognitive remediation programme with original computerised cognitive training and group intervention for schizophrenia: a multicentre randomised trial.

Devising new methods to improve neurocognitive impairment through cognitive remediation is an important research goal. We developed an original computer programme termed the Japanese Cognitive Rehabilitation Programme for Schizophrenia (JCORES) that provides cognitive practice across a broad range of abilities. The current study examined for the first time whether a cognitive remediation programme, including both computerised cognitive training using JCORES and group intervention such as enhancing meta-cognition and teaching strategies, is more effective than treatment as usual for improving neurocognitive and social functioning. Sixty-two outpatients with schizophrenia were randomised to either a cognitive remediation group or a control group. Participants engaged in two computerised cognitive training sessions and one group meeting per week for 12 weeks. The average number of total sessions attended (computerised cognitive practice + group intervention) was 32.3 (89.7%). The cognitive remediation group showed significantly more improvements in verbal memory, composite score of the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J), and general psychopathology on the Positive and Negative Syndrome Scale (PANSS) than the control group. These findings demonstrate that a cognitive remediation programme is feasible in Japan and is a more effective way to improve neurocognitive functioning and psychiatric symptoms.

Efficacy of cognitive rehabilitation using computer software with individuals living with schizophrenia: A randomized controlled trial in Japan.

OBJECTIVE: Cognitive impairment is common in schizophrenia, and is associated with poor psychosocial functioning. Previous studies had inconsistently shown improvement in cognitive functions with cognitive remediation therapy. This study examined whether cognitive remediation is effective in improving both cognitive and social functions in schizophrenia in outpatient settings that provide learning-based psychiatric rehabilitation. This study is the first randomized controlled trial of cognitive remediation in Japan. METHOD: Study participants were individuals with schizophrenia from 6 outpatient psychiatric medical facilities who were randomly assigned either a cognitive remediation program or treatment as usual. The cognitive remediation intervention includes Cognitive training using computer software (CogPack; Japanese version) administered twice a week and a weekly group over 12 weeks and was based on the Thinking Skills for Work program. Most study participants were attending day treatment services where social skills training, psychoeducation for knowledge about schizophrenia, group activities such as recreation and sport, and other psychosocial treatment were offered. Cognitive and social functioning were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) and Life Assessment Scale for Mentally Ill (LASMI) at pre- and postintervention. RESULTS: Of the 60 people with schizophrenia enrolled, 29 were allocated to the cognitive remediation group and 31 were allocated to the treatment as usual group. Processing speed, executive function, and the composite score of the BACS showed significantly greater improvement for the cognitive remediation group than the treatment as usual group. In addition, there was significant improvement in interpersonal relationships and work skills on the LASMI for the cognitive remediation group compared with the treatment as usual group. Changes from pretreatment to posttreatment in verbal fluency and interpersonal relationships were significantly correlated, as well as changes in attention and work skills. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The present findings showed that providing cognitive remediation on addition to psychiatric rehabilitation contributed to greater improvement in both cognitive and social functioning than psychiatric rehabilitation alone. Cognitive remediation may enhance the efficacy of psychiatric rehabilitation improving social functioning. (PsycINFO Database Record

Facial expression perception correlates with verbal working memory function in schizophrenia.

AIMS: Facial emotion perception is considered to provide a measure of social cognition. Numerous studies have examined the perception of emotion in patients with schizophrenia, and the majority has reported impaired ability to recognize facial emotion perception. We aimed to investigate the correlation between facial expression recognition and other domains of social cognition and neurocognition in Japanese patients with schizophrenia. METHODS: Participants were 52 patients with schizophrenia and 53 normal controls with no history of psychiatric diseases. All participants completed the Hinting Task and the Social Cognition Screening Questionnaire. The Brief Assessment of Cognition in Schizophrenia was administered only to the patients. Facial emotion perception measured by the Facial Emotion Selection Test (FEST) was compared between the patients and normal controls. RESULTS: Patients performed significantly worse on the FEST compared to normal control subjects. The FEST total score was significantly positively correlated with scores of the Brief Assessment of Cognition in Schizophrenia attention subscale, Hinting Task, Social Cognition Screening Questionnaire Verbal Working Memory and Metacognition subscales. Stepwise multiple regression analysis revealed that verbal working memory function was positively related to the facial emotion perception ability in patients with schizophrenia. CONCLUSIONS: These results point to the concept that facial emotion perception and some types of working memory use common cognitive resources. Our findings may provide implications for cognitive rehabilitation and related interventions in schizophrenia.

Risperidone-associated urinary incontinence in patients with autistic disorder with mental retardation.

We report several cases in which patients with autistic disorder with mental retardation who received risperidone experienced urinary incontinence. We retrospectively investigated the medical records of patients housed in facilities for patients with autistic disorder with mental retardation. Those who had undergone a medical examination at a hospital in Tokyo from April 1999 to March 2009 were included in the study.Retrospective data were gathered including age, sex, IQ, birth weight, dosage of risperidone, urinary density, as well as existence of urinary and fecal incontinence. We divided the participants into those who did and did not experience urinary incontinence after taking risperidone and compared the 2 groups. Risperidone had been prescribed to 35 patients. In spite of the fact that no patient had a history of urinary incontinence, 14 patients experienced urinary incontinence after receiving risperidone. Moreover, 4 of these 14 patients also had fecal incontinence. Among the variables we examined, the only significant difference between groups was in sex, with significantly more women experiencing incontinence compared with men. When the dose of risperidone was reduced or the patients switched to other drugs, urinary incontinence of the patients improved.Hence, risperidone may have a casual relationship with urinary incontinence. Further research is needed to understand the pathophysiology of possible effect.

New instrument for measuring multiple domains of social cognition: construct validity of the Social Cognition Screening Questionnaire (Japanese version).

AIM: The present study aimed to test the construct validity and internal consistency of the Social Cognition Screening Questionnaire (SCSQ) (Japanese version). METHODS: We first tested whether the subscale scores and the total score of the SCSQ could discriminate patients with schizophrenia from normal controls. Next, we tested the internal consistency. Finally, we investigated the relation between the subscale scores and other measures of social cognition and social functioning that were presumed to correspond to the subscale's scores, including the Hinting Task, the Ambiguous Intentions Hostility Questionnaire (AIHQ), the Beck Cognitive Insight Scale and the Social Functioning Scale. RESULTS: The subscale scores and the total score appeared to show more robust between-group differences than other measures of social cognition, such as the AIHQ and the Hinting Task. The total score distinguished the patients from normal controls with an area under the receiver-operator curve of 0.84, which indicated a high level of discrimination. The Cronbach's alpha for the four subscales was 0.72, which was considered acceptable. In terms of criterion-related validity, theory of mind, metacognition and hostility bias subscale scores showed significant correlations with the Hinting Task, Beck Cognitive Insight Scale and AIHQ, respectively. Moreover, the theory of mind subscale score showed a significant correlation with four domain scores of the Social Functioning Scale. The present results indicated good construct validity and internal consistency of the SCSQ. CONCLUSIONS: Although this is an interim report with a small sample size, the SCSQ holds promise as an efficient measure for social cognition.

Effects of risperidone and aripiprazole on neurocognitive rehabilitation for schizophrenia.

AIM: Methods to improve neurocognitive impairments are of important research interest. This study sought to examine the synergistic effects of neurocognitive rehabilitation and antipsychotics for schizophrenia. METHODS: Subjects were 43 patients diagnosed with schizophrenia or schizoaffective disorder in a randomized trial of the effects of neurocognitive rehabilitation or a quasi-randomized experimental trial of supported employment with neurocognitive rehabilitation. We compared the effects of risperidone and aripiprazole in neurocognitive rehabilitation for schizophrenia. Subjects were divided into the following groups: (i) the control-risperidone group (CR group) (n = 13); (ii) the rehabilitation-risperidone group (RR group) (n = 9); (iii) the control-aripiprazole group (CA group) (n = 10); and (iv) the rehabilitation-aripiprazole group (RA group) (n = 11). Subjects in the rehabilitation group were engaged in computer-based cognitive exercises (24 sessions) with bridging group (12 sessions) over 12 weeks. Psychiatric symptoms, neurocognitive functioning and social functioning assessments were evaluated at baseline and at 12 weeks. RESULTS: A two-way anova with neurocognitive rehabilitation and antipsychotic medication as factors revealed a significant interaction effect on motor speed. Working memory and motor speed significantly improved in the RA group compared with the CA group. We found no significant improvements between the CR group and the RR group. CONCLUSION: A synergistic effect of neurocognitive rehabilitation and aripiprazole was observed as improvement of motor speed. In patients treated with aripiprazole, neurocognitive rehabilitation appeared to improve working memory and motor speed. Further studies of synergistic effects of neurocognitive rehabilitation and antipsychotic medication are necessary to verify these findings.

[Efficacy and application of cognitive rehabilitation: the importance of combining social skills training with cognitive rehabilitation].

Many researchers and practitioners have suggested that improving the cognition of patients with schizophrenia is very important for achieving true "recovery". There is a strong relationship between cognitive function and social functioning; cognitive function affects functional outcomes of schizophrenic patents. Therefore, rehabilitation methods to improve cognitive function have been developed. These methods are generally referred to as "cognitive rehabilitation" or "cognitive remediation". Recently, there has been an increase in clinical research regarding cognitive rehabilitation. We found more than 170 clinical trials of cognitive rehabilitation by searching the literature database PubMed, and the number of trials has increased markedly since 2005. Some meta-analyses of cognitive rehabilitation treatments have already been published (Wykes, 2011; McGurk, 2007; Krabbendam, 2003). These studies reported that the efficacy of cognitive rehabilitations showed a medium effect size for cognitive functions (0.4-0.5). We implemented a multicenter, randomized, controlled trial to examine the efficacy of cognitive training software in patients with schizophrenia. We found that the neurocognitive function and some domains of social functioning showed greater improvement in people who received cognitive training using specialized software than in those receiving standard treatment. The results of our clinical trial indicate that the combination of cognitive and specific rehabilitation to improve social functioning (i.e., social skills training) is valuable to achieve "recovery" in people with schizophrenia.

The effects of the combination of cognitive training and supported employment on improving clinical and working outcomes for people with schizophrenia in Japan.

BACKGROUND: In Japan, Job assistance for SMI have been not active. Compared with mental retardation, employment rate of SMI was low. The needs of the effective job assistance for SMI are growing. The purpose of this study was to determine the effectiveness of the combination approach of Cognitive Remediation (CR) and Supported Employment (SE) in clinical outcomes, including cognitive functioning and psychiatric symptoms besides vocational outcomes. METHODS: The participants diagnosed with schizophrenia or schizoaffective disorder were assigned to CR+SE group (n=52) and SE group (n=57). CR comprised computer based trainings using COGPACK and group works. SE was individualized vocational support provided by employment specialists. Outcome measures included cognitive functioning, psychiatric symptoms, social functioning, performance of tasks as clinical outcomes, employment rate, duration of employment, and earned wage as vocational outcome. RESULTS: CR+SE group displayed significantly better psychiatric symptoms (F=3.490, p<.10), interpersonal relations (F=11.695, p<.01), and social and cognitive functioning including verbal memory (F=9.439, p<.01), digit sequencing (F=5.544, p<.05), token motor tasks (F=6.685, p<.05), and overall cognitive functioning (F=8.136, p<.01). We did not find any significant difference between two groups in terms of employment rate and earned wage. DISCUSSIONS: This is the first controlled study to determine the effectiveness of CR on vocational outcomes in Japan. The results showed that CR and SE programs were feasible in Japan and that CR using COGPACK had favorable effects on cognitive functioning, psychiatric symptoms, and social functioning, which is consistent with previous researches.

[Approaches for suicide prevention in Osaka Psychiatric Medical Center: the importance of multi-disciplinary cooperation and partnerships with other organizations].

Suicide is a very common problem in psychiatric practice today. Therefore, almost all staff of psychiatric hospitals have encountered the suicide of one or more of their patients. Our hospital, Osaka Psychiatric Medical Center, is a public psychiatric hospital in Japan. We provide treatment and support for patients from the acute to chronic phases of psychiatric disorders, and patients range from children to the elderly. Because we accept many patients with severe mental illness from other hospitals, many of our staff are routinely confronted with patients' violence or suicidal attempts. If a patient commits suicide, the relevant staff immediately have a conference to implement measures for preventing a recurrence. At the same time, information about the incident is conveyed to the medical safety management office and made known to all staff in our hospital. This office was established in 2007. Currently, all information about incidents and accidents in our hospital (e.g., suicide, problems between patients, problems with hospital facilities) is aggregated in the office and distributed to all staff members through the hospital intranet. This system makes it possible for staff to consider countermeasures against similar incidents and accidents, even if not involved in the incident. Additionally, we make an effort to develop cooperative relationships with organizations including the police, public health centers, and the fire department. The social welfare council in Hirakata City, where our hospital is located, provides some services to prevent suicide (e.g., telephone counseling, meetings with bereaved family members). Our hospital cooperates with these services by providing lecturers. The partnerships with these organizations help regarding the mental crises of patients in our hospital and fulfill a role to prevent suicide. Multi-disciplinary cooperation and partnerships with community organizations are not special approaches to suicide prevention, but ordinary approaches in everyday clinical practice. The most important factor is the relationship between staff and organizations relevant to preventing suicide.

[Two adolescent cases of pseudoseizure with mental retardation].

We experienced two cases of complicated pseudoseizure, whose diagnosis and treatment were based on Kretschmer's concept of "primitive hysteria". The first case was a 16-year-old boy who experienced a convulsion before a swimming class which he disliked. He was immediately brought to the emergency department of our hospital. Initially, he was treated as a true epileptic patient, and his convulsion continued for hours. We monitored the patient by video, which aided in making a precise diagnosis. He also showed a pain disorder. The second case was a 16-year-old girl who developed hyperventilation and convulsion during her graduation ceremony. The characteristics of her convulsion were similar to the first case. Four days after her admission to our hospital, we concluded that her symptoms were a part of primitive hysteria. After her discharge, she experienced some intermittent episodes of convulsion. There was also a possibility of sexual abuse from her father. Both patients had a family history of mental retardation and an unstable home life, as well as similar symptoms. Even in a modern general hospital, there is a lack of understanding about pseudoseizure, thus, medication may be unnecessary for undiagnosed patients. DSM-IV-TR as well as ICD-10 criteria do not mention anything about primitive hysteria. However, we recommend revitalization of this concept because it is a useful, appropriate, and necessary description of pseudoseizure with complications.

Prefrontal cerebral activity during a simple "rock, paper, scissors" task measured by the noninvasive near-infrared spectroscopy method.

We conducted a noninvasive near-infrared spectroscopy (NIRS) study using the game of rock, paper, scissors (RPS) as a simple neurocognitive task for the prefrontal cortex (PFC) in 15 healthy volunteers. We employed an opposite "to lose" RPS task coupled with a normal "to win" RPS task, since the former requires inhibition of behavior, one of the most important functions of the prefrontal cortex. During the NIRS examination, subjects had to present one of the three RPS hands in response to hands displayed randomly on a computer screen every 1.5 s, and were required to show hands that lose to the computer, or that beat the computer. We measured the relative concentrations of oxyhemoglobin (oxy-Hb) using the prefrontal probes of the NIRS system during the tasks. The increases in oxy-Hb during the "to win" RPS task were small, but were quite large and laterally dominant during the "to lose" RPS task. The difference between the two tasks might have been due to the participants' cognitive conflict with losing on the RPS. We conclude that losing is better than winning on the RPS as a sensitive indicator in the NIRS examination of PFC.