International Experience of Implementing Cognitive Remediation for People With Psychotic Disorders.

BACKGROUND: Cognitive remediation (CR) is an effective therapy for the cognitive impact of mental illness, especially schizophrenia. Global efforts are being made to implement CR into routine mental health services with the aim of improving functional outcomes for the population of people recovering from mental illness. Implementation and dissemination of CR in heterogeneous settings require knowledge gleaned from formal implementation research and pragmatic experiential learning. This article describes cross-cultural approaches to CR implementation, focusing on initiatives in France, the United States, Australia, and Japan. METHOD: Key leaders in the implementation of CR in France, the United States, Australia, and Japan were asked to describe the implementation and dissemination process in their settings with respect to the categories of context, implementation, outcomes, facilitators, and barriers. RESULTS: All 4 sites noted the role of collaboration to leverage the implementation of CR into mental health rehabilitation services. In France, high-level, government organizational backing enhanced the dissemination of CR. Academic and clinical service partnerships in the United States facilitated the dissemination of programs. The advocacy from service users, families, and carers can aid implementation. The support from international experts in the field can assist in initiating programs but maintenance and dissemination require ongoing training and supervision of staff. CONCLUSIONS: CR is an effective intervention for the cognitive impact of schizophrenia. Programs can be implemented in diverse settings globally. Adaptations of CR centering upon the core components of effective CR therapy enhance outcomes and enable programs to integrate into diverse settings.

The evaluation study for social cognition measures in Japan: Psychometric properties, relationships with social function, and recommendations.

AIM: Patients with schizophrenia can have significant subjective difficulties in social cognition, but few undergo testing or treatment for social cognition. The Social Cognition Psychometric Evaluation (SCOPE) study recommends six social cognitive measures; however, the reliability and validity of these measures in different cultural and linguistic areas has not been adequately examined. We examined the psychometric properties of nine social cognitive measures and the relationship to social function, with the aim of determining the level of recommendation for social cognitive measures in clinical practice in Japan. METHODS: For our test battery, an expert panel previously selected nine measures: the Bell Lysaker Emotion Recognition Task (BLERT); Facial Emotion Selection Test (FEST); Hinting Task (Hinting); Metaphor and Sarcasm Scenario Test (MSST); Intentionality Bias Task (IBT); Ambiguous Intentions and Hostility Questionnaire (AIHQ); Social Attribution Task-Multiple Choice (SAT-MC); SAT-MCII; and Biological Motion (BM) task. In total, 121 outpatients with schizophrenia and 70 healthy controls were included in the analysis, and the results were provided to an expert panel to determine the recommendations for each measure. The quantitative psychological indices of each measure were evaluated for practicality, tolerability, test-retest reliability, correlation with social function, and the incremental validity of social function. RESULTS: Hinting and FEST received the highest recommendations for use in screening, severity assessment, and longitudinal assessment, followed by BLERT, MSST AIHQ, SAT-MC, and SAT-MCII, with IBT and BM receiving the lowest recommendations. CONCLUSION: This study provides a uniform assessment tool that can be used in future international clinical trials for social cognitive impairment.

The association between emotion malleability beliefs and severe psychological distress stratified by sex, age, and presence of any psychiatric disorders.

Background: Recent studies have shown an association between psychological distress and emotion malleability beliefs, meaning mindsets about whether one's emotions are fixed or changeable. However, most studies have not examined the association between these beliefs and sociodemographic factors. Methods: A nationwide cross-sectional Internet survey of residents of Japan aged 15-79 years was conducted using sampling weights for national estimates to investigate the association between emotion malleability beliefs and sociodemographic factors and between fixed beliefs and severe psychological distress (SPD). SPD was defined as a Kessler 6 Scale score of ≥13. Adjusted odds ratios for SPD were calculated considering potential confounders. Further analyses were stratified by sex, age and presence of any psychiatric disorder. Results: The analysis included 23,142 participants (female, 48.64%). Fixed beliefs were associated with female sex, age < 45 years, and presence of psychiatric disorders. These beliefs were associated with SPD, and additional analysis showed stronger associations with SPD among female respondents, respondents aged 45-59 years, and those aged ≥60 years. Conclusion: Results indicate that female sex, age < 45 years, and current mental disorders were associated with fixed emotion malleability beliefs. Associations between fixed emotion malleability beliefs and SPD were particularly strong among female respondents and people aged ≥45 years compared with the general population. Our study extends the association between emotion malleability beliefs and psychological health to the general population. Future studies should explore mechanisms underlying individual differences in emotion beliefs.

Mediation Effects of Social Cognition on the Relationship between Neurocognition and Social Functioning in Major Depressive Disorder and Schizophrenia Spectrum Disorders.

BACKGROUND: In schizophrenia spectrum disorders (SSD), social cognition mediates the relationship between neurocognition and social functioning. Although people with major depressive disorder (MDD) also exhibit cognitive impairments, which are often prolonged, little is known about the role of social cognition in MDD. METHODS: Using data obtained through an internet survey, 210 patients with SSD or MDD were selected using propensity score matching based on their demographics and illness duration. Social cognition, neurocognition, and social functioning were evaluated using the Self-Assessment of Social Cognition Impairments, Perceived Deficits Questionnaire, and Social Functioning Scale, respectively. The mediation effects of social cognition on the relationship between neurocognition and social functioning were examined in each group. Invariances of the mediation model across the two groups were then analyzed. RESULTS: The SSD and MDD groups had mean ages of 44.49 and 45.35 years, contained 42.0% and 42.8% women, and had mean illness durations of 10.76 and 10.45 years, respectively. In both groups, social cognition had significant mediation effects. Configural, measurement, and structural invariances across the groups were established. CONCLUSION: The role of social cognition in patients with MDD was similar to that in SSD. Social cognition could be a common endophenotype for various psychiatric disorders.

Mental health care use and related factors in adolescents and young adults with cancer.

PURPOSE: The actual state of mental health care use and related factors in adolescent and young adult (AYA) patients with cancer is not well understood in Japan. This study aimed to (1) examine the actual state of mental health care use among AYA patients with cancer and (2) describe socio-demographic and related factors associated with mental health care use. METHODS: We retrospectively reviewed the medical records of AYA patients with cancer aged 15-39 who first visited the National Cancer Center Hospital in Japan (NCCH) between January 2018 and December 2020. Logistic regression was used to analyze the association between social background characteristics and mental health care use. The association between the patient's course of cancer treatment and mental health care use was analyzed to help identify which patients might benefit from early mental health intervention. RESULTS: Among 1,556 patients, 945 AYA patients with cancer were registered. The median age at the time of the study was 33 years (range, 15-39 years). The prevalence of mental health care use was 18.0% (170/945). Age 15-19 years, female gender, urogenital cancer, gynecological cancer, bone or soft tissue cancer, head and neck cancer, and stage II-IV disease were associated with mental health care use. Regarding treatment, palliative treatment, chemotherapy, and hematopoietic stem cell transplantation were associated with mental health care use. CONCLUSION: Factors associated with mental health care use were identified. Our findings potentially contribute to psychological support interventions for AYA patients with cancer.

Relationship between objective cognitive functioning and work performance among Japanese workers.

OBJECTIVES: We aimed to explore the relationship between objective cognitive functioning and work performance among Japanese workers. METHODS: From February to November 2019, this cross-sectional study enrolled workers aged 18-65 years from 10 companies located in a metropolitan area of Japan. We emailed invitations to participate to employees of companies that had agreed to cooperate with the study. We measured work performance with the question, "How would you rate your performance (compared with your optimum performance) over the past 4 weeks?" Responses were made via a visual analog scale (range: 0-100). Cognitive functioning was assessed using the THINC-integrated tool (THINC-it®). THINC-it® is a brief, objective computerized cognitive assessment battery. Associations between work performance and cognitive functioning tests were examined using logistic regression analysis. RESULTS: In total, 353 individuals provided e-consent to participate, of whom 276 were included in the analysis (after omitting those with missing values). The median work performance was used to divide participants into high- (scoring ≥ 80%) and low- (scoring < 80%) performing groups. The P-values for trends indicated that association between cognitive domains, such as attention, executive functioning and working memory was significant (P < .05). Work performance was significantly associated with cognitive function for the two tests that assess attention, executive functioning, and working memory in general workers. CONCLUSIONS: Our results suggest that objective cognitive functioning may be related to work performance. Longitudinal investigations may allow for the establishment of causality.

Valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia (VICTORY-S): study protocol for an interventional, open-label, randomized comparison of combined treatment with cognitive remediation and lurasidone or paliperidone.

Background: Cognitive impairment, a core feature of schizophrenia, is associated with poor outcomes. Pharmacotherapy and psychosocial treatment, when used alone, have inadequate effect sizes for cognitive impairment, leading to recent interest in combination interventions. A previous study examined the additive effect of cognitive remediation on lurasidone in patients with schizophrenia, which was negative. Although improvement in cognitive function was suggested for lurasidone, it was inconclusive because there was no antipsychotic control in the study. To clarify whether lurasidone has a meaningful impact on cognitive function in combination with cognitive remediation, we use paliperidone as a control antipsychotic in this study. We hypothesize that combination with lurasidone will improve cognitive and social function to a greater extent than paliperidone. Methods: The valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia study is a multicenter, interventional, open-label, rater-blind, randomized comparison study, comparing the effect of lurasidone plus cognitive remediation with that of paliperidone plus cognitive remediation in patients with schizophrenia. The Neuropsychological Educational Approach to Remediation (NEAR) is used for cognitive remediation. Eligible patients will be randomized 1:1 to receive lurasidone or paliperidone combined with NEAR (6 weeks antipsychotic alone followed by 24 weeks combination antipsychotic plus NEAR). The primary endpoint is the change from baseline in the tablet-based Brief Assessment of Cognition in Schizophrenia composite T-score at the end of the NEAR combination treatment period. Secondary endpoints will include change from baseline in social function, schizophrenia symptoms, and quality of life at the end of the NEAR combination treatment period. Furthermore, change from baseline to the end of the pharmacotherapy period and change from the end of the pharmacotherapy period to the end of the NEAR combination treatment period will be assessed for all endpoints. Safety will also be evaluated. Discussion: Achievement of adequate cognitive function is central to supporting social function, which is a key treatment goal for patients with schizophrenia. We think this study will fill in the gaps of the previous study and provide useful information regarding treatment decisions for patients with schizophrenia. Clinical trial registration: Japan Registry of Clinical Trials ID, jRCTs031200338.

Pharmacological interventions for social cognitive impairments in schizophrenia: A protocol for a systematic review and network meta-analysis.

Background: Social cognitive impairments adversely affect social functioning (e.g., employment status) in patients with schizophrenia. Although pharmacological interventions have been suggested to provide some benefits on social cognition, little information is available on the comparative efficacy of pharmacotherapy. Thus, the aim of this planned systematic review and network meta-analysis is to perform a quantitative comparison of the effects of various psychotropic drugs, including supplements, on social cognition disturbances of schizophrenia. Methods: The literature search will be carried out using the PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov, and International Clinical Trials Registry Platform databases from inception onward. Randomized controlled trials that examined the efficacy of drugs in social cognitive disturbances will be included, based on the most recent studies and the broader literature than previously searched. This protocol defines a priori the methods that will be used for study selection, data collection, quality assessment, and statistical syntheses. Discussion: The findings this work are expected to help promote the development of better therapeutics of social cognitive impairments in schizophrenia and related psychiatric conditions. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021293224].

Perceptions of and subjective difficulties with social cognition in schizophrenia from an internet survey: Knowledge, clinical experiences, and awareness of association with social functioning.

AIM: Social cognition impacts social functioning in schizophrenia; however, little is known about how patients with schizophrenia themselves perceive social cognition. This study, using an internet survey, aimed to investigate their knowledge of social cognition, clinical experiences related to social cognition, awareness of social cognition's role in one's social life, and the relationships between subjective difficulties with social cognition and social functioning. METHODS: Data from 232 outpatients with schizophrenia (SZ) and 494 healthy controls (HC) were obtained through an internet survey and were weighted according to the demographics of the national population. A newly developed survey questionnaire on knowledge, experience, and awareness of social cognition was administered. Subjective difficulties were evaluated using the Self-Assessment of Social Cognition Impairments and the Observable Social Cognition Rating Scale. RESULTS: Less than a quarter of both groups were familiar with the term or concept of social cognition. Less than 5% of both groups had experienced being assessed or treated for social cognition. More than half of both groups were aware of the relationship between social cognition and social functioning. The SZ group had higher levels of subjective difficulties than the HC group across all social cognitive domains. The attributional bias domain of subjective difficulties was negatively associated with social functioning. CONCLUSION: Patients with schizophrenia had substantial subjective difficulties in social cognition, which they perceived as being related to social functioning. However, their knowledge of social cognition was limited, and the assessment and treatment might not be widespread in regular clinical practice.

Sex Differences in Social Cognition and Association of Social Cognition and Neurocognition in Early Course Schizophrenia.

Background: Both impairment and sex differences in social cognition and neurocognition have been documented in schizophrenia. However, whether sex differences exist in the association between social cognition and neurocognition are not known. We aimed to investigate the contribution of areas of neurocognition to theory of mind (ToM) and hostility bias, representing social cognition, according to sex in early course schizophrenia. Methods: In this cross-sectional study, we assessed neurocognition using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS) and assessed the ToM and hostility bias subdomains of social cognition using the Social Cognition Screening Questionnaire (SCSQ) in 131 participants (65 female, 66 male) diagnosed with schizophrenia within 5 years of onset. Sex differences were analyzed using t-tests. The associations of neurocognitive subdomains with ToM and hostility bias according to sex were analyzed using multiple regression analysis. Results were adjusted by age, estimated premorbid intelligence quotient, and symptomatology. Results: No sex differences were found in ToM (p = 0.071) or hostility bias (p = 0.057). Higher verbal fluency was significantly associated with higher ToM in females (p < 0.01), whereas higher executive function was significantly associated with higher ToM in males (p < 0.05). Higher verbal fluency was significantly associated with lower hostility bias in females (p < 0.05), whereas neurocognition and hostility bias were not significantly associated in males. Conclusion: The results suggest that neurocognition associated with social cognition differ according to sex. These differences should be considered for more effective treatment of social cognition.

Study Protocol: The Evaluation Study for Social Cognition Measures in Japan (ESCoM).

In schizophrenia, social cognitive impairment is considered one of the greatest obstacles to social participation. Although numerous measures have been developed to assess social cognition, only a limited number of them have become available in Japan. We are therefore planning this evaluation study for social cognition measures in Japan (ESCoM) to confirm their psychometric characteristics and to promote research focused on social cognition. Participants in the cross-sectional observational study will be 140 patients with schizophrenia recruited from three Japanese facilities and 70 healthy individuals. In our primary analysis, we will calculate several psychometric indicators with a focus on whether they can independently predict social functioning. In secondary analyses, we will assess the reliability and validity of the Japanese translations of each measure and conduct an exploratory investigation of patient background, psychiatric symptoms, defeatist performance belief, and gut microbiota as determinants of social cognition. The protocol for this study is registered in UMIN-CTR, unique ID UMIN000043777.

Perilla Oil and Bifidobacterium for Alleviating Fear of Cancer Recurrence in Breast Cancer Survivors: Study Protocol for a Three-Arm Phase II Randomized Controlled Study (POB Study).

The fear of cancer recurrence (FCR) is the most common and most severe unmet need among cancer survivors. Safe treatments for the FCR that are easily disseminated are greatly needed. Our primary aim is a preliminary evaluation of the efficacy and effect size of perilla oil, which is rich in omega-3 fatty acids, and Bifidobacterium, a probiotic, on FCR in breast cancer survivors after the completion of chemotherapy. This study has been planned as an exploratory clinical study (phase II) and will be conducted as a three-arm, 12-week parallel group, masked-rater randomized controlled trial. Fifteen participants will be randomized with 1:1:1 allocation to receive Bifidobacterium plus perilla oil, Bifidobacterium alone, or no intervention (control). Interventions will end within 12 weeks after the random allocation of each participant. The participants will be outpatients with invasive breast cancer aged 20 years or older whose chemotherapy was completed at least 6 months before registration; hormone therapy may be ongoing. The primary outcome will be severity of FCR at 12 weeks assessed by masked raters using the 4-item Concerns about Recurrence Scale concerning overall fear of recurrence. The study protocol for the current study is registered in the Japan Registry of Clinical Trials (jRCTs031200029).

Evaluation of Social Cognition Measures for Japanese Patients with Schizophrenia Using an Expert Panel and Modified Delphi Method.

Social cognition is strongly linked to social functioning outcomes, making it a promising treatment target. Because social cognition measures tend to be sensitive to linguistic and cultural differences, existing measures should be evaluated based on their relevance for Japanese populations. We aimed to establish an expert consensus on the use of social cognition measures in Japanese populations to provide grounds for clinical use and future treatment development. We assembled a panel of experts in the fields of schizophrenia, social psychology, social neuroscience, and developmental disorders. The panel engaged in a modified Delphi process to (1) affirm expert consensus on the definition of social cognition and its constituent domains, (2) determine criteria to evaluate measures, and (3) identify measures appropriate for Japanese patients with a view toward future quantitative research. Through two online voting rounds and two online video conferences, the panel agreed upon a definition and four-domain framework for social cognition consistent with recent literature. Evaluation criteria for measures included feasibility and tolerability, reliability, clinical effectiveness, validity, and international comparability. The panel finally identified nine promising measures, including one task originally developed in Japan. In conclusion, we established an expert consensus on key discussion points in social cognition and arrived at an expert-selected set of measures. We hope that this work facilitates the use of these measures in Japanese clinical scenarios. We plan to further examine these measures in a psychometric evaluation study.

Urbanization level and neighborhood deprivation, not COVID-19 case numbers by residence area, are associated with severe psychological distress and new-onset suicidal ideation during the COVID-19 pandemic.

BACKGROUND: Recent studies indicate an urgent need to take action against mental health issues during the COVID-19 pandemic. However, the association between larger-scale environmental factors such as living conditions and mental health problems during the pandemic is currently unknown. METHODS: A nationwide, cross-sectional internet survey was conducted in Japan between August and September 2020 to examine the association between urbanization level and neighborhood deprivation as living conditions and COVID-19 case numbers by prefecture. Prevalence ratios (PRs) for severe psychological distress, suicidal ideation, and new-onset suicidal ideation during the pandemic were adjusted for potential confounders. RESULTS: Among 24,819 responses analyzed, the prevalence of mental health problems was 9.2% for severe psychological distress and 3.6% for new-onset suicidal ideation. PRs for severe psychological distress were significantly associated with higher urbanization level (highest PR = 1.30, 95% CI = 1.08-1.56). PRs for new-onset suicidal ideation were significantly associated with higher urbanization level (highest PR = 1.83, 95% CI = 1.37-2.45) and greater neighborhood deprivation (highest PR = 1.35, 95% CI = 1.06-1.72). Severe psychological distress and new-onset suicidal ideation were significantly more prevalent when there was higher urbanization plus lower neighborhood deprivation (PR = 1.34 [1.15-1.56], and 1.57 [1.22-2.03], respectively). CONCLUSION: These findings suggest that it is not the number of COVID-19 cases by residence area but higher urbanization level and greater neighborhood deprivation (lower neighborhood-level socioeconomic status) that are associated with severe psychological distress and new-onset suicidal ideation during the pandemic. These findings differ in part from evidence obtained before the pandemic.

Validation of the MUSIC Model of Motivation Inventory for use with cognitive training for schizophrenia spectrum disorders: A multinational study.

AIM: Low motivation is a core symptom of schizophrenia which significantly impacts successful engagement in and benefit from psychosocial treatments. Therefore, it is important for clinicians to design psychosocial treatments to effectively motivate and engage patients during the treatment. The MUSIC® Model of Academic Motivation Inventory (MMI) is an 18-item instrument with five scales that assess students' motivation during academic tasks. The objective of the current study was to validate the MMI for use with schizophrenia-spectrum patients undergoing cognitive training. METHODS: Participants included 181 people with schizophrenia spectrum disorders enrolled in cognitive training in four countries. A confirmatory factor analysis (CFA) assessed construct validity. Quality of fit was determined using the Comparative Fit Index (CFI), the Standardized Root Mean Square Residual (SRMR), and the Root Mean Square Error of Approximation (RMSEA). Pearson's correlation coefficients assessed construct validity and Cronbach's alphas assessed reliability. Furthermore, we examined factor loadings for each inventory item and assessed predictive validity by analyzing MMI scales with attendance outcomes. RESULTS: Consistent with the original MMI validation studies used in academic settings, we found CFI values indicated a good fit, as did the SRMR and RMSEA values. The scales were correlated yet distinct. Cronbach's alpha values ranged from good to excellent and factor loadings showed that all items loaded very well onto their intended factors. The MMI had a positive relationship to treatment intensity. CONCLUSION: The MMI is a valid and reliable tool to use with individuals with schizophrenia spectrum disorders undergoing a cognitive training intervention.

Neural Correlates for Intrinsic Motivational Deficits of Schizophrenia; Implications for Therapeutics of Cognitive Impairment.

The ultimate goal of the treatment of schizophrenia is recovery, a notion related to improvement of cognitive and social functioning. Cognitive remediation therapies (CRT), one of the most effective cognition enhancing methods, have been shown to moderately improve social functioning. For this purpose, intrinsic motivation, related to internal values such as interest and enjoyment, has been shown to play a key role. Although the impairment of intrinsic motivation is one of the characteristics of schizophrenia, its neural mechanisms remain unclear. This is related to the lack of feasible measures of intrinsic motivation, and its response to treatment. According to the self-determination theory (SDT), not only intrinsic motivation, but extrinsic motivation has been reported to enhance learning and memory in healthy subjects to some extent. This finding suggests the contribution of different types of motivation to potentiate the ability of the CRT to treat cognitive impairment of schizophrenia. In this paper, we provide a review of psychological characteristics, assessment methods, and neural correlates of intrinsic motivation in healthy subjects and patients with schizophrenia. Particularly, we focus on neuroimaging studies of intrinsic motivation, including our own. These considerations are relevant to enhancement of functional outcomes of schizophrenia.

A case of schizophrenia comorbid for tetralogy of Fallot treated with clozapine: further considerations on a role for 22q.11.2 in the proneness for seizures.

We present a case of schizophrenia comorbid for tetralogy of Fallot, without chromosome 22q.11.2 deletion or duplication, treated successfully with a combination of clozapine and antiepileptic drugs. Although clozapine by itself initially triggered convulsive seizures, we continued it with co-administration of valproate and topiramate. This combined treatment did not affect cardiac function of the patient, who experienced a favorable clinical course in terms of symptomatology and functional outcomes. To our knowledge, we provide the first report on a patient with tetralogy of Fallot, in whom 22q.11.2 was not deleted and clozapine-induced seizures were observed.

Neurocognitive features in male patients with schizophrenia exhibiting serious violence: a case control study.

BACKGROUND: The relationship between violence and neurocognitive function in schizophrenia is unclear. We examined the backgrounds and neurocognitive functions of violent and nonviolent patients with schizophrenia to identify factors associated with serious violence. METHODS: Thirty male patients with schizophrenia who were hospitalized after committing serious violent acts were compared with 24 hospitalized male patients with schizophrenia and no history of violence. We evaluated psychiatric symptoms using the Positive and Negative Syndrome Scale (PANSS) and neurocognitive functions using the Brief Assessment of Cognition in Schizophrenia (BACS)-Japanese version. RESULTS: Repeated-measures analyses of variance on BACS subcomponents z-scores showed that the violent and control groups had different neuropsychological profiles at trend level (p = 0.095). Post hoc analyses of variance indicated that the violent group had significantly better working memory and executive function than the control group. In post hoc ANOVAs also controlling for the effect of the presence of substance abuse on cognitive function, violent or nonviolent group had a significant main effect on executive function but not on working memory. CONCLUSIONS: Patient with violent or non-violent schizophrenia have distinct neuropsychological profiles. These results may help develop improved psychosocial treatments.