Deconstructing the genetic architecture of treatment-resistant schizophrenia in East Asian ancestry.

BACKGROUND: Treatment-resistant schizophrenia (TRS) affects a substantial proportion of patients who do not respond adequately to antipsychotic medications, yet the underlying biological mechanism remains poorly understood. This study investigates the link between the genetic predisposition to schizophrenia and TRS. METHODS: 857 individuals diagnosed with schizophrenia were divided into TRS (n = 142) and non-TRS (n = 715) based on well-defined TRS criteria. Polygenic risk scores (PRS) were calculated using schizophrenia genome-wide association summary statistics from East-Asian and European ancestry populations. PRS was estimated using both P-value thresholding and Bayesian framework methods. Logistic regression analyses were performed to differentiate between TRS and non-TRS individuals. RESULTS: The schizophrenia PRS derived from the East-Asian training dataset effectively distinguished between TRS and non-TRS individuals (R2 = 0.029, p = 4.86 ×10-5, pT = 0.1, OR = 1.52, 95% CI = 1.242-1.861), with higher PRS values observed in the TRS group. Similar PRS analysis was conducted based on the European ancestry GWAS summary statistics, but we found superior prediction based on the East-Asian ancestry discovery data. CONCLUSION: This study reveals an association between common risk variants for schizophrenia and TRS status, suggesting that the genetic burden of schizophrenia may partly contribute to treatment resistance in individuals with schizophrenia. These findings propose the potential use of genetic risk factors for early TRS identification and timely access to clozapine. However, the ancestral background of the discovery sample is crucial for successfully implementing PRS in clinical settings.

Solar-Light-Responsive Zinc-Air Battery with Self-Regulated Charge-Discharge Performance based on Photothermal Effect.

It is extremely challenging to significantly increase the voltaic efficiency, power density, and cycle stability of a Zn-air battery by just adjusting the catalytic performance of the cathode with nanometers/atomistic engineering because of the restriction of thermodynamic equilibrium potential. Herein, inspired by solar batteries, the S-atom-bridged FeNi particles and N-doped hollow carbon nanosphere composite configuration (FeNi-S,N-HCS) is presented as a prototype of muti-functional air electrode material (intrinsic electrocatalytic function and additional photothermal function) for designing photoresponsive all-solid-state Zn-air batteries (PR-ZABs) based on the photothermal effect. The local temperature of the FeNi-S,N-HCS electrode can well respond to the stimuli of sunlight irradiation because of their superior photothermal effect. As expected, under illumination, the power density of the as-fabricated PR-ZABs based on the FeNi-S,N-HCS electrode can be improved from 77 mW cm-2 to 126 mW cm-2. Simultaneously, charge voltage can be dramatically reduced, and cycle lifetime is also prolonged under illumination, because of the expedited electrocatalytic kinetics, the increased electrical conductivity, and the accelerated desorption rate of O2 bubbles from the electrode. By exerting the intrinsic electrocatalytic and photothermal efficiency of the electrode materials, this research paves new ways to improve battery performance from kinetic and thermodynamic perspectives.

Managing treatment resistance in schizophrenia: A joint study in Hong Kong and Singapore.

Objective: This study surveyed clinicians in psychiatry in Hong Kong and Singapore to understand their familiarity and prescribing practices in treatment-resistant schizophrenia (TRS) and clozapine-resistant schizophrenia (CRS). Materials and methods: All clinicians in psychiatry in both regions were invited through email to participate in an anonymous online survey. The survey collected information on the participants' characteristics, their familiarity and experience with clozapine use, and their treatment practices in TRS and CRS. Data collection took place between September 2019 and February 2020 in Hong Kong and December 2018 and March 2019 in Singapore. Results: 261 clinicians responded to the survey, with response rates of 19% (105 out of 556 participants) in Hong Kong and 50% (156 out of 309 participants) in Singapore. The majority of respondents (99.0% in Hong Kong; 87.9% in Singapore) were familiar with treatment guidelines for TRS. However, approximately half (54.2% in Hong Kong; 41.7% in Singapore) delayed the prescription of clozapine when indicated. In terms of alternatives to clozapine, approximately half or more of the clinicians in both regions would use high dose antipsychotics, long-acting injectable antipsychotics, antipsychotic polypharmacy, while the adjuvant use of mood stabilizers and electroconvulsive therapy differed between the two regions. In those with CRS, between 10 and 20% of the respondents added adjuvant mood stabilizers or antipsychotics, and 3-10% would use an antidepressant. Conclusion: Clozapine delays occur in spite of clinicians' familiarity with treatment guidelines. More research is needed to guide the use of augmentation strategies and the search for effective treatments beyond clozapine.

Utility and Barriers to Clozapine Use: A Joint Study of Clinicians' Attitudes From Singapore and Hong Kong.

Objective: This study aimed to survey clinicians' attitudes in Singapore and Hong Kong toward clozapine and elucidate the barriers to its prescription in patients with treatment-resistant schizophrenia.Methods: All clinicians in psychiatry in both regions were invited through email to participate in an anonymous online survey. The survey collected information on the participants' characteristics, their experience with clozapine initiation, perceived usefulness of clozapine, barriers to clozapine initiation, and factors that might improve clozapine use. Data collection took place between December 2018 and March 2019 in Singapore and September 2019 and February 2020 in Hong Kong.Results: A total of 261 clinicians (156 in Singapore, 105 in Hong Kong) responded to the survey. The majority of participants believed that clozapine was an effective and satisfactory treatment for schizophrenia. Clinicians were most concerned about the need for frequent blood monitoring (84.5% in Singapore; 87.5% in Hong Kong), clozapine's tolerability (51.9% in Singapore; 61.6% in Hong Kong), and medical complications (54.8% in Singapore; 49.1% in Hong Kong). Compared to Hong Kong, more clinicians in Singapore endorsed an underutilization of clozapine (67.9% in Singapore; 51.4% in Hong Kong) and a greater need for outpatient resources in terms of clinic and administrative support (74.4% in Singapore; 59.0% in Hong Kong) to improve clozapine prescription.Conclusions: The underutilization of clozapine in treatment-resistant schizophrenia remains a concern in both regions. An integrated clozapine service that addresses the system barriers and clinicians' confidence in prescribing clozapine and managing its adverse effects would greatly improve the utilization of clozapine.

Autistic traits in first-episode psychosis: Rates and association with 1-year recovery outcomes.

AIM: There is a growing appreciation that subthreshold but clinically elevated levels of autistic traits are clinically relevant. This study examined autistic traits in Singaporean patients with first-episode psychosis and their association with 1-year psychosis recovery. METHODS: The relationship between baseline patient characteristics, autistic traits (measured with autism screening questionnaires) and psychosis recovery outcomes at 1-year were examined in 180 adults in the Early Intervention Psychosis Programme in Singapore. RESULTS: Out of 180 participants, 50 (27.8%) had clinically elevated above screening-cut off levels of autistic traits on the self-reported 10-item Autism Spectrum Quotient and 8 (4.4%) on the staff-rated Autism Spectrum Disorder in Adults Screening Questionnaire. At baseline, those with more autistic traits were more likely to be unemployed, economically inactive (ie, students or homemakers); and to have diagnoses of mood disorder with psychotic features, brief psychotic disorder or psychotic disorder not otherwise specified as compared to schizophrenia spectrum and delusional disorder diagnoses. Although most participants showed improvements in their clinical outcomes at 1-year, those with higher autistic traits improved less in the Positive and Negative Syndrome Scale general psychopathology scale and in Global Assessment of Functioning symptomatology. CONCLUSIONS: Autistic traits are common in those with first-episode psychosis and may be associated with poorer clinical outcomes. Validated screening tools should be developed in this population to support earlier reporting.

Rate and predictors of service disengagement among patients with first-episode psychosis.

OBJECTIVE: This study determined the rate of service disengagement among patients in the Early Psychosis Intervention Program (EPIP) in Singapore and predictors of disengagement. METHODS: EPIP is a two-year multidisciplinary program targeting first-episode psychosis. The sample comprised patients consecutively accepted (2001-2009) who had two years of follow-up data. Disengagement was assessed with a semistructured scale. Sociodemographic and clinical variables were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders, the Positive and Negative Syndrome Scale, and the Global Assessment of Functioning. Regression analyses were conducted. RESULTS: Among 775 patients, 109 (14%) disengaged from EPIP within two years. Significant baseline predictors included Malay ethnicity (odds ratio [OR]=1.93, 95% confidence interval [CI]=1.12-3.29) and less than six years of education (OR=2.30, CI=1.23-4.29). CONCLUSIONS: EPIP's engagement strategy should focus on patients of Malay ethnicity and of low educational attainment. Further studies should examine how these factors affect service disengagement.