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Patient response to antipsychotic drugs varies and may be related to clinical and genetic heterogeneity. This study aimed to determine the performance of clinical, genetic, and hybrid models to predict the response of first episode of psychosis (FEP). patients to the antipsychotic risperidone. We evaluated 141 antipsychotic-naïve FEP patients before and after 10 weeks of risperidone treatment. Patients who had a response rate equal to or higher than 50% on the Positive and Negative Syndrome Scale were considered responders (n = 72; 51%). Analyses were performed using a support vector machine (SVM), k-nearest neighbors (kNN), and random forests (RF). Clinical and genetic (with single-nucleotide variants [SNVs]) models were created separately. Hybrid models (clinical+genetic factors) with and without feature selection were created. Clinical models presented greater balanced accuracy 63.3% (confidence interval [CI] 0.46-0.69) with the SVM algorithm than the genetic models (balanced accuracy: 58.5% [CI 0.41-0.76] - kNN algorithm). The hybrid model, which included duration of untreated psychosis, Clinical Global Impression-Severity scale scores, age, cannabis use, and 406 SNVs, showed the best performance (balanced accuracy: 72.9% [CI 0.62-0.84] - RF algorithm). A hybrid model, including clinical and genetic predictors, can provide enhanced predictions of response to antipsychotic treatment., Competing Interests: RAB declares personal fees and non-financial support from Janssen and Ache Laboratórios Farmacêuticos, grants, and personal fees from Roche, outside the submitted work. AG declares personal fees and non-financial support from Janssen, Daiichi Sankyo, Lundbeck, Teva, Cristalia, and Ache Laboratórios Farmacêuticos outside the submitted work. CN declares personal fees and non-financial support from Janssen, Daiichi Sankyo, Lundbeck, Teva, and Ache Laboratórios Farmacêuticos outside the submitted work. No other conflicts of interest declared concerning the publication of this article.

Objective: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data., Methods: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated., Results: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%., Conclusions: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil., Competing Interests: RM has been a consultant/advisor and/or has received honoraria from Daiichi-Sankyo and Janssen. HE has received honoraria for participation as a member of advisory boards, speaker, or travel support from the following pharmaceutical companies: Aché, Cristalia, Daiichi-Sankyo, Janssen, Mantecorp-Hypera, Sandoz, and Teva. DFL has been a consultant/advisor and/or has received honoraria from EMS, Daiichi-Sankyo, Servier, and Greencare. RB has received personal fees from Torrent, Lundbeck, and Ache, and personal fees and non-financial support from Janssen, outside the submitted work. CN has been a consultant/advisor and/or has received honoraria from Ache´, Daiichi-Sankyo, Teva, and Janssen. AG has been a consultant/advisor and/or has received honoraria from Ache´, Daiichi-Sankyo, Torrent, Cristalia, and Janssen. The other authors report no conflicts of interest.

Objective: German psychiatrist Kurt Schneider proposed the concept of first-rank symptoms (FRS) of schizophrenia in 1959. However, their relevance for diagnosis and prediction of treatment response are still unclear. Most studies have investigated FRS in chronic or medicated patients. The present study sought to evaluate whether FRS predict remission, response, or improvement in functionality in antipsychotic-naive first-episode psychosis., Methods: Follow-up study of 100 patients at first episode of psychosis (FEP), with no previous treatment, assessed at baseline and after 2 months of treatment. The participants were evaluated with the standardized Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) and for presence of FRS., Results: Logistic regression analysis showed that, in this sample, up to three individual FRS predicted remission: voices arguing, voices commenting on one's actions, and thought broadcasting., Conclusion: Specific FRS may predict remission after treatment in FEP patients. This finding could give new importance to Kurt Schneider's classic work by contributing to future updates of diagnostic protocols and improving estimation of prognosis.

Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role., Methods: We evaluated the role of three COMT SNPs (rs737865, rs165599, and rs4680) in schizophrenia and their impact on three working memory tasks. For genetic association analyses, 212 individuals with schizophrenia and 257 healthy controls (HCs) were selected. The Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task were administered to 133 schizophrenics and 93 HCs., Results: We found a significant association of rs737865, with the GG genotype exerting a protective effect and the GA haplotype (rs4680/rs165599) exerting a risk effect for schizophrenia. COMT rs4680 AA carriers and rs737865 AA carriers scored lowest on the Keep Track Task. When the genotype*group interaction effect was evaluated, rs165599 exerted opposite effects for VWM and Keep Track task performance in patients and controls, with AA carriers scoring lowest on both tests among controls, but highest among patients., Conclusion: These data support the hypothesis that COMT polymorphisms may be associated with schizophrenia and modulate cognition in patients and controls.

Objectives: To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology., Methods: Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol., Results: Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score., Conclusions: Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.

Objectives: To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome of the first hypomanic/manic episode and first depressive episode of bipolar disorder (BD) and to investigate the influence of a history of childhood maltreatment on the expression of prodromal symptoms., Methods: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), information regarding prodromal symptoms was assessed from patients with a DSM-IV diagnosis of BD. History of childhood maltreatment was evaluated using the Childhood Trauma Questionnaire (CTQ)., Results: Forty-three individuals with stable BD were included. On average, the prodrome of mania lasted 35.8 ± 68.7 months and was predominantly subacute or insidious, with rare acute presentations. The prodrome of depression lasted 16.6 ± 23.3 months and was also predominantly subacute or insidious, with few acute presentations. The prodromal symptoms most frequently reported prior to the first hypomanic or manic episode were mood lability, depressive mood, and impatience. A history of childhood abuse and neglect was reported by 81.4% of participants. Presence of childhood maltreatment was positively associated with prodromal symptoms, including social withdrawal, decreased functioning, and anhedonia., Conclusions: This study provides evidence of a long-lasting, symptomatic prodrome prior to first hypomanic/manic and depressive episode in BD and suggests that a history of childhood maltreatment influences the manifestations of this prodrome.

Objective: To conduct a comprehensive review of current evidence on factors for nonadherence to treatment in individuals with first-episode psychosis (FEP)., Methods: MEDLINE, LILACS, PsycINFO, and SciELO databases were searched with the keywords first episode psychosis, factor, adherence, nonadherence, engagement, disengagement, compliance, and intervention. References of selected studies were consulted for relevant articles., Results: A total of 157 articles were screened, of which 33 articles were retained for full review. The factors related to nonadherence were: a) patient-related (e.g., lower education level, persistent substance use, forensic history, unemployment, history of physical abuse); b) environment-related (e.g., no family involved in treatment, social adjustment difficulties); c) medication-related (e.g., rapid remission of negative symptoms when starting treatment, therapeutic alliance); and d) illness-related (e.g., more positive symptoms, more relapses). Treatment factors that improve adherence include a good therapeutic alliance and a voluntary first admission when hospitalization occurs., Conclusion: The results of this review suggest that nonadherence to treatment in FEP is multifactorial. Many of these factors are modifiable and can be specifically targeted in early intervention programs. Very few studies have assessed strategies to raise adherence in FEP.

Objectives: The Positive and Negative Syndrome Scale (PANSS) was developed to assess the symptoms of schizophrenia dimensionally. Although it is widely used in clinical trials in Brazil, it is not fully validated. The aim of this study is to assess the factor structure of the Brazilian PANSS and generate validation data for its current version., Methods: A total of 292 patients diagnosed with schizophrenia were enrolled., Results: Principal component analysis suggested a forced five-factor final model that accounted for 58.44% of the total variance, composed of negative, disorganization/cognition, excitement, positive, and depression/anxiety., Conclusion: The Brazilian PANSS has a similar factor structure and internal consistency compared to versions in several other languages.