BackgroundLonger duration of untreated psychosis (DUP) predicts worse response to treatment and functional outcomes in first episode of schizophrenia (FES). Longer DUP also seem to particulary affect the severity of negative symptoms, but most studies enrolled previously medicated patients and did not focus on differential effects on schizophrenia symptomatic dimensions. This study investigates how DUP influences the five dimensions of symptoms of schizophrenia on antipsychotic naïve FEP patients before and after two months of treatment.MethodsDrug-naïve patients at FES (n = 97) were recruited from the Inpatient Psychiatric Unit of Santa Casa de Misericórdia de São Paulo (Sao Paulo, Brazil), between 2011 and 2016. Subjects were assessed at hospital admission and after two months of follow up. All patients were treated with antipsychotics after the diagnosis was confirmed with the Structured Clinical Interview for DSM-IV (SCID-I). The Positive and Negative Syndrome Scale (PANSS) was administered at baseline and after two months of treatment. The PANSS items were grouped in five factors: positive, negative, disorganized/cognitive, mood/depression and excitement/hostility factors. The factors percentage reduction from baseline after treatment were correlated with the DUP, controlled for sex, age, years of education.ResultsThe mean years of education of the sample was 9.2 (± 2.6 SD), mean age was 24.9 (± 7.0 SD), 62.9% were male and 42.7% were unemployed or had stopped their studies because of symptoms. Pearson correlation coefficients of the factors with DUP were: Positive = - 0.311 (p < 0.001); Negative= -0.340 (p < 0.001); Disorganized = -0.188 (p = 0.033); Hostility = -0.201 (p= 0.023); Depression = 0.030 (p = 0.389).DiscussionShorter DUP enhanced the early response to treatment in the positive, negative, disorganized and hostility dimensions. In line with the literature, our findings support that reducing the DUP may be one of the few interventions for a more favorable response to treatment on negative symptoms.

BackgroundTreatment-resistant schizophrenia (TRS) may underlie a specific biological signature among patients with schizophrenia. The main lines of evidence suggest a glutamatergic rather than dopaminergic dysfunction in TRS, with lower levels of striatal dopamine and higher levels of glutamate in anterior cingulate. Whether this biological signature relates to a distinct symptomatic profile remains unclear. Our objective is to define a symptom profile of patients with TRS.MethodsWe used two samples of patients with schizophrenia. First, we followed a discovery sample of inpatients (n=203) to prospectively identify TRS predictors, then we tested the predictors in a replication sample of outpatients (n=207). The samples were collected independently. All patients were assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Severity Scale (CGI-S) and the Global Assessment of Functioning Scale (GAF). Diagnosis was confirmed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). TRS was defined according the criteria of the Schizophrenia Algorithm of the International Psychopharmacology Algorithm Project (IPAP). Initially, we tested if patients with disorganized subtype were more likely to be TRS, and grouped the patients into disorganized or non-disorganized schizophrenia according to SCID-I. Then, we checked which PANSS items at the baseline predicted TRS at the follow-up through multiple logistic regression analyses. A receiver operating characteristic (ROC) curve with the best items was performed at the follow-up.ResultsTRS was more common in disorganized schizophrenia in the inpatient sample (73.8% vs 22.4%, P < 0.001) and in the outpatient sample (68.2% vs 28.2%, P < 0.001) in comparison to non-disorganized schizophrenia. They also presented worse scores on PANSS, CGI-S and GAF (P < 0.001). In the second step, three PANSS items, P2 (conceptual disorganization), N5 (difficulty in abstract thinking) and G9 (unusual thought content), predicted TRS with 78.4% accuracy (P = 0.011, P = 0.010 and P <0.001). The ROC analysis using the sum of PE+N5G+G9 predicted TRS with a sensitivity of 72.3%, and a specificity of 82.4%. In the outpatient sample, logistic regression analysis of the model P2+N5+G9 discriminated TRS with 69.3% accuracy (P <0.001).DiscussionNon-paranoid clinical presentations, specially disorganized characteristics, may consist in clinical markers of TRS. Further Cross-validation of such clinical findings and biological features may improve prediction of TRS

BackgroundPrincipal component analyses (PCA) studies show that schizophrenia symptoms are usually grouped into five domains. However, to infer a latent dimensional structure, confirmatory factor analysis (CFA) is more appropriate than PCA. Most CFA studies addressing the five-factor model yielded poor fit indices. One single study achieved a good fit using a multilevel CFA structure with the interviewers as level. Other possible reasons for sample heterogeneity and subsequent poor model adjustments, such as differences in patients’ clinical profiles across clinical units and clinical staging, were not measured in this study. We aimed to replicate the effect of the CFA multilevel analyses and evaluate the possible influence of other heterogeneity sources as levels, i.e., clinical staging, on the Positive and Negative Syndrome Scale (PANSS) five-factor structure.Methods700 patients with schizophrenia at four different centers had their PANSS analyzed. A Confirmatory Factor Analysis (CFA) was conducted using the following fit index: Comparative Fit Index (CFI) and Non-Normed Fit Index (NNFI) >0.95, the Root Mean Square Errors of Approximation (RMSEA) <0.06, and Weighted Root Mean Square Residual (WRMR) <1.0. Thereafter, we performed multilevel analyses considering the following levels: i) centers, ii) interviewers and iii) clinical staging for schizophrenia (first episode, treatment-resistant schizophrenia and non-treatment resistant schizophrenia).ResultsThe mean (SD) age was 34.9 (10.3) years, mean age of onset was 21.7 (7.5), mean duration of illness means was 13.2 (9.7) years, and 64.3% of the sample was male. The CFA model without multilevel analyses yielded poor fit indices: RMSEA = 0.102 (90% CI: 0.097 – 0.107; Cfit was <0.001), CFI = 0.921 and NNFI = 0.906 and WRMR = 1.952. When the multilevel analysis was applied, all models reached an acceptable fit: i) centers: RMSEA = 0.044 (90% CI: 0.038 – 0.049; CFit = 0.964), CFI = 0.981, NNFI = 0.977, and WRMR = 1.860; ii) interviewers: RMSEA = 0.047 (90% CI: 0.041 – 0.053; CFit = 0.765), CFI = 0.947, NNFI = 0.938, and WRMR = 1.531; iii) clinical stage: RMSEA = 0.052 (90% CI: 0.046 – 0.058; CFit = 0.274), CFI = 0.988, NNFI = 0.985, and WRMR = 2.433.DiscussionGood CFA model fits were only achieved when the multilevel structure was applied. Besides the bias generated by data collection (i.e., local of data collection and raters), the clinical staging is a potential source of variability to consider in schizophrenia dimensional structure. As dimensional approaches gain relevance to reduce heterogeneity in schizophrenia and to investigate their biological substrates, reliable methods to address latent dimensions are required.

BackgroundFormal thought disorder (FTD) is a multidimensional dysfunction characterized by inability to maintain a coherent speech in spoken or written language, poor social cognition and disorganized thought itself.Presence of formal thought disorder has been associated with poor prognosis in schizophrenia, but the association with treatment response is yet to be determinate. Formal thought disorder has a close relation to disorganized symptoms in schizophrenia, which were independently associated with treatment resistance and poor response to standard antipsychotics. Formal thought disorder investigation could provide a clinical construct better delimited to assess disorganized symptoms in schizophrenia.We investigated the association between FTD, remission and treatment resistance in patients with schizophrenia.MethodsThis study reunite a sample of 213 patients, between 14 and 69 years, who met DSM-IV criteria for schizophrenia.The analyses were conducted in two samples conducted independently. In both samples, Diagnostic evaluation was performed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), response to treatment was primarily assessed through PANSS, functional impairment was assessed by GAF and disease severity, by CGI. The first sample was a follow-up study that enrolled inpatients. Participants were rated at baseline and after four weeks of antipsychotic treatment. If the participant did not reduce a minimum of 40% of baseline PANSS, the antipsychotic was switched. If the participant did not reduce a minimum of 40% in total PANSS in the following antipsychotic trial, the participant was considered as treatment resistant schizophrenia (TRS) and clozapine, introduced. The second sample was enrolled in an outpatient clinic specialized in schizophrenia.Illness remission was defined as a severity of mild (score of 3 on a scale of 1 to 7) or less for P1, P2, P3, G9, G5, N1, N4 and N6 PANSS`s items.To stablish FTD severity, PANSS items related to high scores at the Thought and Language Index (TLI) were considered: P2, P6, N1, N2, N5, N6, G7 and G9.ResultsMost subjects were male (56.8%) and the mean age was 34.42 (±12.33 SD).The FTD failed to associate with remission (t = 4.007, p = 0,491) or treatment resistance (t = -3.768, p = 0.988) in both samples.FTD had a negative correlation with GAF (r = -0.473, p<0.01) and a positive correlation with CGI (r = 0.530, p<0.01).DiscussionFTD had a stronger association with global functioning and severity measures, rather than treatment symptomatic outcomes. In future studies, we will investigate whether FTD show distinctive clinical features commonly related to disorganized syndrome, i.e. earlier age of onset.

ResumoObjetivo: Investigar quais fatores atuam como indicadores de reinternação de pacientes com distúrbios psiquiátricos que obtiveram alta em enfermaria psiquiátrica.Métodos: Estudo retrospectivo com revisão de 200 prontuários e resumos de alta de pacientes internados no período de 2000 a 2013 na enfermaria psiquiátrica do Hospital das Clínicas Luzia de Pinho Melo, de Mogi das Cruzes (SP), para levantamento de dados.Resultados: Observou-se que idade (p = 0,004), número de medicações na alta (p = 0,006), número de tomadas por dia (p = 0,011), presença de estresse social (p = 0,002) e baixo suporte social (p = 0,001) foram preditores estatisticamente significativos de reinternação.Conclusão: Apesar de o estudo ser limitado pelo método retrospectivo, evidencia-se que um bom suporte social e flexibilidade nas tomadas das medicações estão associados com menores taxas de reinternação. Sugere-se investimento em psicoeducação familiar e participação do paciente na escolha terapêutica.Palavras-chave: Indicadores, reinternação psiquiátrica, recaídas psiquiátricas. AbstractObjective: To investigate which factors act as predictors of readmission in patients with psychiatric disorders discharged from a psychiatric ward.Methods: This retrospective study was based on the review of 200 medical records and discharge summaries of patients admitted to the psychiatric ward of Hospital das Clínicas Luzia de Pinho Melo, in Mogi das Cruzes, state of São Paulo, Brazil, between 2000 and 2013.Results: The following factors were statistically significant predictors of readmission: patient age (p = 0.004), number of medications at discharge (p = 0.006), number of daily doses (p = 0.011), social stress (p = 0.002), and low social support (p = 0.001). Conclusion:Even though the study is limited by the retrospective method adopted, the findings suggest that good social support and flexibility in the number of doses are associated with lower readmission rates. We suggest investing in family psychoeducation and involving the patient in treatment decision-making.