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Psychosis presentation can be affected by genetic and environmental factors. Differentiating between affective and non-affective psychosis (A-FEP and NA-FEP, respectively) may influence treatment decisions and clinical outcomes. The objective of this paper is to examine differences between patients with A-FEP or NA-FEP in a Latin American sample.Patients from two cohorts of patients with a FEP recruited from Brazil and Chile. Subjects included were aged between 15 and 30 years, with an A-FEP or NA-FEP (schizophrenia-spectrum disorders) according to DSM-IV-TR. Sociodemographic data, duration of untreated psychosis and psychotic/mood symptoms were assessed. Generalized estimating equation models were used to assess clinical changes between baseline-follow-up according to diagnosis status.A total of 265 subjects were included. Most of the subjects were male (70.9 %), mean age was 21.36 years. A-FEP and NA-FEP groups were similar in almost all sociodemographic variables, but A-FEP patients had a higher probability of being female. At baseline, the A-FEP group had more manic symptoms and a steeper reduction in manic symptoms scores during the follow- up. The NA-FEP group had more negative symptoms at baseline and a higher improvement during follow-up. All domains of The Positive and Negative Syndrome Scale improved for both groups. No difference for DUP and depression z-scores at baseline and follow-up.The sample was recruited at tertiary hospitals, which may bias the sample towards more severe cases.This is the largest cohort comparing A-FEP and NA-FEP in Latin America. We found that features in FEP patients could be used to improve diagnosis and support treatment decisions.

Brain-derived neurotrophic factor (BDNF) and the immune-inflammatory response system (IRS) have been implicated in the pathophysiology of schizophrenia. However, no research examined the associations between BDNF and immune activation both before and after treatment in antipsychotic-naïve first episode psychosis (AN-FEP). This study aims to examine serum BDNF levels and their association with IRS and the compensatory immune-regulatory reflex system (CIRS) in AN-FEP before and after risperidone treatment. We included 31 AN-FEP and 22 healthy controls. AN-FEP showed reduced levels of BDNF as compared to controls, and BDNF levels normalized after treatment with risperidone. BDNF levels were inversely correlated with a greater IRS response. Higher levels of IRS/CIRS biomarkers were associated with lower levels of BDNF including M1 macrophage, T-helper (Th)-1, Th-2, and Th-17, and T-regulatory (Treg) cell responses. Our findings indicate that AN-FEP is characterized by decreased levels of BDNF, which are normalized after treatment with risperidone. BDNF levels were inversely associated with activated immune-inflammatory pathways. The findings support the hypothesis that, increased IRS is linked to neurotoxicity, and that a decrease in BDNF may be part of the IRS/CIRS responses in FEP and, thus, be involved in the development of psychosis.

Treatment-resistant schizophrenia (TRS) occurs in one-third of the patients, but the molecular determinants of poor antipsychotic response remain unclear. We compared genetic data of patients with TRS (n = 63) with non-TRS (n = 111) by polygenic risk scores (PRS) calculated by PRSice software using PGC2_SCZ (Psychiatric Genomics Consortium - Schizophrenia) data. TRS criteria followed the International Psychopharmacology Algorithm Project SCZ algorithm. Statistical clustering and functional enrichment analyses of genes harboring TRS-linked variants were performed. Individuals on the top three deciles of schizophrenia PRS distribution exhibited higher odds of being refractory to antipsychotics than those on the bottom three deciles. Clusters of interacting variant-harboring genes were identified among the association signals. They are upregulated in the dorsolateral prefrontal, orbitofrontal, temporal, and inferior parietal areas during adolescence and early adulthood. Similar gene modules were found using transcriptional data from the same brain regions in individuals with schizophrenia. Genes were enriched among markers of cortical interneurons and somatosensory pyramidal cells. Finally, the enrichment of the clustered genes in drug-response expression signatures revealed compounds that could be employed to identify novel antipsychotic targets. In conclusion, we identified variant-harboring genes that may predispose SCZ patients to poor antipsychotic response and found statistically enriched clusters which provided functional and spatiotemporal context for TRS, suggesting that genotypic variation may converge to biological alterations at the interplay between actin dynamics and synaptic organization.

BACKGROUND: Depressive symptoms are common on first episode psychosis, with a prevalence of up to 83% of a full depressive episode. These symptoms are related to worst functionality and higher suicide rates. In literature, longer duration of untreated psychosis (DUP) and a worse premorbid are related to these symptoms. DUP is one of the most modifiable factors on FEP, with shorter DUP predicting better outcomes in patients with schizophrenia. Only a few studies explore the relation between depressive symptoms and DUP, with no studies in a Brazilian population. Therefore, our aim was to investigate the association between depressive symptoms, functionality and DUP of antipsychotic naive-FEP (AN-FEP) patients in a 10-week follow-up study. METHODS: We recruited 88 AN-FEP patients with first episode psychosis admitted to a psychiatric emergency service. We assessed diagnosis according to Structured Clinical Interview for DSM-IV (SCID-I). Depressive symptoms were measured with the depressive dimension of Positive and Negative Symptoms Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Clinical Global Impression Scale (CGI-S). We adopted the CDSS cut-off of 6, according to the Brazilian validation. All patients were treated with risperidone and revaluated after 10 weeks. For analysis, we performed non-parametric correlation tests (Spearman’s correlation). RESULTS: Prevalence of depressive syndrome according to CDSS was 20.4% at baseline, and 11.1% after treatment. Also, 4,6% of the patients started an antidepressant treatment. We found a mean DUP of 166 days (SD = 282, median = 47 days). We found a correlation between DUP and depressive dimension at baseline (r = -0.397; p < 0.001) and on follow-up (r = -0.322, p = 0.012). At both assessments, CDSS and the depressive scale of CGI-S scores did not show significant correlation with DUP. DISCUSSION: Prevalence of depression and median DUP was in line with the worldwide range. Surprisingly, this is the first study that shows a negative correlation between depressive symptoms and DUP, which is opposite to what most studies demonstrates and to what we expected. Depression is a common feature in FEP, yet their risk factors remain unclear. The relation between DUP and depressive symptoms should be more studied to understand the real influence of DUP in these patients.