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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.

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.