Abstract

BackgroundSchizophrenia is a disorder with prevalence rates of 1% in the general population. Science turned its efforts towards researching prodromal states, named “Ultra-high Risk” (UHR), in the hopes of impeding conversion to psychosis. Cognitive impairments are recognized among core features of schizophrenia and it is noted that they are already present at early stages of psychosis, such as ultra-high risk for psychosis (UHR). Schizophrenia in women has a more favorable outcome than in men with the disease in part mediated by cognitive performance. Neurotrophins, such as brain-derived neurotrophic factor (BDNF), play crucial roles in the expression of synaptic plasticity underpinning cognitive function, particularly expression of learning and memory. Previous studies showed conflicting results regarding neurotrophin levels in patients with psychosis. We hypothesized that UHR individuals would also show altered BDNF and cognitive performance levels.MethodsA sample of over 2500 individuals aged between 18 and 30 years old, from the city of São Paulo, Brazil, was drawn and screened with the Prodromal Questionnaire (PQ). 236 subjects with high scores (18+ points in the positive PQ subscale) where selected for psychiatric assessment with the SIPS (Structured Interview for Psychosis-Risk Syndromes), and 98 individuals were classified as UHR. Whole blood sample was collected and BDNF levels were analyzed with ELISA kits (Thermo-Fisher). Cognitive performance was measured by the emotion recognition task available via the UPenn Computerized neuropsychological testing (). Data was available for 93 UHR individuals (95%) and for 62 (46%) controls. IBM SPSS Statistics v23 for Mac was used to analyze data.ResultsBDNF levels and performance on emotion recognition task did not differ between control and UHR individuals. Differences were also not found if sample was analyzed according to sex. However, in UHR women (63% of UHR sample), worse performance was significantly associated with a higher BDNF level (Pearson correlation coefficient=-0.288, p=0.031).DiscussionIn our study, we found a correlation of worse emotion recognition task and higher BDNF levels in UHR women. This might be due a compensatory mechanism in which patients more severely impaired at baseline show higher BDNF levels. Estrogen might play a role in this difference as it induces BDNF expression. Several studies with psychotic patients shows higher BDNF levels in affected individuals as well as one study with UHR individual show higher BDNF levels within this group, but none showed differences between sexes. One study showed that treatment with selective estrogen receptor raloxifene increased activation in the right hippocampus and left inferior frontal gyrus areas, which are involved in facial recognition.Overall, literature suggests that women outperform men regarding overall cognitive function, including emotion recognition. Our findings might be related to a before homeostasis state has been reached in which baseline measures for emotion recognition in UHR women could be worse than in men but along time ameliorated via estrogen-induced BDNF expression.

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