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Objective: Neurocognitive dysfunction is a common feature of bipolar disorder even in euthymia, and psychopharmacological treatment could have an effect on cognition. Long-term prescription of benzodiazepines in bipolar disorder is a common practice, and their effect on neurocognition has not been well studied in this population. The aim of this study was to evaluate the impact of concomitant benzodiazepine long-term use on neurocognitive function in stable euthymic bipolar disorder patients. Methods: Seventy-three euthymic bipolar disorder outpatients and 40 healthy individuals were assessed using a neurocognitive battery. Patients were classified in two groups according to the presence of benzodiazepines in their treatment: the benzodiazepine group ( n = 34) and the non- benzodiazepine group ( n = 39). Neurocognitive performance was compared between the groups using a multivariate analysis of covariance, considering age, number of depressive episodes, adjuvant antipsychotic drugs, Young Mania Rating Scale score and Hamilton Depression Rating Scale score as covariates. Results: Both bipolar disorder groups (benzodiazepine and non-benzodiazepine) showed an impairment in memory domains (Immediate Visual Memory [ p = 0.013], Working Memory [ p < 0.001], and Letter-Number Sequence [ p < 0.001] from the Wechsler Memory Scale-Revised-III) and slower processing speed functions (Stroop Colour [ p < 0.001]) relative to the control group. Nevertheless, the benzodiazepine group showed a greater impairment in executive functions (Conceptual Level Responses [ p = 0.024] from the Wisconsin Card Sorting Test and Frontal Assessment Battery [ p = 0.042]). Conclusion: Although memory and processing speed impairments were found in bipolar disorder, regardless of their benzodiazepine treatment, benzodiazepine users presented additional neurocognitive impairments in terms of executive functioning. These findings support restricted prescription of benzodiazepines in individuals with bipolar disorder.

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IntroductionSchizophrenia is a severe mental disorder characterized by negative (e.g., social withdrawal, apathy, anhedonia) and positive (e.g., hallucinations, delusions, disorganized behaviour) symptoms. Schizophrenia prodromal symptoms typically emerge during the adolescence. These symptoms consist of attenuated and/or intermittent psychotic symptoms and define the ultra-high risk (UHR) states of schizophrenia. Approximately, 30% of UHR individuals develop schizophrenia. It is important to find biomarkers associated with the conversion of schizophrenia in UHR individuals in order to develop preventive and therapeutic strategies, as well as to gain knowledge in the ethiopathology of the disorder. In this regard, epigenetic variations have been identified as potential biomarkers associated with the conversion to schizophrenia, but the lack of research prevent to draw final conclusions.ObjectivesThe objective of this communication is to report the study protocol of the research project named “Epigenetic variations associated with the conversion of schizophrenia in ultra-high risk adolescents”. Its aim is to analyze the epigenetic marks that predict the development of schizophrenia in UHR youths.MethodsA 4-year observational follow-up study will be conducted, assessing three groups of adolescents who have sought clinical hep: 1) UHR group composed of individuals who have developed schizophrenia at the end of the follow-up; 2) UHR group composed of individuals who did not develop schizophrenia at the end of the follow-up; 3) a group composed of non-UHR individuals. Epigenetic marks will be analyzed in the peripheral blood of all the participants each 6 months. Clinical (i.e., positive and negative symptoms, depressive symptoms, anxiety symptoms, global functioning, traumatic events, alcohol and other toxics consumption) and sociodemographic data (i.e., age, sex, migration status, ethnicity, socio-cultural status, academic achievements) will be also assessed through standardized questionnaires.ResultsWe hypothesize that specific epigenetic marks will predict the conversion of schizophrenia in the UHR group. Moreover, interactions between epigenetic variations and sociodemographic data will differentiate the three groups after the follow-up.ConclusionsThe findings of this project will help to develop preventive and therapeutic strategies, as well as to gain knowledge in the etiopathological pathways of schizophrenia.Disclosure of InterestNone Declared