Background Evidence suggests that environmental factors not only increase psychosis liability but also influence the prognosis and outcomes of psychotic disorders. We investigated temporal and cross-sectional associations of a weighted score of cumulative environmental liability for schizophrenia – the exposome score for schizophrenia (ES-SCZ) – with functioning in first-episode psychosis (FEP). Methods Data were derived from the baseline and 1-month assessments of the Athens FEP Research Study that enrolled 225 individuals with FEP. The Global Assessment of Functioning (GAF) and the Personal and Social Performance Scale (PSP) were used to measure social, occupational, and psychological functioning. The ES-SCZ was calculated based on the previously validated method. Results ES-SCZ was associated with the total scores of GAF and PSP at baseline and 1-month assessments. These findings remained significant when accounting for several associated alternative explanatory variables, including other environmental factors (obstetric complications, migration, ethnic minority), clinical characteristics (duration of untreated psychosis, symptom severity, previous antipsychotic use), and family history of psychosis, demonstrating that the association between ES-SCZ and functioning is over and above other risk factors and cannot be explained by symptom severity alone. Functioning improved from baseline to 1-month assessment, but no significant ES-SCZ-by-time interaction was found on functioning, indicating that functioning changes were not contingent on ES-SCZ. Conclusions Our findings suggest that rather than a predictor of functional improvement, ES-SCZ represents a stable severity indicator that captures poor functioning in early psychosis. Environmental risk loading for schizophrenia (ES-SCZ) can be beneficial for clinical characterization and incorporated into transdiagnostic staging models.

Background Validated clinical prediction models of short-term remission in psychosis are lacking. Our aim was to develop a clinical prediction model aimed at predicting 4−6-week remission following a first episode of psychosis. Method Baseline clinical data from the Athens First Episode Research Study was used to develop a Support Vector Machine prediction model of 4-week symptom remission in first-episode psychosis patients using repeated nested cross-validation. This model was further tested to predict 6-week remission in a sample of two independent, consecutive Danish first-episode cohorts. Results Of the 179 participants in Athens, 120 were male with an average age of 25.8 years and average duration of untreated psychosis of 32.8 weeks. 62.9% were antipsychotic-naïve. Fifty-seven percent attained remission after 4 weeks. In the Danish cohort, 31% attained remission. Eleven clinical scale items were selected in the Athens 4-week remission cohort. These included the Duration of Untreated Psychosis, Personal and Social Performance Scale, Global Assessment of Functioning and eight items from the Positive and Negative Syndrome Scale. This model significantly predicted 4-week remission status (area under the receiver operator characteristic curve (ROC-AUC) = 71.45, P < .0001). It also predicted 6-week remission status in the Danish cohort (ROC-AUC = 67.74, P < .0001), demonstrating reliability. Conclusions Using items from common and validated clinical scales, our model significantly predicted early remission in patients with first-episode psychosis. Although replicated in an independent cohort, forward testing between machine learning models and clinicians’ assessment should be undertaken to evaluate the possible utility as a routine clinical tool.

Aims: Athens First-Episode Psychosis (FEP) Research study, aims to explore the potential associations between multiple genetic, environmental and neurometabolic risk factors of psychotic disorders, through the clinical management of FEP patients with minimal exposure (<2 weeks) to antipsychotic treatment at entry. The goal of this paper is to introduce the background, rationale and design of the study and present its preliminary findings. Methods: We developed a longitudinal cohort study of FEP patients 16-45 years old, presenting at the emergency units of five psychiatric hospitals across Athens, Greece. Research timeline includes baseline, 1-month and 1-year follow-up. Clinical, genetic, environmental, cognitive and biochemical parameters are measured, using psychometric tools, clinical interviews and laboratory tests. A descriptive analysis of baseline and 1-month assessments was performed including demographic characteristics, family history, medication, clinical picture, traumatic experiences, drug use and cognitive functioning.Results: During the last 3 years, 130 subjects have been enrolled in the study. Data so far reveal that, despite the severity of baseline presentation, at 1-month the majority (57.4%) met the Andreasen symptom severity criteria for remission, without the time criterion and showed mild functional improvement. Several environmental adversities and poor cognitive performance were identified, which need to be further elaborated.Conclusions: Athens FEP Research study is the first gene-environment interaction study in Greece. In this article we introduce the organization and methodological framework of the project, along with its basic initial findings. Future analysis will allow the validation of tractable predictors and risk factors implicated in the development and outcome of psychosis.