; for the PRONIA Consortium IMPORTANCE Social and occupational impairments contribute to the burden of psychosis and depression. There is a need for risk stratification tools to inform personalized functional-disability preventive strategies for individuals in at-risk and early phases of these illnesses. OBJECTIVE To determine whether predictors associated with social and role functioning can be identified in patients in clinical high-risk (CHR) states for psychosis or with recent-onset depression (ROD) using clinical, imaging-based, and combined machine learning; assess the geographic, transdiagnostic, and prognostic generalizability of machine learning and compare it with human prognostication; and explore sequential prognosis encompassing clinical and combined machine learning. DESIGN, SETTING, AND PARTICIPANTS This multisite naturalistic study followed up patients in CHR states, with ROD, and with recent-onset psychosis, and healthy control participants for 18 months in 7 academic early-recognition services in 5 European countries. Participants were recruited between February 2014 and May 2016, and data were analyzed from April 2017 to January 2018. AIN OUTCOMES AND MEASURES Performance and generalizability of prognostic models. RESULTS A total of 116 individuals in CHR states (mean [SD] age, 24.0 [5.1] years; 58 [50.0%] female) and 120 patients with ROD (mean [SD] age, 26.1 [6.1] years; 65 [54.2%] female) were followed up for a mean (SD) of 329 (142) days. Machine learning predicted the 1-year social-functioning outcomes with a balanced accuracy of 76.9% of patients in CHR states and 66.2% of patients with ROD using clinical baseline data. Balanced accuracy in models using structural neuroimaging was 76.2% in patients in CHR states and 65.0% in patients with ROD, and in combined models, it was 82.7% for CHR states and 70.3% for ROD. Lower functioning before study entry was a transdiagnostic predictor. Medial prefrontal and temporo-parietooccipital gray matter volume (GMV) reductions and cerebellar and dorsolateral prefrontal GMV increments had predictive value in the CHR group; reduced mediotemporal and increased prefrontal-perisylvian GMV had predictive value in patients with ROD. Poor prognoses were associated with increased risk of psychotic, depressive, and anxiety disorders at follow-up in patients in the CHR state but not ones with ROD. Machine learning outperformed expert prognostication. Adding neuroimaging machine learning to clinical machine learning provided a 1.9-fold increase of prognostic certainty in uncertain cases of patients in CHR states, and a 10.5-fold increase of prognostic certainty for patients with ROD. CONCLUSIONS AND RELEVANCE Precision medicine tools could augment effective therapeutic strategies aiming at the prevention of social functioning impairments in patients with CHR states or with ROD.

This prognostic study evaluates whether psychosis transition can be predicted in patients with clinical high-risk syndromes or recent-onset depression by multimodal machine learning that optimally integrates clinical and neurocognitive data, structural magnetic resonance imaging, and polygenic risk scores for schizophrenia.

Abstract The early detection and intervention in psychoses prior to their first episode are presently based on the symptomatic ultra-high-risk and the basic symptom criteria. Current models of symptom development assume that basic symptoms develop first, followed by attenuated and, finally, frank psychotic symptoms, though interrelations of these symptoms are yet unknown. Therefore, we studied for the first time their interrelations using a network approach in 460 patients of an early detection service (mean age = 26.3 y, SD = 6.4; 65% male; n = 203 clinical high-risk [CHR], n = 153 first-episode psychosis, and n = 104 depression). Basic, attenuated, and frank psychotic symptoms were assessed using the Schizophrenia Proneness Instrument, Adult version (SPI-A), the Structured Interview for Psychosis-Risk Syndromes (SIPS), and the Positive And Negative Syndrome Scale (PANSS). Using the R package qgraph, network analysis of the altogether 86 symptoms revealed a single dense network of highly interrelated symptoms with 5 discernible symptom subgroups. Disorganized communication was the most central symptom, followed by delusions and hallucinations. In line with current models of symptom development, the network was distinguished by symptom severity running from SPI-A via SIPS to PANSS assessments. This suggests that positive symptoms developed from cognitive and perceptual disturbances included basic symptom criteria. Possibly conveying important insight for clinical practice, central symptoms, and symptoms “bridging” the association between symptom subgroups may be regarded as the main treatment targets, in order to prevent symptomatology from spreading or increasing across the whole network.

Disturbances in time experience have been argued to play a significant, if not causative role in the clinical presentation of schizophrenia. Phenomenological considerations suggest a fragmented or dis-articulated time experience causing both primary symptoms such as hallucinations, delusions, and self-disorders, as well as an intersubjective desynchronization. We employed content analysis on material collected from patients diagnosed with schizophrenia using the Time Questionnaire to generate hypotheses on possible disturbances of time experience in schizophrenia. As a key result we find evidence for the distinction between acute psychotic and post-psychotic syndromes. Acute psychosis is predominantly a disturbance of the passage of time, whereas the remission from psychosis is primarily defined by changes in the experience of the explicit structure of time integrating past, present, and future. We discuss our findings with regards to previous insights and observations on time experience and time perception. We suggest our findings hold significance for the diagnostic and therapeutic understanding of schizophrenia as well as for future integrative research on time experience in general.

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Recent life events have been implicated in the onset and progression of psychosis. However, psychological processes that account for the association are yet to be fully understood. Using a network approach, we aimed to identify pathways linking recent life events and symptoms observed in psychosis. Based on previous literature, we hypothesized that general symptoms would mediate between recent life events and psychotic symptoms. We analyzed baseline data of patients at clinical high risk for psychosis and with recent-onset psychosis (n = 547) from the Personalised Prognostic Tools for Early Psychosis Management (PRONIA) study. In a network analysis, we modeled links between the burden of recent life events and all individual symptoms of the Positive and Negative Syndrome Scale before and after controlling for childhood trauma. To investigate the longitudinal associations between burden of recent life events and symptoms, we analyzed multiwave panel data from seven timepoints up to month 18. Corroborating our hypothesis, burden of recent life events was connected to positive and negative symptoms through general psychopathology, specifically depression, guilt feelings, anxiety and tension, even after controlling for childhood trauma. Longitudinal modeling indicated that on average, burden of recent life events preceded general psychopathology in the individual. In line with the theory of an affective pathway to psychosis, recent life events may lead to psychotic symptoms via heightened emotional distress. Life events may be one driving force of unspecific, general psychopathology described as characteristic of early phases of the psychosis spectrum, offering promising avenues for interventions.

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CHR subjects who perceive the most important person in their individual social environment to be limited in their stress coping skills had a higher risk of conversion to the first psychotic episode. The importance of this risk factor was further demonstrated by an improvement of risk estimation in the original EPOS predictor model. Perceiving a reference person as stress-prone and thus potentially unreliable might amplify self-experienced uncertainty and anxiety, which are often associated with the prodromal phase. Such an enforcement of stress-related processes could promote a conversion to psychosis.