Association between exposome score for schizophrenia and functioning in first-episode psychosis: results from the Athens first-episode psychosis research study

Abstract

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.

Exposome and Trans-syndromal Developmental Trajectories Toward Psychosis

“…, 2021a ( 48 ) Multinational study of individuals with SCZ, unaffected siblings, and control subjects (EUGEI and GROUP) ES-SCZ was associated with poor global functioning domains in control subjects, siblings, and patients in EUGEI, also after controlling for PRS-SCZ Results were replicated independently in GROUP Erzin et al. , 2021b ( 47 ) One-year follow-up study of individuals with FEP in Greece (Athens FEP Research Study) ES-SCZ was associated with poor global and specific functioning domains at baseline and 1 month, also after controlling for demographic, familial, and other environmental factors and clinical features ES-SCZ predicted poor improvement in symptom severity (particularly negative symptoms) from baseline to 1 month assessment AUC, area under the receiver operating characteristic curve; Emet, aggregate environmental score weighted by the meta-analytic estimates; Esum, environmental sum score; ES-SCZ, exposome score for schizophrenia; EUGEI, European Network of National Networks studying Gene-Environment Interactions in Schizophrenia; FEP, first-episode psychosis; GROUP, Genetic Risk and Outcome of Psychosis Study; LR, likelihood ratio; NEMESIS-2, Netherlands Mental Health Survey and Incidence Study-2; OR, odds ratio; PRS-SCZ, polygenic risk score for schizophrenia; SCZ, schizophrenia. …”

“…We have investigated the predictive performance and the utility of ES-SCZ in the general population cohort and independent samples of individuals with PSD ( Table 1 ). Overall, these studies show that ES-SCZ, an index of environmental predisposition, can be used to test gene × environment ( 44 ) and environment × environment ( 45 ) interactions, improve psychosis prediction and risk stratification in the general population ( 43 , 46 ), and enhance clinical outcome prognostication in individuals with PSD ( 47 , 48 ). ES-SCZ offers a practical and consistent solution that can be applied across independent samples (given consistent collection of exposures across samples) to yield comparable findings.…”

Estimating the Association Between Exposome and Psychosis as Well as General Psychopathology: Results From the ABCD Study

“…Another disadvantage of the one-exposure-one-outcome approach is that it focuses on individual outcomes, thereby ignoring the trans-syndromal nature of psychopathology and nonspecific pluripotent effects of environmental exposures ( 23 , 30 , 31 , 32 ). Studies that apply the exposome score for schizophrenia show that the exposomic vulnerability for schizophrenia is associated not only with PSD but also with general mental health problems and functioning ( 12 , 29 , 33 , 34 ). This finding should not be surprising, given the fact that psychosis expression is on a continuum and coincides with other symptom dimensions ( 25 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ).…”

Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis

“…In addition, poor functioning in FEP patients was significantly associated with the cumulative environmental load for schizophrenia in a large data set of FEP patients, unaffected siblings and healthy controls from the EUGEI study (Erzin et al, 2021b). And these cross-sectional associations were replicated in a relatively short follow-up duration study from the Athens FEP Research Study (Erzin et al, 2021a). Both studies emphasized the clinical utility of exposome score for the stratification of potential poor outcome in in FEP.…”