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. 2021 Mar 19;64(1):e25.
doi: 10.1192/j.eurpsy.2021.19.

Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Gamze Erzin  1   2 , Lotta-Katrin Pries  2 , Jim van Os  2   3   4 , Laura Fusar-Poli  5 , Philippe Delespaul  2   6 , Gunter Kenis  2 , Jurjen J Luykx  3   7   8 , Bochao D Lin  7 , Alexander L Richards  9 , Berna Akdede  10 , Tolga Binbay  10 , Vesile Altınyazar  11 , Berna Yalınçetin  12 , Güvem Gümüş-Akay  13   14   15 , Burçin Cihan  16 , Haldun Soygür  17 , Halis Ulaş  10 , Eylem Şahin Cankurtaran  18 , Semra Ulusoy Kaymak  19 , Marina M Mihaljevic  20   21 , Sanja Andric-Petrovic  20   21 , Tijana Mirjanic  22 , Miguel Bernardo  23   24   25 , Gisela Mezquida  23   24   25 , Silvia Amoretti  23   24   25 , Julio Bobes  25   26   27   28 , Pilar A Saiz  25   26   27   28 , Maria Paz García-Portilla  25   26   27   28 , Julio Sanjuan  25   29 , Eduardo J Aguilar  25   29 , Jose Luis Santos  25   30 , Estela Jiménez-López  25   31 , Manuel Arrojo  32 , Angel Carracedo  33   34 , Gonzalo López  25   35 , Javier González-Peñas  25   35 , Mara Parellada  25   35 , Nadja P Maric  20   36 , Cem Atbaşoğlu  37 , Alp Ucok  38 , Köksal Alptekin  10   12 , Meram Can Saka  37 ; Genetic Risk and Outcome of Psychosis (GROUP) investigators; Celso Arango  25   35 , Micheal C O'Donovan  9 , Bart P F Rutten  2 , Sinan Guloksuz  2   39
Affiliations

Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Gamze Erzin et al. Eur Psychiatry. .

Abstract

Background: A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.

Methods: This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.

Results: ES-SCZ was associated with the GAF dimensions in patients (symptom: B = -1.53, p-value = 0.001; disability: B = -1.44, p-value = 0.001), siblings (symptom: B = -3.07, p-value < 0.001; disability: B = -2.52, p-value < 0.001), and healthy controls (symptom: B = -1.50, p-value < 0.001; disability: B = -1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.

Conclusions: Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

Keywords: cannabis; childhood trauma; environment; functioning; psychosis.

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Conflict of interest statement

Celso Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen-Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering-Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda. Michael O’Donovan is supported by a collaborative research grant from Takeda Pharmaceuticals. Maria Paz Garcia-Portilla has been a consultant to and/or has received honoraria/grants from Angelini, Alianza Otsuka-Lundbeck, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, and Sage Therapeutics.

Figures

Figure 1.
Figure 1.
Linear prediction lines with 95% confidence interval of a scatter plot of the exposome score for schizophrenia (ES-SCZ; higher scores reflect an increase of environmental vulnerability) on the symptom and disability dimensions of the Global Assessment of Functioning (GAF; higher scores reflect an increase in functioning) scale per group (controls, siblings, and patients).
See this image and copyright information in PMC

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