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Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study
- Gamze Erzin, Lotta-Katrin Pries, Jim van Os, Laura Fusar-Poli, Philippe Delespaul, Gunter Kenis, Jurjen J. Luykx, Bochao D. Lin, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem Şahin Cankurtaran, Semra Ulusoy Kaymak, Marina M. Mihaljevic, Sanja Andric-Petrovic, Tijana Mirjanic, Miguel Bernardo, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, Maria Paz García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, Jose Luis Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram Can Saka, Genetic Risk and Outcome of Psychosis (GROUP) investigators, Celso Arango, Micheal C. O’Donovan, Bart P. F. Rutten, Sinan Guloksuz
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- Journal:
- European Psychiatry / Volume 64 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 19 March 2021, e25
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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.
MethodsThis 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.
ResultsES-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.
ConclusionsOur 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.
Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway
- Jim van Os, Lotta-Katrin Pries, Margreet ten Have, Ron de Graaf, Saskia van Dorsselaer, Philippe Delespaul, Maarten Bak, Gunter Kenis, Bochao D. Lin, Jurjen J. Luykx, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem Şahin Cankurtaran, Semra Ulusoy Kaymak, Marina M. Mihaljevic, Sanja Andric Petrovic, Tijana Mirjanic, Miguel Bernardo, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, María Paz García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, José Luis Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram Can Saka, Celso Arango, Michael O'Donovan, Bart P. F. Rutten, Sinan Guloksuz
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- Journal:
- Psychological Medicine / Volume 52 / Issue 10 / July 2022
- Published online by Cambridge University Press:
- 19 October 2020, pp. 1910-1922
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Background
There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.
MethodsWe analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.
ResultsThe impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).
ConclusionsThe results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.
A replication study of JTC bias, genetic liability for psychosis and delusional ideation
- Cécile Henquet, Jim van Os, Lotta K. Pries, Christian Rauschenberg, Philippe Delespaul, Gunter Kenis, Jurjen J. Luykx, Bochao D. Lin, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem S. Cankurtaran, Semra U. Kaymak, Marina M. Mihaljevic, Sanja S. Petrovic, Tijana Mirjanic, Miguel Bernardo, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, Maria P. García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, Jose L. Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram C. Saka, Celso Arango, Michael O'Donovan, Bart P.F. Rutten, Sinan Gülöksüz
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- Journal:
- Psychological Medicine / Volume 52 / Issue 9 / July 2022
- Published online by Cambridge University Press:
- 13 October 2020, pp. 1777-1783
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Background
This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.
MethodsData were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.
ResultsJTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.
ConclusionsThese findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene–environment interaction. The EUGEI study
- Jim van Os, Lotta-Katrin Pries, Philippe Delespaul, Gunter Kenis, Jurjen J. Luykx, Bochao D. Lin, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem Şahin Cankurtaran, Semra Ulusoy Kaymak, Marina M. Mihaljevic, Sanja Andric Petrovic, Tijana Mirjanic, Miguel Bernardo, Bibiana Cabrera, Julio Bobes, Pilar A. Saiz, María Paz García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, José Luis Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram Can Saka, Genetic Risk and Outcome Investigators (GROUP), Celso Arango, Michael O'Donovan, Bart P. F. Rutten, Sinan Guloksuz
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- Journal:
- Psychological Medicine / Volume 50 / Issue 11 / August 2020
- Published online by Cambridge University Press:
- 15 August 2019, pp. 1884-1897
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Background
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
MethodsWe conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
ResultsIn both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
ConclusionsThe degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.