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The association between exposome score for schizophrenia and metabolic parameters in individuals with schizophrenia and healthy controls: Findings from the EUGEI study
- G. Erzin, C. Atbaşoğlu, L. Fusar-Poli, M. C. Saka, A. Üçok, K. Alptekin, J. V. Os, G. Gümüş Akay, S. Gülöksüz
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S264
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Introduction
Exposome is all nongenetic exposures from the prenatal period to death. Exposome score for schizophrenia (ES-SCZ) is a cumulative measure of environmental liability for schizophrenia. Our previous studies showed that the ES-SCZ is associated with mental and physical health outcome.
ObjectivesThe aim of the study is to investigate the association of the ES-SCZ with metabolic parameters in individuals with schizophrenia and healthy controls.
MethodsThis study obtained 124 individuals with schizophrenia and 440 healthy controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions, Work Package 6 (Vulnerability and Severity) Turkey dataset. The ES-SCZ was calculated by summing log-odds weighted environmental exposures (childhood adversities, winter birth, hearing impairment and cannabis use). Linear regression analysis was used to investigate the association between ES-SCZ and metabolic parameters. After that analysis age and sex were added as covariates.
ResultsThere was an association between ES-SCZ and diastolic blood pressure (B = -2.69 [95% CI -4.74; -.65], P-value = 0.010) in schizophrenia. ES-SCZ was associated with the fasting glucose level (B = -6.23 [95% CI -11.59; -.87], P-value = 0.023); high density lipid level (B = 1.77 [95% CI .27; 3.27], P-value = 0.021) in control and these results remained significant after adjusting for age and sex.
ConclusionsES-SCZ was associated with important metabolic parameters. These findings show that ES-SCZ is not only related to increasing the risk for psychosis development but may also influence comorbidities. This result is important since it may increase our knowledge of ES-SCZ and contribute to the importance and framework of its clinical implementation.
Disclosure of InterestNone Declared
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.
Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum
- L.-K. Pries, G. A. Dal Ferro, J. van Os, P. Delespaul, G. Kenis, B. D. Lin, J. J. Luykx, A. L. Richards, B. Akdede, T. Binbay, V. Altınyazar, B. Yalınçetin, G. Gümüş-Akay, B. Cihan, H. Soygür, H. Ulaş, E. Şahin Cankurtaran, S. Ulusoy Kaymak, M. M. Mihaljevic, S. Andric Petrovic, T. Mirjanic, M. Bernardo, G. Mezquida, S. Amoretti, J. Bobes, P. A. Saiz, M. Paz García-Portilla, J. Sanjuan, E. J. Aguilar, J. L. Santos, E. Jiménez-López, M. Arrojo, A. Carracedo, G. López, J. González-Peñas, M. Parellada, N. P. Maric, C. Atbaşoğlu, A. Ucok, K. Alptekin, M. Can Saka, Genetic Risk and Outcome of Psychosis (GROUP) investigators, C. Arango, M. O'Donovan, S. Tosato, B. P. F. Rutten, S. Guloksuz
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 29 / 2020
- Published online by Cambridge University Press:
- 17 November 2020, e182
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Aims
Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.
MethodsThe sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).
ResultsBoth genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.
ConclusionsThe interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.
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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- 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.
Organic cucumber production in the greenhouse: A case study from Turkey
- Y. Tuzel, A. Gul, O. Tuncay, D. Anac, N. Madanlar, Z. Yoldas, M. Gumus, I.H. Tuzel, S. Engindeniz
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- Renewable Agriculture and Food Systems / Volume 20 / Issue 4 / December 2005
- Published online by Cambridge University Press:
- 12 February 2007, pp. 206-213
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Organic farming seems to be a solution in environmentally sensitive zones such as the protection zone of Tahtalı Dam, which supplies fresh water to Izmir, the third largest city in Turkey. Greenhouse vegetable production is the major agricultural activity in this area (Menderes Township). However, due to the pollution risk from agriculture, governmental authorities have issued a regulation discouraging the use of chemicals within the collection basin of the dam. An on-farm project was conducted in 2001 to introduce organic greenhouse vegetable production in the Tahtalı Dam preservation area and to serve as a model for other areas in Turkey facing similar ecological problems. Two irrigation levels and four organic fertilizers were tested on the growth of cucumbers (Cucumis sativus cv. Sardes). The four fertilizers were two rates of farmyard and poultry manure (30 and 50 tons ha−1) with and without two organic fertilizers based on either bacteria or algae. During the growing period, pests and diseases were monitored weekly and preparations allowed in organic agriculture were used when necessary. Plant diseases did not create any significant problem, but the pest population, in particular spidermites, increased. No significant differences in cucumber yield were found between the fertilizer and irrigation treatments tested. However, it should be noted that yields from the addition of 30 tons ha−1 of farmyard or poultry manure and organic fertilizers were the same as those for 50 tons ha−1 of manure alone. The average total yield was 13 kg m−2, within an acceptable range for short-term crop production in this region, but 55% lower than a conventional substrate culture trial nearby. However, due to reduced production costs and a price premium for organic products, the organic produce yielded a net return of US$1.12–1.79 per m2 whereas that for conventional bag culture produce was US$0.55 per m2. Our results indicate that, under present conditions, organic greenhouse cucumber production has less environmental impact and is more economic than conventional bag culture, due to reduced chemical input and reduced operating and initial investment costs.