7 results
Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia: an international multicenter study
- Konstantinos N. Fountoulakis, Elena Dragioti, Antonis T. Theofilidis, Tobias Wiklund, Xenofon Atmatzidis, Ioannis Nimatoudis, Erik Thys, Martien Wampers, Luchezar Hranov, Trayana Hristova, Daniil Aptalidis, Roumen Milev, Felicia Iftene, Filip Spaniel, Pavel Knytl, Petra Furstova, Tiina From, Henry Karlsson, Maija Walta, Raimo K. R. Salokangas, Jean-Michel Azorin, Justine Bouniard, Julie Montant, Georg Juckel, Ida S. Haussleiter, Athanasios Douzenis, Ioannis Michopoulos, Panagiotis Ferentinos, Nikolaos Smyrnis, Leonidas Mantonakis, Zsófia Nemes, Xenia Gonda, Dora Vajda, Anita Juhasz, Amresh Shrivastava, John Waddington, Maurizio Pompili, Anna Comparelli, Valentina Corigliano, Elmars Rancans, Alvydas Navickas, Jan Hilbig, Laurynas Bukelskis, Lidija I. Stevovic, Sanja Vodopic, Oluyomi Esan, Oluremi Oladele, Christopher Osunbote, Janusz K. Rybakowski, Pawel Wojciak, Klaudia Domowicz, Maria L. Figueira, Ludgero Linhares, Joana Crawford, Anca-Livia Panfil, Daria Smirnova, Olga Izmailova, Dusica Lecic-Tosevski, Henk Temmingh, Fleur Howells, Julio Bobes, Maria P. Garcia-Portilla, Leticia García-Alvarez, Gamze Erzin, Hasan Karadağ, Avinash De Sousa, Anuja Bendre, Cyril Hoschl, Cristina Bredicean, Ion Papava, Olivera Vukovic, Bojana Pejuskovic, Vincent Russell, Loukas Athanasiadis, Anastasia Konsta, Nikolaos K. Fountoulakis, Dan Stein, Michael Berk, Olivia Dean, Rajiv Tandon, Siegfried Kasper, Marc De Hert
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- Journal:
- CNS Spectrums / Volume 27 / Issue 6 / December 2022
- Published online by Cambridge University Press:
- 09 August 2021, pp. 716-723
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Background
The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia.
MethodsTwenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects.
ResultsThere was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness.
DiscussionOur results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.
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.
N-acetyltransferase-2 polymorphisms and schizophrenia
- Pilar Alejandra Saiz, Maria P Garcia-Portilla, Celso Arango, Blanca Morales, Victoria Alvarez, Eliecer Coto, Juan M Fernandez, Manuel Bousono, Julio Bobes
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- European Psychiatry / Volume 21 / Issue 5 / July 2006
- Published online by Cambridge University Press:
- 16 April 2020, pp. 333-337
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Modeling psychological function in patients with schizophrenia with the PANSS: an international multi-center study
- Konstantinos N. Fountoulakis, Elena Dragioti, Antonis T. Theofilidis, Tobias Wiklund, Xenofon Atmatzidis, Ioannis Nimatoudis, Erik Thys, Martien Wampers, Luchezar Hranov, Trayana Hristova, Daniil Aptalidis, Roumen Milev, Felicia Iftene, Filip Spaniel, Pavel Knytl, Petra Furstova, Tiina From, Henry Karlsson, Maija Walta, Raimo K.R. Salokangas, Jean-Michel Azorin, Justine Bouniard, Julie Montant, Georg Juckel, Ida S. Haussleiter, Athanasios Douzenis, Ioannis Michopoulos, Panagiotis Ferentinos, Nikolaos Smyrnis, Leonidas Mantonakis, Zsófia Nemes, Xenia Gonda, Dora Vajda, Anita Juhasz, Amresh Shrivastava, John Waddington, Maurizio Pompili, Anna Comparelli, Valentina Corigliano, Elmars Rancans, Alvydas Navickas, Jan Hilbig, Laurynas Bukelskis, Lidija I. Stevovic, Sanja Vodopic, Oluyomi Esan, Oluremi Oladele, Christopher Osunbote, Janusz K. Rybakowski, Pawel Wojciak, Klaudia Domowicz, Maria L. Figueira, Ludgero Linhares, Joana Crawford, Anca-Livia Panfil, Daria Smirnova, Olga Izmailova, Dusica Lecic-Tosevski, Henk Temmingh, Fleur Howells, Julio Bobes, Maria P. Garcia-Portilla, Leticia García-Alvarez, Gamze Erzin, Hasan Karadağ, Avinash De Sousa, Anuja Bendre, Cyril Hoschl, Cristina Bredicean, Ion Papava, Olivera Vukovic, Bojana Pejuskovic, Vincent Russell, Loukas Athanasiadis, Anastasia Konsta, Dan Stein, Michael Berk, Olivia Dean, Rajiv Tandon, Siegfried Kasper, Marc De Hert
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- Journal:
- CNS Spectrums / Volume 26 / Issue 3 / June 2021
- Published online by Cambridge University Press:
- 15 April 2020, pp. 290-298
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Background
The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.
MethodsTwenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.
ResultsThe results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.
ConclusionsThe current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
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.