Browsing by Author "Akdede, Berna (7801341519)"

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. Methods Data 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. Results JTC 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. Conclusions These 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. Copyright © The Author(s), 2020. Published by Cambridge University Press.

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. Methods Data 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. Results JTC 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. Conclusions These 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. Copyright © The Author(s), 2020. Published by Cambridge University Press.

Background: Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. Study design: We applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan. We subsequently calculated clustered-specific polygenic risk scores for 743 individuals with schizophrenia and 743 sex- and age-matched healthy controls. Study results: Clustering revealed a set of 183 genes that was significantly upregulated prenatally and downregulated postnatally and 162 genes that showed the opposite pattern. The prenatally upregulated set of genes was functionally annotated to fundamental cell cycle processes, while the postnatally upregulated set was associated with the immune system and neuronal communication. We found an interaction between the 2 scores; higher prenatal polygenic risk showed a stronger association with schizophrenia diagnosis at higher levels of postnatal polygenic risk. Importantly, this finding was replicated in an independent clinical cohort of 3233 individuals. Conclusions: We provide genetics-based evidence that schizophrenia is shaped by disruptions of separable biological processes acting at distinct phases of neurodevelopment. The modeling of genetic risk factors that moderate each other’s effect, informed by the timing of their expression, will aid in a better understanding of the development of schizophrenia. © The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = –0.45 to –0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = –0.14 to –0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = –0.88 to –0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = –0.13 to –0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = –0.21 to –0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = –0.45 to –0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = –0.14 to –0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = –0.88 to –0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = –0.13 to –0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = –0.21 to –0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic "risk" and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke's R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P <. 001), patients from siblings (OR = 1.58, P <. 001), and siblings from controls (OR = 1.21, P =. 001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome. © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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. Methods We 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. Results The 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). Conclusions The 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. Copyright © The Author(s) 2020. Published by Cambridge University Press.

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. Methods We 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. Results The 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). Conclusions The 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. Copyright © The Author(s) 2020. Published by Cambridge University Press.

Background: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls. Methods: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group. Results: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings. Conclusions: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum. © 2023

Background: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls. Methods: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group. Results: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings. Conclusions: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum. © 2023

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. © 2021 Elsevier Masson SAS. All rights reserved.

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy-genetic liability measures suggest gene-environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS-SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene-environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS-SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early-life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS-SCZ at 75% with alternative cut-points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures. © 2019 World Psychiatric Association

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy-genetic liability measures suggest gene-environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS-SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene-environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS-SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early-life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS-SCZ at 75% with alternative cut-points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures. © 2019 World Psychiatric Association

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. © 2014 The Author.

Background First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.Methods We 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.Results In 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.Conclusions The 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. Copyright © Cambridge University Press 2019.

Background First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.Methods We 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.Results In 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.Conclusions The 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. Copyright © Cambridge University Press 2019.

Schizophrenia is frequently accompanied with social cognitive disturbances. Cannabis represents one established environmental factor associated with the onset and progression of schizophrenia. The present cross-sectional study aimed to investigate the association of facial emotion recognition (FER) performance with cannabis use in 2039 patients with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). FER performance was measured using the Degraded Facial Affect Recognition Task (DFAR). Better FER performance as indicated by higher DFAR-total scores was associated with lifetime regular cannabis use in schizophrenia (B = 1.36, 95% CI 0.02 to 2.69), siblings (B = 2.17, 95% CI 0.79 to 3.56), and HC (B = 3.10, 95% CI 1.14 to 5.06). No associations were found between DFAR-total and current cannabis use. Patients with schizophrenia who started to use cannabis after the age of 16 showed better FER performance than patients who started earlier (B = 2.50, 95% CI 0.15 to 4.84) and non-users (B = 3.72, 95 CI 1.96 to 5.49). Better FER performance was found also in siblings who started to use cannabis after 16 compared to non-users (B = 2.37, 95% CI 0.58 to 4.16), while HC using cannabis performed better than non-users at DFAR-total regardless of the age at onset. Our findings suggest that lifetime regular cannabis use may be associated with better FER regardless of the psychosis risk, but that FER might be moderated by age at first use in people with higher genetic risk. Longitudinal studies may clarify whether there is a cause-and-effect relationship between cannabis use and FER performance in psychotic and non-psychotic samples. © 2022

Schizophrenia is frequently accompanied with social cognitive disturbances. Cannabis represents one established environmental factor associated with the onset and progression of schizophrenia. The present cross-sectional study aimed to investigate the association of facial emotion recognition (FER) performance with cannabis use in 2039 patients with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). FER performance was measured using the Degraded Facial Affect Recognition Task (DFAR). Better FER performance as indicated by higher DFAR-total scores was associated with lifetime regular cannabis use in schizophrenia (B = 1.36, 95% CI 0.02 to 2.69), siblings (B = 2.17, 95% CI 0.79 to 3.56), and HC (B = 3.10, 95% CI 1.14 to 5.06). No associations were found between DFAR-total and current cannabis use. Patients with schizophrenia who started to use cannabis after the age of 16 showed better FER performance than patients who started earlier (B = 2.50, 95% CI 0.15 to 4.84) and non-users (B = 3.72, 95 CI 1.96 to 5.49). Better FER performance was found also in siblings who started to use cannabis after 16 compared to non-users (B = 2.37, 95% CI 0.58 to 4.16), while HC using cannabis performed better than non-users at DFAR-total regardless of the age at onset. Our findings suggest that lifetime regular cannabis use may be associated with better FER regardless of the psychosis risk, but that FER might be moderated by age at first use in people with higher genetic risk. Longitudinal studies may clarify whether there is a cause-and-effect relationship between cannabis use and FER performance in psychotic and non-psychotic samples. © 2022

Introduction: White noise speech illusions index liability for psychotic disorder in case– control comparisons. In the current study, we examined i) the rate of white noise speech illusions in siblings of patients with psychotic disorder and ii) to what degree this rate would be contingent on exposure to known environmental risk factors (childhood adversity and recent life events) and level of known endophenotypic dimensions of psychotic disorder [psychotic experiences assessed with the Community Assessment of Psychic Experiences (CAPE) scale and cognitive ability]. Methods: The white noise task was used as an experimental paradigm to elicit and measure speech illusions in 1,014 patients with psychotic disorders, 1,157 siblings, and 1,507 healthy participants. We examined associations between speech illusions and increasing familial risk (control-> sibling-> patient), modeled as both a linear and a categorical effect, and associations between speech illusions and level of childhood adversities and life events as well as with CAPE scores and cognitive ability scores. Results: While a positive association was found between white noise speech illusions across hypothesized increasing levels of familial risk (controls-> siblings-> patients) [odds ratio (OR) linear 1.11, 95% confidence interval (CI) 1.02–1.21, p = 0.019], there was no evidence for a categorical association with sibling status (OR 0.93, 95% CI 0.79–1.09, p = 0.360). The association between speech illusions and linear familial risk was greater if scores on the CAPE positive scale were higher (p interaction = 0.003; ORlow CAPE positive scale 0.96, 95% CI 0.85–1.07; ORhigh CAPE positive scale 1.26, 95% CI 1.09–1.46); cognitive ability was lower (p interaction < 0.001; ORhigh cognitive ability 0.94, 95% CI 0.84–1.05; ORlow cognitive ability 1.43, 95% CI 1.23–1.68); and exposure to childhood adversity was higher (p interaction < 0.001; ORlow adversity 0.92, 95% CI 0.82–1.04; ORhigh adversity 1.31, 95% CI 1.13–1.52). A similar, although less marked, pattern was seen for categorical patient– control and sibling–control comparisons. Exposure to recent life events did not modify the association between white noise and familial risk (p interaction = 0.232). Conclusion: The association between white noise speech illusions and familial risk is contingent on additional evidence of endophenotypic expression and of exposure to childhood adversity. Therefore, speech illusions may represent a trait-dependent risk marker. © 2019 Schepers, Lousberg, Guloksuz, Pries, Delespaul, Kenis, Luykx, Lin, Richards, Akdede, Binbay, Altınyazar, Yalınçetin, Gümüş-Akay, Cihan, Soygür, Ulaş, Şahin Cankurtaran, Ulusoy Kaymak, Mihaljevic, Andric Petrovic, Mirjanic, Bernardo, Cabrera, Bobes, Saiz, García-Portilla, Sanjuan, Aguilar, Luis Santos, Jiménez-López, Arrojo, Carracedo, López, González-Peñas, Parellada, Maric, Atbaşoğlu, Ucok, Alptekin, Can Saka, Arango, Rutten and van Os.