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BackgroundIndividuals with schizophrenia are at greater risk for metabolic syndrome (MetS) which is associated with cognitive deficits in the general population. MetS might be potentially an important contributing factor to cognitive impairment in schizophrenia.MethodIn the current systematic review and meta-analysis, the findings of 18 studies investigating the association between MetS (and its components) with cognitive impairment in schizophrenia are reviewed.ResultsCo-morbidity of MetS (d = 0.28) and diabetes mellitus (d = 0.28) were both associated with more severe cognitive deficits in schizophrenia. There was also evidence for a significant relationship between cognitive impairment in schizophrenia and each of the components of MetS including hypertension, dyslipidemia, abdominal obesity and diabetes.ConclusionsMetS is significantly associated with cognitive impairment in schizophrenia and can potentially contribute to functional decline observed in some patients with schizophrenia throughout the course of illness. [ABSTRACT FROM PUBLISHER]

Background: Effort-based decision-making has been proposed as a potential mechanism contributing to transdiagnostic motivational deficits in psychotic disorder and bipolar disorder. However, very limited information is available about deficits in effort-cost-decision-making in the early stages of psychotic disorder and no study has investigated effort allocation deficits before the onset of bipolar disorder. Our aim was to investigate effort-based-decision-making in ultra-high-risk for psychosis (UHR-P) and bipolar disorder (UHR-BD)., Methods: Effort-cost decision-making performance was evaluated in UHR-P ( n = 72) and UHR-BD ( n = 68) and healthy controls ( n = 38). Effort-Expenditure for Reward Task (EEfRT) was used., Results: Compared to controls, both UHR-P and UHR-BD groups were associated with a reduced possibility to choose the harder task when the reward magnitudes and/or the likelihood of receiving the reward were high. In both groups, effort allocation abnormalities were associated with poor social functioning., Conclusions: The current findings suggest that difficulties in effort-cost computation are transdiagnostic markers of illness liability in psychotic and bipolar disorders. In early intervention services, effort-based decision-making abnormalities should be considered as a target for interventions to manage motivational deficits in individuals at high risk for psychosis and BD.

Background: The relationship between childhood trauma (CT) and psychotic symptoms in patients with schizophrenia (SCZ), and subthreshold psychotic experiences in non-clinical populations is well-established. However, little is known about the relationship between subtypes of trauma and specific symptoms in patients, their siblings, and controls. It is also not clear which variables mediate the relationship between trauma and psychotic symptoms., Methods: Seven hundred and forty-two patients with SCZ, 718 of their unaffected siblings and 1039 controls from three EU-GEI sites were assessed for CT, symptom severity, and cognitive schemas about self/others. CT was assessed with the Childhood Trauma Questionnaire, and cognitive schemas were assessed by The Brief Core Schema Scale., Results: Patients with psychosis were affected by CT more than their siblings and controls in all domains. Childhood emotional abuse and neglect were more common in siblings than controls. CT was related to negative cognitive schemas toward self/others in patients, siblings, and controls. We found that negative schemas about self-mediated the relationship between emotional abuse and thought withdrawal and thought broadcasting. Approximately 33.9% of the variance in these symptoms was explained by the mediator. It also mediated the relationship between sexual abuse and persecutory delusions in SCZ., Conclusions: Our findings suggest that childhood abuse and neglect are more common in patients with schizophrenia than their siblings and healthy controls, and have different impacts on clinical domains which we searched. The relationship between CT and positive symptoms seems to be mediated by negative cognitive schemas about self in schizophrenia.

Background: Schizophrenia and bipolar disorder are associated with neurocognitive and social-cognitive impairments. To date very few studies investigated social cognition in first-episode bipolar disorder (FEBD). Our main aim was to investigate the differences in social cognition and neurocognition between FEBD and first-episode psychosis (FEP). Another aim was to investigate neurocognitive correlates of negative symptoms and attenuated psychotic symptoms in FEBD., Methods: This study included 55 FEBD, 64 FEP and 43 healthy controls. A comprehensive neuropsychological battery assessing social cognition, processing speed, verbal and visual memory, working memory, sustained attention, and executive functions was administered to all participants., Results: Both FEBD and FEP were associated with widespread deficits in all neurocognitive domains and social cognition. Both FEP (d = -1.19) and FEBP (d = -0.88) were also impaired in social cognition. In FEP, effect sizes (Cohen's d) of neurocognitive deficits ranged from -0.71 to -1.56. FEBD was also associated with relatively milder but similar neurocognitive deficits (d = -0.61 to-1.17). FEBD group performed significantly better than FEP group in verbal and visual memory, processing speed, and executive function domains (d = -0.40 to-0.52). Negative symptoms and social functioning were associated with neuropsychological impairment in both groups. The severity of attenuated psychotic symptoms was associated with poorer verbal memory in FEBD (r = -0.39, p < 0.01)., Limitations: The cross-sectional nature of the current study is the main limitation., Conclusions: Neurocognitive and social-cognitive deficits are evident in both FEBD and FEP. In FEBD, more severe memory deficits might be markers of clinical overlap and shared neurobiological vulnerability with psychotic disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Schizophrenia and bipolar disorder are associated with significant deficits in neurocognition and social cognition. Unlike the studies in chronic stages of these disorders, very limited information is available regarding neurocognitive and social-cognitive impairment before the onset of bipolar disorder. Our main aim was to investigate the differences in neurocognition and social cognition between individuals at ultra-high risk for psychosis (UHR-P) and bipolar disorder (UHR-BD)., Methods: This study included 152 help-seeking individuals identified as UHR-P (n = 78) and UHR-BD (n = 74), who were compared with a healthy control group (n = 43). A comprehensive neuropsychological battery was administered to all participants., Results: UHR-P was associated with widespread deficits in all neurocognitive and social-cognitive domains. Effect sizes (Cohen's d) of these deficits ranged from -0.57 to -1.34. UHR-BD was associated with significant deficits in processing speed, executive functions, sustained attention and social cognition (d = -0.48 to-0.70, p < 0.05). UHR-P performed significantly worse than UHR-BD in social cognition, processing speed, verbal memory and executive function domains (d = -0.39 to-0.64, p < 0.05). Negative symptoms were associated with impaired social cognition in the UHR-P group and verbal memory deficits in the UHR-BD group. Cognitive impairment was associated with functional impairment in both groups., Conclusions: While UHR-P is associated with more widespread cognitive impairment, deficits in processing speed, executive functions, sustained attention and social cognition might be common features of both UHR groups. In early intervention services, cognition should be considered as a target for assessment and intervention not only for individuals at high risk for psychosis but also for bipolar disorder., Competing Interests: Declaration of competing interest The authors have no conflicts of interest regarding subject of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest Celso Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Julio Bobes has received research grants and served as a consultant, advisor, or speaker within the last 5 years for AB-Biotics, Acadia Pharmaceuticals, Alkermes, Allergan, Ambrosetti-Angelini, Biogen, Casen Recordati, D&A Pharma, Exeltis, Gilead, Indivior, GW Pharmaceuticals, Janssen-Cilag, Jazz Pharmaceuticals, Lundbeck, Mundipharma, Newron, Otsuka, Pfizer, Roche, Sage Therapeutics, Servier, Schwabe Farma Ibérica, Shire, and Takeda and has received research funding from the Spanish Ministry of Economy and Competiveness –Centro de Investigación Biomedica en Red area de Salud Mental (CIBERSAM) and Instituto de Salud Carlos III– and the Spanish Ministry of Health. Maria Paz García-Portilla has been a consultant to and/or has received honoraria/grants from Angelini, Otsuka-Lundbeck Alliance, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, and Sage Therapeutics. Pilar A. Sáiz has been a consultant to and/or has received honoraria/research grants from Adamed, Alter Medica, Angelini Pharma, CIBERSAM, Ethypharm Digital Therapy, European Commission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas, and Servier. Miguel Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda., (Copyright © 2023. Published by Elsevier B.V.)

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., Competing Interests: Conflicts of Interest 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. 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., (Copyright © 2022. Published by Elsevier B.V.)

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.

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.

Background: Social cognition impairments, such as facial emotion recognition (FER), have been acknowledged since the earliest description of schizophrenia. Here, we tested FER as an intermediate phenotype for psychosis using two approaches that are indicators of genetic risk for schizophrenia: the proxy-genetic risk approach (family design) and the polygenic risk score for schizophrenia (PRS-SCZ)., Methods: The sample comprised 2039 individuals with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). The Degraded Facial Affect Recognition Task (DFAR) was applied to measure the FER accuracy. Schizotypal traits in siblings and HC were assessed using the Structured Interview for Schizotypy-Revised (SIS-R). The PRS-SCZ was trained using the Psychiatric Genomics Consortium results. Regression models were applied to test the association of DFAR with psychosis risk, SIS-R, and PRS-SCZ., Results: The DFAR-total scores were lower in individuals with schizophrenia than in siblings (RR = 0.97 [95% CI 0.97, 0.97]), who scored lower than HC (RR = 0.99 [95% CI 0.99-1.00]). The DFAR-total scores were negatively associated with SIS-R total scores in siblings (B = -2.04 [95% CI -3.72, -0.36]) and HC (B = -2.93 [95% CI -5.50, -0.36]). Different patterns of association were observed for individual emotions. No significant associations were found between DFAR scores and PRS-SCZ., Conclusions: Our findings based on a proxy genetic risk approach suggest that FER deficits may represent an intermediate phenotype for schizophrenia. However, a significant association between FER and PRS-SCZ was not found. In the future, genetic mechanisms underlying FER phenotypes should be investigated trans-diagnostically., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Methods: The 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)., Results: Both 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., Conclusions: The 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.