Early and late contingent negative variation (CNV) reflect different aspects of deficits in schizophrenia.

Abnormal reward processing and psychomotor slowing are well-known in schizophrenia (SZ). As a slow frontocentral potential, contingent negative variation (CNV) is associated with anticipatory attention, motivation and motor planning. The present study aims to evaluate the early and late amplitude and latencies of CNV in patients with SZ compared to healthy controls during a reward processing task and to show its association with clinical symptoms. We recruited 21 patients with SZ and 22 healthy controls to compare early and late CNV amplitude and latency values during a Monetary Incentive Delay (MID) Task between groups. Patients' symptom severity, levels of negative symptoms and depressive symptoms were assessed. Clinical features of the patients were further examined for their relation with CNV components. In conclusion, we found decreased early CNV amplitudes in SZ during the reward condition. They also displayed diminished and shortened late CNV responses for incentive cues, specifically at the central location. Furthermore, early CNV amplitudes exhibited a significant correlation with positive symptoms. Both CNV latencies were linked with medication dosage and the behavioural outcomes of the MID task. We revealed that early and late CNV exhibit different functions in neurophysiology and correspond to various facets of the deficits observed in patients. Our findings also emphasized that slow cortical potentials are indicative of deficient motivational processes as well as impaired reaction preparation in SZ. To gain a deeper understanding of the cognitive and motor impairments associated with psychosis, future studies must compare the effects of CNV in the early and late phases.

The relationship between childhood trauma, psychotic symptoms, and cognitive schemas in patients with schizophrenia, their siblings, and healthy controls: results from the EU-GEI study.

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.

Reduced Reward Processing in Schizophrenia: A Comprehensive EEG Event-Related Oscillation Study.

It is well known that abnormal reward processing is a characteristic feature of various psychopathologies including schizophrenia (SZ). Reduced reward anticipation has been suggested as a core symptom of SZ. The present study aims to evaluate the event-related oscillations (EROs) delta, theta, alpha, beta, and gamma in patients with SZ during the Monetary Incentive Delay (MID) task, which elicits the neural activity of reward processing. Twenty-one patients with SZ and twenty-two demographically matched healthy controls were included in the study. EROs were compared between groups and correlation analyses were conducted to determine a possible relationship between clinical scores and ERO values. Compared with healthy controls, the SZ group had reduced (1) delta and theta amplitudes in the reward condition (2) total beta and non-incentive cue-related beta amplitudes, and (3) incentive cue-related frontal gamma amplitudes. These reductions can be interpreted as impaired dopaminergic neurotransmission and disrupted cognitive functioning in the reward processing of SZ. In contrast, SZ patients showed higher incentive cue-related theta and occipital gamma amplitudes compared to controls. These increments may reflect negative symptoms in SZ. Moreover, theta amplitudes showed a negative correlation with Calgary Depression Scale for Schizophrenia scores and a positive correlation with attentional impulsivity. This is the first study showing the impairments of SZ patients in EROs from delta to gamma frequency bands compared with healthy controls during reward anticipation. Being the first comprehensive study, our results can be interpreted as providing evidence for disrupted brain dynamics in the reward processing of SZ studied by EROs. It may become possible to help patients' wellness by improving our understanding of reward processing in schizophrenia and developing innovative rehabilitation treatments based on these findings.

Enhanced Punishment Responses in Patients With Schizophrenia: An Event-Related Potential Study.

It is well known that abnormal reward processing is a characteristic feature of various psychopathologies including schizophrenia. Reduced reward anticipation has been suggested as a core symptom of schizophrenia. The Monetary Incentive Delay Task (MID) is frequently used to detect reward anticipation. The present study aims to evaluate the amplitude and latency of event-related potential (ERP) P300 in patients with schizophrenia (SCH) compared to healthy controls during the MID task. Twenty patients with SCH and 21 demographically matched healthy controls (HC) were included in the study. ERP P300 amplitude and latency values were compared between groups using an MID task in which reward and loss cues were presented. Relations between P300 and clinical facets were investigated in the patient group. SCH group had enhanced mean P300 amplitudes and delayed peak latency in the punishment condition compared with HC. These higher responses were also associated with negative symptoms. SCH group showed altered reward processing as being more sensitive to loss of reward conditions as firstly evidenced by electrophysiological methods, possibly due to abnormality in various systems including social withdrawal, social defeat, and behavioral inhibition system.

Deficits in Analytic and Common-Sense Reasoning in Schizophrenia.

ABSTRACT: Human rationality has a dual nature including analytic and common-sense thinking. Symptoms of schizophrenia have been suggested to be related to deficits in these aspects of logical reasoning. However, empirical studies investigating logical reasoning errors in schizophrenia and their clinical and neurocognitive correlates are scarce. Formal thought disorder and theory of mind (ToM) might be particularly important for understanding logical reasoning errors in schizophrenia. The current study compared the performances of 80 patients with schizophrenia with those of 49 healthy controls on syllogistic and counterfactual reasoning tasks and investigated clinical, neuropsychological, and social cognitive correlates of logical reasoning in schizophrenia. Patients with schizophrenia were impaired in both analytic and common-sense thinking. ToM impairment was a significant predictor of analytic reasoning abilities in schizophrenia. Executive functions and verbal memory were also significantly associated with analytic reasoning in schizophrenia. Further studies investigating logical reasoning errors in the early phases of the illness are needed.

Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

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.

Choroidal structural analysis in ultra-high risk and first-episode psychosis.

Both structural and functional alterations in the retina and the choroid of the eye, as parts of the central nervous system, have been shown in psychotic disorders, especially in schizophrenia. In addition, genetic and imaging studies indicate vascular and angiogenesis anomalies in the psychosis spectrum disorders. In this ocular imaging study, choroidal structure and vascularity were investigated using enhanced depth imaging (EDI) optical coherence tomography (OCT) in first-episode psychosis (FEP), ultra-high risk for psychosis (UHR-P), and age- and gender- matched healthy controls (HCs). There were no significant differences between groups in central choroidal thickness, stromal choroidal area (SCA), luminal choroidal area (LCA) and total subfoveal choroidal area. The LCA/SCA ratio (p<0.001) and the choroidal vascularity index (CVI) (p<0.001) were significantly different between FEP, UHR-P and HCs. CVI and LCA/SCA ratio were significantly higher in patients with FEP compared to help-seeking youth at UHR-P. CVI and LCA/SCA ratio were not different between UHR-P and HCs. However, CVI was higher in UHR-P compared to HCs after excluding the outliers for the sensitivity analysis (p = 0.002). Current findings suggest that choroidal thickness is normal, but there are abnormalities in choroidal microvasculature in prodromal and first-episode psychosis. Further longitudinal studies are needed to investigate oculomics, especially CVI, as a promising biomarker for the prediction of conversion to psychosis in individuals at clinical high-risk.

Clinical and developmental characteristics of cognitive subgroups in a transdiagnostic sample of schizophrenia spectrum disorders and bipolar disorder.

Evidence suggests that neurocognitive dysfunction is a transdiagnostic feature of individuals across the continuum between schizophrenia and bipolar disorder. However, there is significant heterogeneity of neuropsychological and social-cognitive abilities in schizophrenia, schizoaffective disorder, and bipolar disorder. The current study aimed to investigate the clinical and developmental characteristics of cognitive subgroups within the schizo-bipolar spectrum. 147 clinically stable patients with schizophrenia, schizoaffective or bipolar disorder were assessed using clinical rating scales for current psychotic and affective symptoms, and a comprehensive neuropsychological battery including measures of social cognition (Hinting and Reading the mind from the Eyes (RMET) task)). Developmental history and premorbid academic functioning were also evaluated. The study also included 36 healthy controls. Neurocognitive subgroups were investigated using latent class analysis (LCA). The optimal number of clusters was determined based on the Bayesian information criterion. A logistic regression analysis was conducted to investigate the predictors of membership to the globally impaired subgroup. LCA revealed two neurocognitive clusters including globally impaired (n = 89, 60.5%) and near-normal cognitive functioning (n = 58, 39.5%) subgroups. The near-normal cognitive functioning subgroup was not significantly different from healthy controls. The globally impaired subgroup had a higher score of developmental abnormalities (p<0.001), poorer premorbid academic functioning, mothers who were less educated and more severe disorganized speech (p = 0.001) and negative symptoms (p = 0.004) compared to the near-normal cognitive functioning group. History of developmental abnormalities and persistent disorganization rather than diagnosis are significant predictors of the subgroup of individuals with global cognitive impairment in the schizophrenia-bipolar disorder continuum.

A Real Environment Based Virtual Reality Psychosocial Treatment May Help Patients with Schizophrenia to Increase Social Functioning: A Preliminary Study. / Gerçek Çevre Temelli Sanal Gerçeklik Psikososyal Tedavisi Sizofreni Hastalarinin Sosyal Islevlerinin Artmasina Yardimci Olabilir: Bir Ön Çalisma.

disorders. The aim of the study is to investigate the impact of the VR Psychosocial Treatment Program (PTP) on psychosocial functioning and symptoms in people with schizophrenia. METHOD: Seven schizophrenia patients who have been admitted to the Schizophrenia Outpatient Unit of Dokuz Eylül University School of Medicine and met the diagnosis of schizophrenia according to DSM-V diagnostic criteria were included in the study. Psychosocial functionality level was assessed by PSP (Personal and Social Performance Scale), positive and negative symptom severity with PANSS (Positive and Negative Syndrome Scale), and social skills with SSC (Social Skills Checklist). VRPTP was continued for a total of 10 sessions and twice a week during five weeks. In this study, a real-environment-based VR-PTP for schizophrenia patients was developed. In the sessions, there were different realenvironment- based VR contents including social interaction components such as cafe, market, bazaar, public transportation. RESULTS: There was a statistically significant difference between the PSP scores before and after the VR application (p=0.018). None of the patients reported motion sickness during VR sessions due to the immersive nature of VR. There was no significant difference between pre and post VR PANSS total and subscale scores. CONCLUSION: In this preliminary study, we discovered that realenvironment- based VR-PTP is effective for improving the social skills of patients with schizophrenia. Cognitive enhancement programs and psychosocial functionality therapies may be carried out using virtual reality in the near future. VR can assist patients in coping with their symptoms and day-to-day challenges.

Quality of Life of Individuals with Bipolar Disorder and Schizophrenia.

Introduction: Quality of life (QoL) is a concept defined as a subjective perception of one's position in life and is negatively affected in many psychiatric illnesses such as bipolar disorder (BD) and schizophrenia (SCZ). It is hypothesized that therapeutic approaches based on QoL can increase the patient's adherence to treatment and contribute to a satisfactory life. This study aimed to compare the QoL of individuals having BD and schizophrenia with that of healthy controls (HCs) and to investigate the impact of the state of remission on QoL. Method: The World Health Organization QoL Scale-Short Form (WHOQOL-Bref) was administered to individuals with BD (n=124) and SCZ (n=74) and to HCs (n=81) to evaluate QoL. The WHOQOL-Bref subscale and total scores were compared between the groups using multifactor analysis of covariance (MANCOVA) by considering age and education level as the covariates. Then, the patient groups were compared using MANCOVA based on the state of remission by taking age, level of education, and Global Assessment of Functioning scores as the covariates. The relationship between clinical features and QoL scores was evaluated using correlation analysis, and linear regression analysis was applied for the variables that were found to be significant. Results: It was found that individuals with SCZ or BD had lower WHOQOL-Bref psychological, social, and total scores than HCs. Those with SCZ additionally had lower physical and environmental subscale scores than HCs. Furthermore, those with SCZ had lower WHOQOL-Bref physical, psychological, social, and total scores than individuals with BD. There was no significant difference in WHOQOL-Bref scores between individuals with BD and SCZ in the remission period. WHOQOL-Bref physical, psychological, and total scores were found to be significantly lower in unremitted BD patients when compared with remitted BD patients. Unremitted BD patients were found to have significantly lower WHOQOL-Bref psychological, environmental, and total scale scores than unremitted SCZ patients. Conclusion: It can be concluded that the QoL of individuals with BD is between that of healthy individuals and those with SCZ. However, unremitted BD patients have lower QoL than unremitted SCZ patients. Both patient groups display similar features during remission. Identifying the similarities and differences in terms of QoL in both patient groups is of great importance to develop the best type of treatment for the patients.

The association between cannabis use and facial emotion recognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

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.

Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway.

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.

A replication study of JTC bias, genetic liability for psychosis and delusional ideation.

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.

Examining facial emotion recognition as an intermediate phenotype for psychosis: Findings from the EUGEI study.

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.

Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

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.

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

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.

Neurocognitive functioning during symptomatic states and remission in bipolar disorder and schizophrenia: A comparative study.

Aims Patients with bipolar disorder present milder cognitive impairment in comparison to patients with schizophrenia. Psychotic symptoms are associated with poorer cognitive functioning in both disorders. We aim to compare cognitive dysfunction between bipolar disorder and schizophrenia across symptomatic and remitted states. Methods An extensive cognitive battery was used to assess bipolar disorder patients (32 in manic episodes with psychotic features, 44 in euthymia), patients with schizophrenia (41 symptomatic, 39 remitted), and 55 healthy controls. A global cognitive factor and six neurocognitive domain factors were identified using principal component analyses. Results Global cognition components differed according to both illness and remission status; working memory differed according to remission status regardless of diagnosis; verbal fluency differed according to diagnosis regardless of remission status. An omnibus F test revealed that the remission state had a significant impact on processing speed in schizophrenia. Conclusion Our data suggest that both disorders are associated with state dependent (i.e., global cognition and working memory) and diagnosis dependent (i.e., global cognition and verbal fluency) neurocognitive dysfunctions. Processing speed was exclusively influenced by symptomatic states of schizophrenia.

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.

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.

White Noise Speech Illusions: A Trait-Dependent Risk Marker for Psychotic Disorder?

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.