Help-seeking from traditional healers in patients with severe mental illness and its relationship with internalized stigma.

BACKGROUND: Help-seeking from traditional healers (TH) is common in patients with severe mental illness. However, the differences between patients with schizophrenia and bipolar disorder are not well-known. Although internalized stigma is also common in patients with severe mental illness, its impact on help-seeking from TH is not studied. AIM: To investigate help-seeking from TH and the relationship between help-seeking from TH and internalized stigma in patients with schizophrenia and bipolar disorder. METHODS: In this cross-sectional study, we collected information about help-seeking from TH and clinical characteristics by using a semi-structured interview form from 310 patients with schizophrenia and bipolar disorder in two sites with different socio-cultural backgrounds. We measured internalized stigma by using The Internalized Stigma of Mental Illness (ISMI) scale. RESULTS: We found that 47% of the patients visited TH in any phase of their illness, and 46% of them sought help from TH before their first contact with a psychiatrist. Those who grew up in rural areas, were less educated, who attempted suicide before, with resistance to treatment, and with a family member who also admitted to TH were more frequent among the help-seekers from TH. This group also had more hospitalizations and higher Clinical Global Impression scores. Internalized stigma was found to be higher in the schizophrenia group, and it was related to help-seeking from TH and delay in admission to psychiatric facilities. CONCLUSION: Our findings suggest that help-seeking from TH is common both in patients with schizophrenia and bipolar disorder, and it has socio-cultural, illness-related, and stigma-related predictors.

Illness-related outcomes of illicit substance use disorder in adolescents with early onset schizophrenia: a multicenter study.

OBJECTIVES: Lifetime co-occurring substance use disorders are common at the time of presentation for the treatment of primary psychosis. Our aim was to investigate the clinical characteristics of adolescents with early-onset schizophrenia/schizoaffective disorder (EOS), categorized as either with (EOS + SUD) or without SUD (non-SUD/EOS), in a multi-center sample. METHODS: Between 2016 and 2022, 255 patients were evaluated across three tertiary-care inpatient units. Diagnoses were confirmed by the treating physician according to the DSM-5 during the hospital stay. The severity of symptoms was measured using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The EOS + SUD group exhibited a higher illness onset, fewer years of education, longer duration of untreated psychosis (DUP), a higher frequency of male gender, more frequent hospitalizations, increased use of clozapine and zuclopenthixol LAI, along with higher rates of post-traumatic stress disorder and conduct disorder. Notably, differences in DUP, clozapine use, and the number of hospitalizations did not persist in the multivariate logistic regression model. CONCLUSIONS: Our findings support the notion of SUD playing a role in modifying the course of illness in EOS. Future studies should emphasize exploring treatment responses to medications and interventions among youth with dual diagnoses.

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.

Face and emotion recognition in individuals diagnosed with schizophrenia, ultra-high risk for psychosis, unaffected siblings, and healthy controls in a sample from Turkey.

Face and emotion recognition are crucial components of social cognition. We aimed to compare them in patients diagnosed with schizophrenia (SCZ), ultra-high risk for psychosis (UHR), unaffected siblings of schizophrenia patients (SIB), and healthy controls (HC). METHODS: One hundred sixty-six participants (45 SCZ, 14 UHR, 45 SIB, and 62 HC) were interviewed with the Structured Clinical Interview for DSM-5 (SCID-5). Positive and Negative syndrome scale (PANSS), PennCNB Facial Memory (CPF), and Emotion Recognition Task (ER40) were applied. RESULTS: In CPF, SCZ performed significantly lower than SIB and HC. SIB was also significantly lower than HC for total correct responses. The sample size of the UHR group was small, and the statistical comparisons did not reach a significance, however, a trend towards decreased performance between the SCZ and SIB was found. In ER40, SCZ performed significantly lower than HC and SIB in all domains, except for the insignificant findings for angry ER between SIB and SCZ. SIB also performed significantly lower than HC for angry, negative, and total ER. UHR was similar to SCZ for happy and sad ER and performed significantly lower than HC for happy ER. The effect of SCZ diagnosis on the efficiency of CPF and ER40 was significant when corrected for age and education. For SCZ, PANSS also significantly affected the CPF and ER40. CONCLUSION: Our findings suggest varying levels of face and emotion recognition deficits in individuals with SCZ, UHR, and SIB. Face and emotion recognition deficits are promising schizophrenia endophenotypes related to social cognition.

Discriminant analysis using MRI asymmetry indices and cognitive scores of women with temporal lobe epilepsy or schizophrenia.

PURPOSE: This study aims to assess the diagnostic power of brain asymmetry indices and neuropsychological tests for differentiating mesial temporal lobe epilepsy (MTLE) and schizophrenia (SCZ). METHODS: We studied a total of 39 women including 13 MTLE, 13 SCZ, and 13 healthy individuals (HC). A neuropsychological test battery (NPT) was administered and scored by an experienced neuropsychologist, and NeuroQuant (CorTechs Labs Inc., San Diego, California) software was used to calculate brain asymmetry indices (ASI) for 71 different anatomical regions of all participants based on their 3D T1 MR imaging scans. RESULTS: Asymmetry indices measured from 10 regions showed statistically significant differences between the three groups. In this study, a multi-class linear discriminant analysis (LDA) model was built based on a total of fifteen variables composed of the most five significantly informative NPT scores and ten significant asymmetry indices, and the model achieved an accuracy of 87.2%. In pairwise classification, the accuracy for distinguishing MTLE from either SCZ or HC was 94.8%, while the accuracy for distinguishing SCZ from either MTLE or HC was 92.3%. CONCLUSION: The ability to differentiate MTLE from SCZ using neuroradiological and neuropsychological biomarkers, even within a limited patient cohort, could make a substantial contribution to research in larger patient groups using different machine learning techniques.

Minor physical anomalies may be related to treatment resistance in patients with schizophrenia.

This study investigates the relationship between minor physical anomalies (MPA) and treatment resistance in schizophrenia (TRS). We evaluated 137 patients and 100 healthy controls by using a modified Waldrup MPA scale. Thirteen MPA items were found more frequently in the schizophrenia group than in the controls. The total MPA score was higher in TRS, and MPAs in the eye and mouth regions were more frequent in TRS (n = 57) than in non-TRS. Total MPA score was correlated to Brief Psychiatric Rating Scale-Expanded (BPRS-E) total and BPRS-positive scores in TRS. Our findings suggest that MPA might contribute to treatment resistance in schizophrenia.

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.

Visual P3 abnormalities in patients with first-episode schizophrenia, unaffected siblings of schizophrenia patients and individuals at ultra-high risk for psychosis.

Cued version of the continuous performance test (AX-CPT) assesses sustained attention, working memory and cognitive control processes, which have been reported as impaired in schizophrenia. This study investigated visual P3 event-related potential elicited during cued CPT in patients with schizophrenia and in individuals who were at clinical or genetic high risk for psychosis to determine whether any abnormality may provide a marker of vulnerability for psychosis. Visual P3 elicited during cued CPT have not been reported in individuals at high risk for psychosis. Visual Go and NoGo P3 potentials were assessed in 34 antipsychotic-naive patients with first-episode schizophrenia (FES), 25 clinically unaffected siblings of these patients (familial high-risk for psychosis, FHR), 49 antipsychotic-naive individuals at ultra-high risk for psychosis (UHR) and 37 healthy control (HC) participants. FES patients had overall smaller P3 amplitudes than all other groups. P3 amplitude of the UHR participants was in-between the HC participants and FES patients. The anteroposterior P3 topography differed between the groups, with FES patients and FHR participants showing a more frontally distributed P3 compared with the HC participants. These findings suggest that the reduction in visual P3 amplitude may provide a vulnerability marker for psychosis in individuals who are at clinical high risk for psychosis and that a more frontally distributed visual P3 may be a marker of genetic liability for psychosis.

Measuring discrimination experienced by people with a mental illness: replication of the short-form DISCUS in six world regions.

BACKGROUND: The Discrimination and Stigma Scale (DISC) is a patient-reported outcome measure which assesses experiences of discrimination among persons with a mental illness globally. METHODS: This study evaluated whether the psychometric properties of a short-form version, DISC-Ultra Short (DISCUS) (11-item), could be replicated in a sample of people with a wide range of mental disorders from 21 sites in 15 countries/territories, across six global regions. The frequency of experienced discrimination was reported. Scaling assumptions (confirmatory factor analysis, inter-item and item-total correlations), reliability (internal consistency) and validity (convergent validity, known groups method) were investigated in each region, and by diagnosis group. RESULTS: 1195 people participated. The most frequently reported experiences of discrimination were being shunned or avoided at work (48.7%) and discrimination in making or keeping friends (47.2%). Confirmatory factor analysis supported a unidimensional model across all six regions and five diagnosis groups. Convergent validity was confirmed in the total sample and within all regions [ Internalised Stigma of Mental Illness (ISMI-10): 0.28-0.67, stopping self: 0.54-0.72, stigma consciousness: -0.32-0.57], as was internal consistency reliability (α = 0.74-0.84). Known groups validity was established in the global sample with levels of experienced discrimination significantly higher for those experiencing higher depression [Patient Health Questionnaire (PHQ)-2: p < 0.001], lower mental wellbeing [Warwick-Edinburgh Well-being Scale (WEMWBS): p < 0.001], higher suicidal ideation [Beck Hopelessness Scale (BHS)-4: p < 0.001] and higher risk of suicidal behaviour [Suicidal Ideation Attributes Scale (SIDAS): p < 0.001]. CONCLUSIONS: The DISCUS is a reliable and valid unidimensional measure of experienced discrimination for use in global settings with similar properties to the longer DISC. It offers a brief assessment of experienced discrimination for use in clinical and research settings.

Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium.

INTRODUCTION: Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR. METHODS: We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction. RESULTS: Our sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %). IMPLICATIONS: Our findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR.

Impaired Effort Allocation in Patients with Recent-Onset Schizophrenia and Its Relevance to Negative Symptoms Assessments and Persistent Negative Symptoms.

(1) Background: Our aims in this study were (i) to compare effort allocation capacity measured between patients with recent-onset schizophrenia (SCZ) and healthy controls (HCs), (ii) within the SCZ, to investigate the association of effort allocation capacity with negative symptoms (NS), and (iii) to compare this association with the type of NS scale used. (2) Methods: Thirty-one patients with SCZ and 30 HCs participated in the study. The NS was examined using an older-generation (Scale for the Assessment of Negative Symptoms, SANS), a newer-generation (Brief Negative Symptoms Scale, BNSS), and a self-rated (Self-evaluation of Negative Symptoms Scale, SNS) negative symptom scale, as well as longitudinally by using persistent NS (PNS) distinction. (3) Results: The SCZ group was less willing to expend effort in high/moderate-probability and -magnitude conditions but more in low-probability and -magnitude conditions. A general reduction in effort allocation capacity was also present. Patients with PNS were less likely to choose hard tasks than non-PNS patients. Clinician-rated scales correlated with 50% probability and moderate-reward-magnitude conditions. Correlations with the SNS were minimal. (4) Conclusions: Our findings suggest that patients with SCZ may show a general reduction in effort allocation capacity and make inefficient choices, although they are not totally reward-insensitive. The effects of NS on effort expenditure can be more pronounced when the rewarding stimulus is vague.

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.

Validation of the Turkish version of the self-evaluation of negative symptoms scale (SNS).

OBJECTIVES: The Self-Evaluation of Negative Symptoms Scale (SNS) is a self-report scale that evaluates a patient's subjective experience on all five domains of the negative symptoms. This study aimed to present the adaptation and validation study of the Turkish version of SNS(SNS-TR). METHODS: Seventy-five patients and 50 controls were recruited for this study. After the approval of the translation, participants were asked to fill out SNS-TR by themselves. They were interviewed with the Brief Negative Symptoms Scale (BNSS), Positive and Negative Syndrome Scale (PANSS), and Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: SNS-TR showed good internal consistency in the reliability analysis with Cronbach's alpha= 0.873. Subscale-total score correlation coefficients were significant (p < 0.01). In the validity analyses, the total and subscale scores of SNS-TR showed positive correlations with the total and subscales of BNSS, with only one exception of BNSS lack of distress subscales. The total score of SNS-TR demonstrated a significant correlation with PANSS-total, PANSS-negative subscale, PANSS-general subscale, and CDSS scores. Confirmatory factor analysis showed acceptable values for the five-factor structure, similar to the original version. CONCLUSION: To conclude, our study indicates that SNS-TR is an easily applicable self-evaluation tool with good psychometric properties for assessing negative symptoms. KEY POINTSSNS is a novel and easily applicable self-report scale for examining negative symptoms in schizophrenia patients, allowing them to evaluate their subjective experience on all five domains of the negative symptoms.It shows good internal consistency (α= 0.873) which is similar to the original version (α = 0.867).Confirmatory factor analysis scores were found in acceptable ranges and SNS-TR confirm the five-factor structure.Using this scale in clinical practice would empower both the physician's examinations and patient participation through treatment and follow-up course.

Menstrual Cycle-Related Changes in Women with Schizophrenia: A Resting-State fMRI Study.

INTRODUCTION: Different influences of ovarian hormones in schizophrenia (SCZ) have been reported, but no study to date has assessed their effects on the brain dynamics at rest. The present study aimed to examine the hormonal and clinical changes related to the menstrual cycle and alterations in the resting-state functional connectivity (RS-FC) depending on cycle phase and/or hormonal fluctuations in SCZ. METHOD: This study was conducted based on both between- and within-subject experimental designs, including 13 clinically stable female patients with SCZ (32 ± 7.7 years) and 13 healthy women (30 ± 7.3 years). RS-functional magnetic resonance imaging (fMRI) scanning, as well as hormonal and clinical assessments, was applied to each participant twice during two cycle phases: early follicular and mid-luteal. RESULTS: A difference in mid-luteal progesterone levels was found between groups, with a large effect size (Cohen's d) of 0.8 (p < 0.05). Also, the estradiol levels negatively correlated with the negative symptom severity of the patients during their mid-luteal phase. In the patients, estrogen positively correlated with the auditory network connectivity in the left amygdala during the early follicular phase. In the controls, progesterone had positive correlations with the connectivity of the posterior default mode and the left frontoparietal networks in the bilateral precuneus during the early follicular phase and had a negative correlation with the executive control network connectivity in the mid-luteal phase. CONCLUSION: The present study showed hormonal differences between groups and suggested that the levels of cycle-dependent hormones might be associated with the changes in clinical symptom severity and the RS-FC in the groups. Our RS-fMRI findings warrant further investigation.

European Validation of the Self-Evaluation of Negative Symptoms (SNS): A Large Multinational and Multicenter Study.

BACKGROUND: Negative symptoms are usually evaluated with scales based on observer ratings and up to now self-assessments have been overlooked. The aim of this paper was to validate the Self-evaluation of Negative Symptoms (SNS) in a large European sample coming from 12 countries. We wanted to demonstrate: (1) good convergent and divergent validities; (2) relationships between SNS scores and patients' functional outcome; (3) the capacity of the SNS compared to the Brief Negative Symptom Scale (BNSS) to detect negative symptoms; and (4) a five-domain construct in relation to the 5 consensus domains (social withdrawal, anhedonia, alogia, avolition, blunted affect) as the best latent structure of SNS. METHODS: Two hundred forty-five subjects with a DSM-IV diagnosis of schizophrenia completed the SNS, the Positive and Negative Syndrome Scale (PANSS), the BNSS, the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Spearman's Rho correlations, confirmatory factor analysis investigating 4 models of the latent structure of SNS and stepwise multiple regression were performed. RESULTS: Significant positive correlations were observed between the total score of the SNS and the total scores of the PANSS negative subscale (r = 0.37; P < 0.0001) and the BNSS (r = 0.43; p < 0.0001). SNS scores did not correlate with the level of insight, parkinsonism, or the total score of the PANSS positive subscale. A positive correlation was found between SNS and CDSS (r = 0.35; p < 0.0001). Among the 5 SNS subscores, only avolition subscores entered the regression equation explaining a lower functional outcome. The 1-factor and 2-factor models provided poor fit, while the 5-factor model and the hierarchical model provided the best fit, with a small advantage of the 5-factor model. The frequency of each negative dimension was systematically higher using the BNSS and the SNS vs. the PANSS and was higher for alogia and avolition using SNS vs. BNSS. CONCLUSION: In a large European multicentric sample, this study demonstrated that the SNS has: (1) good psychometric properties with good convergent and divergent validities; (2) a five-factor latent structure; (3) an association with patients' functional outcome; and (4) the capacity to identify subjects with negative symptoms that is close to the BNSS and superior to the PANSS negative subscale.

Altered Resting State Functional Connectivity and Its Correlation with Cognitive Functions at Ultra High Risk for Psychosis.

The aim of this study is to identify robust resting state-functional connectivity (rs-FC) alterations and their correlations with the neuropsychological characteristics of Ultra-High Risk (UHR) for psychosis subjects compared to healthy controls (HCs). Twenty individuals with UHR and sixteen HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI) and a cognitive battery evaluating attention, episodic memory and executive functions. Compared to HCs, UHR individuals showed working memory and set-shifting impairments. In functional connectivity (FC) analyses, the Default Mode Network (DMN) of the UHR subjects displayed increased FC with the visual areas and decreased FC with the Dorsal Attention Network (DAN). Additionally, the salience network (SN) of the UHR subjects displayed increased connectivity with wide posterior cortical areas in the temporal, parietal and occipital lobes, corresponding to posterior nodes of the SN itself, the Somato-Motor Network (SMN) and the DAN. The SN connectivity with the left SMN and DAN was positively correlated with the Trail Making Test - B scores of the UHR subjects. These findings show that the SN and DMN, which mostly show abnormal connectivity patterns in psychosis, are also affected in UHR subjects, while the SN plays a more central role with its hyperconnectivity to the DAN and SMN.

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.

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.

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.