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.

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.

Maintenance Therapy of Psychosis Spectrum Disorders in a Real-World Setting: Antipsychotics Prescription Patterns and Long-Term Benzodiazepine Use.

Background: Maintenance therapy of patients with primary psychosis spectrum disorders (PSD) in the Western Balkans has received limited interest so far. The present study aimed to investigate long-term prescription patterns among outpatients with PSD. Methods: Information about prescription of antipsychotics (AP), benzodiazepines (BZD) and other psychotropic medication over a 6-month period was collected from outpatients (n = 134; ICD-10 diagnosis F20-29) recruited by a larger multi-site study, to find mean daily number of psychotropic drugs, AP prescription patterns (including AP daily dose, route of administration, monotherapy vs. polypharmacy) and BZD utilization (long-term add-on BZD therapy). Additionally, sex-differences in the variables were explored. Results: Clinically stable outpatients (age 41.7 ± 11.0; male 62.7%; duration of untreated illness 12.7 ± 8.7 years; mean number of lifetime hospitalizations 2.6 ± 0.7) were prescribed 2.8 ± 1.1 psychotropic medications daily. The mean 6-month AP dose was 14.2 ± 7.8 mg olanzapine equivalents. Long-acting injectable AP was prescribed to 25.2% of the patients. Long-term AP monotherapy was found in 52.7% patients and most of them were prescribed second generation AP (65.2%). Long-term AP polypharmacy (42.7%) was more common in males (p = 0.015). The most frequent co-prescription patterns were first generation AP plus clozapine. The highest rate of long-term AP co-prescription was found for BZD (in 42.7% cases, average 6-months daily dose of 2.8 ± 2.7 mg lorazepam equivalents) and anticholinergics (33.6%). Conclusion: Existing appropriately designed interventions aiming to safely switch the inappropriate therapeutic regimens, i.e. very high prevalence of long-term AP polypharmacy and non-rational BZD co-prescription, should be implemented in the region of Western Balkans.

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.

Maintenance phase treatment of psychotic disorders in outpatients from Serbia - focus on long-term benzodiazepine use.

Introduction: Prescribing trends in maintenance therapy of patients with primary psychotic disorders (PSD) may vary worldwide. Present study aimed to investigate prescription patterns in a sample of outpatients with PSD from Serbia.Methods: In a sample of 73 PSD outpatients we analysed the rate of antipsychotic polypharmacy and psychotropic polypharmacy, concomitant continual benzodiazepine use, and associations between therapy, psychotic symptoms and quality of life.Results: Maintenance therapy (median daily dose 321 mg of chlorpromazine equivalents) predominantly consisted of monotherapy with second generation antipsychotics (45.2%), followed by antipsychotic polypharmacy based on first and second generation combination (25.0%). The median number of psychotropic drugs was 3. Benzodiazepines were continually prescribed to more than 60% of patients (mean daily dose 2.9 ± 2.0 mg lorazepam equivalents). Patients with benzodiazepine use had significantly more psychotropic medications and more antipsychotic polypharmacy, poorer quality of life and more severe psychopathology in comparison to another group.Conclusion: The present study demonstrated new information regarding the prescription patterns of psychotropic drugs in outpatients with PSD in Serbia, amplified with clinically relevant information. This study also revealed distinct prescription patterns concerning antipsychotic/benzodiazepine polypharmacy. Overall, such findings are likely to contribute to improving clinical practice and care for patients with PSD in general.KeypointsPresent exploratory research aimed to elucidate trends of antipsychotics polypharmacy and concomitant use of psychotropic medications including benzodiazepines in the maintenance treatment of outpatients with schizophrenia and other psychotic disorders, amplified with clinically relevant information (symptoms and quality of life).'Antipsychotic (AP) polypharmacy' was defined as concurrent use of more than one AP for at least 1 month; 'Psychotropic polypharmacy' was defined as the combination of AP and a different class of psychotropic drugs medication for at least one month.The median number of prescribed psychotropic drugs was 3 (mean 3.1 ± 1.1) and the average AP daily dose was moderate (median 321 mg of chlorpromazine equivalents). However, the rates of AP polypharmacy (45.2%) and benzodiazepine prescription on a continual basis (>60%) found in our sample could be considered relatively high.Outpatients with higher AP daily dose and higher BPRS symptom score were receiving more benzodiazepines.For improvement of the local, as well as general clinical practice and care for patients with psychotic disorders, and for education in psychiatry, such analyses need to be done on a regular basis and on larger samples.

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.

Implementation of early detection and intervention services for psychosis in Central and Eastern Europe: Current status.

AIM: Unequal development of early detection (ED) and early intervention (EI) programs/services for psychosis has been shown across Europe. The present report aims to fill in the knowledge gap regarding the implementation and several other important aspects of ED/EI services in Central and Eastern Europe (CEE), a region with highly underdeveloped mental health service research. METHODS: A 17-item questionnaire was created to address the information regarding ED/EI organization and factors limiting their implementation. This questionnaire was distributed to professionals recognized as experts in the field from 23 CEE countries. The data were collected between December 2017 and February 2018. RESULTS: We found that ED/EI services were rather an exception than a rule in CEE. The majority of the countries involved in the present survey reported no national plans or programmes for ED/EI development. The existing services were mostly state-funded, hospital-based, healthcare sites for both adolescent and adult help-seekers. The lack of adequate infrastructure, finances and governmental support, as well as the insufficient number of staff, were identified as the most important factors limiting service implementation. CONCLUSIONS: Although ED/EI services for psychosis exist in some CEE countries, this could be largely attributed to enthusiastic individuals and organizations, rather than to a strategic development. To the best of our knowledge, this was the first mapping of ED/EI development in the region, which could be used as a starting point to plan the improvement of services, to accelerate their implementation and to facilitate timely detection of and intervention in psychosis across Europe.

Sex differences in facial emotion recognition in health and psychotic disorders.

BACKGROUND: Previous studies examining sex-differences in facial emotion recognition (FER) in psychosis yielded inconsistent results. Although females are considered to be superior in FER in health, it remains unclear whether the specific sex-difference is present in psychosis. We aimed to examine whether women and men differ in FER ability in health and in psychosis, and to explore potential sex differences in the illness' effects on FER. METHODS: Remitted psychotic patients and controls were assessed using the CANTAB Emotion Recognition Task (ERT) examining accuracies/response latencies in identifying basic emotional expressions. General linear model was performed to assess the effects of group, sex and their interactions on ERT performance. RESULTS: Healthy females showed FER advantage in comparison to healthy males, while the aforementioned sex-difference was not observed in remitted psychotic patients. Our results also demonstrated the existence of overall FER deficit in psychosis in comparison to healthy controls, as well as the differential illness' effects on the recognition accuracy of facial expression of anger in males and females-suggesting that females with psychotic disorders undergo more profound deterioration of FER ability than their male counterparts. CONCLUSION: The assessment of sex-differences in FER and other important features of psychosis is important for better understanding of its neurobiological basis and for the development of targeted treatments for improved functioning.

Prescribing practices in Southeastern Europe - focus on benzodiazepine prescription at discharge from nine university psychiatric hospitals.

There is much concern about the widespread long-term use of benzodiazepines. Our manuscript addressed its use in the region of Southeastern Europe, which seems extensive, but insufficiently explored. At nine university psychiatric hospitals (Croatia, Macedonia and Serbia), we retrospectively analyzed discharge summary documents to find the prevalence of discharge benzodiazepine prescriptions and the prescribed benzodiazepine doses. This study included 1047 adult subjects and showed that 81.9% of them had benzodiazepines prescribed in the discharge summary document, with high mean daily dose of around 5mg lorazepam equivalents. Factors associated with the prescriptions were exclusively clinical factors (diagnosis of schizophrenia spectrum disorders, more lifetime hospitalizations, psychiatric comorbidity, co-prescription of antidepressant or mood stabilizer, shorter duration of the hospitalization), while socio-demographic factors were not found to influence benzodiazepine discharge prescriptions. Similarly, factors which influenced the prescription of higher daily benzodiazepine dose were more lifetime psychiatric hospitalizations and co-prescription of antidepressant or mood stabilizer, as well as the diagnosis of mental/behavioral disorders due to substance use and co-prescribed antipsychotic. Our data are emphasizing an urgent need for guidelines and improved education of both health care professionals and patients, in order to prevent long term benzodiazepine (mis)use and related side-effects.