A Comparative Study on Mental Disorder Conceptualization: A Cross-Disciplinary Analysis.

The conceptualization of mental disorders varies among professionals, impacting diagnosis, treatment, and research. This cross-disciplinary study aimed to understand how various professionals, including psychiatrists, psychologists, medical students, philosophers, and social sciences experts, perceive mental disorders, their attitudes towards the disease status of certain mental states, and their emphasis on biological versus social explanatory attributions. A survey of 371 participants assessed their agreement on a variety of conceptual statements and the relative influence of biological or social explanatory attribution for different mental states. Our findings revealed a consensus on the need for multiple explanatory perspectives in understanding psychiatric conditions and the influence of social, cultural, moral, and political values on diagnosis and classification. Psychiatrists demonstrated balanced bio-social explanatory attributions for various mental conditions, indicating a potential shift from the biological attribution predominantly observed among medical students and residents in psychiatry. Further research into factors influencing these differing perspectives is necessary.

Screening for depression in the Serbian general population sample: an alternative to the traditional patient health questionnaire-9 cut-off score.

BACKGROUND: The Patient Health Questionnaire (PHQ-9) score ≥ 10 balances best sensitivity and specificity when detecting probable depression in patients. In the general population, different cut-offs are suggested. European studies on general populations validating the PHQ-9 against a diagnostic interview to detect depression are rare. METHODS: This was a cross-sectional observational epidemiological survey using multistage household probabilistic sampling to recruit a representative adult sample (N = 1203; age = 43.7 ± 13.6; 48.7% male). Mental disorders including current major depressive episode (MDE) were observer-rated (Mini International Neuropsychiatric Interview). The PHQ-9, quality of life (QoL), and loneliness were self-assessed. We performed validity and reliability tests of the PHQ-9 and receiver operating curve (ROC) analysis. RESULTS: The Serbian PHQ-9 was internally consistent and correlated in the expected directions with QoL and loneliness. At the cut-off score ≥ 8, sensitivity was .85 and specificity was .91. ROC analysis showed that the area under the curve was .95, indicating that the Serbian PHQ-9 can discriminate very well between persons with/without MDE. CONCLUSIONS: When the PHQ-9 is assessed against the structured diagnostic interview in the general population to detect depression, the cut-off of ≥8 balances best sensitivity and specificity.

Factor structure of the brief psychiatric rating scale-expanded among outpatients with psychotic disorders in five Southeast European countries: evidence for five factors.

The Brief Psychiatric Rating Scale (BPRS) is a useful tool for measuring the severity of psychopathological symptoms among patients with psychosis. Many studies, predominantly in Western countries, have investigated its factor structure. This study has the following aims: (a) to further explore the factor structure of the BPRS-Expanded version (BPRS-E, 24 items) among outpatients with psychotic disorders in Southeast European countries; (b) to confirm the identified model; and (c) to investigate the goodness-of-fit of the three competing BPRS-E factor models derived from previous studies. The exploratory factor analysis (EFA) produced a solution with 21 items grouped into five factors, thus supporting the existence of a fifth factor, i.e., Disorganization. A follow-up confirmatory factor analysis (CFA) revealed a 19-item model (with two items removed) that fit the data well. In addition, the stability of two out of three competing factor models was confirmed. Finally, the BPRS-E model with 5 factors developed in this cross-national study was found to include a greater number of items compared to competing models.

Clozapine prescription rates in Southeast Europe: A cross-sectional study.

Introduction: International reports indicate that clozapine is under prescribed. Yet, this has not been explored in Southeast European (SEE) countries. This cross-sectional study investigates clozapine prescription rates in a sample of 401 outpatients with psychosis from Bosnia and Herzegovina, Kosovo by United Nations resolution, North Macedonia, Montenegro and Serbia. Methods: Descriptive analysis was used to explore clozapine prescription rates; daily antipsychotic dosage was calculated and converted into olanzapine equivalents. Patients receiving clozapine were compared to those not receiving clozapine; next those that were on clozapine monotherapy were compared to those who were on clozapine polytherapy regime. Results: It was showed that clozapine was prescribed to 37.7% of patients (with cross-country variation: from 25% in North Macedonia to 43.8% in Montenegro), with average dose of 130.7 mg/daily. The majority of patients on clozapine (70.5%) were prescribed at least one more antipsychotic (the most frequent combination was with haloperidol). Discussion: Our findings suggested that clozapine prescription rate in SEE outpatients is higher than in Western Europe. The average dose is significantly below the optimal therapeutic dosage recommended by clinical guidelines, and clozapine polytherapy is common. This might indicate that clozapine is prescribed mainly for its sedative effect rather than antipsychotic. We hope that this finding will be taken up by relevant stakeholders to address this non-evidence-based practice.

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.

Theory of Mind in Typical Adults: Sex-Differences and Its Associations with Anxiety and Depression Symptoms.

OBJECTIVE: Despite an increased interest in research of theory of mind (ToM) in recent years - both related to psychopathology (depression and anxiety spectrum disorders) and within the typical adults, the existing literature is scarce and presents some conflicting results. Present study aimed to explore sex differences in ToM, alongside its associations with current anxiety and depression symptoms, in a large sample of typical adults collected online. METHOD: Participants completed the 15-minutes survey obtaining socio-demographic data, current self-reported depression and anxiety symptom severity, and ToM ability (the Reading the Mind in the Eyes Task). The sample comprised 605 participants -mostly younger adults, women, and high school graduate/student population. RESULTS: The majority of participants reported minimal/mild depressive and anxiety symptoms that were significantly more severe in women. Women also displayed significantly better overall ToM ability than men. Significant negative correlation between the severity of current depressive and anxiety symptoms and ToM ability was also observed, but only in individuals expressing the symptoms requiring clinical attention (such association was absent in those exhibiting minimal/mild symptoms). CONCLUSIONS: Present research adds to the existing knowledge on the association between ToM ability, anxiety, and depressive symptoms in typical adults as well as on the sex-differences in this important social cognitive domain. Exploring the factors representing indicators of vulnerability for depression-anxiety spectrum disorders is important for their timely detection and treatment.

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.

Non-pharmacological interventions for schizophrenia-analysis of treatment guidelines and implementation in 12 Southeast European countries.

This study aimed to analyze treatment guidelines of 12 SEE countries to identify non-pharmacological interventions recommended for schizophrenia, explore the evidence base supporting recommendations, and assess the implementation of recommended interventions. Desk and content analysis were employed to analyze the guidelines. Experts were surveyed across the 12 countries to assess availability of non-pharmacological treatments in leading mental health institutions, staff training, and inclusion in the official service price list. Most SEE countries have published treatment guidelines for schizophrenia focused on pharmacotherapy. Nine countries-Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Moldova, Montenegro, North Macedonia, and Serbia-included non-pharmacological interventions. The remaining three countries-Kosovo (UN Resolution), Romania, and Slovenia-have not published such treatment guidelines, however they are on offer in leading institutions. The median number of recommended interventions was seven (range 5-11). Family therapy and psychoeducation were recommended in most treatment guidelines. The majority of recommended interventions have a negative or mixed randomized controlled trial evidence base. A small proportion of leading mental health institutions includes these interventions in their official service price list. The interventions recommended in the treatment guidelines seem to be rarely implemented within mental health services in the SEE countries.

Treatment Approaches for First Episode and Early-Phase Schizophrenia in Adolescents and Young Adults: A Delphi Consensus Report from Europe.

PURPOSE: Although first-episode psychosis (FEP) in youth, particularly early-onset schizophrenia (EOS), is managed similarly to adult-onset schizophrenia, few antipsychotics are approved for people aged 13-18 years. We aimed to explore areas of uncertainty in EOS management and provide evidence-based recommendations to mental health specialists. We used the Delphi methodology to gain knowledge in areas lacking evidence-based strategies. This standardized methodology consists of the development of a questionnaire by content experts, which is then submitted to a broader panel of professionals (panelists) to survey their level of agreement on the topics proposed. MATERIALS AND METHODS: The developed questionnaire covered patient management from diagnosis to maintenance treatment and was administered to a broader panel of specialists across Europe. Based on an analysis of responses received in this first round, the items that needed further insight were submitted to the panel for a second round and then reanalysed. RESULTS: An initial set of 90 items was developed; in round I, consensus was reached for 83/90 items (92%), while it was reached for 7/11 (64%) of the items sent out for rerating in round II. Feedback for rounds I and II was obtained from 54/92 and 48/54 approached experts, respectively. There was broad agreement on diagnostic standards, multimodal approaches and focus on adverse events, but uncertainty in terms of pharmacological strategies (including clozapine) in case of failure and antipsychotic dosing in younger patients. CONCLUSION: Despite knowledge about diagnostic clues and integrated management of EOS, this study highlights the lack of standardization in treating EOS, with safety arguments having a major role in the decision-making process. Targeted clinical trials and systematic dissemination across Europe of current scientific evidence on the value of early intervention services is hoped to contribute to standardized and improved quality care for patients with early-phase psychosis and schizophrenia.

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.

Non-pharmacological treatments for schizophrenia in Southeast Europe: An expert survey.

BACKGROUND: Non-pharmacological treatment for schizophrenia includes educational, psychotherapeutic, social, and physical interventions. Despite growing importance of these interventions in the holistic treatment of individuals with schizophrenia, very little is known about their availability in South-East European countries (SEE). OBJECTIVE: To explore mental health care experts' opinions of the availability of non-pharmacological treatment for people with schizophrenia in SEE. METHODS: An online survey containing 11 questions was completed by one mental health expert from each of the following SEE countries: Albania, Bosnia and Herzegovina (B&H), Bulgaria, Croatia, Greece, Kosovo†, Montenegro, Moldova, North Macedonia, Romania, Serbia, and Slovenia. Data were collected on estimated rates of received non-pharmacological interventions, type of services delivering these interventions, and expert views of availability barriers. RESULTS: In eight countries, the estimated percentage of people with schizophrenia who receive non-pharmacological treatments was below 35%. The primary explanations for the low availability of non-pharmacological treatments were: lack of human and financial resources, lack of training for clinicians, and pharmacotherapy dominance in the treatment for schizophrenia. CONCLUSION: Lack of personal and institutional resources and state support were identified as primary obstacles to staff training and delivering non-pharmacological treatments to people with schizophrenia on individual and systemic levels, respectively. This evidence can be used to improve holistic, evidence-based treatment for schizophrenia in the SEE countries.

Mental health in the second year of the COVID-19 pandemic: protocol for a nationally representative multilevel survey in Serbia.

INTRODUCTION: The COVID-19 pandemic is likely to have a prolonged impact on mental health (MH); however, the long-term MH effects of the COVID-19 pandemic remain unknown. The Serbian national survey-CoV2Soul.RS-was launched to document the MH status of the Serbian population following the COVID-19 pandemic and to contribute to an international evidence base about MH prevalence rates during different phases of the pandemic. METHODS AND ANALYSIS: This cross-sectional study was designed to collect a nationally representative sample (N=1200; age 18-65 years; estimated start/end-June/November 2021) using multistage probabilistic household sampling. Trained staff will conduct in-person diagnostic interviews. A battery of self-report instruments will be administered to assess the quality of life (QoL), general distress and associated protective and harmful psychological and societal factors. Analyses will be conducted to delineate the prevalence rates of MH disorders, how MH conditions and QoL vary with respect to sociodemographic variables, personality, health status and traumatic events during the COVID-19 pandemic, and to test how these relations depend on geographical region. Moreover, this study was designed to explore mechanisms linking personality and the perception of pandemic consequences and associated distress. Prevalence rates of MH disorders will be calculated using descriptive statistics. For additional analyses, we will use correlations, analysis of variance and regression analyses. The hierarchical structure of the data will be explored using multilevel random coefficient modelling. Structural equation modelling will be used to investigate the indirect effects of personality on distress through relevant variables. ETHICS AND DISSEMINATION: Ethical Committees of the Faculty of Medicine (1322-VII/31) and Faculty of Philosophy in Belgrade (02-33/273) and Faculty of Philosophy in Novi Sad (05-27, br.893/1) approved the protocol. Only respondents able to provide informed consent will participate in the study. Research reports will be submitted to peer-reviewed journals and the results will be placed on the website www.cov2soul.rs to be available to funders, researchers, policy-makers and interested laypeople, and will be advertised through social media. TRIAL REGISTRATION NUMBER: NCT04896983.

Determinants of quality of life among individuals seeking mental health care after termination of state of emergency due to the coronavirus disease 2019 pandemic.

ABSTRACT: Prompted by the need to measure the impact of the coronavirus disease 2019 on main areas of quality of life related to mental health (MH), the COV-19-impact on quality of life (COV19-QoL) scale has been developed recently. We measured how patients seeking face-to-face MH care perceived the coronavirus disease 2019 impact on QoL and how socio-demographic factors, stress, and personality contributed to QoL in this diagnostically diverse population.Patients aged 18 to 65 years (n = 251) who came for the first time to the outpatient units during the 6-week index-period (May 21-July 1, 2020) were included. The cross-sectional assessment involved sociodemographic variables, working diagnosis, personality traits (7-dimension model, including HEXACO and DELTA), stress (list of threatening experiences and proximity to virus), and COV19-QoL.The perceived impact of the pandemic on QoL was above the theoretical mean of a 5-point scale (COV19-Qol = 3.1 ±â€Š1.2). No association between total COV19-QoL score, sociodemographic parameters, and working diagnoses was found in the present sample. After testing whether positional (threatening experiences), or dispositional (personality) factors were predominant in the perceived impact of COV-19 on QoL, significant predictors of the outcome were personality traits Disintegration (B = 0.52; P < .01) and Emotionality (B = 0.18; P < .05).It seems that pervasiveness and uncertainty of the pandemic threat triggers-especially in those high on Disintegration trait-a chain of mental events with the decrease of QoL as a final result. Present findings could be used to establish a profile of MH help seeking population in relation to this biological disaster, and to further explore QoL and personality in different contexts.

The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls.

Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.

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.

Long-Term Benzodiazepine Prescription During Maintenance Therapy of Individuals With Psychosis Spectrum Disorders-Associations With Cognition and Global Functioning.

BACKGROUND: Cognitive difficulties have a significant impact on life functioning and overall well-being in patients with psychosis spectrum disorders (PSDs). There are indications that continuous use of benzodiazepines (BZDs) in various patient groups has a detrimental effect on cognition. Our aim was to explore the association between long-term BZD prescription, global functioning, and cognitive functioning in persons with PSD. METHODS: This exploratory study included 55 PSD patients, recruited from 2 outpatient services in Serbia. Patients were grouped into BZD long-term prescription group and BZD-other group. Brief Psychiatric Rating Scale was used for symptom assessment, functioning was measured by Global Assessment and Functioning Scale, and cognition was assessed by the Global Assessment of Functioning-Cognition in Schizophrenia Scale. RESULTS: The sample comprised 52.7% patients who were prescribed with BZD for 6 months or more continually (29/55), with a mean daily dose of 3.16 ± 0.66 mg lorazepam equivalents. There were no differences between study groups in any of the sociodemographic characteristics, duration of illness, or antipsychotic daily dosages. The BZD long-term prescription group had lower global (P < 0.01) and cognitive functioning (P < 0.01), higher Brief Psychiatric Rating Scale scores (1.86 vs 1.58, respectively, P < 0.01), and more psychotropic drugs prescribed on a daily basis than the other group (median: 4 vs 2, respectively, P < 0.01). CONCLUSIONS: The study explored a topic that continues to be underresearched, especially in the Balkans. Prospective studies and comprehensive cognitive batteries are needed to further elucidate the associations between polypharmacy, long-term BZD use, cognitive functioning, and global functioning during maintenance therapy of individuals with PSD.

Sex differences in macular thickness of the retina in patients with psychosis spectrum disorders.

INTRODUCTION: Imaging of retinal structure in psychosis spectrum disorders (PSD) is a novel approach to studying effect of this illness class on CNS structure. Studies of optical coherence tomography (OCT) have revealed significant reductions in regarding: retinal nerve fiber layer (RNFL), macular thickness (MT), ganglion cell-inner plexiform layer (GC-IPL) and macular volume (MV). Sex differences in retinal structure in PSD have not been previously explored. METHODS: This cross-sectional pilot study included 81 participant of age matched patients and controls. There were no differences between genders regarding illness duration and antipsychotic daily dose in the patient group. SD-OCT assessed RNFL, GC-IPL, MT, MV, and optic nerve cup-to-disc (C/D) ratio. In order to assess the main effects of illness, sex, and illness × sex interaction on the retinal parameters, general linear model was performed. RESULTS: Patients demonstrated abnormalities on all OCT indices. Effects of sex were observed for central subfield MT and C/D ratio, which were lower in females. An illness × sex interaction effect was observed for the left MT, indicating greater thinning in female patients. CONCLUSION: Sex differences in OCT findings in PSD appear to be most prominent considering macular parameters. These preliminary data may have important implications for the valid interpretation of OCT findings as potential biomarkers for PSD.