Improving treatment of patients with psychosis in low-and-middle-income countries in Southeast Europe: Results from a hybrid effectiveness-implementation, pragmatic, cluster-randomized clinical trial (IMPULSE).

BACKGROUND: In Southeast Europe (SEE) standard treatment of patients with psychosis is largely based on pharmacotherapy with psychosocial interventions rarely available. DIALOG+ is a digital psychosocial intervention designed to make routine care therapeutically effective. This trial simultaneously examined effectiveness of DIALOG+ versus standard care on clinical and social outcomes (Aim 1) and explored intervention fidelity (Aim 2). METHODS: A hybrid type II effectiveness-implementation, cluster-randomized trial was conducted in five SEE countries: Bosnia and Herzegovina, Kosovo*, Montenegro, North Macedonia, and Serbia. The intervention was offered to patients six times across 12 months instead of routine care. The outcomes were subjective quality of life (primary), clinical symptoms, satisfaction with services, and economic costs. Intervention fidelity was operationalized as adherence to the protocol in terms of frequency, duration, content, and coverage. Data were analyzed using multilevel regression. RESULTS: A total of 81 clinicians and 468 patients with psychosis were randomized to DIALOG+ or standard care. The intervention was delivered with high fidelity. The average number of delivered sessions was 5.5 (SD = 2.3) across 12 months. Patients in the intervention arm had better quality of life (MANSA) at 6 months (p = 0.03). No difference was found for other outcomes at 6 months. Due to disruptions caused by the COVID-19 pandemic, 12-month data were not interpretable. CONCLUSIONS: DIALOG+ improved subjective quality of life of individuals with psychosis at 6 months (after four sessions), albeit with small effect size. The intervention has the potential to contribute to holistic care of patients with psychosis.

Covid-19-related stressors, mental disorders, depressive and anxiety symptoms: a cross-sectional, nationally-representative, face-to-face survey in Serbia.

AIM: The Covid-19 pandemic may be associated with an increase in mental disorders and mental distress. However, there are no representative studies testing the impact of stressors directly related to Covid-19. We aimed to determine whether Covid-19-related stressors were associated with mental disorders, depressive and anxiety symptoms in the second year of the pandemic. METHOD: This cross-sectional observational epidemiological survey was conducted from June to October 2021. We interviewed a representative sample of the adult population in Serbia (18-65 years) in the second year of the pandemic, at a time when large parts of the population had been affected by the pandemic in different ways. A multistage probabilistic household sampling of the adult population in 60 municipalities was used. Mental disorders were assessed by in-person interviews using the Mini International Neuropsychiatric Interview. Depressive and anxiety symptoms were measured by PHQ-9 and GAD-7 scales. Covid-19-related stressors (Sars-CoV-2 infection, the infection of a close relative, self-isolation and lack of protective equipment at work), as well as other stressors during the pandemic (not directly related to the risk of the infection), were measured. The associations with mental disorders, depressive and anxiety symptoms were explored through univariable and multivariable regression analyses. RESULTS: In total, 1203 individuals (mean age 43.7 ± 13.6 years, 48.7% male) were interviewed. Most respondents (67.8%) of the sample had already experienced Covid-19-related stressors (20.1% had Sars-CoV-2 infection; 43.2% had a close relative member who had Covid-19; 28.2% reported lack of appropriate protection; 27.5% had been quarantined) and about 50% had already been vaccinated. The prevalence of any mental disorder was 15.2% (95% CI 13.2-17.2): mood disorders 4.6%, anxiety disorders 4.3% and substance use disorders 8.0%. Mean PHQ-9 was 3.2 ± 3.8 and GAD-7 was 2.1 ± 3.1. In this study, one Covid-19 stressor, i.e. lack of protective equipment, was weakly associated with a greater frequency of anxiety disorders (p = 0.023), while the other stressors had significant associations with several groups of mental disorders and symptom levels. CONCLUSIONS: Our study did not provide any evidence that the prevalence of mental disorders exceeds the range of pre-pandemic data reported in the literature. Covid-related stressors, although frequently reported, did not dramatically influence the prevalence of mental disorders. The provision of the appropriate equipment at workplaces might lead to the reduction of anxiety disorders.

The Serbian COVID-19 Stress Scale and vaccine acceptance: is there a place for COVID-19-related distress in explaining attitudes towards vaccination?

OBJECTIVES: Previous research has shown that the COVID-19 Stress Scale (CSS), a measure assessing various dimensions of distress related to the COVID-19 pandemic, is associated with self-protective behaviours; however, it remains unknown whether this distress can be used to predict attitudes towards vaccination. The purpose of this study was to validate the Serbian CSS (Serbian-CSS) and to explore its predictive power over and above certain sociodemographic characteristics, individual difference variables (attitudes and personality) and general distress in relation to COVID-19 vaccine acceptance. STUDY DESIGN: An online cross-sectional study was conducted that targeted users of different social network groups at the beginning of the public COVID-19 vaccination programme in Serbia. METHODS: A large, online study sample (N = 3129) provided self-reported data on COVID-19-related distress, health and sociodemographic indicators, individual difference variables and attitudes towards vaccination. RESULTS: The Serbian-CSS is a valid and reliable instrument that assesses six dimensions of COVID-19 distress. The strongest predictors of vaccine acceptance were attitudes towards immigrants (adjusted odds ratio [AOR] = 0.36, 95% confidence interval [CI] 0.31, 0.41), followed by education (AOR = 1.51, 95% CI 1.27, 1.88) and prepandemic mental health issues (AOR = 1.61, 95% CI 1.30, 2.01). CONCLUSIONS: The level of distress measured by the CSS had a non-substantial contribution to vaccine acceptance, which is probably because of the mild level of distress that was observed at the time of assessment. Public health messaging that relies on the distribution of information is not sufficient to address strongly held beliefs against vaccination. The study provides a benchmark for future cross-cultural research regarding negative affective states associated with the COVID-19 pandemic.

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum.

AIMS: Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. METHODS: The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). RESULTS: Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. CONCLUSIONS: The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.

The acute and medium-term effects of treatment with electroconvulsive therapy on memory in patients with major depressive disorder.

BACKGROUND: Current literature provides insufficient information on the degree of cognitive impairment during and after electroconvulsive therapy (ECT), mostly due to the fact that applied tests lacked sensitivity and flexibility. Our goal was to evaluate cognitive functioning in adult depressed patients treated with bi-temporal ECT, using tests sensitive for detection of possible acute and medium-term memory changes. METHOD: Thirty adult patients with major depressive disorder, treated with a course of bi-temporal ECT, underwent clinical and cognitive measurements three times: at baseline, immediately after a course of ECT, and 1 month later. For cognition assessment, we used learning and visual, spatial and figural memory tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: Bi-temporal ECT has proven to be an effective treatment. The linear mixed model, used to analyze changes in depression severity and patients' cognitive performances over time and to assess dynamic correlations between aforementioned features, did not show any significant memory impairment as a potential acute or medium-term ECT effect. However, it yielded significant improvement on visual memory and learning at the follow-up, which positively correlated with the improvement of depression. CONCLUSION: Good progress is being made in the search for ECT-related acute and medium-term cognitive side-effects by using the tests sensitive to detect memory dysfunction with parallel forms of the tasks (to counter practice effects on repeat testing). Our results on learning and memory in relation to ECT during treatment of depression did not bring forth any prolonged and significant bi-temporal ECT-related memory deficit.

EPA guidance on the early intervention in clinical high risk states of psychoses.

This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n=1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.

EPA guidance on the early detection of clinical high risk states of psychoses.

The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion 'cognitive disturbances' (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The 'genetic risk and functional decline' UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.

Prescribing practices in psychiatric hospitals in Eastern Europe.

BACKGROUND: There has been no evidence about the prescribing practices in psychiatric care in Eastern Europe. AIMS: To examine the patterns of psychotropic prescribing in five countries of Eastern Europe. METHOD: We conducted a one-day census of psychiatric treatments used in eight psychiatric hospitals in Albania, Croatia, Macedonia, Serbia and Romania. We examined clinical records and medication charts of 1304 patients. RESULTS: The use of polypharmacy was frequent across all diagnostic groups. Only 6.8% of patients were on monotherapy. The mean number of prescribed drugs was 2.8 (SD 0.97) with 26.5% receiving two drugs, 42.1% receiving three drugs and 22.1% being prescribed four or more psychotropic drugs. Typical antipsychotics were prescribed to 63% and atypical antipsychotics to 40% of patients with psychosis. Older generations of antidepressants were prescribed to 29% of patients with depression. Anxiolitic drugs were prescribed to 20.4% and benzodiazepines to 68.5% of patients. One third of patients received an anticholinergic drug on a regular basis. CONCLUSIONS: Older generation antipsychotics and antidepressants were used more frequently than in the countries of Western Europe. Psychotropic polypharmacy is a common practice. There is a need for adopting more evidence-based practice in psychiatric care in these countries.

Psychiatric and neuropsychological changes in growth hormone-deficient patients after traumatic brain injury in response to growth hormone therapy.

OBJECTIVE: Traumatic brain injury (TBI) has been recently recognized as a risk factor for cognitive impairment and hypopituitarism, presented most frequently with GH deficiency (GHD). GHD is associated not only with changes in body composition, but also with impaired quality of life, cognitive dysfunctions and some psychiatric sequelae, usually classified as "depression" or "atypical depression". The impact of GH therapy on mental status in TBI patients is still unknown. DESIGN: Psychiatric and cognitive functions were tested in 6 GHD patients at baseline (minimum 3 yr after TBI), reassessed after 6 months of GH therapy as well as 12 months after discontinuation of GH therapy. Psychiatric and cognitive examinations included semi-structured interviews and 3 instruments: Symptom-checklist (SCL-90-R), Zung Depression Inventory, and standard composite neuropsychological battery. RESULTS: Six months of GH therapy in GHD TBI patients improved cognitive abilities (particularly verbal and non-verbal memory) and significantly improved psychiatric functioning. Severity of depression decreased, as well as intensity of interpersonal sensitivity, hostility, paranoid ideation, anxiety, and psychoticism. Somatization, obsessive-compulsive symptoms and phobic anxiety decreased in all except in one patient. In 3 GHD patients who stopped GH therapy for 12 months we registered worsening of the verbal and non-verbal memory, as well symptoms in 3 SCL dimensions: inter-personal sensitivity, anxiety, and paranoid ideation. CONCLUSION: GH-deficient TBI patients are depressed and have cognitive impairment. GH therapy induced reduction of depression, social dysfunction, and certain cognitive domains. Our preliminary data support the necessity of conducting randomized placebo-controlled trials on the effects of GH therapy on neuropsychological and psychiatric status in GHD TBI patients.