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C. Nievergelt, A. Maihofer, Elizabeth G Atkinson, Chia-Yen Chen, Karmel W Choi, Jonathan R. I. Coleman, N. Daskalakis, Laramie E. Duncan et al.

C. Nievergelt, A. Maihofer, Elizabeth G Atkinson, Chia-Yen Chen, Karmel W Choi, RI Jonathan, N. Daskalakis, L. Duncan et al.

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Objective: During the COVID-19 pandemic, fear, anxiety, and depression have become global concerns among the wider public. This study aimed to examine the occurrence of fear, anxiety and depressive symptoms associated with COVID-19, to assess influencing factors that lead to the development of these mental health conditions and to examine any changes in the mental health patterns of the society since the initial study a year ago in Sarajevo, Bosnia and Herzegovina. Method : An anonymous online survey based on Fear of COVID-19 Scale (FCV-19S), General Anxiety Disorder-7 (GAD-7) and Patients Health Questionnaires (PHQs) was conducted in the general population of Sarajevo in Bosnia and Herzegovina. Results: From 1096 subjects, 81.3% were females, 33.8% had a high school degree, 56.4% were married, 53.4% were engaged in intellectual labor, 42.3% experienced fear, 72.9% had anxiety symptoms and 70.3% had depressive symptoms during the COVID-19 pandemic and their mean age was 35.84 ± 10.86. Half (50.1%) of the subjects were COVID-19 positive and 63.8% had COVID-19 symptoms when responding to the questionnaire. Experiencing COVID-19 related fear (OR = 1.972) and having moderate to severe depressive symptoms (OR = 9.514) were associated with the development of mild to severe anxiety symptoms during the COVID-19 pandemic, which were in turn associated with the development of moderate to severe depressive symptoms (OR = 10.203) and COVID-19 related fear (OR = 2.140), respectively, thus creating a potential circulus vicious. COVID-19 positive subjects (OR = 1.454) were also more likely to develop mild to severe anxiety symptoms during the COVID-19 pandemic. Conclusion: In conclusion, the prevalence of fear, anxiety symptoms and depressive symptoms rose dramatically since the beginning of the COVID-19 pandemic in Bosnia and Herzegovina. They were interconnected and were significantly associated with age, gender, marital status and COVID-19 status. Therefore, an urgent mental health intervention is needed for the prevention of mental health problems.

A. Maihofer, Karmel W. Choi, J. Coleman, N. Daskalakis, Christy A. Denckla, E. Ketema, R. Morey, R. Polimanti et al.

J. Mundy, Christopher Hübel, J. Gelernter, D. Levey, R. Murray, M. Skelton, M. Stein, Adam X. Caroline M. Dewlen G. Victoria B. Joseph R. San Maihofer Nievergelt Baker Risborough Calabrese Gal et al.

Abstract Background Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD. Methods Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals. Results Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01–1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001) Conclusions Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.

J. Hunter, R. McCabe, J. Francis, T. Pemovska, E. Ribic, Eldina Smajić Mešević, J. Konjufca, S. Simoska et al.

Background: There are limited resources for improving mental health care across Europe, especially in Low-and-Middle-Income Countries (LMICs) in South-eastern Europe with fewer specialist staff and less funding. Scaling up psychosocial interventions that utilise available time and resources more effectively could improve care for people with psychosis in these settings. One intervention is DIALOG+, delivered via an app on a tablet computer: patients identify life areas to improve and clinicians use a solution-focussed process to help improve these areas. This intervention was piloted across mental healthcare systems in European LMICs, and focus groups were conducted to explore whether such interventions could use available resources effectively to improve care for psychosis in these settings. Methods: Eleven focus groups were conducted with clinicians and patients with psychosis who used the intervention over three months during the pilot study, in Bosnia and Herzegovina, Kosovo United Nations Resolution, Montenegro, North Macedonia and Serbia. The Theoretical Domains Framework (TDF), which describes factors affecting engagement with healthcare interventions, structured topic guides and guided analysis. Codes from the data were mapped onto the TDF, analysed to identify barriers and facilitators, translated into English and checked for inter-rater reliability. Results: 25 clinicians and 23 patients participated in focus groups. Clinicians’ barriers included limited time for sessions and difficulties working with acutely psychotic patients. Patients’ barriers were burden of greater concentration when engaging with DIALOG+ and feeling tense or disturbed during the sessions. Facilitators included motivation to use DIALOG+, positive opinions shared by others, perceived benefits for practice and improving clinician-patient conversations, relationships and care. Conclusions: Barriers to using psychosocial interventions could be overcome even if resources cannot be increased. Despite limited time and other barriers to using DIALOG+, perceived benefits to practice and clinician-patient relationships suggest that psychosocial interventions can use available resources effectively to improve care for psychosis.

Introduction: Diabetes and depression are two common and major non-communicable diseases with significant disease burdens worldwide. Aim: The aim of this study is to obtain the association among A1C levels and symptoms of depression in patients with type 2 diabetes in family medicine offices. Methods: This cross-sectional study was carried out between June 2016 and July 2017. We recruited 150 adults with type 2 diabetes from various family medicine offices. The study questionnaire had two parts; the first one for participants and the second one for family medicine physicians. Participants completed the part of the questionnaire with the PHQ-9 scale and questions regarding demographic data. Family medicine physicians completed the part of the questionnaire with questions concerning clinical data. A univariate and multivariate linear regression analysis was conducted to identify significant predictors of depressive symptoms revealed by the PHQ-9 score. Results: Multiple linear regression showed that the level of A1C was a significant predictor of the PHQ-9 score in all three models. Increases in the A1C level were followed by increases in depressive symptoms. Other significant predictors of a positive PHQ-9 score were smoking, level of education and income. Conclusion: The level of A1C as an indicator of glycemic control has been shown to have a significant association with the scores of the PHQ-9 questionnaire, which identifies the intensity of symptoms of depression. An increase in the level of A1C is followed by an increase in the intensity of symptoms of depression.

T. Pemovska, A. Arënliu, J. Konjufca, F. Uka, J. Hunter, S. Bajraktarov, L. Stevović, S. Jerotić et al.

N. Jovanović, J. Francis, N. Maric, Aliriza Arenliu, Stojan Barjaktarov, A. Kulenović, L. Injac, Yan Feng et al.

Abstract Objectives Psychotic disorders have large treatment gap in low- and middle-income countries (LMICs) in South-Eastern Europe, where up to 45% of affected people do not receive care for their condition. This study will assess the implementation of a generic psychosocial intervention called DIALOG+ in mental health care services and its effectiveness at improving patients’ clinical and social outcomes. Methods This is a protocol for a multi-country, pragmatic, hybrid effectiveness–implementation, cluster-randomised, clinical trial. The trial aims to recruit 80 clinicians and 400 patients across 5 South-Eastern European LMICs: Bosnia and Herzegovina, Kosovo*, Montenegro, Republic of North Macedonia and Serbia. Clusters are clinicians working with patients with psychosis, and each clinician will deliver the intervention to five patients. After patient baseline assessments, clinicians will be randomly assigned to either the DIALOG+ intervention or treatment as usual, with an allocation ratio of 1:1. The intervention will be delivered six times over 12 months during routine clinical meetings. TThe primary outcome measure is the quality of life at 12 months [Manchester Short Assessment of Quality of Life (MANSA)]; the secondary outcomes include mental health symptoms [Brief Psychiatric Rating Scale (BPRS), Clinical Assessment Interview for Negative Symptoms (CAINS), Brief Symptom Inventory (BSI)], satisfaction with services [Client Satisfaction Questionnaire (CSQ-8)] and economic costs at 12 months [based on Client Service Receipt Inventory (CSRI), EQ-5D-5L and Recovering Quality of Life (ReQOL-10)]. The study will assess the intervention fidelity and the experience of clinicians and patients’ about implementing DIALOG+ in real-life mental health care settings. In the health economic assessment, the incremental cost-effectiveness ratio is calculated with effectiveness measured by quality-adjusted life year. Data will also be collected on sustainability and reach to inform guidelines for potentially scaling up and implementing the intervention widely. Conclusion: The study is expected to generate new scientific knowledge on the treatment of people with psychosis in health care systems with limited resources. The learning from LMICs could potentially help other countries to expand the access to care and alleviate the suffering of patients with psychosis and their families. Trial registration: ISRCTN 11913964

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