Although autism has historically been conceptualized as a condition that emerges in early childhood1,2, many autistic people are diagnosed later in life3, 4–5. It is unknown whether earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Using longitudinal data from four independent birth cohorts, we demonstrate that two different socioemotional and behavioural trajectories are associated with age at diagnosis. In independent cohorts of autistic individuals, common genetic variants account for approximately 11% of the variance in age at autism diagnosis, similar to the contribution of individual sociodemographic and clinical factors, which typically explain less than 15% of this variance. We further demonstrate that the polygenic architecture of autism can be broken down into two modestly genetically correlated (rg = 0.38, s.e. = 0.07) autism polygenic factors. One of these factors is associated with earlier autism diagnosis and lower social and communication abilities in early childhood, but is only moderately genetically correlated with attention deficit–hyperactivity disorder (ADHD) and mental-health conditions. Conversely, the second factor is associated with later autism diagnosis and increased socioemotional and behavioural difficulties in adolescence, and has moderate to high positive genetic correlations with ADHD and mental-health conditions. These findings indicate that earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Our findings have important implications for how we conceptualize autism and provide a model to explain some of the diversity found in autism. A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Patients with post-traumatic stress disorder face increased cardiovascular risk. This study examines shared genetic regions between post-traumatic stress disorder and 246 cardiovascular conditions across electronic health records, 82 cardiac imaging, and health behaviors defined by Life’s Essential 8. Post-traumatic stress disorder is genetically correlated with cardiovascular diagnoses in 33 regions, imaging traits in 4 regions, and health behaviors in 44 regions. Potentially shared causal variants between post-traumatic stress disorder and 17 cardiovascular conditions were observed in 11 regions. Subsequent observational analysis in AllofUS cohort showed post-traumatic stress disorder is associated with 13 diagnoses even after accounting for socioeconomic factors and depression. Genetically regulated proteome expression in brain and blood tissues identified 33 blood and 122 brain genes shared between the two conditions, revealing neuronal, immune, metabolic, and calcium-related mechanisms, with several genes as targets for existing drugs. These findings exhibit shared risk loci and genes are involved in tissue-specific mechanisms. Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

DIALOG + is a low-cost intervention proven to improve the subjective quality of life in patients with psychosis and anxiety disorders in low- and middle-income countries. In a recent study, DIALOG + was shown to be feasible for patients in primary care settings with long-term physical conditions and to result in an improvement in patient outcomes. The aim of this qualitative study was to explore the experiences of patients and clinicians using DIALOG + in Bosnia and Herzegovina to gain a better understanding of its impact in this setting. In-depth semi-structured interviews were conducted with 11 patients and 4 physicians, as well as two focus groups with 5 patients in each, all of whom participated in the intervention. Specific life and treatment domains discussed during the sessions between patients and clinicians were also analysed to determine which domains were most frequently addressed and where patients needed the most support. The interviews were audio-recorded, transcribed, and analysed using thematic analysis. Four qualitative themes were identified: (1) DIALOG + structure and solution-oriented approach are helpful; (2) DIALOG + allows space for conversation; (3) Therapeutic relationship is improved, and (4) The intervention has its limitations. DIALOG + is a novel primary care intervention with positive effects on patients’ lives, which enhance primary care. Nevertheless, it presents a new challenge in this setting. It is necessary to make adjustments in primary care, such as providing clinicians with more extensive training and ongoing support, as well as providing more time for the intervention’s implementation. Study was registered prospectively within the ISRCTN Registry: ISRCTN17003451, 02/12/2020.

Introduction The management of long-term physical conditions is a challenge worldwide, absorbing a majority resources despite the importance of acute care. The management of these conditions is done largely in primary care and so interventions to improve primary care could have an enormous impact. However, very little data exist on how to do this. Mental distress is frequently comorbid with long term physical conditions, and can impact on health behaviour and adherence, leading to poorer outcomes. DIALOG+ is a low-cost, patient-centred and solution-focused intervention, which is used in routine patient-clinician meetings and has been shown to improve outcomes in mental health care. The question arises as to whether it could also be used in primary care to improve the quality of life and mental health of patients with long-term physical conditions. This is particularly important for low- and middle-income countries with limited health care resources. Methods An exploratory non-controlled multi-site trial was conducted in Bosnia and Herzegovina, Colombia, and Uganda. Feasibility was determined by recruitment, retention, and session completion. Patient outcomes (quality of life, anxiety and depression symptoms, objective social situation) were assessed at baseline and after three approximately monthly DIALOG+ sessions. Results A total of 117 patients were enrolled in the study, 25 in Bosnia and Herzegovina, 32 in Colombia, and 60 in Uganda. In each country, more than 75% of anticipated participants were recruited, with retention rates over 90% and completion of the intervention exceeding 92%. Patients had significantly higher quality of life and fewer anxiety and depression symptoms at post-intervention follow-up, with moderate to large effect sizes. There were no significant improvements in objective social situation. Conclusion The findings from this exploratory trial suggest that DIALOG+ is feasible in primary care settings for patients with long-term physical conditions and may substantially improve patient outcomes. Future research may test implementation and effectiveness of DIALOG+ in randomized controlled trials in wider primary care settings in low- and middle-income countries. Trial registration All studies were registered prospectively within the ISRCTN Registry. ISRCTN17003451, 02/12/2020 (Bosnia and Herzegovina), ISRCTN14018729, 01/12/2020 (Colombia) and ISRCTN50335796, 02/12/2020 (Uganda).

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.

Introduction Resource-oriented interventions can be a low-cost option to improve care for patients with severe mental illnesses in low-resource settings. From 2018 to 2021 we conducted three randomized controlled trials testing resource-oriented interventions in Bosnia and Herzegovina (B&H), i.e. befriending through volunteers, multi-family groups, and improving patient-clinician meetings using the DIALOG+ intervention. All interventions were applied over 6 months and showed significant benefits for patients’ quality of life, social functioning, and symptom levels. In this study, we explore whether patient experiences point to common processes in these interventions. Methods In-depth semi-structured interviews were conducted with 15 patients from each intervention, resulting in a total sample of 45 patients. Patients were purposively selected at the end of the interventions including patients with different levels of engagement and different outcomes. Interviews explored the experiences of patients and were audio-recorded, transcribed, and analysed using the thematic analysis framework proposed by Braun and Clark. Results Three broad themes captured the overall experiences of patients receiving resource-oriented interventions: An increased confidence and agency in the treatment process; A new and unexpected experience in treatment; Concerns about the sustainability of the interventions. Conclusions The findings suggest that the three interventions – although focusing on different relationships of the patients – lead to similar beneficial experiences. In addition to being novel in the context of the mental health care system in B&H, they empower patients to take a more active and confident role in treatment. Whilst strengthening patients’ agency in their treatment may be seen as a value in itself, it may also help to achieve significantly improved treatment outcomes. This shows promise for the implementation of these interventions in other low-resource countries with similar settings.

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.

The assessment of negative symptoms is crucial for development of adequate therapeutic interventions. This is a challenging task due to complex clinical presentation and lack of reliable and valid instruments. This study examined the psychometric characteristics of the Clinical Assessment Interview for Negative Symptoms (CAINS). The sample consisted of 81 persons with schizophrenia or schizoaffective disorder recruited from two health institutions in the Sarajevo Canton: the Clinical Center of the University of Sarajevo and the Psychiatric Hospital of the Sarajevo Canton. The 13 CAINS items grouped into four factors (expression, motivation and satisfaction in the recreational domain, motivation and satisfaction with social relationships, motivation and satisfaction with job and education). The four-factor solution accounted for 87.83% of the variance of manifest items. The reliabilities of extracted factors were as follows: for motivation and satisfaction with social relationships α = 0.897, for motivation and satisfaction with job and education α = 0.961, for Motivation and satisfaction in the recreation domain α = 0.981, and for expression α = 0.938. The highest correlation between factors was found between Motivation and satisfaction with recreation and Motivation and satisfaction with social relationships. On the other hand, the lowest correlation was found between motivation and satisfaction with social relations and motivation and satisfaction with job and education. In conclusion, the study showed that the latent structure of CAINS is adequate, clearly interpretable, and consisted of four factors. The measure can be used for assessment of the negative symptoms in outpatients with psychosis in Bosnia and Herzegovina.

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.

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.