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.

Introduction Posttraumatic stress disorder in the paediatric population has clinical features. The Clinician-Administered PTSD Scale for DSM-5,child and adolescent version (CAPS-CA-5) is the gold standard for the positive diagnosis. Objectives The objectives of our work were to translate the CAPS-CA-5 into Tunisian dialectal Arabic and to validate it in our Tunisian sociocultural context. Methods This is a descriptive cross-sectional study conducted in the child psychiatry department of Mongi Slim Hospital and the forensic medicine department of Charles-Nicolle Hospital (Tunisia), among children older than seven years who were exposed to a potentially traumatic event at least one month before. We validated the tool through translation, content, construct validity and reliability. The statistical processing for this data was carried out using SPSS 26 software. Results We conducted our study with 150 patients. The validation was made on 146 records after the exclusion of 4 incompleted assessments. We initially translated the CAPS-CA-5 into Tunisian dialect. We validated the content through pre-test and scientific committee evaluation. Afterwards, we validated the construction. We calculated the Bartlett’s sphericity test (p<0.001) .The KMO index that was 0.766. Concerning the reliability study, we found a Cronbach’s alpha coefficient equal to 0.92. We studied also the inter-raters reliability; we found an intra-class coefficient between 0.8 and 1 Conclusions We validated the first Tunisian diagnostic tool for PTSD in children according to the DSM-5 criteria with satisfactory psychometric qualities. Disclosure of Interest None Declared

Background: Globally, life expectancy is increasing, leading to an equal proportion of elderly and young individuals, which carries extensive implications. In Bosnia and Herzegovina (BiH), the average age at death in 2021 was 77 years, positioning BiH in the middle of the global list of average life expectancy. Current studiesinvestigate whether the prevalence of psychiatric disorders increases or decreases with age, but results are inconsistent regarding the role of age.There is no prior research on mental disorders in the elderly population in BiH. The experience of the previous war in BiH and the post-war complex “transitional period” have been associated with specific challenges to the mental health of this population, inspiring our research topic. Objective: The aim of this study was to investigate the psychiatric morbidity in hospitalized individuals aged≥55 years. Methods: The sample consisted of all patients over age 55 treated at the Department of Psychiatry in Tuzla between January 2018 and December 2020 (N=637), divided into four age categories. Data were obtained from medical records, and for research purposes, a specific questionnaire was constructed. Results: The predominant psychiatric morbidity stemmed from the category of affective disorders, most common within the “55-64 years” age group, while organic mental disorders were more prevalent in other age groups.Substance use disorders were present in patients aged “55-64 years”, with a sharp decline in their prevalence in older age. Female participants had a significantly higher prevalence of affective, psychotic, neurotic, and stress-related disorders, whereas male participants exhibited an increased prevalence of organic mental and substance use disorders. Conclusion: In total sample, the most prevalent diagnoses belong to the category of affective disorders. Female were most frequently diagnosed with affective disorders, whereas organic mental disorders and substance use disorders prevail in male.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10−8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship. METHODS Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (rg) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons). RESULTS ADHD and PTSD had consistent rg (rg range, 0.43-0.52; p <  .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186-0.552; p = 7.68 × 10-5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10-4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98-3.53). CONCLUSIONS Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.