Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Understading of the suicidal behaviour: an idiographic approach through the interpretative phenomenological analysis

Suicidal behaviors are a puzzling phenomenon that over time concerns the scientific community.Their multifactorial nature makes their study complex and often the interpretations interfere with each other. Suicide attempts, as a manifestation of suicidal behaviors, appear to differ greatly from other suicidal behaviors. Studies so far have focused mainly on quantitative characteristics, which, looking for causes and predisposing factors, disregarded the dynamics of the uniqueness of each individual attempting self-destruction.The aim of the current study is to investigate, through semi-structured interviews, the understanding of recent suicide attempts by the participants. Through the interpretative phenomenological analysis approach, participants attempted to share their experience by highlighting the data they considered important.The results highlighted three core themes that appeared to have been consistent with the stories told by the participants: there were key gaps in their interaction with their environment, inability to self-sustain, and the above gradually created the desire for death, which was spontaneous and sometimes deliberate. The three themes were divided intosub-themes, which facilitated a holistic study of the interviews. The dominant factor that seems to have been decisive for each participant’s action was the temporary lack of understanding of his life.Intervention at the level of prevention seems to be a hindrance to suicidal behaviors, as early recognition of precursors leading to suicide may reduce impulsive self-destructive actions.Οι αυτοκτονικές συμπεριφορές αποτελούν ένα αινιγματικό φαινόμενο το οποίο διαχρονικά απασχολεί την επιστημονική κοινότητα. Η πολυπαραγοντική φύση τους καθιστά σύνθετη τη μελέτη τους και συχνά οι εκάστοτε ερμηνείες αλληλοσυγκρούονται. Οι απόπειρες αυτοκτονίας, ως μια έκφανση των αυτοκτονικών συμπεριφορών φαίνεται να διαφέρουν σε σημαντικό βαθμό σε σχέση με τις υπόλοιπες αυτοκτονικές συμπεριφορές. Οι έως τώρα μελέτες έδιναν έμφαση κυρίως σε ποσοτικά χαρακτηριστικά, τα οποία, αναζητώντας αιτίες και προδιαθεσικούς παράγοντες, παραγνώριζαν τη δυναμική της μοναδικότητας του κάθε ατόμου που προβαίνει σε απόπειρα αυτοκαταστροφής. Στόχος της παρούσας μελέτης είναι η διερεύνηση, μέσα από ημιδομημένες συνεντεύξεις, της νοηματοδότησης των πρόσφατων αποπειρών αυτοκτονίας στις οποίες προέβησαν οι συμμετέχοντες. Μέσα από την ιδιογραφική φαινομενολογική προσέγγιση, επιχειρήθηκε να μοιραστούν οι συμμετέχοντες την εμπειρία τους αναδεικνύοντας οι ίδιοι τα στοιχεία που έκριναν ως σημαντικά. Τα αποτελέσματα ανέδειξαν τρεις βασικούς τομείς οι οποίοι φαίνεται να είχαν συνοχή στις ιστορίες που αφηγούνταν οι συμμετέχοντες: υπήρχαν βασικά κενά στην αλληλεπίδραση με το περιβάλλον τους, αδυναμία αυτοσυντήρησης και τα παραπάνω δημιουργούσαν σταδιακά την επιθυμία του θανάτου, η οποία εκδηλωνόταν άλλοτε αυθόρμητα και άλλοτε προμελετημένα. Οι τρεις τομείς διαιρέθηκαν σε υποθέματα, τα οποία διευκόλυναν μια ολιστική μελέτη των συνεντεύξεων. Ο κυρίαρχος παράγοντας που φαίνεται να υπήρξε καθοριστικός σε κάθε συμμετέχοντα ήταν η πρόσκαιρη έλλειψη νοηματοδότησης της ζωής του. Η παρέμβαση σε επίπεδο πρόληψης φαίνεται ότι μπορεί να αποτελέσει τροχοπέδη για τις αυτοκτονικές συμπεριφορές, καθώς η έγκαιρη αναγνώριση των πρόδρομων σημείων που οδηγούν στην αυτοκτονικότητα ενδεχομένως θα μειώσει τις παρορμητικές αυτοκαταστροφικές πράξεις

Alexithymia, anxiety and depression in patients with psoriasis: a case-control study

Background: Alexithymia, the difficulty in describing or recognizing emotions, has been associated with various psychosomatic pathologies including psoriasis. The aim of this study was to examine the prevalence of alexithymia and its association with anxiety and depression in patients with psoriasis compared with healthy participants, while taking into consideration demographic and clinical variables. Methods: One hundred and eight psoriatic patients and 100 healthy participants from the general population completed the Toronto Alexithymia Scale (TAS-20) and the Hospital Anxiety and Depression Scale (HADS). The severity of patients’ psoriasis was clinically assessed using the Psoriasis Area and Severity Index (PASI). Results: Psoriatic patients had higher levels of alexithymia compared with healthy participants. While a rather high rate of psoriatic patients presented anxiety and depression as defined by the HADS, the differences that were found in comparison with the control group were not significant. Neither alexithymia nor its dimensions, difficulty in identifying feelings (DIF), difficulty in describing feelings (DDF) and externally oriented thinking (EOT), were associated with gender or psoriasis severity. Age was associated only with EOT, which was independent of depression and anxiety. Higher anxiety and depression were connected with higher alexithymia and DIF, while higher anxiety with higher DDF as well. Conclusions: The alexithymia prevalence was higher in psoriatic patients than that in healthy participants, while it was positively correlated with anxiety and depression. Difficulty in identifying feelings was connected with both anxiety and depression, whereas difficulty in describing them was only with anxiety. Finally, externally oriented thinking was predicted only from age

Fine-mapping genomic loci refines bipolar disorder risk genes

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI)

Genome-wide association study of over 40,000 bipolar disorder cases provides novel biological insights

Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating eQTL data implicated 15 genes robustly linked to BD via gene expression, including druggable genes such as HTR6, MCHR1, DCLK3 and FURIN. This GWAS provides the best-powered BD polygenic scores to date, when applied in both European and diverse ancestry samples. Analyses of BD subtypes indicated high but imperfect genetic correlation between BD type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads and prioritize genes for functional follow-up studies