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  • 1
    In: Australian & New Zealand Journal of Psychiatry, SAGE Publications, Vol. 56, No. 9 ( 2022-09), p. 1177-1186
    Kurzfassung: Chronic pain and depression are highly comorbid and difficult-to-treat disorders. We previously showed this comorbidity is associated with higher depression severity, lower antidepressant treatment effectiveness and poorer prognosis in the Australian Genetics of Depression Study. Objective: The current study aimed to assess whether a genetic liability to chronic pain is associated with antidepressant effectiveness over and above the effect of genetic factors for depression in a sample of 12,863 Australian Genetics of Depression Study participants. Methods: Polygenic risk scores were calculated using summary statistics from genome-wide association studies of multisite chronic pain and major depression. Cumulative linked regressions were employed to assess the association between polygenic risk scores and antidepressant treatment effectiveness across 10 different medications. Results: Mixed-effects logistic regressions showed that individual genetic propensity for chronic pain, but not major depression, was significantly associated with patient-reported chronic pain (Pain PRS OR = 1.17 [1.12, 1.22]; MD PRS OR = 1.01 [0.98, 1.06]). Significant associations were also found between lower antidepressant effectiveness and genetic risk for chronic pain or for major depression. However, a fully adjusted model showed the effect of Pain PRS (adjOR = 0.93 [0.90, 0.96]) was independent of MD PRS (adjOR = 0.96 [0.93, 0.99]). Sensitivity analyses were performed to assess the robustness of these results. After adjusting for depression severity measures (i.e. age of onset; number of depressive episodes; interval between age at study participation and at depression onset), the associations between Pain PRS and patient-reported chronic pain with lower antidepressant effectiveness remained significant (0.95 [0.92, 0.98] and 0.84 [0.78, 0.90] , respectively). Conclusion: These results suggest genetic risk for chronic pain accounted for poorer antidepressant effectiveness, independent of the genetic risk for major depression. Our results, along with independent converging evidence from other studies, point towards a difficult-to-treat depression subtype characterised by comorbid chronic pain. This finding warrants further investigation into the implications for biologically based nosology frameworks in pain medicine and psychiatry.
    Materialart: Online-Ressource
    ISSN: 0004-8674 , 1440-1614
    Sprache: Englisch
    Verlag: SAGE Publications
    Publikationsdatum: 2022
    ZDB Id: 2003849-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Australian & New Zealand Journal of Psychiatry, SAGE Publications, Vol. 57, No. 3 ( 2023-03), p. 423-431
    Kurzfassung: Each year, around one million people die by suicide. Despite its recognition as a public health concern, large-scale research on causal determinants of suicide attempt risk is scarce. Here, we leverage results from a recent genome-wide association study (GWAS) of suicide attempt to perform a data-driven screening of traits causally associated with suicide attempt. Methods: We performed a hypothesis-generating phenome-wide screening of causal relationships between suicide attempt risk and 1520 traits, which have been systematically aggregated on the Complex-Traits Genomics Virtual Lab platform. We employed the latent causal variable (LCV) method, which uses results from GWAS to assess whether a causal relationship can explain a genetic correlation between two traits. If a trait causally influences another one, the genetic variants that increase risk for the causal trait will also increase the risk for the outcome inducing a genetic correlation. Nonetheless, a genetic correlation can also be observed when traits share common pathways. The LCV method can assess whether the pattern of genetic effects for two genetically correlated traits support a causal association rather than a shared aetiology. Results: Our approach identified 62 traits that increased risk for suicide attempt. Risk factors identified can be broadly classified into (1) physical health disorders, including oesophagitis, fibromyalgia, hernia and cancer; (2) mental health-related traits, such as depression, substance use disorders and anxiety; and (3) lifestyle traits including being involved in combat or exposure to a war zone, and specific job categories such as being a truck driver or machine operator. Conclusions: Suicide attempt risk is likely explained by a combination of behavioural phenotypes and risk for both physical and psychiatric disorders. Our results also suggest that substance use behaviours and pain-related conditions are associated with an increased suicide attempt risk, elucidating important causal mechanisms that underpin this significant public health problem.
    Materialart: Online-Ressource
    ISSN: 0004-8674 , 1440-1614
    Sprache: Englisch
    Verlag: SAGE Publications
    Publikationsdatum: 2023
    ZDB Id: 2003849-5
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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