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- Edwards, Alexis C., et al.
(author)
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Alcohol Use Disorder and Risk of Suicide in a Swedish Population-Based Cohort
- 2020
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In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 177:7, s. 627-634
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The authors examined the association between alcohol use disorder (AUD) and risk of suicide, before and after accounting for psychiatric comorbidity, and assessed the extent to which the observed association is due to a potentially causal mechanism or genetic and familial environmental confounding factors that increase risk for both. METHODS: Longitudinal population-wide Swedish medical, criminal, and pharmacy registries were used to evaluate the risk of death by suicide as a function of AUD history. Analyses employed prospective cohort and co-relative designs, including data on 2,229,880 native Swedes born between 1950 and 1970 and observed from age 15 until 2012. RESULTS: The lifetime rate of suicide during the observation period was 3.54% for women and 3.94% for men with AUD, compared with 0.29% and 0.76% of women and men, respectively, without AUD. In adjusted analyses, AUD remained robustly associated with suicide: hazard ratios across observation periods ranged from 2.61 to 128.0 among women and from 2.44 to 28.0 among men. Co-relative analyses indicated that familial confounding accounted for some, but not all, of the observed association. A substantial and potentially causal relationship remained after accounting for a history of other psychiatric diagnoses. CONCLUSIONS: AUD is a potent risk factor for suicide, with a substantial association persisting after accounting for confounding factors. These findings underscore the impact of AUD on suicide risk, even in the context of other mental illness, and implicate the time frame shortly after a medical or criminal AUD registration as critical for efforts to reduce alcohol-related suicide.
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2. |
- Kendler, Kenneth S., et al.
(author)
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An Extended Swedish Adoption Study of Anxiety Disorder and Its Cross-Generational Familial Relationship With Major Depression
- 2022
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In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 179:9, s. 640-649
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To clarify, using an extended adoption design, the sources of parent-offspring transmission for anxiety disorder (AD) and its major subforms and their familial cross-generational relationship with major depression (MD). METHODS: Offspring (born 1960-1992) and their parents, from six family types (intact, not-lived-with biological father or mother, lived-with step-father or step-mother, and adoptive), were ascertained from Swedish national samples. Diagnoses were obtained from national medical registers. We assessed three sources of parent-child resemblance: genes plus rearing, genes only, and rearing only. To test comorbidity effects, single diagnoses were assigned in comorbid cases based on frequency and recency. RESULTS: For AD to AD parent-child transmission, best-estimate tetrachoric correlations for the three types of parent-offspring relationships genes plus rearing, genes only, and rearing only-equaled +0.16 (95% CI=0.16, 0.16), +0.12 (95% CI=0.10, 0.13), and +0.06 (95% CI=0.04, 0.07), respectively, with broadly similar results for MD to MD transmission. Cross-disorder cross-generation correlations were modestly lower, with genetic and rearing correlations for AD and MD estimated at +0.83 (95% CI=0.76, 0.90) and +0.83 (95% CI=0.69, 0.96), respectively. Analyses for panic disorder and generalized anxiety disorder (GAD) produced comparable findings, with the genetic correlation with MD modestly higher for generalized anxiety disorder than panic disorder. Applying a diagnostic hierarchy to comorbid cases resulted in a decline in cross-disorder cross-generation transmission with the estimated genetic correlation equaling +0.46 (95% CI=0.30, 0.62). CONCLUSIONS AND RELEVANCE: For AD and its major subforms, cross-generational transmission includes both genetic and rearing effects. In traditional analyses, AD and MD demonstrate highly correlated genetic and rearing effects. The genetic correlation weakened when applying a diagnostic hierarchy.
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3. |
- Kendler, Kenneth S., et al.
(author)
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Pattern of Risks for Psychiatric and Substance Use Disorders in the Offspring of Parents With Alcohol Use Disorder
- 2024
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In: The American journal of psychiatry. - 1535-7228. ; 181:4, s. 322-329
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The authors sought to clarify the components of the familial liability to alcohol use disorder (AUD) by examining parent-offspring transmission in a large Swedish population sample. METHODS: To this end, 1,244,516 offspring in intact families with a mean age at follow-up of 37.7 years (SD=6.8) were examined. Hazard ratios for offspring of parents with AUD were calculated using Cox models for risk of five disorders assessed from Swedish medical and criminal registries: AUD, drug use disorders, attention deficit hyperactivity disorder, major depression, and anxiety disorders. RESULTS: The hazard ratio for the offspring was highest for AUD (hazard ratio=2.36), followed by drug use disorder (hazard ratio=2.04), attention deficit hyperactivity disorder (hazard ratio=1.82), major depression (hazard ratio=1.43), and anxiety disorder (hazard ratio=1.43). The risks for AUD were statistically indistinguishable between the children having mothers with AUD compared with those having fathers with AUD and between sons and daughters of a parent with AUD. All risks for offspring having two parents with AUD were higher than those having one parent with AUD, but the increase with two parents with AUD was greatest for AUD, followed by drug use disorder and attention deficit hyperactivity disorder. Age at AUD onset of the parents predicted risk among the offspring more strongly for AUD and drug use disorder, followed by attention deficit hyperactivity disorder, and then major depression and anxiety disorders. Number of recurrences of the parents with AUD predicted risks for all disorders equally. The risk pattern of disorders for the offspring of not-lived-with fathers with AUD was similar to that in the main analysis of intact families. No evidence was found for sex-specific transmission of AUD or a familial female protective effect. CONCLUSIONS: Familial and likely genetic liability to AUD has three components: a nonspecific risk of common internalizing and externalizing disorders, a moderately specific risk of externalizing disorders, and a highly specific risk of AUD.
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4. |
- Kendler, Kenneth S., et al.
(author)
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The Rearing Environment and Risk for Major Depression : A Swedish National High-Risk Home-Reared and Adopted-Away Co-Sibling Control Study
- 2020
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In: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 177:5, s. 447-453
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Journal article (peer-reviewed)abstract
- Objective: The authors sought to clarify the role of rearing environment in the etiology of major depression. Methods: Defining high risk as having at least one biological parent with major depression, the authors identified a Swedish National Sample of 666 high-risk full sibships and 2,596 high-risk half sibships containing at least one homereared and one adopted-away sibling. Major depression was assessed from national medical registries. Results: Controlling for sex, parental age at birth, and, for half siblings, history of major depression in the nonshared parent, the risk for major depression in the matched adopted compared with home-reared full and half siblings was reduced by 23% (95% CI=7-36) and by 19% (95% CI=10-38), respectively. This protective rearing effect was not influenced by the relative educational status of the biological and adoptive parents. However, in both full and half sibships, the protective effect of adoption disappeared when an adoptive parent or stepsibling had major depression or the adoptive home was disrupted by parental death or divorce. Conclusions: In matched full and half sibships at high risk for major depression, compared with individuals raised in their home environment, those reared in adoptive homes (homes selected in Sweden for their high-quality rearing environment) had a significantly reduced risk for major depression. This protective effect disappeared if an adoptive parent had major depression or if the adoptive home experienced parental death or divorce during childhood/adolescence. The rearing environment has a meaningful impact on risk for major depression, and this effect is likely mediated both by parental depression and the continuity or disruption of the home environment.
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5. |
- Kendler, Kenneth S., et al.
(author)
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The sources of parent-child transmission of risk for suicide attempt and deaths by suicide in swedish national samples
- 2020
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In: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 177:10, s. 928-935
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Journal article (peer-reviewed)abstract
- Objective: The authors aimed to clarify the sources of parent-child transmission for suicide attempt and death by suicide. Methods: Three sources of parent-child resemblance (genes plus rearing, genes only, and rearing only) were examined in parents and offspring from four family types from Swedish national samples: intact nuclear families, families with a not-lived-with biological father, families with a stepfather, and adoptees and their biological and adoptive parents. Parent-child resemblance was assessed primarily by tetrachoric correlation. Results: For suicide attempt to suicide attempt transmission, best-estimate tetrachoric correlations for genes plus rearing, genes only, and rearing only were 0.23 (95% CI=0.23, 0.24), 0.13 (95% CI=0.11, 0.15), and 0.14 (95% CI=0.11, 0.16), respectively. Suicide attempt was more strongly transmitted to male offspring compared with female offspring. Parental psychiatric disorders accounted for 40% of the genetic transmission but had no impact on rearing effects. For suicide death to suicide death transmission, best estimates of tetrachoric correlations for genes plus rearing, genes only, and rearing only were 0.16 (95% CI=0.15, 0.18), 0.07 (95% CI=0.02, 0.12), and 20.05 (95% CI=20.17, 0.07), respectively. Although the suicide attempt-suicide death genetic correlation was high (0.84), the hypothesis that they reflect behaviors only differing in severity on the same continuum of genetic liability could be rejected. Conclusions: The transmission of suicide attempt across generations is moderately strong and arises equally from genetic and rearing effects. Parental psychiatric illness explains almost half of the genetic transmission of suicide attempt but none of the rearing effect. Suicide death is modestly transmitted across generations, probably via genetic effects, although rearing may play a role. While suicide attempt and suicide death share a substantial proportion of their hereditary risk, they do not, from a genetic perspective, simply reflect milder and more severe forms of the same diathesis.
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