| 41. |
- Di Prinzio, Patsy, et al.
(författare)
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Intellectual disability and psychotic disorders in children : Association with maternal severe mental illness and exposure to obstetric complications in a whole-population cohort
- 2018
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 175:12, s. 1232-1242
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Children of mothers with severe mental illness are at significantly increased risk of developing intellectual disability. Obstetric complications are also implicated in the risk for intellectual disability. Moreover, children of mothers with severe mental illness are more likely to be exposed to obstetric complications. The purpose of this study was to examine the independent and joint contributions of familial severe mental illness and obstetric complications to the risk of intellectual disability. Method: Record linkage across Western Australian whole-population psychiatric, inpatient, birth, and midwives' registers identified 15,351 children born between 1980 and 2001 to mothers with severe mental illness and 449,229 children born to mothers with no mental illness. Multivariable models were adjusted for paternal psychiatric status, parental intellectual disability, and other family and sociodemographic covariates. Results: The risk of intellectual disability was increased among children of mothers with severe mental illness compared with children of unaffected mothers. The impact varied across maternal diagnostic groups. For children of mothers with schizophrenia, the unadjusted odds ratio was 3.8 (95% CI=3.0, 4.9) and remained significant after simultaneous adjustment for exposure to obstetric complications and other covariates (odds ratio=1.7, 95% CI=1.3, 2.3). The odds ratio for exposure to obstetric complications also remained significant after adjustment (odds ratio=1.7, 95% CI=1.6, 1.8). For intellectual disability of a genetic basis, the adjusted odds ratio for maternal schizophrenia was elevated but not statistically significant. Among children with intellectual disability, 4.2% later developed a psychotic disorder, compared with 1.1% of children without intellectual disability. Conclusions: Maternal severe mental illness and exposure to obstetric complications contribute separately to the risk of intellectual disability, suggesting potentially different causal pathways.
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| 42. |
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| 43. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 44. |
- Dong, Li, et al.
(författare)
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Effects of the Circadian Rhythm Gene Period 1 (Per1) on Psychosocial Stress-Induced Alcohol Drinking
- 2011
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 168:10, s. 1090-1098
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Circadian and stress-response systems mediate environmental changes that affect alcohol drinking. Psychosocial stress is an environmental risk factor for alcohol abuse. Circadian rhythm gene period 1(Per1) is targeted by stress hormones and is transcriptionally activated in corticotropin releasing factor-expressing cells. The authors hypothesized that Per1 is involved in integrating stress response and circadian rhythmicity and explored its relevance to alcohol drinking. Method: In mice, the effects of stress on ethanol intake in mPer1-mutant and wild-type mice were assessed. In humans, single nucleotide polymorphisms (SNPs) in hPer1 were tested for association with alcohol drinking behavior in 273 adolescents and an adult case-control sample of 1,006 alcohol-dependent patients and 1,178 comparison subjects. In vitro experiments were conducted to measure genotype-specific expression and transcription factor binding to hPer1. Results: The mPer1-mutant mice showed enhanced alcohol consumption in response to social defeat stress relative to their wild-type littermates. An association with the frequency of heavy drinking in adolescents with the hPer1 promoter SNP rs3027172 and with psychosocial adversity was found. There was significant interaction between the rs3027172 genotype and psychosocial adversity on this drinking measure. In a confirmatory analysis, association of hPer1 rs3027172 with alcohol dependence was shown. Cortisol-induced transcriptional activation of hPer1 was reduced in human B-lymphoblastoid cells carrying the risk genotype of rs3027172. Binding affinity of the transcription factor Snail1 to the risk allele of the hPer1 SNP rs3027172 was also reduced. Conclusions: The findings indicate that the hPer1 gene regulates alcohol drinking behavior during stressful conditions and provide evidence for underlying neurobiological mechanisms.
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| 45. |
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| 46. |
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| 47. |
- Edwards, Alexis C., et al.
(författare)
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Alcohol Use Disorder and Risk of Suicide in a Swedish Population-Based Cohort
- 2020
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 177:7, s. 627-634
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Tidskriftsartikel (refereegranskat)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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| 48. |
- Edwards, Alexis C., et al.
(författare)
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Protective Effects of Pregnancy on Risk of Alcohol Use Disorder
- 2019
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 176:2, s. 138-145
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: The authors sought to clarify the etiology of the association between pregnancy and reduced risk of alcohol use disorder. METHODS:: The authors used data from longitudinal population-wide Swedish medical, pharmacy, and criminal registries to evaluate whether rates of alcohol use disorder are lower during pregnancy. They compared pregnant women born between 1975 and 1992 (N=322,029) with matched population controls, with female relatives discordant for pregnancy, and with pre- and postpregnancy periods within individuals. They further compared rates of alcohol use disorder between pregnant women and their partners. RESULTS:: Pregnancy was inversely associated with alcohol use disorder across all analyses (odds ratios, 0.17-0.32). In co-relative analyses, the strength of the association increased among more closely related individuals. Within individuals, rates of alcohol use disorder were substantially decreased during pregnancy relative to the prepregnancy period (odds ratios, 0.25-0.26), and they remained reduced during postpartum periods (odds ratios, 0.23-0.31). Results were similar for second pregnancies (odds ratio, 0.23). The partners of pregnant women also exhibited reductions in alcohol use disorder (odds ratio, 0.45). Among women who became pregnant at earlier ages and those with a history of criminal behavior, the negative association between pregnancy and alcohol use disorder was especially pronounced, but no moderation was observed for a personal or maternal parental history of alcohol use disorder. CONCLUSIONS:: The findings suggest that pregnancy plays a critical, and likely causal, motivational role in reducing alcohol use disorder risk among women and, to a lesser extent, their partners. These results extend our understanding of the relationship between pregnancy and alcohol use, demonstrating that even a severe condition such as alcohol use disorder is subject to the protective effects of pregnancy.
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