| 1. |
- Roberson-Nay, Roxann, et al.
(författare)
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Longitudinal Stability of Genetic and Environmental Influences on Irritability : From Childhood to Young Adulthood
- 2015
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Ingår i: American Journal of Psychiatry. - Arlington, USA : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 172:7, s. 657-664
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Little is known about genetic influences on juvenile irritability and whether such influences are developmentally stable and/or dynamic. This study examined the temporal pattern of genetic and environmental effects on irritability using data from a prospective, four-wave longitudinal twin study.Method: Parents and their twin children (N=2,620 children) from the Swedish Twin Study of Child and Adolescent Development reported on the children's irritability, defined using a previously identified scale from the Child Behavior Checklist.Results: Genetic effects differed across the sexes, with males exhibiting increasing heritability from early childhood through young adulthood and females exhibiting decreasing heritability. Genetic innovation was also more prominent in males than in females, with new genetic risk factors affecting irritability in early and late adolescence for males. Shared environment was not a primary influence on irritability for males or females. Unique, nonshared environmental factors suggested strong effects early for males followed by an attenuating influence, whereas unique environmental factors were relatively stable for females.Conclusions: Genetic effects on irritability are developmentally dynamic from middle childhood through young adulthood, with males and females displaying differing patterns. As males age, genetic influences on irritability increase while nonshared environmental influences weaken. Genetic contributions are quite strong in females early in life but decline in importance with age. In girls, nonshared environmental influences are fairly stable throughout development.
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| 2. |
- Viktorin, Alexander, et al.
(författare)
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Heritability of perinatal depression and genetic overlap with nonperinatal depression
- 2016
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Ingår i: The American Journal of Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0002-953X .- 1535-7228.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The authors investigated the relative importance of genetic and environmental influences on perinatal depression, and the genetic overlap between perinatal depression and nonperinatal depression. METHOD: Analyses were conducted using structural equation modeling for 1) the lifetime version of the Edinburgh Postnatal Depression Scale in 3,427 Swedish female twins and 2) clinical diagnoses of depression separated into perinatal depression and nonperinatal depression in a Swedish population-based cohort of 580,006 sisters. RESULTS: In the twin study, the heritability of perinatal depression was estimated at 54% (95% CI=35%-70%), with the remaining variance attributable to nonshared environment (46%; 95% CI=31%-65%). In the sibling design, the heritability of perinatal depression was estimated at 44% (95% CI=35%-52%) and the heritability of nonperinatal depression at 32% (95% CI=24%-41%). Bivariate analysis showed that 14% of the total variance (or 33% of the genetic variance) in perinatal depression was unique for perinatal depression. CONCLUSIONS: The heritability of perinatal depression was estimated at 54% and 44%, respectively, in separate samples, and the heritability of nonperinatal depression at 32%. One-third of the genetic contribution was unique to perinatal depression and not shared with nonperinatal depression, suggesting only partially overlapping genetic etiologies for perinatal depression and nonperinatal depression. The authors suggest that perinatal depression constitutes a subset of depression that could be prioritized for genomic discovery efforts. The study findings have direct translational impact that can assist clinicians in the counseling of their patients regarding risk and prognosis of perinatal depression.
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| 3. |
- Viktorin, Alexander, et al.
(författare)
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The risk of switch to mania in patients with bipolar disorder during treatment with antidepressants alone and in combination with a mood stabilizer
- 2014
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Ingår i: The American Journal of Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0002-9556 .- 0002-953X .- 1535-7228.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study examined the risk of antidepressant-induced manic switch in patients with bipolar disorder treated either with antidepressant monotherapy or with an antidepressant in conjunction with a mood stabilizer. Method: Using Swedish national registries, the authors identified 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year. Patients were categorized into those receiving antidepressant monotherapy and those receiving an antidepressant plus a mood stabilizer. A within-individual design was used to control for confounding by disorder severity, genetic makeup, and early environmental factors. Cox regression analyses conditioned on individual were used to compare the rate of mania 0–3 months and 3–9 months after the start of antidepressant treatment with a preceding non-treatment period. Results: Nearly 35% of the patients were treated with antidepressant monotherapy. The increased risk of treatment-emergent mania was confined to patients on antidepressant monotherapy (hazard ratio=2.83, 95% CI=1.12, 7.19). Among patients treated with a concurrent mood stabilizer, no acute change in risk of mania was observed during the 3 months after the start of antidepressant treatment (hazard ratio=0.79, 95% CI=0.54, 1.15), and a decreased risk was observed during the period 3–9 months after treatment initiation (hazard ratio=0.63, 95% CI=0.42, 0.93). Conclusions: In this national registry study, antidepressant monotherapy was associated with an increased risk of mania. However, no risk of mania was seen in patients receiving an antidepressant while treated with a mood stabilizer. The results highlight the importance of avoiding antidepressant monotherapy in the treatment of bipolar disorder.
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| 4. |
- 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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| 5. |
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| 6. |
- Mahjani, Behrang, et al.
(författare)
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The Genetic Architecture of Obsessive-Compulsive Disorder: Contribution of Liability to OCD From Alleles Across the Frequency Spectrum.
- 2022
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 179:3
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Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder (OCD) is known to be substantially heritable; however, the contribution of genetic variation across the allele frequency spectrum to this heritability remains uncertain. The authors used two new homogeneous cohorts to estimate the heritability of OCD from inherited genetic variation and contrasted the results with those of previous studies.The sample consisted of 2,090 Swedish-born individuals diagnosed with OCD and 4,567 control subjects, all genotyped for common genetic variants, specifically >400,000 single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥0.01. Using genotypes of these SNPs to estimate distant familial relationships among individuals, the authors estimated the heritability of OCD, both overall and partitioned according to MAF bins.Narrow-sense heritability of OCD was estimated at 29% (SE=4%). The estimate was robust, varying only modestly under different models. Contrary to an earlier study, however, SNPs with MAF between 0.01 and 0.05 accounted for 10% of heritability, and estimated heritability per MAF bin roughly followed expectations based on a simple model for SNP-based heritability.These results indicate that common inherited risk variation (MAF ≥0.01) accounts for most of the heritable variation in OCD. SNPs with low MAF contribute meaningfully to the heritability of OCD, and the results are consistent with expectation under the "infinitesimal model" (also referred to as the "polygenic model"), where risk is influenced by a large number of loci across the genome and across MAF bins.
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| 7. |
- Sigström, Robert, 1982, et al.
(författare)
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Association Between Polygenic Risk Scores and Outcome of ECT
- 2022
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 179:11, s. 844-852
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Tidskriftsartikel (refereegranskat)abstract
- Identifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode.Between 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping. The present study included 2,320 participants (median age, 51 years; 62.8% women) who had received an ECT series for a major depressive episode (77.1% unipolar depression), who had a registered treatment outcome, and whose polygenic risk scores (PRSs) could be calculated. Ordinal logistic regression was used to estimate the effect of PRS on Clinical Global Impressions improvement scale (CGI-I) score after each ECT series.Greater PRS for major depressive disorder was significantly associated with less improvement on the CGI-I (odds ratio per standard deviation, 0.89, 95% CI=0.82, 0.96; R2=0.004), and greater PRS for bipolar disorder was associated with greater improvement on the CGI-I (odds ratio per standard deviation, 1.14, 95% CI=1.05, 1.23; R2=0.005) after ECT. PRS for schizophrenia was not associated with improvement. In an overlapping sample (N=1,207) with data on response and remission derived from the self-rated version of the Montgomery-Åsberg Depression Rating Scale, results were similar except that schizophrenia PRS was also associated with remission.Improvement after ECT is associated with polygenic liability for major depressive disorder and bipolar disorder, providing evidence of a genetic component for ECT clinical response. These liabilities may be considered along with clinical predictors in future prediction models of ECT outcomes.
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| 8. |
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| 9. |
- 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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| 10. |
- 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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