| 1. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- 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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| 3. |
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| 4. |
- Watson, Hunna J., et al.
(författare)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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| 5. |
- Hussain, Alia A., et al.
(författare)
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Increased lipid and lipoprotein concentrations in anorexia nervosa : A systematic review and meta-analysis
- 2019
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Ingår i: International Journal of Eating Disorders. - : John Wiley & Sons. - 0276-3478 .- 1098-108X. ; 52:6, s. 611-629
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Forskningsöversikt (refereegranskat)abstract
- Objective: Alterations in blood lipid concentrations in anorexia nervosa (AN) have been reported; however, the extent, mechanism, and normalization with weight restoration remain unknown. We conducted a systematic review and a meta-analysis to evaluate changes in lipid concentrations in acutely-ill AN patients compared with healthy controls (HC) and to examine the effect of partial weight restoration.Method: A systematic literature review and meta-analysis (PROSPERO: CRD42017078014) were conducted for original peer-reviewed articles.Results: Forty-eight studies were eligible for review; 33 for meta-analyses calculating mean differences (MD). Total cholesterol (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), high-density lipoprotein (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), low-density lipoprotein (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglycerides (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), and apolipoprotein B (Apo B; MD = 11.8 mg/dL, CI = 2.3, 21.2) were significantly higher in acutely-ill AN than HC. Partially weight-restored AN patients had higher total cholesterol (MD = 14.8 mg/dL, CI = 2.1, 27.5) and LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Pre- versus post-weight restoration differences in lipid concentrations did not differ significantly.Discussion: We report aggregate evidence for elevated lipid concentrations in acutely-ill AN patients compared with HC, some of which persist after partial weight restoration. This could signal an underlying adaptation or dysregulation not fully reversed by weight restoration. Although concentrations differed between AN and HC, most lipid concentrations remained within the reference range and meta-analyses were limited by the number of available studies.
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| 6. |
- Mustelin, L., et al.
(författare)
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Risk of eating disorders in immigrant populations
- 2017
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Ingår i: Acta Psychiatrica Scandinavica. - Stockholm : Wiley. - 0001-690X .- 1600-0447. ; 136:2, s. 156-165
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The risk of certain psychiatric disorders is elevated among immigrants. To date, no population studies on immigrant health have addressed eating disorders. We examined whether risk of eating disorders in first- and second-generation immigrants differs from native-born Danes and Swedes. Method: All individuals born 1984–2002 (Danish cohort) and 1989–1999 (Swedish cohort) and residing in the respective country on their 10th birthday were included. They were followed up for the development of eating disorders based on out-patient and in-patient data. Results: The risks of all eating disorder types were lower among first-generation immigrants compared to the native populations: Incidence-rate ratio (95% confidence interval) was 0.39 (0.29, 0.51) for anorexia nervosa, 0.60 (0.42, 0.83) for bulimia nervosa, and 0.62 (0.47, 0.79) for other eating disorders in Denmark and 0.27 (0.21, 0.34) for anorexia nervosa, 0.30 (0.18, 0.51) for bulimia nervosa, and 0.39 (0.32, 0.47) for other eating disorders in Sweden. Likewise, second-generation immigrants by both parents were at lower risk, whereas those with only one foreign-born parent were not. Conclusion: The decreased risk of eating disorders among immigrants is opposite to what has been observed for other psychiatric disorders, particularly schizophrenia. Possible explanations include buffering sociocultural factors and underdetection in health care.
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| 7. |
- Salehi, Alireza M., et al.
(författare)
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Serum profiling of anorexia nervosa : A 1H NMR-based metabolomics study
- 2021
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 49, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of pathophysiological mechanisms underlying anorexia nervosa (AN) is incomplete. The aim was to conduct a metabolomics profiling of serum samples from women with AN (n = 65), women who have recovered from AN (AN-REC, n = 65), and age-matched healthy female controls (HC, n = 65). Serum concentrations of 21 metabolites were measured using proton nuclear magnetic resonance (1H NMR). We used orthogonal partial least-squares discriminant analysis (OPLS-DA) modeling to assign group classification based on the metabolites. Analysis of variance (ANOVA) was used to test for metabolite concentration differences across groups. The OPLS-DA model could distinguish between the AN and HC groups (p = 9.05 × 10–11 R2Y = 0.36, Q2 = 0.37) and between the AN-REC and HC groups (p = 8.47 × 10–6, R2Y = 0.36, Q2 = 0.24,), but not between the AN and AN-REC groups (p = 0.63). Lower methanol concentration in the AN and AN-REC group explained most of the variance. Likewise, the strongest finding in the univariate analyses was lower serum methanol concentration in both AN and AN-REC compared with HC, which withstood adjustment for body mass index (BMI). We report for the first time lower serum concentrations of methanol in AN. The fact that low methanol was also found in recovered AN suggests that low serum concentration of methanol could either be trait marker or a scar effect of AN.
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| 8. |
- Schaumberg, Katherine, et al.
(författare)
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The Science Behind the Academy for Eating Disorders' Nine Truths About Eating Disorders
- 2017
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Ingår i: European eating disorders review. - : WILEY. - 1072-4133 .- 1099-0968. ; 25:6, s. 432-450
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Forskningsöversikt (refereegranskat)abstract
- ObjectiveIn 2015, the Academy for Eating Disorders collaborated with international patient, advocacy, and parent organizations to craft the Nine Truths About Eating Disorders'. This document has been translated into over 30 languages and has been distributed globally to replace outdated and erroneous stereotypes about eating disorders with factual information. In this paper, we review the state of the science supporting the Nine Truths'. MethodsThe literature supporting each of the Nine Truths' was reviewed, summarized and richly annotated. ResultsMost of the Nine Truths' arise from well-established foundations in the scientific literature. Additional evidence is required to further substantiate some of the assertions in the document. Future investigations are needed in all areas to deepen our understanding of eating disorders, their causes and their treatments. ConclusionsThe Nine Truths About Eating Disorders' is a guiding document to accelerate global dissemination of accurate and evidence-informed information about eating disorders. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
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| 9. |
- Termorshuizen, Jet D., et al.
(författare)
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Longer-term impact of COVID-19 among individuals with self-reported eating disorders in the United States, the Netherlands, and Sweden
- 2023
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Ingår i: International Journal of Eating Disorders. - : WILEY. - 0276-3478 .- 1098-108X. ; 56:1, s. 80-90
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Tidskriftsartikel (refereegranskat)abstract
- Objective We assessed eating disorder (ED) illness status, symptomatology, treatment access, anxiety, and depression in the first year of the COVID-19 pandemic among individuals with a pre-existing ED in the United States (US), the Netherlands (NL), and Sweden (SE). Methods Participants completed online surveys in April-July 2020, at the early stage of the pandemic, and one year later. At one-year follow-up, we added questions addressing retrospective changes in ED symptoms, treatment, and anxiety/depression since the start of the COVID-19 pandemic. We present descriptive statistics and assess change in ED symptomatology, treatment, and anxiety/depression among those with an active or lingering ED. Results Participants (US n = 132; NL n = 219; SE n = 702) were mostly young and female with a history of anorexia nervosa (>60% in all three countries). Across countries, respondents reported impact of COVID-19 on ED symptoms at both time points, with improvement in US and NL at one-year follow-up, and stable but less impact on ED symptoms in SE. Furthermore, at one-year follow-up, roughly half of those in treatment reported reduced treatment access and quality, and the majority of the sample reported increased anxiety and depressive mood since the start of the pandemic. Discussion Our findings suggest that the self-perceived impact of COVID-19 changed over time but remained concerning even one year after the start of the pandemic. Clinicians, community organizations, and policy makers are encouraged to address potentially changing treatment needs in the face of public health emergency events. Public Significance Our findings suggest that the impact of COVID-19 on individuals with eating disorders decreased over time but remained concerning even one year after the start of the pandemic and that the impact differed across countries. Clinicians, community organizations, and policy makers are encouraged to incorporate this knowledge to address potentially changing treatment needs in the face of public health emergency events.
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| 10. |
- Yao, Shuyang, et al.
(författare)
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Familial liability for eating disorders and suicide attempts : evidence from a population registry in Sweden
- 2017
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Ingår i: JAMA Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2168-622X .- 2168-6238.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Suicide attempts are common in individuals with eating disorders. More precise understanding of the mechanisms underlying their co-occurrence is needed. Objective: To examine the association between eating disorders and suicide attempts and whether familial risk factors contribute to the association. Design: A cohort design following a Swedish birth cohort 1979-2001 from age 6 until 31/12/2009. Setting: Information was acquired from Swedish national registers. Participants: Individuals born 1979-2001 and living in Sweden before age 6 (N= 2,268,786) were eligible for the study. Each individual was linked to his/her biological full-siblings, maternal half-siblings, paternal half-siblings, full-cousins, and half-cousins. Eating disorders were captured by three variables: any eating disorder, anorexia nervosa (AN), and bulimia nervosa (BN), identified by any lifetime diagnoses recorded in the registers. Suicide attempts were defined as any suicide attempts, including death by suicide, recorded in the registers. We examined the association between eating disorders and death by suicide separately, but were underpowered to explore familial liability for this association. Results: Individuals with any eating disorder had increased risk of suicide attempts (OR=5.28, 95%CI [5.04, 5.54]) and death by suicide (OR=5.39, 95%CI [4.00, 7.25]). The risks attenuated but remained significant after adjusting for comorbid major depressive disorder, anxiety disorders, and substance use disorder. Similar results were found for AN and BN, except that adjusted OR of death by suicide in BN became insignificant, possibly due to insufficient power. Individuals (index) who had a full-sibling with any eating disorder had increased risk of suicide attempts (OR=1.41, 95%CI [1.29, 1.53]). The risk attenuated for any eating disorder in more distant relatives (maternal half-siblings, OR=1.10, 95%CI [0.90, 1.34]; paternal half-siblings, OR=1.21, 95%CI [0.98, 1.49]; full-cousins, OR=1.11, 95%CI [1.06, 1.18]; half-cousins, OR=0.90, 95%CI [0.78, 1.03]). This familial pattern remained stable after adjusting for the index individuals’ eating disorders. Similar patterns were found for AN and BN. Conclusions and Relevance: Our results suggest increased risk of suicide attempts in individuals with lifetime eating disorders and their relatives. The pattern of familial co-aggregation suggests familial liability for the association between eating disorders and suicide. Psychiatric comorbidities partially explain this association, suggesting particularly high-risk presentations.
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| 11. |
- Yao, Shuyang, et al.
(författare)
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Genetic and environmental contributions to diagnostic fluctuation in anorexia nervosa and bulimia nervosa
- 2021
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 51:1, s. 62-69
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anorexia nervosa and bulimia nervosa are two severe eating disorders associated with high premature mortality, suicidal risk and serious medical complications. Transition between anorexia nervosa and bulimia nervosa over the illness course and familial co-aggregation of the two eating disorders imply aetiological overlap. However, genetic and environmental liabilities to the overlap are poorly understood. Quantitative genetic research using clinical diagnosis is needed.METHODS: We acquired a clinical diagnosis of anorexia nervosa (prevalence = 0.90%) and bulimia nervosa (prevalence = 0.48%) in a large population-based sample (N = 782 938) of randomly selected full-sisters and maternal half-sisters born in Sweden between 1970 and 2005. Structural equation modelling was applied to quantify heritability of clinically diagnosed anorexia nervosa and bulimia nervosa and the contributions of genetic and environmental effects on their overlap.RESULTS: The heritability of clinically diagnosed anorexia nervosa and bulimia nervosa was estimated at 43% [95% confidence interval (CI) (36-50%)] and 41% (31-52%), respectively, in the study population, with the remaining variance explained by variance in unique environmental effects. We found statistically significant genetic [0.66, 95% CI (0.49-0.82)] and unique environmental correlations [0.55 (0.43-0.66)] between the two clinically diagnosed eating disorders; and their overlap was about equally explained by genetic and unique environmental effects [co-heritability 47% (35-58%)].CONCLUSIONS: Our study supports shared mechanisms for anorexia nervosa and bulimia nervosa and extends the literature from self-reported behavioural measures to clinical diagnosis. The findings encourage future molecular genetic research on both eating disorders and emphasize clinical vigilance for symptom fluctuation between them.
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| 12. |
- Yao, Shuyang, et al.
(författare)
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Risk of being convicted of theft and other crimes in anorexia nervosa and bulimia nervosa : A prospective cohort study in a Swedish female population
- 2017
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Ingår i: International Journal of Eating Disorders. - : John Wiley & Sons. - 0276-3478 .- 1098-108X. ; 50:9, s. 1095-1103
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We examined epidemiological associations between anorexia nervosa (AN) and bulimia nervosa (BN) and risks of committing theft and other crimes in a nationwide female population.Method: Females born in Sweden during 1979-1998 (N=957,106) were followed from age 15 for up to 20 years using information on clinically diagnosed AN and BN (exposures), convictions of theft and other crimes (outcomes), psychiatric comorbidities, and familial relatedness from Swedish national registers. We estimated hazard ratios (HRs) of criminality in exposed versus unexposed females using Cox proportional hazards regressions and explored how comorbidities and unmeasured familial factors explained the associations.Results: The cumulative incidence of convictions of theft (primarily petty theft) and other crimes was higher in exposed females (AN: 11.60% theft, 7.39% other convictions; BN: 17.97% theft, 13.17% other convictions) than in unexposed females (approximate to 5% theft, approximate to 6% other convictions). The significantly increased risk of being convicted of theft in exposed females (AN: HR=2.51, 95% confidence interval=[2.29, 2.74], BN: 4.31 [3.68, 5.05]) was partially explained by comorbidities; unmeasured familial factors partially explained the association with convictions of theft in BN but not in AN. Females with BN had a doubled risk of convictions of other crimes, which was partially explained by comorbidities.Discussion: Individuals with eating disorders had increased risk for convictions of theft and potentially other crimes. Results underscore the importance of regular forensic screening and encourage research on mechanisms underlying the relation between crime and eating disorder psychopathology and efforts to determine how best to address such relation in treatment.
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| 13. |
- Baker, Jessica H., et al.
(författare)
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Body Dissatisfaction in Adolescent Boys
- 2019
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Ingår i: Developmental Psychology. - : American Psychological Association (APA). - 0012-1649 .- 1939-0599. ; 55:7, s. 1566-1578
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Tidskriftsartikel (refereegranskat)abstract
- Body dissatisfaction is a significant mental health symptom present in adolescent girls and boys. However, it is often either disregarded in adolescent boys or examined using assessments that may not resonate with males. The present study addresses these issues, examining the manifestation, etiology, and correlates of 3 facets of body dissatisfaction in adolescent boys. Adolescent male twins aged 16- to 17-years-old from the Swedish Twin Study of Child and Adolescent Development were included along with a female comparison group: 915 monozygotic and 671 dizygotic same-sex twins. Body dissatisfaction was defined using measures of height dissatisfaction, muscle dissatisfaction, and the body dissatisfaction subscale of the Eating Disorder Inventory (EDI-BD). We examined the prevalence of body dissatisfaction, whether the facets of body dissatisfaction were phenotypically and etiologically distinct, and associations with specific externalizing and internalizing symptoms. For boys, muscle dissatisfaction scores were greater than height dissatisfaction scores. Results also indicated that height and muscle dissatisfaction were phenotypically and etiologically distinct from the EDI-BD. Unique associations were observed with externalizing and internalizing symptoms: muscle dissatisfaction with symptoms of bulimia nervosa and the EDI-BD with internalizing symptoms, body mass index, and drive for thinness. The facets of body dissatisfaction were also largely distinct in girls and unique between-sex associations with externalizing and internalizing symptoms emerged. Overall, male-oriented aspects of body dissatisfaction are distinct from female-oriented aspects of body dissatisfaction. To capture the full picture of male body dissatisfaction, multiple facets must be addressed.
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| 14. |
- Birgegard, Andreas, et al.
(författare)
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Proposal for increasing diagnostic clarity in research and clinical practice by renaming and reframing atypical anorexia nervosa as "Restrictive Eating Disorder" (RED)
- 2023
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Ingår i: Eating Behaviors. - : ELSEVIER. - 1471-0153 .- 1873-7358. ; 50
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Tidskriftsartikel (refereegranskat)abstract
- Atypical anorexia nervosa (AAN) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM5), is characterized by meeting all criteria for anorexia nervosa (AN) except for weight being within or above the "normal" range despite significant weight loss. The current definition is plagued by several problems, resulting in widely heterogeneous operationalizations in research and clinical practice. As such, the poorly defined diagnosis of AAN negatively impacts affected individuals and frustrates research attempts to better understand the syndrome. We consider conceptual flaws in the AAN description and contend that the undefined weight range and nature of weight loss renders these two factors functionally inapplicable in research and practice. They also represent a departure from the originally intended use of the AAN category, i.e., arresting a negative weight trajectory likely to result in AN, making the target population, and the application of the label, unclear. We propose revised criteria and a new name, restrictive eating disorder (RED), intended to reduce stigma and encompass a wide but better-defined range of presentations. The RED criteria focus on clinically significant restrictive behavior that disrupts normal living (i.e., impairment), and cognitive symptoms of overevaluation, disturbed experience, and lack of recognition of illness seriousness. We believe that RED may enable more appropriate clinical application, but also inspire coordinated research toward a more valid psychiatric nosology in the eating disorders field.
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| 15. |
- Cesta, Carolyn E., et al.
(författare)
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Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring : prenatal androgen exposure or genetic confounding?
- 2020
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 50:4, s. 616-624
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences.METHODS: A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models.RESULTS: PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys.CONCLUSIONS: Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.
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| 16. |
- Hedman, Anna, et al.
(författare)
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Bidirectional relationship between eating disorders and autoimmune diseases
- 2019
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Ingår i: Journal of Child Psychology and Psychiatry. - Stockholm : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 60:7, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immune system dysfunction may be associated with eating disorders (ED) and could have implications for detection, risk assessment, and treatment of both autoimmune diseases and EDs. However, questions regarding the nature of the relationship between these two disease entities remain. We evaluated the strength of associations for the bidirectional relationships between EDs and autoimmune diseases.METHODS: In this nationwide population-based study, Swedish registers were linked to establish a cohort of more than 2.5 million individuals born in Sweden between January 1, 1979 and December 31, 2005 and followed up until December 2013. Cox proportional hazard regression models were used to investigate: (a) subsequent risk of EDs in individuals with autoimmune diseases; and (b) subsequent risk of autoimmune diseases in individuals with EDs.RESULTS: We observed a strong, bidirectional relationship between the two illness classes indicating that diagnosis in one illness class increased the risk of the other. In women, the diagnoses of autoimmune disease increased subsequent hazards of anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED). Similarly, AN, BN, and OED increased subsequent hazards of autoimmune diseases.Gastrointestinal-related autoimmune diseases such as, celiac disease and Crohn's disease showed a bidirectional relationship with AN and OED. Psoriasis showed a bidirectional relationship with OED. The previous occurence of type 1 diabetes increased the risk for AN, BN, and OED. In men, we did not observe a bidirectional pattern, but prior autoimmune arthritis increased the risk for OED.CONCLUSIONS: The interactions between EDs and autoimmune diseases support the previously reported associations. The bidirectional risk pattern observed in women suggests either a shared mechanism or a third mediating variable contributing to the association of these illnesses.
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| 17. |
- Javaras, Kristin N., et al.
(författare)
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Sex- and age-specific incidence of healthcare-register-recorded eating disorders in the complete swedish 1979-2001 birth cohort
- 2015
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Ingår i: International Journal of Eating Disorders. - : Wiley-Blackwell. - 0276-3478 .- 1098-108X. ; 48:8, s. 1070-81
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the sex- and age-specific incidence of healthcare-register-recorded anorexia nervosa (AN) and other eating disorders (OED) in a complete birth cohort, and assess whether incidence varies by diagnostic period and (sub-) birth cohort.METHOD: We used the actuarial method and Poisson models to examine the incidence of AN and OED from 1987 to 2009 (when individuals were 8-30 years old) for a cohort of 2.3 million individuals (48.7% female) born from 1979 to 2001 in Sweden, identified using Swedish registers.RESULTS: For both sexes, incidences of AN and OED increased considerably for diagnostic periods after 2000, but differed little by birth cohort. In 2009, AN incidence in the peak age category was 205.9 cases/100,000 persons (95% CI: 178.2, 233.5) for females (14-15 years), versus 12.8 cases/100,000 (95% CI: 5.6, 20.1) for males (12-13 years). OED incidence in the peak age category was 372.1 cases/100,000 (95% CI: 336.4, 407.9) for females (16-17 years), versus 22.2 cases/100,000 (95% CI: 13.3, 31.1) for males (14-15 years).DISCUSSION: Our finding of an increase in healthcare-register-recorded eating disorders for diagnostic periods after 2000 likely reflects improved detection and expanded register coverage in Sweden. The peak of eating disorder incidence in adolescence, which began unexpectedly early for AN in males, suggests the importance of vigilance for signs of AN in young boys and early primary prevention efforts. Waiting until later could miss critical windows for intervention that could prevent disorders from taking root.
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| 18. |
- Javaras, Kristin N., et al.
(författare)
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Shared Genetic Factors Contributing to the Overlap between Attention-Deficit/Hyperactivity Disorder Symptoms and Overweight/Obesity in Swedish Adolescent Girls and Boys
- 2022
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 25:6, s. 226-233
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Tidskriftsartikel (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) and obesity are positively associated, with increasing evidence that they share genetic risk factors. Our aim was to examine whether these findings apply to both types of ADHD symptoms for female and male adolescents. We used data from 791 girl and 735 boy twins ages 16-17 years to examine sex-specific phenotypic correlations between the presence of ADHD symptoms and overweight/obese status. For correlations exceeding .20, we then fit bivariate twin models to estimate the genetic and environmental correlations between the presence of ADHD symptoms and overweight/obese status. ADHD symptoms and height/weight were parent- and self-reported, respectively. Phenotypic correlations were .30 (girls) and .08 (boys) for inattention and overweight/obese status and .23 (girls) and .14 (boys) for hyperactivity/impulsivity and overweight/obese status. In girls, both types of ADHD symptoms and overweight/obese status were highly heritable, with unique environmental effects comprising the remaining variance. Furthermore, shared genetic effects explained most of the phenotypic correlations in girls. Results suggest that the positive association of both types of ADHD symptoms with obesity may be stronger in girls than boys. Further, in girls, these associations may stem primarily from shared genetic factors.
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| 19. |
- 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, s. 216-225
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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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| 20. |
- Martin, Cederlöf, 1980-, et al.
(författare)
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Etiological overlap between obsessive-compulsive disorder and anorexia nervosa : a longitudinal cohort, multigenerational family and twin study
- 2015
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Ingår i: World Psychiatry. - Hoboken, USA : Wiley-Blackwell. - 1723-8617 .- 2051-5545. ; 14:3, s. 333-338
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Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder (OCD) often co-occurs with anorexia nervosa (AN), a comorbid profile that complicates the clinical management of both conditions. This population-based study aimed to examine patterns of comorbidity, longitudinal risks, shared familial risks and shared genetic factors between OCD and AN at the population level. Participants were individuals with a diagnosis of OCD (N=19,814) or AN (N=8,462) in the Swedish National Patient Register between January 1992 and December 2009; their first-, second- and third-degree relatives; and population-matched (1:10 ratio) unaffected comparison individuals and their relatives. Female twins from the population-based Swedish Twin Register (N=8,550) were also included. Females with OCD had a 16-fold increased risk of having a comorbid diagnosis of AN, whereas males with OCD had a 37-fold increased risk. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for a later diagnosis of AN (risk ratio, RR=3.6), whereas individuals first diagnosed with AN had an even greater risk for a later diagnosis of OCD (RR=9.6). These longitudinal risks were about twice as high for males than for females. First- and second-degree relatives of probands with OCD had an increased risk for AN, and the magnitude of this risk tended to increase with the degree of genetic relatedness. Bivariate twin models revealed a moderate but significant degree of genetic overlap between self-reported OCD and AN diagnoses (ra =0.52, 95% CI: 0.26-0.81), but most of the genetic variance was disorder-specific. The moderately high genetic correlation supports the idea that this frequently observed comorbid pattern is at least in part due to shared genetic factors, though disorder-specific factors are more important. These results have implications for current gene-searching efforts and for clinical practice.
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| 21. |
- Schaumberg, Katherine, et al.
(författare)
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Patterns of diagnostic transition in eating disorders : a longitudinal population study in Sweden
- 2019
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 49:5, s. 819-827
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transition across eating disorder diagnoses is common, reflecting instability of specific eating disorder presentations. Previous studies have examined temporal stability of diagnoses in adult treatment-seeking samples but have not uniformly captured initial presentation for treatment. The current study examines transitions across eating disorder diagnostic categories in a large, treatment-seeking sample of individuals born in Sweden and compares these transitions across two birth cohorts and from initial diagnosis.METHODS: Data from Swedish eating disorders quality registers were extracted in 2013, including 9622 individuals who were seen at least twice from 1999 to 2013. Patterns of remission were examined in the entire sample and subsequently compared across initial diagnoses. An older (born prior to 1990) and younger birth cohort were also identified, and analyses compared these cohorts on patterns of diagnostic transition.RESULTS: Although diagnostic instability was common, transition between threshold eating disorder diagnoses was infrequent. For all diagnoses, transition to remission was likely to occur following a diagnosis state that matched initial diagnosis, or through a subthreshold diagnostic state. Individuals in the younger cohort were more likely to transition to a state of remission than those in the older cohort.CONCLUSIONS: Results indicate more temporal continuity in eating disorder presentations than suggested by previous research and highlight the importance of early detection and intervention in achieving remission.
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| 22. |
- Seidel, Maria, et al.
(författare)
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Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT) : a study of discordant monozygotic twins with anorexia nervosa.
- 2020
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Ingår i: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a "scar" due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects.METHODS: Comprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters.DISCUSSION: The multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and "scar" effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.
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| 23. |
- Thornton, Laura M., et al.
(författare)
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Binge-eating disorder in the Swedish national registers : Somatic comorbidity
- 2017
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Ingår i: International Journal of Eating Disorders. - Hoboken, USA : John Wiley & Sons. - 0276-3478 .- 1098-108X. ; 50:1, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate associations between binge-eating disorder (BED) and somatic illnesses and determine whether medical comorbidities are more common in individuals who present with BED and comorbid obesity.Method: Cases (n = 850) were individuals with a BED diagnosis in the Swedish eating disorders quality registers. Ten community controls were matched to each case on sex, and year, month, and county of birth. Associations of BED status with neurologic, immune, respiratory, gastrointestinal, skin, musculoskeletal, genitourinary, circulatory, and endocrine system diseases were evaluated using conditional logistic regression models. We further examined these associations by adjusting for lifetime psychiatric comorbidity. Amongst individuals with BED, we explored whether comorbid obesity was associated with risk of somatic disorders.Results: BED was associated with most classes of diseases evaluated; strongest associations were with diabetes [odds ratio (95% confidence interval) = 5.7 (3.8; 8.7)] and circulatory systems [1.9 (1.3; 2.7)], likely indexing components of metabolic syndrome. Amongst individuals with BED, those with comorbid obesity were more likely to have a lifetime history of respiratory [1.5 (1.1; 2.1)] and gastrointestinal [2.6 (1.7; 4.1)] diseases than those without comorbid obesity. Increased risk of some somatic disease classes in individuals with BED was not simply due to obesity or other lifetime psychiatric comorbidity.Discussion: The association of BED with many somatic illnesses highlights the morbidity experienced by individuals with BED. Clinicians treating patients with BED should be vigilant for medical comorbidities. Nonpsychiatric providers may be the first clinical contact for those with BED underscoring the importance of screening in primary care.
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| 24. |
- Watson, Hunna J., et al.
(författare)
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A register-based case-control study of health care utilization and costs in binge-eating disorder
- 2018
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Ingår i: Journal of Psychosomatic Research. - : Elsevier. - 0022-3999 .- 1879-1360. ; 108, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Capturing trends in healthcare utilization may help to improve efficiencies in the detection and diagnosis of illness, to plan service delivery, and to forecast future health expenditures. For binge-eating disorder (BED), issues include lengthy delays in detection and diagnosis, missed opportunities for recognition and treatment, and morbidity. The study objective was to compare healthcare utilization and expenditure in people with and without BED. Methods: A case-control design and nationwide registers were used. All individuals diagnosed with BED at eating disorder clinics in Sweden between 2005 and 2009 were included (N = 319, 97% female, M age = 22 years). Ten controls (N = 3190) were matched to each case on age-, sex-, and location of birth. Inpatient, hospital-based outpatient, and prescription medication utilization and expenditure were analyzed up to eight years before and four years after the index date (i.e., date of diagnosis of the BED case). Results: Cases had significantly higher inpatient, hospital-based outpatient, and prescription medication utilization and expenditure compared with controls many years prior to and after diagnosis of BED. Utilization and expenditure for controls was relatively stable over time, but for cases followed an inverted U-shape and peaked at the index year. Care for somatic conditions normalized after the index year, but care for psychiatric conditions remained significantly higher. Conclusion: Individuals with BED had substantially higher healthcare utilization and costs in the years prior to and after diagnosis of BED. Since previous research shows a delay in diagnosis, findings indicate clear opportunities for earlier detection and clinical management. Training of providers in detection, diagnosis, and management may help curtail morbidity. A reduction in healthcare utilization was observed after BED diagnosis. This suggests that earlier diagnosis and treatment could improve long-term health outcomes and reduce the economic burden associated with BED.
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| 25. |
- Watson, Hunna J., et al.
(författare)
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A Register-Based Case-Control Study of Prescription Medication Utilization in Binge-Eating Disorder
- 2016
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Ingår i: The primary care companion for CNS disorders. - Memphis, USA : Physicians Postgraduate Press, Inc.. - 2155-7780. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Individuals with binge-eating disorder (BED) experience psychiatric and somatic comorbidities and obesity, but the nature and magnitude of prescription medication utilization is unclear. We investigated utilization using Swedish registry data and a case-control design.Methods: Cases were identified from Riksät and Stepwise longitudinal registers and were individuals diagnosed with BED per DSM-IV-TR criteria between July 1, 2006, and December 31, 2009, at eating disorder clinics (n = 238, 96% female, mean age = 22.8 years). For each case, 10 controls were matched on sex and year, month, and county of birth (n = 2,380). An index date was derived for each control, which was the date of diagnosis of BED in the corresponding case. The association between BED and prescription medication utilization was investigated before and within 12 months after diagnosis.Results: Before diagnosis, cases were significantly more likely than matched controls to have been prescribed nervous system (odds ratio = 6.4; 95% confidence limit = 4.7, 8.6), tumors and immune disorders (3.5; 1.3, 9.3), cardiovascular (2.2; 1.4, 3.5), digestion and metabolism (2.1; 1.5, 2.9), infectious diseases (1.9; 1.4, 2.6), skin (1.8; 1.3, 2.5), and respiratory system (1.3; 1.0, 1.8) medications. Cases also had higher odds of prescription use than controls across most categories within 12 months after diagnosis. Several associations were significant after accounting for lifetime psychiatric comorbidity and obesity.Conclusions: Individuals with BED had increased utilization of psychiatric and nonpsychiatric medications compared with matched controls. Findings confirm that the illness burden of BED extends to high medication utilization and underscore the importance of thorough medication reviews when treating individuals with BED.
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