| 1. |
- Kowalec, Kaarina, et al.
(författare)
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Increased schizophrenia family history burden and reduced premorbid IQ in treatment-resistant schizophrenia : a Swedish National Register and Genomic Study
- 2021
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 26, s. 4487-4495
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Tidskriftsartikel (refereegranskat)abstract
- A high proportion of those with schizophrenia experience treatment non-response, placing them at higher risk for mortality and suicide attempts, compared to treatment responders. The clinical, social, and economic burden of treatment-resistant schizophrenia (TRS) are substantial. Previous genomic and epidemiological studies of TRS were often limited by sample size or lack of comprehensive genomic data. We aimed to systematically understand the clinical, demographic, and genomic correlates of TRS using epidemiological and genetic epidemiological modelling in a Swedish national population sample (n = 24,706) and then in a subgroup with common variant genetic risk scores, rare copy-number variant burden, and rare exonic burden (n = 4936). Population-based analyses identified increasing schizophrenia family history to be significantly associated with TRS (highest quartile of familial burden vs. lowest: adjusted odds ratio (aOR): 1.31, P = 4.8 × 10-8). In males, a decrease of premorbid IQ of one standard deviation was significantly associated with greater risk of TRS (minimal aOR: 0.94, P = 0.002). In a subset of cases with extensive genomic data, we found no significant association between the genetic risk scores of four psychiatric disorders and two cognitive traits with TRS (schizophrenia genetic risk score: aOR = 1.07, P = 0.067). The association between copy number variant and rare variant burden measures and TRS did not reach the pre-defined statistical significance threshold (all P ≥ 0.005). In conclusion, direct measures of genomic risk were not associated with TRS; however, premorbid IQ in males and schizophrenia family history were significantly correlated with TRS and points to new insights into the architecture of TRS.
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| 2. |
- Kowalec, Kaarina, et al.
(författare)
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The association between family history and genomic burden with schizophrenia mortality : a Swedish population-based register and genetic sample study
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with schizophrenia (SCZ) have a 2-3-fold higher risk of mortality than the general population. Heritability of mortality in psychiatric disorders has been proposed; however, few have investigated SCZ family history and genetic variation, with all-cause and specific causes of death. We aimed to identify correlates of SCZ mortality using genetic epidemiological and genetic modelling in two samples: a Swedish national population sample and a genotyped subsample. In the Swedish national population sample followed from the first SCZ treatment contact until emigration, death or end of the follow-up, we investigated a standardised measure of SCZ family history. In a subgroup with comprehensive genetic data, we investigated the impact of common and rare genetic variation. Cox proportional hazards regression was used to estimate the association between various factors and mortality (all and specific causes). A total of 13727 SCZ cases fulfilled criteria for the population-based analyses (1268 deaths, 9.2%). The genomic subset contained 4991 cases (1353 deaths, 27.1%). Somatic mutations associated with clonal hematopoiesis with unknown drivers were associated with all-cause mortality (HR 1.77, 95% CI: 1.26-2.49). No other heritable measures were associated with all-cause mortality nor with any specific causes of death. Future studies in larger, comparable cohorts are warranted to further understand the association between hereditary measures and mortality in SCZ.
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| 3. |
- Ahrén, Jennie C., et al.
(författare)
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We are family - parents, siblings, and eating disorders in a prospective total-population study of 250,000 Swedish males and females
- 2013
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Ingår i: International Journal of Eating Disorders. - : Wiley-Blackwell. - 0276-3478 .- 1098-108X. ; 46:7, s. 693-700
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We examined how parental characteristics and other aspects of family background were associated with the development of eating disorders (ED) in males and females.Method: We used register data and record linkage to create the prospective, total-population study the Stockholm Youth Cohort. This cohort comprises all children and adolescents who were ever residents in Stockholm County between 2001 and 2007, plus their parents and siblings. Individuals born between 1984 and 1995 (N = 249, 884) were followed up for ED from age 12 to end of 2007. We used Cox regression modeling to investigate how ED incidence was associated with family socioeconomic position, parental age, and family composition.Results: In total, 3,251 cases of ED (2,971 females; 280 males) were recorded. Higher parental education independently predicted a higher rate of ED in females [e.g., adjusted hazard ratio (HR) 1.69 (95% CI: 1.42, 2.02) for degree-level vs. elementary-level maternal education], but not in males [HR 0.73 (95% CI: 0.42, 1.28), p < 0.001 for gender interaction]. In females, an increasing number of full-siblings was associated with lower rate of ED [e.g., fully adjusted HR 0.92 (95% CI: 0.88, 0.97) per sibling], whereas an increasing number of half-siblings was associated with a higher rate [HR 1.05 (95% CI: 1.01, 1.09) per sibling].Discussion: The effect of parental education on ED rate varies between males and females, whereas the effect of number of siblings varies according to whether they are full or half-siblings. A deeper understanding of these associations and their underlying mechanisms may provide etiological insights and inform the design of preventive interventions
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| 4. |
- Björkenstam, Charlotte, et al.
(författare)
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Self-reported suicide ideation and attempts, and medical care for intentional self-harm in lesbians, gays and bisexuals in Sweden
- 2016
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 70:9, s. 895-901
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Tidskriftsartikel (refereegranskat)abstract
- Background Minority sexual orientation is a robust risk indicator for self-reported suicidal ideation and attempts. However, little is known about patterns of medical care for intentional self-harm in this vulnerable population. We investigate sexual orientation-related differences in self-reported lifetime suicide symptoms and medical care for intentional self-harm between 1969 and 2010, including age at initial treatment and recurrence. Methods We used data from the Stockholm Public Health Cohort, a population-based sample of 874 lesbians/gays, 841 bisexuals and 67980 heterosexuals, whose self-administered surveys have been linked to nationwide registers. Estimates of risk for medical care were calculated as incidence rate ratios (IRR) with 95% CIs. Results Both suicidal ideation and attempts were more commonly reported by lesbian/gay and bisexual (LGB) individuals. Adjusting for risk-time and confounding, lesbians (IRR 3.8, 95% CI 2.7 to 5.4) and bisexual women (IRR 5.4, 95% CI 4.4 to 6.6) experienced elevated risk for medical care for intentional self-harm, as compared to heterosexual women. Gay men evidenced higher risk (IRR 2.1, 95% CI 1.3 to 3.4) as compared to heterosexual men. Recurrent medical care was more frequent in LGB individuals, especially in bisexual women and gay men. Lesbian and bisexual women were also younger than heterosexual women when they first received medical care for intentional self-harm. Conclusions Positive histories of suicidal ideation, attempts and medical care for intentional self-harm, including higher levels of recurrence, are more prevalent among LGB individuals in contrast to heterosexuals. Lesbian/bisexual women evidence an earlier age of onset of treatment. Tailored prevention efforts are urgently needed.
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| 5. |
- Björkenstam, Charlotte, et al.
(författare)
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Suicide in married couples in Sweden : Is the risk greater in same-sex couples?
- 2016
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 31:7, s. 685-690
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Tidskriftsartikel (refereegranskat)abstract
- Minority sexual orientation is a predictor of suicide ideation and attempts, though its association with suicide mortality is less clear. We capitalize on Sweden's extensively linked databases, to investigate whether, among married individuals, same-sex marriage is associated with suicide. Using a population-based register design, we analyzed suicide risk among same-sex married women and men (n = 6456), as compared to different-sex married women and men (n = 1181723) in Sweden. We selected all newly partnered or married individuals in the intervening time between 1/1/1996 and 12/31/2009 and followed them with regard to suicide until 12/31/2011. Multivariate Poisson regression was used to calculate adjusted incidence risk ratios (IRR) with 95 % confidence intervals (CI). The risk of suicide was higher among same-sex married individuals as compared to different-sex married individuals (IRR 2.7, 95 % CI 1.5-4.8), after adjustment for time at risk and socioeconomic confounding. Sex-stratified analyses showed a tentatively elevated risk for same-sex married women (IRR 2.5, 95 % CI 0.8-7.7) as compared to different-sex married women. Among same-sex married men the suicide risk was nearly three-fold greater as compared to different-sex married (IRR 2.895 % CI 1.5-5.5). This holds true also after adjustment for HIV status. Even in a country with a comparatively tolerant climate regarding homosexuality such as Sweden, same-sex married individuals evidence a higher risk for suicide than other married individuals.
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| 6. |
- Björkenstam, Emma, et al.
(författare)
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Attention De ficit/Hyperactivity Disorder and risk for non-affective psychotic disorder : The role of ADHD medication and comorbidity, and sibling comparison
- 2020
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 218, s. 124-130
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Tidskriftsartikel (refereegranskat)abstract
- Attention Deficit/Hyperactivity Disorder (ADHD) is the most common psychiatric disorder in childhood. It is unclear whether ADHD increases the risk of non-affective psychotic disorder (NAPD). The study included a matched cohort, drawn from all born in Sweden 1987–1991 (n = 548,852). ADHD was defined as ICD diagnosis and/or prescription of ADHD medication. We distinguished between stimulants and non-stimulants, and usage duration (<1 year, 1–2 years and ≥2 years). We calculated odds ratios (OR) with 95% confidence intervals (CI) for NAPD, adjusted for confounders, comorbid autism spectrum disorder (ASD) and substance abuse. ADHD cases were also compared to their unaffected full siblings. We analyzed 18,139 ADHD cases and 72,437 sex and birth year matched controls. NAPD was more common in cases than controls (2.7 and 0.4%, respectively). After adjustment for confounders, ADHD cases had markedly high risk for NAPD (OR: 6.99; 95% CI 6.03–8.10), which attenuated further after adjustment for ASD and substance abuse (OR: 2.57; 95% CI 2.09–3.16). Utilization of ADHD medication increased the risk for NAPD (ORs for change in odds of NAPD for every 5 extra prescriptions of stimulants 1.06 (95% CI 1.02–1.10) and, non-stimulants 1.15 (95% CI 1.01–1.30)). There was no association between usage length of medication and risk for NAPD. The risk was higher in individuals with ADHD than their unaffected siblings (OR: 2.95 (95% CI 2.07–4.20)). Overall, ADHD was associated with elevated risk for NAPD, which is not entirely explained by shared familial factors. The clinical severity leading to medical treatment may also increase NAPD risk.
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| 7. |
- Björkenstam, Emma, et al.
(författare)
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Childhood household dysfunction, school performance and psychiatric care utilisation in young adults : a register study of 96 399 individuals in Stockholm County
- 2016
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 70:5, s. 473-480
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Tidskriftsartikel (refereegranskat)abstract
- Background Exposure to childhood household dysfunction increases the risk of psychiatric morbidity. Although school performance also has been linked with psychiatric morbidity, limited research has considered school performance as a mediating factor. To address this gap in the literature, the current register study examined whether school performance mediates the association between childhood household dysfunction (experienced between birth and age 14 years) and psychiatric care utilisation in young adulthood.Methods We used a Swedish cohort of 96 399 individuals born during 1987–1991. Indicators of childhood household dysfunction were familial death, parental substance abuse and psychiatric morbidity, parental somatic disease, parental criminality, parental separation/single-parent household, public assistance recipiency and residential instability. Final school grades from the 9th year of compulsory school were used to create five categories. Estimates of risk of psychiatric care utilisation (measured as inpatient, outpatient and primary care) after the age of 18 years were calculated as HRs with 95% CIs. Mediation was tested with the bootstrap approach.Results Cumulative exposure to childhood household dysfunction was positively associated with psychiatric care utilisation. Specifically, individuals exposed to three or more indicators with incomplete school grades had the highest risk (HR=3.7 (95% CI 3.3 to 4.1) after adjusting for demographics), compared to individuals exposed to no indicators with highest grades. School performance was found to mediate the relationship.Conclusions Our findings suggest that future efforts to prevent or mitigate the negative effects of childhood household dysfunction on psychiatric morbidity may benefit from integration of strategies that improve school performance among vulnerable youth.
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| 8. |
- Björkenstam, Emma, et al.
(författare)
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Risk of new psychiatric episodes in the year following divorce in midlife : Cause or selection? A nationwide registerbased study of 703,960 individuals
- 2013
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Ingår i: International Journal of Social Psychiatry. - : SAGE Publications. - 0020-7640 .- 1741-2854. ; 59:8, s. 801-804
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine if divorce is associated with an increased risk of psychiatric disorder. Methods: A register-based cohort study of all married or divorced individuals aged 45-54 in Sweden in 2006. After exclusion of 129,669 individuals with a history of psychiatric care in 1987-2005, we followed 703,960 persons for psychiatric disorder during 2007, measured as psychiatric inpatient care, outpatient care and use of psychotropic medication. Marital trajectories were taken into consideration. Data were analysed using Poisson regression. Results: Divorced women and men had a higher risk for psychiatric inpatient care compared to married (ORwomen = 3.2, 95%CI = 1.6-6.3, ORmen = 3.3, 95%CI = 2.0-5.4). The longer the marriage, the lower the risk for psychiatric disorders. Lower educational level increased the risk for psychiatric inpatient care. Conclusions: In conclusion, our study supports both the selection hypothesis, linking healthy individuals to long and stable marriages, and the social causation hypothesis, linking the stress of recent divorce to increased psychiatric disorder for both women and men.
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| 9. |
- Bould, Helen, et al.
(författare)
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Parental mental illness and eating disorders in offspring
- 2015
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Ingår i: International Journal of Eating Disorders. - : Wiley. - 0276-3478 .- 1098-108X. ; 48:4, s. 383-391
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate which parental mental illnesses are associated with eating disorders in their offspring.METHOD: We used data from a record-linkage cohort study of 158,679 children aged 12-24 years at the end of follow-up, resident in Stockholm County from 2001 to 2007, to investigate whether different parental mental illnesses are risk factors for eating disorders in their offspring. The outcome measure was diagnosis of any eating disorder, either from an ICD or DSM-IV code, or inferred from an appointment at a specialist eating disorder clinic.RESULTS: Mental illness in parents is a risk factor for eating disorders in female offspring (Adjusted Hazard Ratio (AHR) 1.57 (95% CI 1.42, 1.92), p < 0.0001). Risk of eating disorders is increased if there is a parental diagnosis of bipolar affective disorder (AHR 2.28 (95% CI 1.39, 3.72), p = 0.004), personality disorder (AHR 1.57 (95% CI 1.01, 2.44), p = 0.043) or anxiety/depression (AHR 1.57 (95% CI 1.32, 1.86), p < 0.0001). There is a lack of statistical evidence for an association with parental schizophrenia (AHR 1.41 (95% CI 0.96, 2.07), p = 0.08), and somatoform disorder (AHR 1.25 (95% CI 0.74, 2.13), p = 0.40). There is no support for a relationship between parental substance misuse and eating disorders in children (AHR 1.08 (95% CI 0.82, 1.43), p = 0.57).DISCUSSION: Parental mental illness, specifically parental anxiety, depression, bipolar affective disorder, and personality disorders, are risk factors for eating disorders in their offspring.
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| 10. |
- Chen, Shuyun, et al.
(författare)
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Random capillary glucose levels throughout pregnancy, obstetric and neonatal outcomes, and long-term neurodevelopmental conditions in children : a group-based trajectory analysis.
- 2023
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gestational diabetes mellitus (GDM) is associated with both short- and long-term risks, although it is unknown if risks vary by severity, timing, and duration of gestational hyperglycemia. We aimed to identify trajectories of random capillary glucose (RCG) levels throughout pregnancy and assess their associations with both obstetric/neonatal outcomes and children's risk of neurodevelopmental conditions (NDCs) (i.e., autism, intellectual disability, and attention-deficit/hyperactivity disorders [ADHD]).METHODS: A population-based cohort study was conducted involving 76,228 children born to 68,768 mothers without pregestational diabetes. Group-based trajectory modeling was utilized to identify distinct glucose trajectories across RCG values throughout the course of pregnancy. The associations between these trajectory groups and obstetric/neonatal outcomes as well as children's NDCs were then assessed using generalized estimating equation models with a logit link. The Benjamini-Hochberg (BH) procedure was employed to adjust P-values for multiple comparisons, controlling the false discovery rate (FDR).RESULTS: Five distinct glucose trajectory groups were identified, each with varying percentages diagnosed with GDM. Their associations with obstetric/neonatal outcomes as well as children's NDCs varied. For example, when compared to the "Persistently Low" group, other groups exhibited varying degrees of increased risk for large-for-gestational-age babies, with the exception of the "High in Early Pregnancy" group. Compared to the "Persistently Low" group, all other trajectory groups were associated with NDC outcomes, except the "High in Mid-Pregnancy" group. However, none of the associations with offspring NDCs remained significant after accounting for the FDR correction.CONCLUSIONS: Persistent high glucose levels or moderately elevated glucose levels throughout pregnancy, as well as transient states of hyperglycemia in early or mid-pregnancy, were found to be associated with increased risks of specific obstetric and neonatal complications, and potentially offspring NDCs. These risks varied depending on the severity, timing, duration, and management of hyperglycemia. The findings underscore the need for continuous surveillance and individualized management strategies for women displaying different glucose trajectories during pregnancy. Limitations such as potential residual confounding, the role of mediators, and small sample size should be addressed in future studies.
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