| 1. |
- Kowalec, Kaarina, et al.
(author)
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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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In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 26, s. 4487-4495
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Journal article (peer-reviewed)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.
(author)
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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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In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Journal article (peer-reviewed)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.
(author)
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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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In: International Journal of Eating Disorders. - : Wiley-Blackwell. - 0276-3478 .- 1098-108X. ; 46:7, s. 693-700
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Journal article (peer-reviewed)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.
(author)
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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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In: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 70:9, s. 895-901
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Journal article (peer-reviewed)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.
(author)
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Suicide in married couples in Sweden : Is the risk greater in same-sex couples?
- 2016
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 31:7, s. 685-690
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Journal article (peer-reviewed)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.
(author)
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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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In: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 218, s. 124-130
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Journal article (peer-reviewed)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.
(author)
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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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In: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 70:5, s. 473-480
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Journal article (peer-reviewed)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.
(author)
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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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In: International Journal of Social Psychiatry. - : SAGE Publications. - 0020-7640 .- 1741-2854. ; 59:8, s. 801-804
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Journal article (peer-reviewed)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.
(author)
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Parental mental illness and eating disorders in offspring
- 2015
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In: International Journal of Eating Disorders. - : Wiley. - 0276-3478 .- 1098-108X. ; 48:4, s. 383-391
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Journal article (peer-reviewed)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.
(author)
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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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In: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21:1
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Journal article (peer-reviewed)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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| 11. |
- Dalman, Christina, 1956
(author)
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Early life risk factors for schizophrenia - studies of foetal and perinatal complications
- 2001
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Doctoral thesis (other academic/artistic)abstract
- Background: Despite intensive research for decades the causes of schizophrenia are largely unknown. A major lead in scientific work is the neurodevelopmental hypothesis i.e. a vulnerability for the illness is believed to be caused by developmental defects of the CNS during foetal life or childhood. The causes may be of genetic or environmental origin. Studies of the brain have been one source of the hypothesis.Additional support for the hypothesis was gathered from research on obstetric complications (OCs) and the later development of schizophrenia. Some thirty studies have been performed on the subject but have been criticised on methodological grounds. There has been a need for further research to investigate the association. The aims of the thesis were to examine in large samples:· Whether there is an association between OCs and psychiatric illness, especially schizophrenia. · Whether this possible risk is associated with any specific kind of complications, according to a proposed classification with four subgroups.· Whether the effect of OCs could be confounded by maternal psychotic illness. · Whether the association between OCs and schizophrenia is modified by gender, age at onset or maternal psychotic illness. · Whether the ICD-9 diagnoses of schizophrenia in the National Inpatient Register used in the studies are in accordance with the criteria-based DSM-IV diagnosis.Methods: OCs were classified into four groups in chronological order because alterations in the brain may differ in topography due to the maturation of the foetus/infant. In a nation-wide cohort study 507,516 persons were followed-up with regard to early age at onset schizophrenia (238 cases). In a case-control study the birth records were scrutinised for 524 cases of schizophrenia and 1,043 controls, born 1960 and onwards. In addition, 509 jaundiced infants and 509 controls were followed-up regarding psychiatric inpatient care. Data on maternal psychotic illness were assessed by record linkage. The diagnosis of schizophrenia was validated from 98 psychiatric case records. Results and conclusions: There was some support for an increased risk of schizophrenia associated with all four proposed groups of OCs: 1. foetal malnutrition/ growth impairment (pre-eclampsia RR 2.5; 95% CI 1.3-4.5, ponderal index<20 RR 3.4; 95% CI 1.1-10.5), 2. prematurity (RR 3.4; 95% CI 1.4-8.2), 3. signs of asphyxia at birth (Apgar score<7 OR 2.7; 95% CI 1.5-4.8), and 4. jaundice (OR 2.1; 95%CI 1.1-3.7), though the latter association was weaker. Further, an increased risk for psychiatric inpatient care was found among persons who had suffered from jaundice compared to non-jaundiced infants (OR 2.5; 95% CI 1.1-5.5). Thus, it seems as if complications at different points of time during foetal life, delivery, and may be neonatal life are associated with schizophrenia. This is supported by other studies of early life risk factors.There was an increased risk for psychotic mothers to have OCs (RR 1.2; 95%CI 1.2-1.3) but there was no support for maternal psychotic illness being a confounder of the association between OCs and schizophrenia. The effect from unknown confounders could not of course be ruled out. Other types of studies are needed to understand the causal relationships. The risk of schizophrenia associated with OCs was not modified by gender, age at onset of illness or the presence of maternal psychotic illness. Even larger studies are needed to further investigate interaction effects.The ICD-9 diagnoses of schizophrenia in the National Inpatient Register were true positives according to DSM-IV criteria in 86% of cases. This is satisfactory for epidemiological studies.
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| 12. |
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| 13. |
- Döring, Nora, et al.
(author)
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Labour market position of young people and premature mortality in adult life : A 26-year follow-up of 569 528 Swedish 18 year-olds
- 2021
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In: The Lancet Regional Health. - : Elsevier BV. - 2666-7762. ; 3
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Journal article (peer-reviewed)abstract
- Background: Throughout the industrialized world, demand for low skilled labour is falling. The length of schooling is increasing in response, but so is the proportion of individuals not finishing upper secondary school. The objective of this study was to evaluate the associations between labour market positions at age 18 and all-cause and suicide- and accident-specific mortality in later adulthood.Methods: Labour market positions at age 18 were categorized for all Swedes born 1972-77 (n=630 959) into four main groups: employed, successful students, students not about to qualify (SNAQs), and individuals not in employment, education or training (NEETs). Cox proportional hazard models were fitted to assess allcause, suicide and accident mortality up to 2016 (ages 39-44), adjusting for high school grades, parental and own prior psychiatric diagnoses, and childhood socioeconomic status.Findings: SNAQs had substantially increased all-cause (men: HR=2.10; 95% CI 1.92-2.28, women: HR=1.64; 95% CI: 1.44-1.86), suicide (men: HR=2.16; CI: 1.86-2.51, women: HR=2.10; 95% CI 1.64-2.69), and accident specific (men: HR=2.08; 95% CI 1.77-2.44, women: 1.87; 95% CI 1.33;2.62) mortality risks compared to successful students. The risks were similar for NEETs. There was no increased risk among full-time employed compared to successful students.Interpretation: Expanding the educational system may be a natural response to falling demand for low skilled labour but not by far one that corrects the major societal challenge of it. Unless educational systems adequately respond to this challenge, only more inequality is to be expected ahead.
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| 14. |
- Galanti, Maria Rosaria, et al.
(author)
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School environment and mental health in early adolescence - a longitudinal study in Sweden (KUPOL)
- 2016
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In: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 16
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Journal article (peer-reviewed)abstract
- Background: Longitudinal studies indicate strong associations between school proficiency and indicators of mental health throughout adulthood, but the mechanisms of such associations are not fully elucidated. The Kupol study is a prospective cohort study in Sweden set up in order to: (i) describe the association of school pedagogic and social environment and its specific dimensions with the risk of mental ill-health and psychiatric disorders in adolescence; (ii) evaluate the direct effects of school pedagogic and social environment on mental health and the effects mediated by the individual's academic achievements; and (iii) assess if school pedagogic and social environment are associated with mental ill-health through epigenetic mechanisms, in particular those involving genes regulating the response to stress.Methods: The Kupol cohort at baseline consists of 3959 children attending the 7th grade of compulsory school (13-14 years old) in 8 regions of central Sweden in the school years 2013-2014 or 2014-2015. Three follow-up surveys in subsequent years are planned. Teachers' and students' perceptions of the culture, climate and ethos of their schools, and students' mental ill-health are assessed at the whole school level by annual questionnaire surveys. In order to conduct epigenetic analyses saliva specimens are collected from a nested sample of students at inception and two years later. Further, class-, family-and child-level information is collected at baseline and during each year of follow-up. Self-reported information is being complemented with register data via record-linkages to national and regional health and administrative registers.Discussion: The topic being investigated is new, and the sample constitutes the largest adolescent cohort in Sweden involved in an ad hoc study. Epigenetic analyses centered on environmental cues to stress response are a thoroughly new approach. Finally a notable feature is the multi-informant and multi-method data collection, with surveys at the school, class, family, and student level. Collaboration and data access: interested investigators should contact the coordinating centre. Additional information is available on the study's website, http://kupolstudien.se/.
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| 15. |
- Gao, Menghan, et al.
(author)
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Psychiatric comorbidity among women with endometriosis : nationwide cohort study in Sweden
- 2020
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In: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 223:3, s. 415.e1-415.e16
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Journal article (peer-reviewed)abstract
- Background Endometriosis is a common gynecologic condition affecting women of reproductive age. It has been linked with greater rates of depression and anxiety in small, cross-sectional, and clinical studies. Other studies have reported that women with endometriosis have increased risk of bipolar disorder. These reports suggest that psychiatric disorders might be more common among women with endometriosis, contributing to increased burden of mental ill-health in this population of women. However, this hypothesis has not been adequately studied.Objectives In this population-based study, we investigated the overall psychiatric comorbidity among women with endometriosis, and the role of familial liability.Study Design Several Swedish national registers were linked and used to follow all women born in Sweden in 1973–1990 for diagnosed psychiatric disorders and endometriosis from age 14 years until year 2016. Sibling comparison analyses were performed in a subsample of 173,650 families.Results After adjustment for birth characteristics and education, women with endometriosis had an increased risk of being later diagnosed with depressive-, anxiety and stress-related disorders, alcohol/drug dependence, and attention-deficit hyperactivity disorder compared with the general population and with their sisters without endometriosis. The adjusted hazard ratios ranged from 1.56 (95% confidence interval, 1.29–1.88) for depressive disorders to 1.98 (95% confidence interval, 1.34–2.93) for attention-deficit hyperactivity disorder in the sibling analysis. Also, women with previous affective psychotic disorders, depressive-, anxiety and stress-related disorders, eating disorders, personality disorders, and attention-deficit hyperactivity disorder were more likely to be later diagnosed with endometriosis. The adjusted hazard ratios ranged from 1.51 (95% confidence interval, 1.30–1.76) for depressive disorders to 1.93 (95% confidence interval, 1.47–2.52) for personality disorders.Conclusion These findings reveal a high degree of comorbidity between endometriosis and many psychiatric disorders that was not entirely explained by shared familial confounding. Clinical practice may consider psychosocial support to women with endometriosis and treating them from a multidisciplinary perspective.
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| 16. |
- Gong, Tong, et al.
(author)
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Perinatal exposure to traffic-related air pollution and autism spectrum disorders
- 2016
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In: Environmental Health Perspectives. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0091-6765. ; 125:1, s. 119-126
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Journal article (peer-reviewed)abstract
- Background: Studies from the United States indicate that exposure to air pollution in early life is associated with autism spectrum disorders (ASD) in children, but the evidence is not consistent with European data. Objective: We aimed to investigate the association between exposure to air pollution from road traffic and the risk of ASD in children, with careful adjustment for socioeconomic and other confounders. Method: Children born and residing in Stockholm, Sweden, during 1993–2007 with an ASD diagnosis were identified through multiple health registers and classified as cases (n = 5,136). A randomly selected sample of 18,237 children from the same study base constituted controls. Levels of nitrogen oxides (NOx) and particulate matter with diameter ≤ 10 μm (PM10) from road traffic were estimated at residential addresses during mother’s pregnancy and the child’s first year of life by dispersion models. Odds ratios (OR) and 95% confidence intervals (CI) for ASD with or without intellectual disability (ID) were estimated using logistic regression models after conditioning on municipality and calendar year of birth as well as adjustment for potential confounders. Result: Air pollution exposure during the prenatal period was not associated with ASD overall (OR = 1.00; 95% CI: 0.86, 1.15 per 10-μg/m3 increase in PM10 and OR = 1.02; 95% CI: 0.94, 1.10 per 20-μg/m3 increase in NOx during mother’s pregnancy). Similar results were seen for exposure during the first year of life, and for ASD in combination with ID. An inverse association between air pollution exposure and ASD risk was observed among children of mothers who moved to a new residence during pregnancy. Conclusion: Early-life exposure to low levels of NOx and PM10 from road traffic does not appear to increase the risk of ASD.
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| 17. |
- Hayes, Joseph F., et al.
(author)
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Prediction of individuals at high risk of chronic kidney disease during treatment with lithium for bipolar disorder
- 2021
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In: BMC Medicine. - : Springer Nature. - 1741-7015. ; 19:1
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Journal article (peer-reviewed)abstract
- Background Lithium is the most effective treatment in bipolar disorder. Its use is limited by concerns about risk of chronic kidney disease (CKD). We aimed to develop a model to predict risk of CKD following lithium treatment initiation, by identifying individuals with a high-risk trajectory of kidney function. Methods We used United Kingdom Clinical Practice Research Datalink (CPRD) electronic health records (EHRs) from 2000 to 2018. CPRD Aurum for prediction model development and CPRD Gold for external validation. We used elastic net regularised regression to generate a prediction model from potential features. We performed discrimination and calibration assessments in an external validation data set. We included all patients aged >= 16 with bipolar disorder prescribed lithium. To be included patients had to have >= 1 year of follow-up before lithium initiation, >= 3 estimated glomerular filtration rate (eGFR) measures after lithium initiation (to be able to determine a trajectory) and a normal (>= 60 mL/min/1.73 m(2)) eGFR at lithium initiation (baseline). In the Aurum development cohort, 1609 fulfilled these criteria. The Gold external validation cohort included 934 patients. We included 44 potential baseline features in the prediction model, including sociodemographic, mental and physical health and drug treatment characteristics. We compared a full model with the 3-variable 5-year kidney failure risk equation (KFRE) and a 3-variable elastic net model. We used group-based trajectory modelling to identify latent trajectory groups for eGFR. We were interested in the group with deteriorating kidney function (the high-risk group). Results The high risk of deteriorating eGFR group included 191 (11.87%) of the Aurum cohort and 137 (14.67%) of the Gold cohort. Of these, 168 (87.96%) and 117 (85.40%) respectively developed CKD 3a or more severe during follow-up. The model, developed in Aurum, had a ROC area of 0.879 (95%CI 0.853-0.904) in the Gold external validation data set. At the empirical optimal cut-point defined in the development dataset, the model had a sensitivity of 0.91 (95%CI 0.84-0.97) and a specificity of 0.74 (95% CI 0.67-0.82). However, a 3-variable elastic net model (including only age, sex and baseline eGFR) performed similarly well (ROC area 0.888; 95%CI 0.864-0.912), as did the KFRE (ROC area 0.870; 95%CI 0.841-0.898). Conclusions Individuals at high risk of a poor eGFR trajectory can be identified before initiation of lithium treatment by a simple equation including age, sex and baseline eGFR. Risk was increased in individuals who were younger at commencement of lithium, female and had a lower baseline eGFR. We did not identify strong predicters of eGFR decline specific to lithium-treated patients. Notably, lithium duration and toxicity were not associated with high-risk trajectory.
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| 18. |
- Hollander, Anna-Clara, et al.
(author)
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Validation study of randomly selected cases of PTSD diagnoses identified in a Swedish regional database compared with medical records : is the validity sufficient for epidemiological research?
- 2019
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In: BMJ Open. - : BMJ. - 2044-6055. ; 9:12
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Journal article (peer-reviewed)abstract
- OBJECTIVES: In Sweden, the patients' diagnoses are recorded in administrative registers. The research value of these registers is determined by their diagnostic validity, that is, if the diagnosis recorded meets the relevant diagnostic criteria. The aim of the study was to assess the validity of post-traumatic stress disorder (PTSD)-diagnoses as compared with case notes in medical records (MRs) and to test if there was a difference in validity by gender, migration status and those with and without psychotic symptoms. We hypothesised that the validity would be sufficient, using both Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV and DSM-5 but higher according to DSM-IV than DSM-5, and that the validity would be the same for men and women, but different for Swedish-born and migrants, and for those with and without psychotic symptoms.DESIGN AND SETTING: A validation of the register-diagnoses using MRs from treatment centres within the Region of Stockholm to examine whether patients with a register-diagnosis of PTSD fulfilled DSM criteria of PTSD according to the case notes in their MRs.PARTICIPANTS: A random sample of 187 patients aged 18-64, who had been diagnosed with PTSD (F43.1 in the ICD-10) were drawn from the Region of Stockholm's MR database 2013-2015.PRIMARY OUTCOME MEASURE: Validity of the PTSD diagnoses according to DSM-IV and DSM-5 as proportions of true positives with 95% CI.RESULTS: The hypothesised sufficient validity of the PTSD diagnoses was confirmed. Although the point-estimates for DSM-IV were higher than for DSM-5, the hypothesis that there would be significant differences in validity between DSM-IV and DSM-5 was not confirmed. There were no significant validity differences by gender, migration status and for those with and without psychotic symptoms.CONCLUSIONS: This study has found that validity of the PTSD diagnoses in the register of the Region of Stockholm to be sufficient for epidemiological research.
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| 19. |
- Kosidou, Kyriaki, et al.
(author)
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Immigration, Transition into Adult Life and Social Adversity in Relation to Psychological Distress and Suicide Attempts among Young Adults
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e46284-
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Journal article (peer-reviewed)abstract
- Background: The increasing incidence of mental health problems among young people is a major concern in many Western countries. The causal mechanisms underlying these trends are not well established, but factors influenced by current societal changes ought to be implicated. Such factors include immigration and social adversity as well as the timing of taking on adult social roles (e.g. gainful employment, parenthood and own housing tenure). We therefore examined relationships between these factors and the risks of psychological distress as well as suicide attempts in young adults, with a focus on gender differences. Methods: We conducted a population-based study including 10,081 individuals aged 18-29, recruited in 2002 and 2006 in Stockholm, Sweden. Data were collected by record linkage and questionnaires. Results: Non-European immigrants had an increased risk of distress, and female non-European immigrants had a markedly higher risk of suicide attempts. Both early parenthood (<= 24 years) and not being a parent, being a student and the lack of own housing tenure were associated with distress, but only in women. In both sexes, financial strain was associated with the increased risk of distress and suicide attempts, while unemployment was only associated with distress. Conclusions: Immigration from outside Europe and social adversity are associated with mental health problems in young adults, especially females. Postponed transition into adulthood is associated with poor mental health in young women. These factors are influenced by current societal changes, and may have contributed to the increasing incidence of mental health problems among young people in Western countries.
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| 20. |
- Kosidou, Kyriaki, et al.
(author)
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Socioeconomic status and risk of psychological distress and depression in the Stockholm Public Health Cohort : A population-based study
- 2011
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In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 134:1-3, s. 160-167
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Journal article (peer-reviewed)abstract
- Background: There is limited evidence whether the association between low socioeconomic status and risk of common mental disorders varies with symptom severity, type of socioeconomic indicator or gender. Methods: A population-based survey was conducted among a random sample of Stockholm County residents aged 18-84 years in 2002. Respondents were reassessed via a follow-up questionnaire in 2007. Participants in both surveys (n = 23794) were categorized according to socioeconomic status at baseline and followed up for onset of psychological distress (according to the twelve-item general health questionnaire) and depression (according to health data registers). Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Occupational class was not associated with risk of psychological distress, regardless of severity or gender. Occupational class was strongly associated with onset of depression in men (OR 3.0 [95% CI 1.5-5.9], comparing unskilled manual workers with higher non-manual workers) but not women. Income was associated with risk of onset of all outcomes, and risks increased with symptom severity. Belonging to the highest household income category was particularly protective of depression in women. Education was unrelated to either outcome in men and women overall. Limitations: Retention rate at follow-up was 76% and depression was ascertained via health service use. Conclusion: Low socioeconomic position is associated with onset of depression but not mild distress. Attributes of occupational class and household income may be respectively more relevant for the development of depression in men and women.
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| 21. |
- Lok, Veeleah, et al.
(author)
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Changes in anxiety and depression during the COVID-19 pandemic in the European population : A meta-analysis of changes and associations with restriction policies
- 2023
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In: European psychiatry. - 0924-9338 .- 1778-3585. ; 66:1
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Research review (peer-reviewed)abstract
- Background. Early studies of common mental disorders (CMDs) during the COVID-19 pandemic mainly report increases; however, more recent findings have been mixed. Also, studies assessing the effects of restriction measures on CMDs show varied results. The aim of this meta-analysis was to assess changes in levels of CMDs from pre-/early to during the pandemic and the effects of restriction policies in the European population.Methods. We searched for studies assessing both pre-pandemic and peri-pandemic self-reported emotional distress and symptoms of depression or anxiety among nationally/regionally representative samples in Europe and collected microdata from those studies. Estimates of corona containment index were related to changes in CMDs using random-effects meta-regression.Results. Our search strategy resulted in findings from 15 datasets drawn from 8 European countries being included in the meta-analysis. There was no evidence of change in the prevalence of emotional distress, anxiety, or depression from before to during the pandemic; but from early pandemic periods to later periods, there were significant decreases in emotional distress and anxiety. Increased school restrictions and social distancing were associated with small increases in self-reported emotional distress.Conclusions. Despite initial concerns of increased emotional distress and mental illness due to the COVID-19 pandemic, the results from this meta-analysis indicate that there was a decrease in emotional distress and no change in anxiety or depression in the general population in Europe. Overall, our findings support the importance of strong governance when implementing periodic and robust restriction measures to combat the spread of COVID-19.
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| 22. |
- Lundin, Andreas, et al.
(author)
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Discriminant validity of the 12-item version of the general health questionnaire in a Swedish case-control study
- 2017
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In: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 71:3, s. 171-179
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Journal article (peer-reviewed)abstract
- BACKGROUND: The 12-item version of the General Health Questionnaire (GHQ-12) is widely used as a proxy for Affective Disorders in public health surveys, although the cut-off points for distress vary considerably between studies. The agreement between the GHQ-12 score and having a clinical disorder in the study population is usually unknown.AIMS: This study aimed to assess the criterion validity and to determine the sensitivity and specificity of the GHQ-12 in the Swedish population.METHODS: This study used 556 patient cases surveyed in specialized psychiatric care outpatient age- and sex-matched with 556 controls from the Stockholm Health Survey. Criterion validity for two scoring methods of GHQ-12 was tested using Receiver Operating Characteristics (ROC) analyses with Area Under the Curve (AUC) as a measure of agreement. Reference standard was (1) specialized psychiatric care and (2) current depression, anxiety or adjustment disorder.RESULTS: Both the Likert and Standard GHQ-12 scoring method discriminated excellently between individuals using specialized psychiatric services and healthy controls (Likert index AUC = 0.86, GHQ index AUC = 0.83), and between individuals with current disorder from healthy controls (Likert index AUC = 0.90, GHQ index AUC = 0.88). The best cut-off point for the GHQ index was ≥4 (sensitivity = 81.7 and specificity = 85.4), and for the Likert index ≥14 (sensitivity = 85.5 and specificity = 83.2).CONCLUSIONS: The GHQ-12 has excellent discriminant validity and is well suited as a non-specific measure of affective disorders in public mental health surveys.
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| 23. |
- Magnusson, Cecilia, et al.
(author)
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Migration and autism-spectrum disorder : population-based study
- 2012
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In: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 201:2, s. 109-115
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Journal article (peer-reviewed)abstract
- Background: Migration has been implicated as a risk factor for autism, but evidence is limited and inconsistent. Aims: To investigate the relationship between parental migration status and risk of autism spectrum disorder, taking into consideration the importance of region of origin, timing of migration and possible discrepancies in associations between autism subtypes. Method: Record-linkage study within the total child population of Stockholm County between 2001 and 2007. Individuals with high- and low-functioning autism were defined as having autism spectrum disorder with and without comorbid intellectual disability, and ascertained via health and habilitation service registers. Results: In total, 4952 individuals with autism spectrum disorder were identified, comprising 2855 children with high-functioning autism and 2097 children with low-functioning autism. Children of migrant parents were at increased risk of low-functioning autism (odds ratio (OR) = 1.5, 95% CI 1.3-1.7); this risk was highest when parents migrated from regions with a low human development index, and peaked when migration occurred around pregnancy (OR=2.3, 95% CI 1.7-3.0). A decreased risk of high-functioning autism was observed in children of migrant parents, regardless of area of origin or timing of migration. Parental age, income or obstetric complications did not fully explain any of these associations. Conclusions: Environmental factors associated with migration may contribute to the development of autism presenting with comorbid intellectual disability, especially when acting in utero. High- and low-functioning autism may have partly different aetiologies, and should be studied separately.
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| 24. |
- Nguyen, Thuy-Dung, et al.
(author)
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Genetic Contribution to the Heterogeneity of Major Depressive Disorder : Evidence From a Sibling-Based Design Using Swedish National Registers
- 2023
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In: American Journal of Psychiatry. - : HighWire Press. - 0002-953X .- 1535-7228. ; 180:10, s. 714-722
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Major depressive disorder (MDD) is highly heterogeneous. Standard typology partly captures the disorder's symptomatic heterogeneity, although whether it adequately captures etiological heterogeneity remains elusive. The aim of this study was to investigate the genetic characterization of MDD heterogeneity.METHODS: Using Swedish patient register data on 1.5 million individuals, the authors identified 46,255 individuals with specialist-diagnosed MDD. Eighteen subgroups were identified based on nine comparison groups defined by clinical and psychosocial features, including severity, recurrence, comorbidities, suicidality, impairment, disability, care unit, and age at diagnosis. A sibling-based design and classic quantitative genetic models were applied to estimate heritability of MDD subgroups and genetic correlations between subgroups.RESULTS: Estimates of heritability ranged from 30.5% to 58.3% across subgroups. The disabled and youth-onset subgroups showed significantly higher heritability (55.1%-58.3%) than the overall MDD sample (45.3%, 95% CI=43.0-47.5), and the subgroups with single-episode MDD and without psychiatric comorbidity showed significantly lower estimates (30.5%-34.4%). Estimates of genetic correlations between the subgroups within comparison groups ranged from 0.33 to 0.90. Seven of nine genetic correlations were significantly smaller than 1, suggesting differences in underlying genetic architecture. These results were largely consistent with previous work using genomic data.CONCLUSIONS: The findings of differential heritability and partially distinct genetic components in subgroups provide important insights into the genetic heterogeneity of MDD and a deeper etiological understanding of MDD clinical subgroups.
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| 25. |
- Nguyen, Thi Thuy Dung, et al.
(author)
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GENETIC CONTRIBUTION TO MAJOR DEPRESSIVE DISORDER HETEROGENEITY- FAMILY DESIGNS USING SWEDISH NATIONAL REGISTERS
- 2021
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In: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 51, s. e110-e111
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Journal article (other academic/artistic)abstract
- Background: Major depressive disorders (MDD) is a common disorder with lifetime prevalence of ∼20%. MDD is phenotypically and genetically heterogenous. Estimated heritability of the disorder ranged between 30% and 50%. Heterogeneity hinders the discovery of genetic risk factors as well as treatment optimization of MDD. Some previous studies demonstrated the heterogeneity of MDD by comparing heritability and genetic correlation of MDD subtypes based on sexes, age at onset, recurrence, vegetative symptoms (atypical MDD). However, the results are inconclusive, and we still lack a comprehensive evidence of MDD subgroups heterogeneity.In our previous study (https://doi.org/10.1101/2021.03.05.21252911), we investigated major depression heterogeneity using genetic data in the UK Biobank cohort. The results indicated that major depression subtypes were divergent in their genetic architectures.Here we aim to unravel heterogeneity in key clinical indicators of MDD by estimating heritability (h2), and genetic correlations (rg) using diagnostic data from the Swedish population.Methods: Using the Swedish registers, we included ∼1.5 million individuals who were born in Sweden between 1977-1993. MDD cases (ICD-10 codes: F32, F33) were identified from the Swedish patients register. We defined 16 MDD clinical subgroups within 8 categories, severity (severe vs mild/moderate cases), anxiety comorbidity (MDD with vs without comorbid anxiety disorder), age at onset (early onset vs late onset), recurrence (recurrent vs single episode), suicidality (suicidal vs non-suicidal MDD), impairment (MDD with vs without impairment), disability (measured by MDD with vs without early retirement), and care unit (inpatient vs outpatient cases).We used structural equation modelling to estimate the proportion of genetic contribution to the liability of MDD subgroups (i.e., heritability), and the variance due to genetic contribution shared between 2 traits (i.e., genetic correlation). We estimated three components, additive genetic (A), shared environment (C), and unique environment (E) by contrasting full siblings and maternal half siblings.Results: Of the entire cohort, ∼88,000 MDD cases (∼5.9%) were identified. Estimated heritability of MDD was ∼40% which agreed with previous studies.Overall, subgroups with more severe manifestation tend to be more heritable compared with the subgroups in the same categories. MDD with comorbid anxiety disorder, early onset, recurrent episodes, suicide, and early retirement had higher heritability than the counterpart subgroups. Estimated heritability ranged between 19.6% (for late onset MDD) and 51.5% (for MDD with early retirement).All estimates for genetic correlation were lower than one which indicate non-identical genetic contribution of the subgroups within the same category. Three of the eight studied subgroup categories (suicidality, impairment, disability) showed genetic correlations (range 0.6-0.7) that significantly differ from one.Discussion: Our study suggested that heterogeneity of MDD can be demonstrated by clinical subgroups. The tendency of divergence in heritability, and the genetic correlations are lower than one in many subgroup categories indicated that the genetic profile of those subgroups are partially distinct. Finally, our results suggested that some clinical indices including suicidality, impairment and disability, may index genetic heterogeneity of MDD better than others indices.
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