| 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. |
- 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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| 4. |
- 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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| 5. |
- Döring, Nora, et al.
(författare)
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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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Ingår i: The Lancet Regional Health. - : Elsevier BV. - 2666-7762. ; 3
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Gao, Menghan, et al.
(författare)
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Psychiatric comorbidity among women with endometriosis : nationwide cohort study in Sweden
- 2020
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 223:3, s. 415.e1-415.e16
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Hayes, Joseph F., et al.
(författare)
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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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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Lok, Veeleah, et al.
(författare)
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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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Ingår i: European psychiatry. - 0924-9338 .- 1778-3585. ; 66:1
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Forskningsöversikt (refereegranskat)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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| 9. |
- Nguyen, Thuy-Dung, et al.
(författare)
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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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Ingår i: American Journal of Psychiatry. - : HighWire Press. - 0002-953X .- 1535-7228. ; 180:10, s. 714-722
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Nguyen, Thi Thuy Dung, et al.
(författare)
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GENETIC CONTRIBUTION TO MAJOR DEPRESSIVE DISORDER HETEROGENEITY- FAMILY DESIGNS USING SWEDISH NATIONAL REGISTERS
- 2021
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 51, s. e110-e111
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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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