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1.
  • Brew, Bronwyn K., et al. (author)
  • Comorbidity of atopic diseases and gastro-oesophageal reflux evidence of a shared cause
  • 2022
  • In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 52:7, s. 868-877
  • Journal article (peer-reviewed)abstract
    • Introduction: Gastro-oesophageal reflux disease (GERD) is the most common non-allergic comorbidity in adults with asthma; however, comorbidity with other atopic diseases such as eczema and hay fever is unclear. The objective was to assess the comorbidity of GERD with asthma and atopic diseases and to investigate possible mechanisms, including genetic and/or affective factors.Methods: A co-twin control study harnessing 46 583 adult twins. Questionnaires on health status were linked to national patient and prescribed drug register data. Analyses tested associations of comorbidity between multiple definitions of atopic diseases (self-report and register-based) with GERD. Comparisons were made between unpaired, monozygotic (MZ) and dizygotic (DZ) twins to assess genetic liability. Affective traits (depression, anxiety and neuroticism) were added to models as possible explanatory factors.Results: The risk of GERD in those with asthma was OR (odds ratio) 1.52 (95% CI 1.38, 1.68), hay fever OR 1.22 (95%CI 1.12, 1.34) and eczema OR 1.23 (95%CI 1.10, 1.38). Adjusting for affective traits completely attenuated the comorbidity associations for hay fever and eczema with GERD, and partly for asthma with GERD. Co-twin control associations attenuated suggesting a shared cause for both GERD and atopic diseases. For example, all twins adjOR 1.32 (95%CI 1.00, 1.74), 0.97 (95% CI 0.76–1.23) and 1.11 (95%CI 0.85–1.45) for self-report asthma, hay fever and eczema with GERD respectively.Conclusions: GERD is a common comorbidity in adults with asthma, hay fever and/or eczema. We found evidence for shared mechanisms suggesting common underlying causes that may involve affective traits requiring further investigation.
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2.
  • Cesta, Carolyn E, et al. (author)
  • Polycystic ovary syndrome, personality, and depression: A twin study.
  • 2017
  • In: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 85, s. 63-68
  • Journal article (peer-reviewed)abstract
    • Women with polycystic ovary syndrome (PCOS) are at elevated risk for suffering from depression. Neuroticism is a personality trait that has been associated with an increased risk for developing major depressive disorder (MDD). The aim of the present study was to quantify and decompose the correlation between neuroticism, PCOS, and MDD into shared and unique genetic and environmental etiologies, by using quantitative genetic methods.In a cohort of 12,628 Swedish female twins born from 1959 to 1985, neuroticism, PCOS identified by symptoms of hyperandrogenemia (i.e., hirsutism) and oligo- and/or anovulation, and lifetime MDD status were determined through questionnaire responses. Structural equation modeling was used to study the genetic and environmental sources of the variation within, and covariation between neuroticism, PCOS, and MDD.Female twins with PCOS (n=752) had significantly higher levels of neuroticism than women without PCOS, and a 2-fold increase in odds for a lifetime prevalence of MDD. The phenotypic correlation between PCOS and MDD was 0.19, with 63% of the correlation attributable to common genetic factors between the two traits. When taking into account neuroticism, 41% was attributable to common genetic factors and 9% attributable to common environmental factors shared between all three traits, with the remainder attributable to components unique to PCOS and MDD.There are common genetic factors between neuroticism, PCOS, and MDD; however, neuroticism shares approximately half of the genetic and environmental components behind the phenotypic correlation between PCOS and MDD, providing some etiological evidence behind the comorbidity between PCOS and depression.
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3.
  • Fabiano, Nicholas, et al. (author)
  • Physical Activity, Suicidal Ideation, Suicide Attempt and Death Among Individuals With Mental or Other Medical Disorders : A Systematic Review of Observational Studies
  • 2024
  • In: Neuroscience and Biobehavioral Reviews. - : Pergamon Press. - 0149-7634 .- 1873-7528. ; 158
  • Research review (peer-reviewed)abstract
    • A growing body of research has demonstrated the potential role for physical activity as an intervention across mental and other medical disorders. However, the association between physical activity and suicidal ideation, attempts, and deaths has not been systematically appraised in clinical samples. We conducted a PRISMA 2020-compliant systematic review searching MEDLINE, EMBASE, and PsycINFO for observational studies investigating the influence of physical activity on suicidal behaviour up to December 6, 2023. Of 116 eligible full-text studies, seven (n=141691) were included. Depression was the most frequently studied c mental condition (43%, k=3), followed by chronic pain as the most common other medical condition (29%, k=2). Two case-control studies examined suicide attempts and found an association between physical activity and a reduced frequency of such attempts. However, in studies examining suicidal ideation (k=3) or suicide deaths (k=2), no consistent associations with physical activity were observed. Overall, our systematic review found that physical activity may be linked to a lower frequency of suicide attempts in non-prospective studies involving individuals with mental disorders.
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4.
  • Haan, Elis, et al. (author)
  • Associations between attention-deficit hyperactivity disorder genetic liability and ICD-10 medical conditions in adults : utilizing electronic health records in a Phenome-Wide Association Study
  • 2024
  • In: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978.
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is often comorbid with other medical conditions in adult patients. However, ADHD is extremely underdiagnosed in adults and little is known about the medical comorbidities in undiagnosed adult individuals with high ADHD liability. In this study we investigated associations between ADHD genetic liability and electronic health record (EHR)-based ICD-10 diagnoses across all diagnostic categories, in individuals without ADHD diagnosis history.METHODS: We used data from the Estonian Biobank cohort (N = 111 261) and generated polygenic risk scores (PRS) for ADHD (PRSADHD) based on the ADHD genome-wide association study. We performed a phenome-wide association study (PheWAS) to test for associations between standardized PRSADHD and 1515 EHR-based ICD-10 diagnoses in the full and sex-stratified sample. We compared the observed significant ICD-10 associations to associations with (1) ADHD diagnosis and (2) questionnaire-based high ADHD risk analyses.RESULTS: After Bonferroni correction (p = 3.3 × 10-5) we identified 80 medical conditions associated with PRSADHD. The strongest evidence was seen with chronic obstructive pulmonary disease (OR 1.15, CI 1.11-1.18), obesity (OR 1.13, CI 1.11-1.15), and type 2 diabetes (OR 1.11, CI 1.09-1.14). Sex-stratified analysis generally showed similar associations in males and females. Out of all identified associations, 40% and 78% were also observed using ADHD diagnosis or questionnaire-based ADHD, respectively, as the predictor.CONCLUSIONS: Overall our findings indicate that ADHD genetic liability is associated with an increased risk of a substantial number of medical conditions in undiagnosed individuals. These results highlight the need for timely detection and improved management of ADHD symptoms in adults.
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5.
  • Karlsson, Ida K., et al. (author)
  • Age-dependent effects of body mass index across the adult life span on the risk of dementia : A cohort study with a genetic approach
  • 2020
  • In: BMC Medicine. - : BioMed Central. - 1741-7015. ; 18:1
  • Journal article (peer-reviewed)abstract
    • Background: While a high body mass index (BMI) in midlife is associated with higher risk of dementia, high BMI in late-life may be associated with lower risk. This study combined genetic designs with longitudinal data to achieve a better understanding of this paradox. Methods: We used longitudinal data from 22,156 individuals in the Swedish Twin Registry (STR) and 25,698 from the Health and Retirement Study (HRS). The STR sample had information about BMI from early adulthood through late-life, and the HRS sample from age 50 through late-life. Survival analysis was applied to investigate age-specific associations between BMI and dementia risk. To examine if the associations are influenced by genetic susceptibility to higher BMI, an interaction between BMI and a polygenic score for BMI (PGSBMI) was included in the models and results stratified into those with genetic predisposition to low, medium, and higher BMI. In the STR, co-twin control models were applied to adjust for familial factors beyond those captured by the PGSBMI. Results: At age 35-49, 5 units higher BMI was associated with 15% (95% CI 7-24%) higher risk of dementia in the STR. There was a significant interaction (p = 0.04) between BMI and the PGSBMI, and the association present only among those with genetic predisposition to low BMI (HR 1.38, 95% CI 1.08-1.78). Co-twin control analyses indicated genetic influences. After age 80, 5 units higher BMI was associated with 10-11% lower risk of dementia in both samples. There was a significant interaction between late-life BMI and the PGSBMI in the STR (p = 0.01), but not the HRS, with the inverse association present only among those with a high PGSBMI (HR 0.70, 95% CI 0.52-0.94). No genetic influences were evident from co-twin control models of late-life BMI. Conclusions: Not only does the association between BMI and dementia differ depending on age at BMI measurement, but also the effect of genetic influences. In STR, the associations were only present among those with a BMI in opposite direction of their genetic predisposition, indicating that the association between BMI and dementia across the life course might be driven by environmental factors and hence likely modifiable. © 2020 The Author(s).
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7.
  • Laidra, Kaia, et al. (author)
  • Estonian National Mental Health Study : Design and methods for a registry‐linked longitudinal survey
  • 2023
  • In: Brain and Behavior. - : John Wiley & Sons. - 2162-3279. ; 13:8
  • Journal article (peer-reviewed)abstract
    • ObjectivesThe Estonian National Mental Health Study (EMHS) was conducted in 2021–2022 to provide population-wide data on mental health in the context of COVID-19 pandemic. The main objective of this paper is to describe the rationale, design, and methods of the EMHS and to evaluate the survey response.MethodsRegionally representative stratified random sample of 20,000 persons aged 15 years and older was drawn from the Estonian Population Register for the study. Persons aged 18 years and older at the time of the sampling were enrolled into three survey waves where they were invited to complete an online or postal questionnaire about mental well-being and disorders, and behavioral, cognitive, and other risk factors. Persons younger than 18 years of age were invited to fill an anonymous online questionnaire starting from wave 2. To complement and validate survey data, data on socio-demographic, health-related, and environmental variables were collected from six national administrative databases and registries. Additionally, a subsample was enrolled into a validation study using ecological momentary assessment.ResultsIn total, 5636 adults participated in the survey wave 1, 3751 in wave 2, and 4744 in wave 3. Adjusted response rates were 30.6%, 21.1%, and 27.6%, respectively. Women and older age groups were more likely to respond. Throughout the three survey waves, a considerable share of adult respondents screened positive for depression (27.6%, 25.1%, and 25.6% in waves 1, 2, and 3, respectively). Women and young adults aged 18 to 29 years had the highest prevalence of depression symptoms.ConclusionsThe registry-linked longitudinal EMHS dataset comprises a rich and trustworthy data source to allow in-depth analysis of mental health outcomes and their correlates among the Estonian population. The study serves as an evidence base for planning mental health policies and prevention measures for possible future crises.
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10.
  • Solmi, Marco, et al. (author)
  • Effects of antipsychotic treatment on cardio-cerebrovascular related mortality in schizophrenia : A subanalysis of a systematic review and meta-analysis with meta-regression of moderators
  • 2024
  • In: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 88, s. 6-20
  • Research review (peer-reviewed)abstract
    • To further explore the role of different antipsychotic treatments for cardio-cerebrovascular mortality, we performed several subgroup, sensitivity and meta-regression analyses based on a large previous meta-analysis focusing on cohort studies assessing mortality relative risk (RR) for cardio-cerebrovascular disorders in people with schizophrenia, comparing antipsychotic treatment versus no antipsychotic. Quality assessment through the Newcastle-Ottawa Scale (NOS) and publication bias was measured. We meta-analyzed 53 different studies (schizophrenia patients: n = 2,513,359; controls: n = 360,504,484) to highlight the differential effects of antipsychotic treatment regimens on cardio-cerebrovascular-related mortality in incident and prevalent samples of patients with schizophrenia. We found first generation antipsychotics (FGA) to be associated with higher mortality in incident samples of schizophrenia (oral FGA [RR=2.20, 95 %CI=1.29-3.77, k = 1] and any FGA [RR=1.70, 95 %CI=1.20-2.41, k = 1]). Conversely, second generation antipsychotics (SGAs) and clozapine were associated with reduced cardio-cerebrovascular-related mortality, in prevalent samples of schizophrenia. Subgroup analyses with NOS score ≥7 (higher quality) demonstrated a significantly increased cardio-cerebrovascular disorder-related mortality, among those exposed to FGAs vs SGAs. Meta-regression analyses demonstrated a larger association between antipsychotics and decreased risk of mortality with longer follow-up, recent study year, and higher number of adjustment variables. Overall, this subanalysis of a systematic review contributes to the evolving understanding of the complex role of antipsychotic treatment for cardio-cerebrovascular mortality in schizophrenia, paving the way for more targeted interventions and improved patient outcomes.
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11.
  • Solmi, Marco, et al. (author)
  • Regional differences in mortality risk and in attenuating or aggravating factors in schizophrenia : A systematic review and meta-analysis
  • 2024
  • In: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 80, s. 55-69
  • Research review (peer-reviewed)abstract
    • People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020-compliant systematic review/random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) versus any control group, and moderators, in people with ICD/DSM-defined schizophrenia, comparing countries and continents. We conducted subgroup, meta-regression analyses, and quality assessment. The primary outcome was all-cause mortality. Secondary outcomes were suicide-, /natural-cause- and other-cause-related mortality. We included 135 studies from Europe (n = 70), North-America (n = 29), Asia (n = 33), Oceania (n = 2), Africa (n = 1). In incident plus prevalent schizophrenia, differences across continents emerged for all-cause mortality (highest in Africa, RR=5.98, 95 %C.I.=4.09-8.74, k = 1, lowest in North-America, RR=2.14, 95 %C.I.=1.92-2.38, k = 16), suicide (highest in Oceania, RR=13.5, 95 %C.I.=10.08-18.07, k = 1, lowest in North-America, RR=4.4, 95 %C.I.=4.07-4.76, k = 6), but not for natural-cause mortality. Europe had the largest association between antipsychotics and lower all-cause mortality/suicide (Asia had the smallest or no significant association, respectively), without differences for natural-cause mortality. Higher country socio-demographic index significantly moderated larger suicide-related and smaller natural-cause-related mortality risk in incident schizophrenia, with reversed associations in prevalent schizophrenia. Antipsychotics had a larger/smaller protective association in incident/prevalent schizophrenia regarding all-cause mortality, and smaller protective association for suicide-related mortality in prevalent schizophrenia. Additional regional differences emerged in incident schizophrenia, across countries, and secondary outcomes. Significant regional differences emerged for all-cause, cause-specific and suicide-related mortality. Natural-cause death was homogeneously increased globally. Moderators differed across countries. Global initiatives are needed to improve physical health in people with schizophrenia, local studies to identify actionable moderators.
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12.
  • Solmi, Marco, et al. (author)
  • Risk factors, prevention and treatment of weight gain associated with the use of antidepressants and antipsychotics : a state-of-the-art clinical review
  • 2024
  • In: Expert Opinion on Drug Safety. - : Ashley Mark Publishing Company. - 1474-0338 .- 1744-764X.
  • Research review (peer-reviewed)abstract
    • INTRODUCTION: People with severe mental illness have poor cardiometabolic health. Commonly used antidepressants and antipsychotics frequently lead to weight gain, which may further contribute to adverse cardiovascular outcomes.AREAS COVERED: We searched MEDLINE up to April 2023 for umbrella reviews, (network-)meta-analyses, trials and cohort studies on risk factors, prevention and treatment strategies of weight gain associated with antidepressants/antipsychotics. We developed 10 clinical recommendations.EXPERT OPINION: To prevent, manage, and treat antidepressant/antipsychotic-related weight gain, we recommend i) assessing risk factors for obesity before treatment, ii) monitoring metabolic health at baseline and regularly during follow-up, iii) offering lifestyle interventions including regular exercise and healthy diet based on patient preference to optimize motivation, iv) considering first-line psychotherapy for mild-moderate depression and anxiety disorders, v) choosing medications based on medications' and patient's weight gain risk, vi) choosing medications based on acute vs long-term treatment, vii) using effective, tolerated medications, viii) switching to less weight-inducing antipsychotics/antidepressants where possible, ix) using early weight gain as a predictor of further weight gain to inform the timing of intervention/switch options, and x) considering adding metformin or glucagon-like peptide-1 receptor agonists, or topiramate (second-line due to potential adverse cognitive effects) to antipsychotics, or aripiprazole to clozapine or olanzapine.
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