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Acute intermittent porphyria: comorbidity and shared familial risks with schizophrenia and bipolar disorder in Sweden.

https://arctichealth.org/en/permalink/ahliterature277339
Source
Br J Psychiatry. 2015 Dec;207(6):556-7
Publication Type
Article
Date
Dec-2015
Author
Martin Cederlöf
Sarah E Bergen
Henrik Larsson
Mikael Landén
Paul Lichtenstein
Source
Br J Psychiatry. 2015 Dec;207(6):556-7
Date
Dec-2015
Language
English
Publication Type
Article
Keywords
Bipolar Disorder - epidemiology
Cohort Studies
Comorbidity
Family Health
Female
Humans
Male
Porphyria, Acute Intermittent - epidemiology
Registries
Risk factors
Schizophrenia - epidemiology
Sweden
Abstract
Acute intermittent porphyria (AIP) has been associated with schizophrenia in some studies, but prior research is limited by the absence of comparison populations. Here, we linked Swedish registers to examine the risk of schizophrenia and bipolar disorder in 717 individuals diagnosed with AIP and their first-degree relatives, compared with matched individuals without AIP and their first-degree relatives. Individuals with AIP had a fourfold increased risk of schizophrenia or bipolar disorder. Similarly, relatives of individuals with AIP had double the risk of schizophrenia or bipolar disorder, suggesting that these associations may be as a result of common genetic influences.
PubMed ID
26494868 View in PubMed
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An epidemiological study of ADHD, substance use, and comorbid problems in incarcerated women in Sweden.

https://arctichealth.org/en/permalink/ahliterature260890
Source
J Atten Disord. 2015 Jan;19(1):44-52
Publication Type
Article
Date
Jan-2015
Author
Maija Konstenius
Henrik Larsson
Lena Lundholm
Bjorn Philips
Geurt van de Glind
Nitya Jayaram-Lindström
Johan Franck
Source
J Atten Disord. 2015 Jan;19(1):44-52
Date
Jan-2015
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Antisocial Personality Disorder - epidemiology
Attention Deficit Disorder with Hyperactivity - epidemiology - psychology
Comorbidity
Cross-Sectional Studies
Diagnostic and Statistical Manual of Mental Disorders
Female
Humans
Middle Aged
Prevalence
Prisoners - psychology - statistics & numerical data
Prisons
Substance-Related Disorders - epidemiology - psychology
Sweden - epidemiology
Young Adult
Abstract
The aim of this study was to examine the prevalence of ADHD and psychiatric comorbidity, including substance use in incarcerated women.
This was a cross-sectional study, consisting of two parts: (a) screening using the ADHD Self-Rating Scale (ASRS) and (b) diagnostic assessment using a structured interview.
A sample of 96 incarcerated women was screened and 56 underwent the diagnostic assessment. Twenty-nine percent of the women met the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnostic criteria for adult ADHD in the diagnostic assessment. Forty-four of the women had misuse of alcohol, and 83% had misuse of narcotics the year prior to the incarceration. The ASRS showed sensitivity of 1.0 and specificity of 0.66.
The prevalence rate of ADHD in incarcerated women was high and comparable to that in male offenders. Illicit stimulant use and antisocial personality disorder were significantly more common in women with ADHD. ASRS is useful as a screener in this population.
PubMed ID
22797213 View in PubMed
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Antipsychotics, mood stabilisers, and risk of violent crime.

https://arctichealth.org/en/permalink/ahliterature258846
Source
Lancet. 2014 Sep 27;384(9949):1206-14
Publication Type
Article
Date
Sep-27-2014
Author
Seena Fazel
Johan Zetterqvist
Henrik Larsson
Niklas Långström
Paul Lichtenstein
Source
Lancet. 2014 Sep 27;384(9949):1206-14
Date
Sep-27-2014
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Antipsychotic Agents - adverse effects
Crime - statistics & numerical data
Female
Humans
Male
Middle Aged
Registries
Risk factors
Sweden - epidemiology
Tranquilizing Agents - adverse effects
Violence - statistics & numerical data
Young Adult
Abstract
Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden.
We used linked Swedish national registers to study 82,647 patients who were prescribed antipsychotics or mood stabilisers, their psychiatric diagnoses, and subsequent criminal convictions in 2006-09. We did within-individual analyses to compare the rate of violent criminality during the time that patients were prescribed these medications versus the rate for the same patients while they were not receiving the drugs to adjust for all confounders that remained constant within each participant during follow-up. The primary outcome was the occurrence of violent crime, according to Sweden's national crime register.
In 2006-09, 40,937 men in Sweden were prescribed antipsychotics or mood stabilisers, of whom 2657 (6?5%) were convicted of a violent crime during the study period. In the same period, 41,710 women were prescribed these drugs, of whom 604 (1?4 %) had convictions for violent crime. Compared with periods when participants were not on medication, violent crime fell by 45% in patients receiving antipsychotics (hazard ratio [HR] 0?55, 95% CI 0?47-0?64) and by 24% in patients prescribed mood stabilisers (0?76, 0?62-0?93). However, we identified potentially important differences by diagnosis-mood stabilisers were associated with a reduced rate of violent crime only in patients with bipolar disorder. The rate of violence reduction for antipsychotics remained between 22% and 29% in sensitivity analyses that used different outcomes (any crime, drug-related crime, less severe crime, and violent arrest), and was stronger in patients who were prescribed higher drug doses than in those prescribed low doses. Notable reductions in violent crime were also recorded for depot medication (HR adjusted for concomitant oral medications 0?60, 95% CI 0?39-0?92).
In addition to relapse prevention and psychiatric symptom relief, the benefits of antipsychotics and mood stabilisers might also include reductions in the rates of violent crime. The potential effects of these drugs on violence and crime should be taken into account when treatment options for patients with psychiatric disorders are being considered.
The Wellcome Trust, the Swedish Prison and Probation Service, the Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare.
Notes
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Comment In: Lancet. 2014 Dec 6;384(9959):2024-525483163
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Comment In: Lancet. 2014 Sep 27;384(9949):1167-824816047
Comment In: Lancet. 2014 Dec 6;384(9959):2025-625483165
PubMed ID
24816046 View in PubMed
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Assessment of Posttraumatic Stress Disorder and Educational Achievement in Sweden.

https://arctichealth.org/en/permalink/ahliterature304015
Source
JAMA Netw Open. 2020 12 01; 3(12):e2028477
Publication Type
Journal Article
Date
12-01-2020
Author
Alba Vilaplana-Pérez
Anna Sidorchuk
Ana Pérez-Vigil
Gustaf Brander
Kayoko Isoumura
Eva Hesselmark
Laura Sevilla-Cermeño
Unnur A Valdimarsdóttir
Huan Song
Andreas Jangmo
Ralf Kuja-Halkola
Brian M D'Onofrio
Henrik Larsson
Gemma Garcia-Soriano
David Mataix-Cols
Lorena Fernández de la Cruz
Author Affiliation
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Source
JAMA Netw Open. 2020 12 01; 3(12):e2028477
Date
12-01-2020
Language
English
Publication Type
Journal Article
Keywords
Adult
Cognition
Educational Status
Female
Humans
International Classification of Diseases
Male
Medical History Taking - statistics & numerical data
Mental Health - statistics & numerical data
Needs Assessment
Risk factors
Siblings
Stress Disorders, Post-Traumatic - complications - diagnosis - epidemiology - psychology
Sweden - epidemiology
Abstract
Posttraumatic stress disorder (PTSD) has been associated with impaired educational performance. Previous studies on the disorder could not control for important measured and unmeasured confounders.
To prospectively investigate the association between PTSD and objective indicators of educational attainment across the life span, controlling for familial factors shared by full siblings, psychiatric comorbidity, and general cognitive ability.
This population-based cohort study included 2?244?193 individuals born in Sweden between January 1, 1973, and December 31, 1997, who were followed-up until December 31, 2013. Clusters of full siblings were used to account for familial factors. Data analyses were conducted between December 2018 and May 2020.
International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of PTSD in the Swedish National Patient Register.
Eligibility to access upper secondary education after finishing compulsory education, finishing upper secondary education, starting a university degree, and finishing a university degree.
Of the final cohort of 2?244?193 individuals (1?151?414 [51.3%] men) included in the analysis, 1?425?326 were assessed for finishing compulsory education (919 with PTSD), 2?001?944 for finishing upper secondary education (2013 with PTSD), and 1?796?407 and 1?356?741 for starting and finishing a university degree (2243 and 2254 with PTSD, respectively). Posttraumatic stress disorder was associated with lower odds of achieving each of the educational milestones during the study period, including 82% lower odds of finishing compulsory education (adjusted odds ratio [aOR], 0.18; 95% CI, 0.15-0.20), 87% lower odds of finishing upper secondary education (aOR, 0.13; 95% CI, 0.12-0.14), 68% lower odds of starting a university degree (aOR, 0.32; 95% CI, 0.28-0.35), and 73% lower odds of finishing a university degree (aOR, 0.27; 95% CI, 0.23-0.31). Estimates in the sibling comparison were attenuated (aOR range, 0.22-0.53) but remained statistically significant. Overall, excluding psychiatric comorbidities and adjusting for the successful completion of the previous milestone and general cognitive ability did not statistically significantly alter the magnitude of the associations.
Posttraumatic stress disorder was associated with educational impairment across the life span, and the associations were not entirely explained by shared familial factors, psychiatric comorbidity, or general cognitive ability. This finding highlights the importance of implementing early trauma-informed interventions in schools and universities to minimize the long-term socioeconomic consequences of academic failure in individuals with PTSD.
PubMed ID
33289847 View in PubMed
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Association and Familial Coaggregation of Idiopathic Dystonia With Psychiatric Outcomes.

https://arctichealth.org/en/permalink/ahliterature312004
Source
Mov Disord. 2020 12; 35(12):2270-2278
Publication Type
Journal Article
Date
12-2020
Author
Davide Martino
Gustaf Brander
Per Svenningsson
Henrik Larsson
Lorena Fernández de la Cruz
Author Affiliation
Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Source
Mov Disord. 2020 12; 35(12):2270-2278
Date
12-2020
Language
English
Publication Type
Journal Article
Keywords
Anxiety Disorders - epidemiology - genetics
Comorbidity
Dystonia
Humans
Mental Disorders - epidemiology - genetics
Quality of Life
Risk factors
Sweden - epidemiology
Abstract
Psychiatric comorbidities are common and major determinants of quality of life in idiopathic dystonia. Their prevalence estimates from service-based studies are heterogeneous.
We explored the association between idiopathic dystonia and depressive disorders, anxiety disorders, suicide attempts, and death by suicide using Swedish population-based registers.
Diagnoses of idiopathic dystonia and psychiatric outcomes from inpatient and outpatient specialist services (1997-2013) were collected from the National Patient Register and the Cause of Death Register. Familial associations were explored using the Multi-Generation Register. Adjusted logistic regression analyses measured associations with psychiatric disorders in individuals with dystonia compared with general population individuals and their unaffected siblings, as well as in full siblings of individuals with dystonia compared with full siblings of unaffected individuals.
Individuals with dystonia were more likely than those without to have a diagnosis of depressive disorder (adjusted odds ratio = 2.00, 95% confidence interval: 1.77-2.26), anxiety disorder (adjusted odds ratio = 2.13, 95% confidence interval: 1.90-2.39), and suicide attempts/death by suicide combined (adjusted odds ratio = 1.80, 95% confidence interval: 1.50-2.17), with odds higher in most idiopathic dystonia forms. In the full sibling comparison, estimates followed the same pattern, with overall attenuated magnitude. Full siblings of individuals with dystonia had higher likelihood of depressive or anxiety disorders and suicide attempts/death by suicide combined compared with siblings of individuals without dystonia.
Different forms of idiopathic dystonia confirm its association with increased risk for depressive and anxiety disorders and suicide attempts. Familial coaggregation of dystonia and these psychiatric comorbidities supports shared genetic and extragenetic factors. © 2020 International Parkinson and Movement Disorder Society.
PubMed ID
32940390 View in PubMed
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Association between ASMT and autistic-like traits in children from a Swedish nationwide cohort.

https://arctichealth.org/en/permalink/ahliterature107579
Source
Psychiatr Genet. 2014 Feb;24(1):21-7
Publication Type
Article
Date
Feb-2014
Author
Lina Jonsson
Henrik Anckarsäter
Anna Zettergren
Lars Westberg
Hasse Walum
Sebastian Lundström
Henrik Larsson
Paul Lichtenstein
Jonas Melke
Author Affiliation
Departments of aPharmacology bForensic Psychiatry, Institute of Neuroscience and Physiology at the Sahlgrenska Academy cGillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, University of Gothenburg dR&D Unit, Swedish Prison and Probation Service, Gothenburg eDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Source
Psychiatr Genet. 2014 Feb;24(1):21-7
Date
Feb-2014
Language
English
Publication Type
Article
Keywords
Acetylserotonin O-Methyltransferase - genetics
Autistic Disorder - genetics
Cohort Studies
Humans
Polymorphism, Genetic
Sweden
Abstract
Individuals with autism spectrum disorders often show low levels of melatonin, and it has been suggested that this decrease may be because of the low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin-synthesis pathway. Also, genetic variants in ASMT have been associated with autism, as well as with low ASMT activity and melatonin levels, suggesting that the low ASMT activity observed in autism may partly be because of variations within the ASMT gene. In this study, we present a symptom-based approach to investigate possible associations between ASMT and autistic-like traits in the general population. To this end, continuous measures of autistic-like traits were assessed in a nationally representative twin cohort (n=1771) from Sweden and six single nucleotide polymorphisms (SNPs), and a duplication of exons 2-8 in ASMT were genotyped. Our results show a nominally significant association, in girls, between one single nucleotide polymorphism (rs5949028) in the last intron of ASMT and social interaction impairments. No significant association, however, was observed with traits related to language impairment or restricted and repetitive behavior. In conclusion, our results support the possible involvement of the ASMT gene in autism spectrum disorders, and our finding that only one of the three traits shows association suggests that genetic research may benefit from adopting a symptom-specific approach to identify genes involved in autism psychopathology.
PubMed ID
23995775 View in PubMed
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Association between attention deficit hyperactivity disorder and asthma: a systematic review and meta-analysis and a Swedish population-based study.

https://arctichealth.org/en/permalink/ahliterature302540
Source
Lancet Psychiatry. 2018 09; 5(9):717-726
Publication Type
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review
Date
09-2018
Author
Samuele Cortese
Shihua Sun
Junhua Zhang
Esha Sharma
Zheng Chang
Ralf Kuja-Halkola
Catarina Almqvist
Henrik Larsson
Stephen V Faraone
Author Affiliation
Center for Innovation in Mental Health, Academic Unit of Psychology, and Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK; New York University Child Study Center, New York, NY, USA; Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK. Electronic address: samuele.cortese@soton.ac.uk.
Source
Lancet Psychiatry. 2018 09; 5(9):717-726
Date
09-2018
Language
English
Publication Type
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review
Keywords
Asthma - epidemiology
Attention Deficit Disorder with Hyperactivity - epidemiology
Comorbidity
Humans
Sweden - epidemiology
Abstract
Several studies have assessed the possible association between attention deficit hyperactivity disorder (ADHD) and asthma. However, existing evidence is inconclusive as to whether this association remains after controlling for possible important confounders. To fill this knowledge gap, we did a systematic review and meta-analysis, followed by a population-based study.
For the systematic review and meta-analysis, we searched PubMed, PsycINFO, Embase, Embase Classic, Ovid MEDLINE, and Web of Knowledge databases up to Oct 31, 2017, for observational studies allowing estimation of the association between asthma and ADHD. No restrictions to date, language, or article type were applied. Unpublished data were collected from authors of the identified studies. We extracted unadjusted and adjusted odds ratios (ORs) from the identified studies and calculated ORs when they were not reported. We assessed study quality using the Newcastle-Ottawa Scale and study heterogeneity using I2 statistics. A random-effects model was used to calculate pooled ORs. The systematic review is registered with PROSPERO (CRD42017073368). To address the fact that the ORs obtained in the meta-analysis were adjusted for confounders that inevitably varied across studies, we did a population-based study of individuals in multiple national registers in Sweden. We calculated an unadjusted OR and an OR that was simultaneously adjusted for all confounders identified in a directed acyclic graph based on the studies of asthma and ADHD identified in our systematic review.
We identified 2649 potentially eligible citations, from which we obtained 49 datasets including a total of 210?363 participants with ADHD and 3?115?168 without. The pooled unadjusted OR was 1·66 (95% CI 1·22-2·26; I2 =99·47) and the pooled adjusted OR was 1·53 (1·41-1·65; I2 =50·76), indicating a significant association between asthma and ADHD. Possible lack of representativeness of the study population was detected with the Newcastle-Ottawa Scale in 42 of 49 datasets. In the population-based study, we included 1?575?377 individuals born between Jan 1, 1992, and Dec 31, 2006, of whom 259?253 (16·5%) had asthma and 57?957 (3·7%) had ADHD. Asthma was significantly associated with ADHD (OR 1·60, 95% CI 1·57-1·63) in the crude model adjusting for sex and year of birth, and this association remained significant after simultaneous adjustment for all covariates (1·45, 1·41-1·48).
The combined results of the meta-analysis and the population-based study support a significant association between asthma and ADHD, which remained even after simultaneously controlling for several possible confounders in the population-based study. Awareness of this association might help to reduce delay in the diagnosis of both ADHD and asthma.
Swedish Research Council and Shire International GmbH.
Notes
CommentIn: Lancet Psychiatry. 2018 Sep;5(9):689-690 PMID 30054260
CommentIn: Lancet Psychiatry. 2018 Dec;5(12):963 PMID 30477653
PubMed ID
30054261 View in PubMed
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The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study.

https://arctichealth.org/en/permalink/ahliterature272129
Source
Bipolar Disord. 2015 May;17(3):340-4
Publication Type
Article
Date
May-2015
Author
Martin Cederlöf
Sarah E Bergen
Niklas Långström
Henrik Larsson
Marcus Boman
Nick Craddock
Per Östberg
Sebastian Lundström
Arvid Sjölander
Klas Nordlind
Mikael Landén
Paul Lichtenstein
Source
Bipolar Disord. 2015 May;17(3):340-4
Date
May-2015
Language
English
Publication Type
Article
Keywords
Bipolar Disorder - epidemiology - genetics
Cohort Studies
Darier Disease - epidemiology - genetics
Genetic Predisposition to Disease
Humans
Odds Ratio
Pedigree
Registries
Risk
Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics
Schizophrenia - epidemiology - genetics
Sweden - epidemiology
Abstract
Darier disease is an autosomal dominant skin disorder caused by mutations in the ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) gene and previously reported to cosegregate with bipolar disorder and schizophrenia in occasional pedigrees. It is, however, unknown whether these associations exist also in the general population, and the objective of this study was to examine this question.
We compared a national sample of individuals with Darier disease and their first-degree relatives with matched unexposed individuals from the general population and their first-degree relatives, respectively. To examine risks for bipolar disorder and schizophrenia, risk ratios and 95% confidence intervals (CIs) were estimated using conditional logistic regressions.
Individuals with Darier disease had a 4.3 times higher risk of being diagnosed with bipolar disorder (95% CI: 2.6-7.3) and a 2.3 times higher risk of being diagnosed with schizophrenia (95% CI: 1.1-5.2) than matched individuals from the general population. Relatives of individuals with Darier disease had a 1.6 times higher risk of having bipolar disorder (95% CI: 1.1-2.5) than relatives of matched individuals from the general population, but no increased risk of schizophrenia (risk ratio = 0.8, 95% CI: 0.4-1.8).
The association between Darier disease and bipolar disorder is manifest also in the population, and our data suggest that genetic variability within the ATP2A2 gene that causes Darier disease also confers susceptibility for bipolar disorder. The Darier-causing mutations merit additional attention in molecular genetic research on bipolar disorder.
PubMed ID
25213221 View in PubMed
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The association between general childhood psychopathology and adolescent suicide attempt and self-harm: A prospective, population-based twin study.

https://arctichealth.org/en/permalink/ahliterature306305
Source
J Abnorm Psychol. 2020 May; 129(4):364-375
Publication Type
Journal Article
Twin Study
Date
May-2020
Author
Lauren M O'Reilly
Erik Pettersson
Patrick D Quinn
E David Klonsky
Sebastian Lundström
Henrik Larsson
Paul Lichtenstein
Brian M D'Onofrio
Author Affiliation
Department of Psychological and Brain Sciences.
Source
J Abnorm Psychol. 2020 May; 129(4):364-375
Date
May-2020
Language
English
Publication Type
Journal Article
Twin Study
Keywords
Adolescent
Anxiety - psychology
Child
Diseases in Twins - psychology
Female
Humans
Impulsive Behavior - physiology
Longitudinal Studies
Male
Mental Disorders - psychology
Prospective Studies
Risk factors
Self Report
Self-Injurious Behavior - psychology
Suicide, Attempted - psychology
Sweden
Twins
Abstract
Few quantitative behavior genetic studies have examined why psychopathology is associated with suicide attempt (SA) and self-harm (SH) in adolescence. The present study analyzed data from the Child and Adolescent Twin Study in Sweden to examine the extent to which genetic and environmental factors explain SA/SH and its association with psychopathology in childhood, an often-cited risk factor of subsequent SA/SH. When children were 9 or 12 years old (n = 30,444), parents completed the Autism-Tics, AD/HD and other Comorbidities Inventory (Larson et al., 2010) regarding their children's psychiatric problems as part of an ongoing, longitudinal study. At age 18 years (n = 10,269), adolescents completed self-report questionnaires, including SA/SH assessments. In a bifactor model of childhood psychopathology, a general factor of psychopathology was a statistically significant predictor of adolescent SA/SH at a higher magnitude (ß, 0.25, 95% confidence interval [CI; 0.15, 0.34] for suicide attempt), as compared with specific factors of inattention, impulsivity, oppositional behavior, and anxiety/emotion symptoms. Quantitative genetic modeling indicated that the additive genetic influences on the general factor accounted for the association with each outcome (ß, 0.24, 95% CI [0.13, 0.34] for suicide attempt). The results remained virtually identical when we fit a higher order factors model. Two additional outcomes demonstrated comparable results. The results extend current literature by revealing the shared genetic overlap between general psychopathology during childhood and adolescent SA/SH. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
PubMed ID
32271026 View in PubMed
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Association Between Maternal Smoking During Pregnancy and Severe Mental Illness in Offspring.

https://arctichealth.org/en/permalink/ahliterature283442
Source
JAMA Psychiatry. 2017 Jun 01;74(6):589-596
Publication Type
Article
Date
Jun-01-2017
Author
Patrick D Quinn
Martin E Rickert
Caroline E Weibull
Anna L V Johansson
Paul Lichtenstein
Catarina Almqvist
Henrik Larsson
Anastasia N Iliadou
Brian M D'Onofrio
Source
JAMA Psychiatry. 2017 Jun 01;74(6):589-596
Date
Jun-01-2017
Language
English
Publication Type
Article
Keywords
Causality
Cohort Studies
Cross-Sectional Studies
Female
Gene-Environment Interaction
Humans
Male
Mental Disorders - epidemiology - etiology - genetics
Pregnancy
Prenatal Exposure Delayed Effects - epidemiology
Registries - statistics & numerical data
Risk
Smoking - adverse effects - epidemiology
Statistics as Topic
Sweden
Abstract
Several recent population-based studies have linked exposure to maternal smoking during pregnancy to increased risk of severe mental illness in offspring (eg, bipolar disorder, schizophrenia). It is not yet clear, however, whether this association results from causal teratogenic effects or from confounding influences shared by smoking and severe mental illness.
To examine the association between smoking during pregnancy and severe mental illness in offspring, adjusting for measured covariates and unmeasured confounding using family-based designs.
This study analyzed population register data through December 31, 2013, for a cohort of 1 680 219 individuals born in Sweden from January 1, 1983, to December 31, 2001. Associations between smoking during pregnancy and severe mental illness in offspring were estimated with adjustment for measured covariates. Cousins and siblings who were discordant on smoking during pregnancy and severe mental illness were then compared, which helped to account for unmeasured genetic and environmental confounding by design.
Maternal self-reported smoking during pregnancy, obtained from antenatal visits.
Severe mental illness, with clinical diagnosis obtained from inpatient and outpatient visits and defined using International Classification of Diseases codes for bipolar disorder and schizophrenia spectrum disorders.
Of the 1 680 219 offspring included in the analysis, 816 775 (48.61%) were female. At the population level, offspring exposed to moderate and high levels of smoking during pregnancy had greater severe mental illness rates than did unexposed offspring (moderate smoking during pregnancy: hazard ratio [HR], 1.25; 95% CI, 1.19-1.30; high smoking during pregnancy: HR, 1.51; 95% CI, 1.44-1.59). These associations decreased in strength with increasing statistical and methodologic controls for familial confounding. In sibling comparisons with within-family covariates, associations were substantially weaker and nonsignificant (moderate smoking during pregnancy: HR, 1.09; 95% CI, 0.94-1.26; high smoking during pregnancy: HR, 1.14; 95% CI, 0.96-1.35). The pattern of associations was consistent across subsets of severe mental illness disorders and was supported by further sensitivity analyses.
This population- and family-based study failed to find support for a causal effect of smoking during pregnancy on risk of severe mental illness in offspring. Rather, these results suggest that much of the observed population-level association can be explained by measured and unmeasured factors shared by siblings.
PubMed ID
28467540 View in PubMed
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