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Martin, J., Walters, R. K., Demontis, D., Mattheisen, M., Lee, S. H., Robinson, E., . . . Neale, B. M. (2018). A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry, 83(12), 1044-1053
Open this publication in new window or tab >>A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder
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2018 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 12, p. 1044-1053Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases.

METHODS: We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls).

RESULTS: Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with r(g) estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15).

CONCLUSIONS: Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
ADHD, Epidemiology, GWAS, Neurodevelopmental disorders, Polygenic risk score analysis, Sex bias
National Category
Neurology Psychiatry
Identifiers
urn:nbn:se:oru:diva-67268 (URN)10.1016/j.biopsych.2017.11.026 (DOI)000433241800013 ()29325848 (PubMedID)2-s2.0-85040102598 (Scopus ID)
Note

Funding Agencies:

National Human Genome Research Institute of the National Institutes of Health (NIH)  R44HG006981 

Wellcome Trust  106047 

Australian National Health and Medical Research Council  1078901  1087889 

Stanley Medical Research Institute  

NIH  1R01MH094469  1R01MH107649-01 

Lundbeck Foundation  R102-A9118  R155-2014-1724 

European Research Council  294838 

European Community's Horizon 2020 Programme (H2020/2014-2020)  667302 

Novo Nordisk Foundation  

Aarhus university  

Copenhagen university  

Merz  

Shire  

Lundbeck  

Rhodes  

Arbor  

KenPharm  

Ironshore  

Akili Interactive Labs  

CogCubed  

Alcobra  

VAYA  

Sunovion  

Genomind  

NeuroLifeSciences  

Neurovance  

Otsuka  

McNeil  

Janssen  

Novartis  

Pfizer  

Eli Lilly 

Available from: 2018-06-15 Created: 2018-06-15 Last updated: 2018-09-06Bibliographically approved
Mataix-Cols, D., Frans, E., Pérez-Vigil, A., Kuja-Halkola, R., Gromark, C., Isomura, K., . . . Larsson, H. (2018). A total-population multigenerational family clustering study of autoimmune diseases in obsessive-compulsive disorder and Tourette's/chronic tic disorders. Molecular Psychiatry, 23(7), 1652-1658
Open this publication in new window or tab >>A total-population multigenerational family clustering study of autoimmune diseases in obsessive-compulsive disorder and Tourette's/chronic tic disorders
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2018 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 7, p. 1652-1658Article in journal (Refereed) Published
Abstract [en]

The association between obsessive-compulsive disorder (OCD) and Tourette's/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013. The risk of 40 ADs was evaluated in individuals with OCD, individuals with TD/CTD and their first- (siblings, mothers, fathers), second- (half siblings) and third-degree (cousins) relatives, compared with population controls. Individuals with OCD and TD/CTD had increased comorbidity with any AD (43% and 36%, respectively) and many individual ADs. The risk of any AD and several individual ADs was consistently higher among first-degree relatives than among second- and third-degree relatives of OCD and TD/CTD probands. The risk of ADs was very similar in mothers, fathers and siblings of OCD probands, whereas it tended to be higher in mothers and fathers of TD/CTD probands (compared with siblings). The results suggest a familial link between ADs in general (that is, not limited to Streptococcus-related conditions) and both OCD and TD/CTD. Additional mother-specific factors, such as the placental transmission of antibodies, cannot be fully ruled out, particularly in TD/CTD.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-63026 (URN)10.1038/mp.2017.215 (DOI)000442358000013 ()29133949 (PubMedID)2-s2.0-85052061087 (Scopus ID)
Funder
The Swedish Brain FoundationForte, Swedish Research Council for Health, Working Life and Welfare, 201500569Swedish Research Council, K2013-61P-22168
Note

Funding Agencies:

Tourette Association of America

Alicia Koplowitz Foundation

NIMH  R01MH105500  R01MH110427

Swedish Research Council through the SIMSAM (Swedish Initiative for Research on Microdata in the Social And Medical Sciences)  340-2013-5867

Available from: 2017-12-07 Created: 2017-12-07 Last updated: 2018-09-06Bibliographically approved
MacCabe, J. H., Sariaslan, A., Almqvist, C., Lichtenstein, P., Larsson, H. & Kyaga, S. (2018). Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression: a Swedish population-based case-control study and sib-pair analysis. British Journal of Psychiatry, 212(6), 370-376
Open this publication in new window or tab >>Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression: a Swedish population-based case-control study and sib-pair analysis
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2018 (English)In: British Journal of Psychiatry, ISSN 0007-1250, E-ISSN 1472-1465, Vol. 212, no 6, p. 370-376Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Many studies have addressed the question of whether mental disorder is associated with creativity, but high-quality epidemiological evidence has been lacking.

AIMS: To test for an association between studying a creative subject at high school or university and later mental disorder.

METHOD: In a case-control study using linked population-based registries in Sweden (N = 4 454 763), we tested for associations between tertiary education in an artistic field and hospital admission with schizophrenia (N = 20 333), bipolar disorder (N = 28 293) or unipolar depression (N = 148 365).

RESULTS: Compared with the general population, individuals with an artistic education had increased odds of developing schizophrenia (odds ratio = 1.90, 95% CI = [1.69; 2.12]) bipolar disorder (odds ratio = 1.62 [1.50; 1.75]) and unipolar depression (odds ratio = 1.39 [1.34; 1.44]. The results remained after adjustment for IQ and other potential confounders.

CONCLUSIONS: Students of artistic subjects at university are at increased risk of developing schizophrenia, bipolar disorder and unipolar depression in adulthood.

Place, publisher, year, edition, pages
Royal College of Psychiatry, 2018
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-66876 (URN)10.1192/bjp.2018.23 (DOI)000434294200007 ()29697041 (PubMedID)
Note

Funding Agencies:

Brain and Behaviour Research Foundation  

Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Psychology and Neuroscience  

Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences  340-2013-5867 

South London and Maudsley National Health Service Foundation Trust 

Available from: 2018-05-23 Created: 2018-05-23 Last updated: 2018-08-02Bibliographically approved
Cortese, S., Sun, S., Zhang, J., Sharma, E., Chang, Z., Kuja-Halkola, R., . . . Faraone, S. V. (2018). Association between attention deficit hyperactivity disorder and asthma: a systematic review and meta-analysis and a Swedish population-based study. Lancet psychiatry, 5(9), 717-726
Open this publication in new window or tab >>Association between attention deficit hyperactivity disorder and asthma: a systematic review and meta-analysis and a Swedish population-based study
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2018 (English)In: Lancet psychiatry, ISSN 2215-0374, E-ISSN 2215-0366, Vol. 5, no 9, p. 717-726Article, review/survey (Refereed) Published
Abstract [en]

Background: 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.

Methods: 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 I (2) 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.

Findings: 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; I-2 = 99.47) and the pooled adjusted OR was 1.53 (1.41-1.65; I-2 = 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, 1.41-10.48).

Interpretation: 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.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-68761 (URN)10.1016/S2215-0366(18)30224-4 (DOI)000442694900018 ()30054261 (PubMedID)
Funder
Swedish Research Council
Note

Funding Agency:

Shire International GmbH 

Available from: 2018-09-07 Created: 2018-09-07 Last updated: 2018-09-07Bibliographically approved
Pérez-Vigil, A., Fernández de la Cruz, L., Brander, G., Isomura, K., Jangmo, A., Feldman, I., . . . Mataix-Cols, D. (2018). Association of Obsessive-Compulsive Disorder With Objective Indicators of Educational Attainment: A Nationwide Register-Based Sibling Control Study. JAMA psychiatry, 75(1), 47-55
Open this publication in new window or tab >>Association of Obsessive-Compulsive Disorder With Objective Indicators of Educational Attainment: A Nationwide Register-Based Sibling Control Study
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2018 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 75, no 1, p. 47-55Article in journal (Refereed) Published
Abstract [en]

Importance: To our knowledge, the association of obsessive-compulsive disorder (OCD) and academic performance has not been objectively quantified.

Objective: To investigate the association of OCD with objectively measured educational outcomes in a nationwide cohort, adjusting for covariates and unmeasured factors shared between siblings.

Design, Setting, And Participants: This population-based birth cohort study included 2 115 554 individuals who were born in Sweden between January 1, 1976, and December 31, 1998, and followed up through December 31, 2013. Using the Swedish National Patient Register and previously validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, we identified persons with OCD; within the cohort, we identified 726 198 families with 2 or more full siblings, and identified 11 482 families with full siblings discordant for OCD. Data analyses were conducted from October 1, 2016, to September 25, 2017.

Main Outcomes and Measures: The study evaluates the following educational milestones: eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, finishing a university degree, and finishing postgraduate education.

Results: Of the 2 115 554 individuals in the cohort, 15 120 were diagnosed with OCD (59% females). Compared with unexposed individuals, those with OCD were significantly less likely to pass all core and additional courses at the end of compulsory school (adjusted odds ratio [aOR] range, 0.35-0.60) and to access a vocational or academic program in upper secondary education (aOR, 0.47; 95% CI, 0.45-0.50 and aOR, 0.61; 95% CI, 0.58-0.63, for vocational and academic programs, respectively). People with OCD were also less likely to finish upper secondary education (aOR, 0.43; 95% CI, 0.41-0.44), start a university degree (aOR, 0.72; 95% CI, 0.69-0.75), finish a university degree (aOR, 0.59; 95% CI, 0.56-0.62), and finish postgraduate education (aOR, 0.52; 95% CI, 0.36-0.77). The results were similar in the sibling comparison models. Individuals diagnosed with OCD before age 18 years showed worse educational attainment across all educational levels compared with those diagnosed at or after age 18 years. Exclusion of patients with comorbid neuropsychiatric disorders, psychotic, anxiety, mood, substance use, and other psychiatric disorders resulted in attenuated estimates, but patients with OCD were still impaired across all educational outcomes.

Conclusions and Relevance: Obsessive-compulsive disorder, particularly when it has an early onset, is associated with a pervasive and profound decrease in educational attainment, spanning from compulsory school to postgraduate education.

Place, publisher, year, edition, pages
Chicago, USA: American Medical Association, 2018
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-63024 (URN)10.1001/jamapsychiatry.2017.3523 (DOI)000419177700010 ()29141084 (PubMedID)
Funder
Swedish Research Council, K2013-61P-22168
Note

Funding Agencies:

International OCD Foundation  

Alicia Koplowitz Foundation  

Junior Researcher grant from the Swedish Research Council for Health, Working Life, and Welfare (FORTE grant)  2015-00569 

Karolinska Institutet PhD stipend (KID-funding) 

Available from: 2017-12-07 Created: 2017-12-07 Last updated: 2018-01-19Bibliographically approved
Pérez-Vigil, A., Fernández de la Cruz, L., Brander, G., Isomura, K., Jangmo, A., Kuja-Halkola, R., . . . Mataix-Cols, D. (2018). Association of Tourette Syndrome and Chronic Tic Disorders With Objective Indicators of Educational Attainment: A Population-Based Sibling Comparison Study. JAMA Neurology, 75(9), 1098-1105
Open this publication in new window or tab >>Association of Tourette Syndrome and Chronic Tic Disorders With Objective Indicators of Educational Attainment: A Population-Based Sibling Comparison Study
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2018 (English)In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 75, no 9, p. 1098-1105Article in journal (Refereed) Published
Abstract [en]

Importance: The influence of Tourette syndrome and chronic tic disorders on academic performance has not been objectively quantified.

Objective: To investigate the association of Tourette syndrome and chronic tic disorders with objectively measured educational outcomes, adjusting for measured covariates and unmeasured factors shared between siblings and taking common psychiatric comorbidities into account.

Design, Setting, and Participants: A population-based birth cohort consisting of all individuals born in Sweden from 1976 to 1998 was followed up until December 2013. Individuals with organic brain disorders, mental retardation, and 2 foreign-born parents were excluded. We further identified families with at least 2 singleton full siblings and families with siblings discordant for Tourette syndrome or chronic tic disorders.

Exposures: Previously validated International Classification of Diseases diagnoses of Tourette syndrome or chronic tic disorders in the Swedish National Patient Register.

Main Outcomes and Measures: Eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, and finishing a university degree.

Results: Of the 2 115 554 individuals in the cohort, 3590 had registered a diagnosis of Tourette syndrome or a chronic tic disorder in specialist care (of whom 2822 [78.6%] were male; median [interquartile] age at first diagnosis, 14.0 [11-18] years). Of 726 198 families with at least 2 singleton full siblings, 2697 included siblings discordant for these disorders. Compared with unexposed individuals, people with Tourette syndrome or chronic tic disorders were significantly less likely to pass all core and additional courses at the end of compulsory school (odds ratios ranging from 0.23 [95% CI, 0.20-0.26] for the handcraft textile/wood course to 0.36 [95% CI, 0.31-0.41] for the English language course) and to access a vocational program (adjusted OR [aOR], 0.31; 95% CI, 0.28-0.34) or academic program (aOR, 0.43; 95% CI, 0.39-0.47) in upper secondary education. Individuals with the disorders were also less likely to finish upper secondary education (aOR, 0.35; 95% CI, 0.32-0.37), start a university degree (aOR, 0.41; 95% CI, 0.37-0.46), and finish a university degree (aOR, 0.39; 95% CI, 0.32-0.48). The results were only marginally attenuated in the fully adjusted sibling comparison models. Exclusion of patients with neuropsychiatric comorbidities, particularly attention-deficit/hyperactivity disorder and pervasive developmental disorders, resulted in attenuated estimates, but patients with Tourette syndrome or chronic tic disorders were still significantly impaired across all outcomes.

Conclusions and Relevance: Help-seeking individuals with Tourette syndrome or chronic tic disorders seen in specialist settings experience substantial academic underachievement across all educational levels, spanning from compulsory school to university, even after accounting for multiple confounding factors and psychiatric comorbidities.

Place, publisher, year, edition, pages
American Medical Association, 2018
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-67137 (URN)10.1001/jamaneurol.2018.1194 (DOI)29813161 (PubMedID)2-s2.0-85053030785 (Scopus ID)
Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2018-09-18Bibliographically approved
Wiggs, K. K., Chang, Z., Quinn, P. D., Hur, K., Gibbons, R., Dunn, D., . . . D'Onofrio, B. M. (2018). Attention-deficit/hyperactivity disorder medication and seizures. Neurology, 90(13), e1104-e1110
Open this publication in new window or tab >>Attention-deficit/hyperactivity disorder medication and seizures
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2018 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, no 13, p. e1104-e1110Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of seizures, but there is uncertainty about whether ADHD medication treatment increases risk among patients with and without preexisting seizures.

METHODS: We followed a sample of 801,838 patients with ADHD who had prescribed drug claims from the Truven Health MarketScan Commercial Claims and Encounters databases to examine whether ADHD medication increases the likelihood of seizures among ADHD patients with and without a history of seizures. First, we assessed overall risk of seizures among patients with ADHD. Second, within-individual concurrent analyses assessed odds of seizure events during months when a patient with ADHD received ADHD medication compared with when the same individual did not, while adjusting for antiepileptic medications. Third, within-individual long-term analyses examined odds of seizure events in relation to the duration of months over the previous 2 years patients received medication.

RESULTS: Patients with ADHD were at higher odds for any seizure compared with non-ADHD controls (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 2.24-2.42 males; OR = 2.31, 95% CI = 2.22-2.42 females). In adjusted within-individual comparisons, ADHD medication was associated with lower odds of seizures among patients with (OR = 0.71, 95% CI = 0.60-0.85) and without (OR = 0.71, 95% CI = 0.62-0.82) prior seizures. Long-term within-individual comparisons suggested no evidence of an association between medication use and seizures among individuals with (OR = 0.87, 95% CI = 0.59-1.30) and without (OR = 1.01, 95% CI = 0.80-1.28) a seizure history.

CONCLUSIONS: Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures.

Place, publisher, year, edition, pages
AAN Publications, 2018
National Category
Psychiatry Neurology
Identifiers
urn:nbn:se:oru:diva-65286 (URN)10.1212/WNL.0000000000005213 (DOI)000439102000002 ()29476037 (PubMedID)
Note

Funding Agencies:

NIMH  R01MH102221 

NIH  T32HD07475 

NIDA  K99DA040727 

Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-09-06Bibliographically approved
Hedman, A., Breithaupt, L., Hübel, C., Thornton, L. M., Tillander, A., Norring, C., . . . Bulik, C. M. (2018). Bidirectional relationship between eating disorders and autoimmune diseases. Journal of Child Psychology and Psychiatry and Allied Disciplines
Open this publication in new window or tab >>Bidirectional relationship between eating disorders and autoimmune diseases
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2018 (English)In: Journal of Child Psychology and Psychiatry and Allied Disciplines, ISSN 0021-9630, E-ISSN 1469-7610Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Immune system dysfunction may be associated with eating disorders (ED) and could have implications for detection, risk assessment, and treatment of both autoimmune diseases and EDs. However, questions regarding the nature of the relationship between these two disease entities remain. We evaluated the strength of associations for the bidirectional relationships between EDs and autoimmune diseases.

METHODS: In this nationwide population-based study, Swedish registers were linked to establish a cohort of more than 2.5 million individuals born in Sweden between January 1, 1979 and December 31, 2005 and followed up until December 2013. Cox proportional hazard regression models were used to investigate: (a) subsequent risk of EDs in individuals with autoimmune diseases; and (b) subsequent risk of autoimmune diseases in individuals with EDs.

RESULTS: We observed a strong, bidirectional relationship between the two illness classes indicating that diagnosis in one illness class increased the risk of the other. In women, the diagnoses of autoimmune disease increased subsequent hazards of anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED). Similarly, AN, BN, and OED increased subsequent hazards of autoimmune diseases.Gastrointestinal-related autoimmune diseases such as, celiac disease and Crohn's disease showed a bidirectional relationship with AN and OED. Psoriasis showed a bidirectional relationship with OED. The previous occurence of type 1 diabetes increased the risk for AN, BN, and OED. In men, we did not observe a bidirectional pattern, but prior autoimmune arthritis increased the risk for OED.

CONCLUSIONS: The interactions between EDs and autoimmune diseases support the previously reported associations. The bidirectional risk pattern observed in women suggests either a shared mechanism or a third mediating variable contributing to the association of these illnesses.

Place, publisher, year, edition, pages
Blackwell Publishing, 2018
Keywords
anorexia nervosa, autoimmunity, bulimia nervosa, cox regression, hazard, immune system, risk
National Category
Public Health, Global Health, Social Medicine and Epidemiology Psychiatry Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:oru:diva-68740 (URN)10.1111/jcpp.12958 (DOI)30178543 (PubMedID)
Available from: 2018-09-10 Created: 2018-09-10 Last updated: 2018-09-16Bibliographically approved
Taylor, M. J., Gustafsson, P., Larsson, H., Gillberg, C., Lundström, S. & Lichstenstein, P. (2018). Examining the Association Between Autistic Traits and Atypical Sensory Reactivity: A Twin Study. Journal of the American Academy of Child and Adolescent Psychiatry, 57(2), 96-102
Open this publication in new window or tab >>Examining the Association Between Autistic Traits and Atypical Sensory Reactivity: A Twin Study
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2018 (English)In: Journal of the American Academy of Child and Adolescent Psychiatry, ISSN 0890-8567, E-ISSN 1527-5418, Vol. 57, no 2, p. 96-102Article in journal (Refereed) Published
Abstract [en]

Objective: Atypical responses to sensory stimuli are common features of autism spectrum disorders (ASD). Consequently, atypical sensory reactivity (SR) is now a diagnostic feature of ASD. Quantitative genetic research on ASD has overlooked these symptoms, however. We therefore investigated the association between autistic traits and SR using twin methods.

Method: Autistic traits and SR were assessed by 2 separate scales in 12,419 Swedish twin pairs (n = 3,586 monozygotic [MZ], n = 8,833 dizygotic [DZ]) when the twins were 9 or 12 years of age. The classic twin design estimated the degree to which etiological factors associated with autistic traits were also associated with SR, and the degree to which such shared factors explained the covariance between these phenotypes. DeFries Fulker analysis estimated the genetic correlation between screening diagnoses of ASD, defined broadly and strictly, and SR.

Results: Autistic traits and SR were both highly heritable (62%-75% and 66%-71%, respectively). There was a moderate phenotypic correlation between autistic traits and SR (r = 0.47). Genetic influences on these phenotypes correlated moderately (genetic correlation = 0.60). These overlapping genetic factors explained most of the correlation between autistic traits and SR. Genetic correlations with SR increased for broad ASD (genetic correlation = 0.72) and strict ASD (genetic correlation = 0.80).

Conclusion: The genetic overlap observed between autistic traits and SR lends quantitative genetic support to the notion that ASD and SR are strongly linked. Stich symptoms may thus comprise part of the ASD genotype, as well as phenotype. Associations persisted across all definitions of ASD, indicating a genetic link between the broader ASD phenotype and SR.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
autism, twin study, sensory reactivity, genetics
National Category
Psychiatry Pediatrics
Identifiers
urn:nbn:se:oru:diva-65028 (URN)10.1016/j.jaac.2017.11.019 (DOI)000424074800009 ()2-s2.0-85041181247 (Scopus ID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Research Council
Note

Funding Agencies:

Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM)  340-2013-5867 

Ann Marie and Per Ahlqvist Foundation 

Available from: 2018-02-16 Created: 2018-02-16 Last updated: 2018-08-20Bibliographically approved
Brikell, I., Ghirardi, L., D'Onofrio, B. M., Dunn, D. W., Almqvist, C., Dalsgaard, S., . . . Larsson, H. (2018). Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study. Biological Psychiatry, 83(2), 173-180
Open this publication in new window or tab >>Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study
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2018 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 2, p. 173-180Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence.

METHODS: We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors.

RESULTS: Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33-3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75-1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54-1.74), full siblings (OR = 1.56, 95% CI = 1.46-1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14-1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96-1.25), and cousins (OR = 1.15, 95% CI = 1.10-1.20). The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23-0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = 20.16-0.79).

CONCLUSIONS: This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
ADHD, Comorbidity, Epilepsy, Genetics, Neurodevelopment, Risk factors
National Category
Neurology Psychiatry
Identifiers
urn:nbn:se:oru:diva-63770 (URN)10.1016/j.biopsych.2017.08.006 (DOI)000417608300014 ()28950988 (PubMedID)2-s2.0-85029753462 (Scopus ID)
Funder
Swedish Research Council, 2013-2280 2014-3831
Note

Funding Agencies:

Swedish Initiative for Research on Microdata in the Social and Medical Sciences framework  340-2013-5867 

National Institute of Mental Health  1R01MH102221 

Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2018-08-31Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6851-3297

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