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Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
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2018 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 5, p. 1189-1197Article in journal (Refereed) Published
Abstract [en]

Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018. Vol. 23, no 5, p. 1189-1197
National Category
Neurology Psychiatry Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Neurology
Identifiers
URN: urn:nbn:se:oru:diva-57358DOI: 10.1038/mp.2017.31ISI: 000431614600011PubMedID: 28348386Scopus ID: 2-s2.0-85016105353OAI: oai:DiVA.org:oru-57358DiVA, id: diva2:1097006
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2015-00075 2015-00569Swedish Research Council, K2013-61 P-22168
Note

Funding Agencies:

Karolinska Institutet PhD stipend

David and Astrid Hagelen Foundation  

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

Indiana Clinical and Translational Sciences Institute: Pediatric Development Team  

Shire 

Available from: 2017-05-21 Created: 2017-05-21 Last updated: 2018-05-18Bibliographically approved

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Larsson, Henrik

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