title: Medical history of discordant twins and environmental etiologies of autism.
abstract: The environmental contributions to autism spectrum disorder (ASD) and their informative content for diagnosing the condition are still largely unknown. The objective of this study was to investigate associations between early medical events and ASD, as well as autistic traits, in twins, to test the hypothesis of a cumulative environmental effect on ASD risk. A total of 80 monozygotic (MZ) twin pairs (including a rare sample of 13 twin pairs discordant for clinical ASD) and 46 dizygotic (DZ) twin pairs with varying autistic traits, were examined for intra-pair differences in early medical events (for example, obstetric and neonatal factors, first year infections). First, differences in early medical events were investigated using multisource medical records in pairs qualitatively discordant for ASD. The significant intra-pair differences identified were then tested in relation to autistic traits in the remaining sample of 100 pairs, applying generalized estimating equations analyses. Significant association of the intra-pair differences in the MZ pairs were found for the cumulative load of early medical events and clinical ASD (Z=-2.85, P=0.004) and autistic traits (β=78.18, P=0.002), as well as infant dysregulation (feeding, sleeping abnormalities, excessive crying and worriedness), when controlling for intelligence quotient and attention deficit hyperactivity disorder comorbidity. The cumulative load of early medical events in general, and infant dysregulation in particular, may index children at risk of ASD owing to non-shared environmental contributions. In clinical practice, these findings may facilitate screening and early detection of ASD.
authors.affiliation: Karolinska Institutet Center for Neurodevelopmental Disorders, Pediatric Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.|Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Willfors
authors.affiliation: Karolinska Institutet Center for Neurodevelopmental Disorders, Pediatric Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.|Prima Child and Adult Psychiatry, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Carlsson
authors.affiliation: Department of Molecular Medicine and Surgery, Center of Molecular Medicine, Karolinska Institutet, Solna, Sweden.|Department of Clinical Genetics, Karolinska University Hospital, Solna, Sweden.
authors.forename: B-M
authors.initials: BM
authors.lastname: Anderlid
authors.affiliation: Department of Molecular Medicine and Surgery, Center of Molecular Medicine, Karolinska Institutet, Solna, Sweden.|Department of Clinical Genetics, Karolinska University Hospital, Solna, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Nordgren
authors.affiliation: Karolinska Institutet Center for Neurodevelopmental Disorders, Pediatric Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.|Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Kostrzewa
authors.affiliation: Karolinska Institutet Center for Neurodevelopmental Disorders, Pediatric Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.|Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.|Child and Adolescent Psychiatry, Stockholm County Council, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Berggren
authors.affiliation: Genes Environment Lifespan laboratory, Department of Psychological Sciences, Birkbeck, University of London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ronald
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Kuja-Halkola
authors.affiliation: Karolinska Institutet Center for Neurodevelopmental Disorders, Pediatric Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.|Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Tammimies
authors.affiliation: Karolinska Institutet Center for Neurodevelopmental Disorders, Pediatric Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.|Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.|Child and Adolescent Psychiatry, Stockholm County Council, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Bölte
mesh_terms: D000293:Adolescent; D000328:Adult; D001034:Apgar Score; D001249:Asthma / Q000453:epidemiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000523:psychology; D000067877:Autism Spectrum Disorder / Q000453:epidemiology / Q000523:psychology; D001321:Autistic Disorder / Q000453:epidemiology / Q000523:psychology*; D001724:Birth Weight; D001946:Breech Presentation / Q000453:epidemiology; D002543:Cerebral Hemorrhage / Q000453:epidemiology; D002648:Child; D004485:Eczema / Q000453:epidemiology; D004777:Environment; D004827:Epilepsy / Q000453:epidemiology; D019959:Feeding and Eating Disorders of Childhood / Q000453:epidemiology; D005260:Female; D005316:Fetal Distress / Q000453:epidemiology; D005759:Gastroenteritis / Q000453:epidemiology; D006330:Heart Defects, Congenital / Q000453:epidemiology; D006801:Humans; D006849:Hydrocephalus / Q000453:epidemiology; D051556:Hyperbilirubinemia, Neonatal / Q000453:epidemiology; D006967:Hypersensitivity / Q000453:epidemiology; D007003:Hypoglycemia / Q000453:epidemiology; D008297:Male; D008831:Microcephaly / Q000453:epidemiology; D010033:Otitis Media / Q000453:epidemiology; D010102:Oxygen Inhalation Therapy; D011247:Pregnancy; D011704:Pyelonephritis / Q000453:epidemiology; D018805:Sepsis / Q000453:epidemiology; D012893:Sleep Wake Disorders / Q000453:epidemiology; D013548:Sweden / Q000453:epidemiology; D013921:Thrombocytopenia / Q000453:epidemiology; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D014786:Vision Disorders / Q000453:epidemiology; D055815:Young Adult