title: Elevated fetal steroidogenic activity in autism.
abstract: Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.
authors.affiliation: Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Baron-Cohen
authors.affiliation: 1] Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK [2] Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: B
authors.initials: B
authors.lastname: Auyeung
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institute Copenhagen, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Nørgaard-Pedersen
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institute Copenhagen, Copenhagen, Denmark.
authors.forename: D M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: 1] Department of Clinical Biochemistry and Immunology, Statens Serum Institute Copenhagen, Copenhagen, Denmark [2] Department of Child and Adolescent Neuropsychiatry, Rostock University Medical Centre, Rostock, Germany [3] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: M W
authors.initials: MW
authors.lastname: Abdallah
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institute Copenhagen, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Melgaard
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institute Copenhagen, Copenhagen, Denmark.
authors.forename: A S
authors.initials: AS
authors.lastname: Cohen
authors.affiliation: 1] Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK [2] Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK.
authors.forename: B
authors.initials: B
authors.lastname: Chakrabarti
authors.affiliation: 1] Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK [2] Division of Child Neurology and Psychiatry, Stella Maris Scientific Institute, Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ruta
authors.affiliation: 1] Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK [2] Department of Psychology, University of Cyprus, Nicosia, Cyprus [3] Centre for Applied Neuroscience, University of Cyprus, Nicosia, Cyprus.
authors.forename: M V
authors.initials: MV
authors.lastname: Lombardo
mesh_terms: D000704:Analysis of Variance; D020817:Asperger Syndrome / Q000097:blood*; D001321:Autistic Disorder / Q000097:blood*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D025341:Principal Component Analysis; D013256:Steroids / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D013256:Steroids; D006854:Hydrocortisone