Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding?
Adolescent
Adult
Androgens
/ metabolism
Attention Deficit Disorder with Hyperactivity
/ epidemiology
Autism Spectrum Disorder
/ epidemiology
Child
Child, Preschool
Cohort Studies
Family
Female
Follow-Up Studies
Humans
Male
Polycystic Ovary Syndrome
/ epidemiology
Pregnancy
Prenatal Exposure Delayed Effects
/ epidemiology
Registries
/ statistics & numerical data
Sex Factors
Sweden
/ epidemiology
Tic Disorders
/ epidemiology
Tourette Syndrome
/ epidemiology
Androgens
epidemiology
familial confounding
neuropsychiatric disorders
polycystic ovary syndrome
Journal
Psychological medicine
ISSN: 1469-8978
Titre abrégé: Psychol Med
Pays: England
ID NLM: 1254142
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
pubmed:
13
3
2019
medline:
9
3
2021
entrez:
13
3
2019
Statut:
ppublish
Résumé
Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences. A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models. PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys. Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.
Sections du résumé
BACKGROUND
Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences.
METHODS
A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models.
RESULTS
PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys.
CONCLUSIONS
Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.
Identifiants
pubmed: 30857571
pii: S0033291719000424
doi: 10.1017/S0033291719000424
pmc: PMC7093321
doi:
Substances chimiques
Androgens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
616-624Références
Curr Opin Neurol. 2013 Apr;26(2):111-21
pubmed: 23426380
J Clin Endocrinol Metab. 2015 Sep;100(9):3400-7
pubmed: 26192874
Epidemiology. 2012 Sep;23(5):713-20
pubmed: 22781362
PLoS Biol. 2011 Jun;9(6):e1001081
pubmed: 21695109
BMJ Open. 2015 Jun 22;5(6):e007520
pubmed: 26100027
Clin Endocrinol (Oxf). 2012 Dec;77(6):898-904
pubmed: 22612600
Horm Behav. 2007 May;51(5):597-604
pubmed: 17462645
JAMA Psychiatry. 2015 Aug;72(8):787-93
pubmed: 26083307
Pflugers Arch. 2013 May;465(5):557-71
pubmed: 23588379
J Clin Psychopharmacol. 1998 Aug;18(4):324-31
pubmed: 9690699
Mol Psychiatry. 2016 Oct;21(10):1441-8
pubmed: 26643539
Int Rev Neurobiol. 2013;112:239-79
pubmed: 24295624
Eur J Obstet Gynecol Reprod Biol. 2013 Feb;166(2):151-5
pubmed: 23122578
Fertil Steril. 2004 Jan;81(1):19-25
pubmed: 14711538
Dev Med Child Neurol. 2006 Dec;48(12):962-5
pubmed: 17109783
Psychoneuroendocrinology. 2017 Nov;85:63-68
pubmed: 28825976
Dev Psychopathol. 2004 Spring;16(2):407-20
pubmed: 15487603
Int J Psychiatry Med. 2015;50(3):317-25
pubmed: 26449924
Biol Psychiatry. 2017 Nov 1;82(9):651-659
pubmed: 27889187
Hum Reprod. 2002 Oct;17(10):2573-9
pubmed: 12351531
J Clin Endocrinol Metab. 2006 May;91(5):1660-6
pubmed: 16522691
Fertil Steril. 2016 Nov;106(6):1510-1520.e2
pubmed: 27530062
Horm Behav. 2009 May;55(5):570-8
pubmed: 19446073
Psychoneuroendocrinology. 2016 Nov;73:196-203
pubmed: 27513883
Nat Rev Endocrinol. 2011 Apr;7(4):219-31
pubmed: 21263450
Psychoneuroendocrinology. 1992 Nov;17(6):553-63
pubmed: 1287677
Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14348-53
pubmed: 26578781
Neuropsychiatr Dis Treat. 2017 May 16;13:1331-1339
pubmed: 28553119
J Clin Psychopharmacol. 1994 Apr;14(2):131-5
pubmed: 8195454
Am J Public Health. 2013 Oct;103 Suppl 1:S46-55
pubmed: 23927516
J Clin Endocrinol Metab. 2006 Jun;91(6):2100-4
pubmed: 16219714
Transl Psychiatry. 2018 Aug 1;8(1):136
pubmed: 30065244
J Obstet Gynaecol. 2010;30(5):444-6
pubmed: 20604643
Hum Reprod. 2010 Feb;25(2):544-51
pubmed: 19910321
J Clin Endocrinol Metab. 2010 May;95(5):2180-6
pubmed: 20228162
J Child Psychol Psychiatry. 2017 Mar;58(3):231-239
pubmed: 27545745