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Psychoneuroendocrinology. 2015 Oct;60:195-205. doi: 10.1016/j.psyneuen.2015.06.017. Epub 2015 Jun 26.

Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study.

Author information

1
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Child and Adolescent Psychiatry Research Center, Stockholm, Sweden. Electronic address: hedvig.engberg@ki.se.
2
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland.
3
Department of Pediatric Endocrinology, Astrid Lindgren Children Hospital, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
4
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
5
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
6
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
7
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Pediatric Surgery, Astrid Lindgren Children Hospital, Karolinska University Hospital, Stockholm, Sweden.
8
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Child and Adolescent Psychiatry Research Center, Stockholm, Sweden.
9
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.

Abstract

Congenital adrenal hyperplasia (CAH) is a chronic condition and individuals are exposed to elevated androgen levels in utero as a result of the endogenous cortisol deficiency. Prenatal androgen exposure has been suggested to influence mental health, but population based studies on psychiatric morbidity among girls and women with CAH are lacking. Therefore, we performed a cohort study based on Swedish nationwide registers linked with the national CAH register. Girls and women with CAH due to 21-hydroxylase deficiency (n = 335) born between January 1915 and January 2010 were compared with aged-matched female (n = 33500) and male controls (n = 33500). Analyses were stratified by phenotype [salt wasting (SW), simple virilizing (SV), and non-classical type (NC)] and by CYP21A2 genotype subgroups (null, I2splice, I172N, and P30L). Results are presented as estimated risks (OR, 95%CI) of psychiatric disorders among girls and women with CAH compared with age-matched controls. Any psychiatric diagnoses were more common in CAH females compared with female and male population controls [1.9 (1.4-2.5), and 2.2 (1.7-2.9)]. In particular, the risk of alcohol misuse was increased compared with female and male population controls [2.8 (1.7-4.7) and 2.1 (1.2-3.5)], and appeared most common among the girls and women with the most severe null genotype [6.7 (2.6-17.8)]. The risk of stress and adjustment disorders was doubled compared with female population controls [2.1 (1.3-3.6)]. Girls and women with CAH have an increased risk of psychiatric disorders in general and substance use disorders in particular compared with unexposed females, with the highest risk among those with the most severe genotype. Prenatal androgen exposure and deficient endogenous cortisol and/or adrenaline production may provide explanations for these findings, but other factors related to CAH cannot be excluded.

KEYWORDS:

21-hydroxylase deficiency; Alcohol misuse; Anxiety; Depression; Drug misuse; Psychiatric disorders

PMID:
26184920
DOI:
10.1016/j.psyneuen.2015.06.017
[Indexed for MEDLINE]

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