Anna Nordenström1,2, Agnieszka Butwicka3,4, Angelica Lindén Hirschberg1,5, Catarina Almqvist3,6, Agneta Nordenskjöld1,7,8, Henrik Falhammar9,10, Louise Frisén11,12. 1. Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 2. Department of Paediatric Endocrinology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 3. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 4. Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland. 5. Department of Obstetrics and Gynaecology, Karolinska University Hospital, Stockholm, Sweden. 6. Lung and Allergy Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 7. Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 8. Paediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 9. Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden. 10. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 11. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 12. Child and Adolescent Psychiatry Research Centre, Stockholm, Sweden.
Abstract
BACKGROUND: Congenital adrenal hyperplasia (CAH) is one of the most common monogenic autosomal recessive disorders with an incidence of one in 15 000. About one in 70 individuals in the general population are carriers of a severe CYP21A2 mutation. It has been suggested that this confers a survival advantage, perhaps as a result of increased activity in the hypothalamic-pituitary-adrenal axis. We investigated vulnerability to psychological stress in obligate carriers. METHOD: The Swedish CAH Registry encompasses more than 600 patients. Parents, that is obligate carriers of the CYP21A2 mutation, were identified through the Multigeneration Register. The diagnosis of the child was used as the psychological stressor. Psychiatric diagnoses before and after the birth of a child with CAH were compared to those of controls derived from (i) the general population, (ii) parents of children with hypospadias and (iii) parents of children with diabetes mellitus type 1 (T1DM). RESULTS: Parents of children with CAH had less risk of being diagnosed with any psychiatric disorder (OR, 0·6), an affective disorder (OR, 0·5) or substance misuse (OR, 0·5) after the diagnosis of the child, compared to the general population. Their risk was also decreased compared to parents of a child with hypospadias (OR, 0·6, 0·4 and 0·2, respectively) and parents of a child with T1DM (OR 0·7, 0·6 and 0·2, respectively). The CYP21A2 carriers had a lower risk of developing mood and stress-related disorders after the diagnosis of the child. CONCLUSION: Obligate CYP21A2 carriers had a reduced risk of a psychiatric diagnosis and were less vulnerable to a psychologically stressful situation, at least with respect to receiving a psychiatric diagnosis. This indicates a better ability to cope with psychological stress among heterozygous carriers of severe CYP21A2 mutations, which may contribute to the apparent survival advantage.
BACKGROUND:Congenital adrenal hyperplasia (CAH) is one of the most common monogenic autosomal recessive disorders with an incidence of one in 15 000. About one in 70 individuals in the general population are carriers of a severe CYP21A2 mutation. It has been suggested that this confers a survival advantage, perhaps as a result of increased activity in the hypothalamic-pituitary-adrenal axis. We investigated vulnerability to psychological stress in obligate carriers. METHOD: The Swedish CAH Registry encompasses more than 600 patients. Parents, that is obligate carriers of the CYP21A2 mutation, were identified through the Multigeneration Register. The diagnosis of the child was used as the psychological stressor. Psychiatric diagnoses before and after the birth of a child with CAH were compared to those of controls derived from (i) the general population, (ii) parents of children with hypospadias and (iii) parents of children with diabetes mellitus type 1 (T1DM). RESULTS: Parents of children with CAH had less risk of being diagnosed with any psychiatric disorder (OR, 0·6), an affective disorder (OR, 0·5) or substance misuse (OR, 0·5) after the diagnosis of the child, compared to the general population. Their risk was also decreased compared to parents of a child with hypospadias (OR, 0·6, 0·4 and 0·2, respectively) and parents of a child with T1DM (OR 0·7, 0·6 and 0·2, respectively). The CYP21A2 carriers had a lower risk of developing mood and stress-related disorders after the diagnosis of the child. CONCLUSION: Obligate CYP21A2 carriers had a reduced risk of a psychiatric diagnosis and were less vulnerable to a psychologically stressful situation, at least with respect to receiving a psychiatric diagnosis. This indicates a better ability to cope with psychological stress among heterozygous carriers of severe CYP21A2 mutations, which may contribute to the apparent survival advantage.
Authors: José Gulfo; Ricard Castel; Angelo Ledda; María Del Mar Romero; Montserrat Esteve; Mar Grasa Journal: Sci Rep Date: 2019-09-30 Impact factor: 4.379