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Glucocorticoids and the risk of schizophrenia spectrum disorder in childhood and adolescence - A Danish nationwide study

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  • Brian Villumsen Broberg, Centre for Neuropsychiatric Schizophrenia Research, CNSR, & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, University of Copenhagen, Denmark. Electronic address: brian@cnsr.dk.
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  • Iris E Sommer, Department of Neuroscience and Department of Psychiatry, University Medical Center, Groningen, Netherlands; Department of Biological and Medical Psychology, Faculty of Psychology, University of Bergen, Bergen, Norway.
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  • Michael Eriksen Benros, Copenhagen University Hospital, Mental Health Centre Copenhagen, Hellerup, Denmark.
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  • Birte Yding Glenthøj, Centre for Neuropsychiatric Schizophrenia Research, CNSR, & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, University of Copenhagen, Denmark; University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark.
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  • Christiane Gasse
  • Ole Köhler-Forsberg

Glucocorticoids can have psychosis as a potential side effect, but have also been suggested to yield protective effects due to anti-inflammatory properties. Nonetheless, knowledge is sparse on the association between glucocorticoid treatment and development of psychosis, which we aimed to study in this first large-scale longitudinal study. Among all individuals born in Denmark 1995-2003 (n=597,257), we compared individuals who had redeemed ≥1 prescription for glucocorticoids to an active comparator group and a non-exposed group concerning subsequent development of schizophrenia spectrum disorders until 2013. Hazard rate ratios (HRR) were estimated using Cox regression adjusted for calendar year, age, gender, urbanization, somatic diseases, parental educational level and psychiatric history. The risk for a subsequent diagnosis of early-onset schizophrenia spectrum disorder (N=1141) was increased after exposure to both non-systemic (HRR=1.47; 95%-CI=1.25-1.73; N=371) and systemic glucocorticoids (HRR=1.66; 95%-CI=1.13-2.43; N=34), when compared to non-exposed individuals. Similar elevated risks were observed when comparing to the active comparator group, for schizophrenia and acute psychosis, and within an older cohort. The risk of psychosis was elevated the most within the first year after exposure to glucocorticoids (P<0.001) without any indication for a dose-response association. However, in individuals with asthma, exposure to glucocorticoids did not further increase the risk of psychosis. Glucocorticoid exposure was associated with an increased risk for psychotic disorders, which may be explained by an effect of the underlying somatic disease, such as asthma. A potential beneficial effect of glucocorticoids on psychotic symptoms should be investigated in clinical trials.

Original languageEnglish
JournalSchizophrenia Research
Volume199
Pages (from-to)116-122
ISSN0920-9964
DOIs
Publication statusPublished - 2018

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