title: Altered systemic cortisol metabolism in bipolar disorder and schizophrenia spectrum disorders.
abstract: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is suggested as a pathophysiological factor in bipolar disorder and schizophrenia. Increased clearance of cortisol was recently indicated as a component in the HPA axis hyperdrive. The aim of the present study was to test the model of increased cortisol metabolism in a new replication sample separately and combined with a previously published sample of bipolar disorder and schizophrenia. Spot urine was sampled from 212 healthy controls (HC) and 221 patients with a schizophrenia spectrum disorder (SCZ, n = 115) and bipolar disorder (BD, n = 106). Of these, a subsample of 169 HC and 155 patients was included in a previous report. Urinary free cortisol, cortisone and their metabolites were measured, and the activities of 5α-reductase, 5β-reductase and 11β-HSD were estimated and analyzed for differences between groups. In the new sample, there was increased enzyme activity in SCZ for 5β-reductase (p = 0.024 vs HC; p = 0.027 vs BD) and 11β-HSD2 (p = 0.014 vs HC; p = 0.004 vs BD). In the combined sample, there was increased activity in SCZ for 5α-reductase (p < 0.001 vs HC; p = 0.020 vs BD), 5β-reductase (p < 0.001 vs HC; p = 0.045 vs BD) and 11β-HSD2 (p < 0.001 vs HC; p = 0.043 vs BD), and in BD for 5β-reductase (p = 0.002), 11β-HSD2 (p = 0.039) and 5α-reductase (trend, p = 0.084) (all vs HC). The findings confirm increased systemic cortisol metabolism in BD and SCZ. This is most consistent in SCZ, with BD taking an intermediate position. The design makes it impossible to determine the direction of the effect. However, the findings merit further study of cortisol metabolism as a possible component in the HPA axis dysfunction and pathophysiology of BD and SCZ.
authors.affiliation: KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen, Norway. Electronic address: n.e.steen@medisin.uio.no.
authors.forename: Nils Eiel
authors.initials: NE
authors.lastname: Steen
authors.affiliation: Institute of Medicine, University of Bergen, Bergen, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen, Norway.
authors.forename: Paal
authors.initials: P
authors.lastname: Methlie
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Research and Development, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Steinar
authors.initials: S
authors.lastname: Lorentzen
authors.affiliation: KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dieset
authors.affiliation: KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Monica
authors.initials: M
authors.lastname: Aas
authors.affiliation: KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Nerhus
authors.affiliation: KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Haram
authors.affiliation: KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.affiliation: KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway; Hormone Laboratory, Oslo University Hospital, Oslo, Norway.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Berg
authors.affiliation: KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000378:metabolism*; D013760:Tetrahydrocortisol / Q000031:analogs & derivatives / Q000378:metabolism; D013761:Tetrahydrocortisone / Q000378:metabolism; D055815:Young Adult
chemical_list: C006461:allotetrahydrocortisol; D013761:Tetrahydrocortisone; D013760:Tetrahydrocortisol; D006854:Hydrocortisone
keywords: 11β-Hydroxysteroid dehydrogenase; 5α reductase; 5β reductase; Hypothalamic-pituitary-adrenal-axis; Psychosis; Severe mental disorders