SRD5A2 is associated with increased cortisol metabolism in schizophrenia spectrum disorders |
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| Authors: | Nils Eiel Steen Martin Tesli Anna K Khler Paal Methlie Sigrun Hope Elizabeth A Barrett Sara Larsson Erlend Mork Kristian Lvs Jan Ivar Rssberg Ingrid Agartz Ingrid Melle Srdjan Djurovic Steinar Lorentzen Jens P Berg Ole A Andreassen |
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| Institution: | a Section for Psychosis Research, Clinic of Mental Health and Addiction, Oslo University Hospital, Ullevål Hospital, P.O. Box 4956 Nydalen, 0424 Oslo, Norway;b Acute Psychiatric Emergency Unit, Clinic of Mental Health and Addiction, Oslo University Hospital, Aker Hospital, P.O. Box 4959 Nydalen, 0424 Oslo, Norway;c Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318 Oslo, Norway;d Institute of Medicine, University of Bergen, P.O.Box 7804, 5020 Bergen, Norway;e Hormone Laboratory, Haukeland University Hospital, 5021 Bergen, Norway;f Department of Psychiatry, Ostfold Hospital, 1603 Fredrikstad, Norway;g The National Centre for Suicide Research and Prevention, Institute of Clinical Medicine, University of Oslo, Sognsvannsveien 21, 0372 Oslo, Norway;h Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway;i Department of Psychiatric Research, Diakonhjemmet Hospital, P.O. Box 85, Vinderen, 0319 Oslo, Norway;j Department of Medical Genetics, Oslo University Hospital, Ullevål Hospital, P.O. Box 4956 Nydalen, 0424 Oslo, Norway;k Department of Research and Development, Clinic of Mental Health and Addiction, Oslo University Hospital, Aker Hospital, P.O. Box 4959 Nydalen, 0424 Oslo, Norway;l Department of Medical Biochemistry, Oslo University Hospital, Ullevål Hospital, P.O. Box 4956 Nydalen, 0424 Oslo, Norway;m Hormone Laboratory, Oslo University Hospital, Aker Hospital, P.O. Box 4959 Nydalen, 0424 Oslo, Norway |
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| Abstract: | ObjectiveDysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is documented in bipolar disorder and schizophrenia, but the mechanism is unclear; recently, increased activity of cortisol metabolizing enzymes was indicated in these disorders. We investigated whether five genes involved in cortisol metabolism were associated with altered activity of cortisol metabolizing enzymes in bipolar disorder (BD) and schizophrenia spectrum disorders (SCZ).MethodsA case–control sample of subjects with BD (N = 213), SCZ (N = 274) and healthy controls (N = 370) from Oslo, Norway, were included and genotyped from 2003 to 2008. A sub-sample (healthy controls: N = 151; SCZ: N = 40; BD: N = 39) had estimated enzyme activities based on measurements of urinary free cortisol, urinary free cortisone and metabolites. A total of 102 single nucleotide polymorphisms (SNPs) in the SRD5A1, SRD5A2, AKR1D1, HSD11B1 and HSD11B2 genes were genotyped, and significant SNPs analyzed in the sub-sample.ResultsThere was a significant association of rs6732223 in SRD5A2 (5α-reductase) with SCZ (p = 0.0043, Bonferroni corrected p = 0.030, T risk allele). There was a significantly increased 5α-reductase activity associated with rs6732223 (T allele) within the SCZ group (p = 0.011).ConclusionsThe present data suggest an interaction between SCZ and SRD5A2 variants coding for the enzyme 5α-reductase, giving rise to increased 5α-reductase activity in SCZ. The findings may have implications for cortisol metabolizing enzymes as possible drug targets. |
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| Keywords: | 5α -Reductase Bipolar disorder HPA Schizophrenia Severe mental disorders |
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