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Transcriptional changes in the stress pathway are related to symptoms in schizophrenia and to mood in schizoaffective disorder

Lee, CH, Sinclair, D ORCID: 0000-0001-5961-1007, O'Donnell, M, Galletly, C, Liu, D, Weickert, CS and Weickert, TW 2019 , 'Transcriptional changes in the stress pathway are related to symptoms in schizophrenia and to mood in schizoaffective disorder' , Schizophrenia Research, vol. 213 , pp. 87-95 , doi: 10.1016/j.schres.2019.06.026.

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Abstract

Altered levels of stress-signalling transcripts have been identified in post-mortem brains of people withschizophrenia, and since stress effects may be expressed throughout the body, there should be similarchanges in peripheral cells. However, the extent to which these markers are altered in peripheral whiteblood cells of people with schizophrenia is not known. Furthermore, how peripheral cortisol and stressrelated mRNA are associated with negative symptom severity and emotional states in people withschizophrenia versus schizoaffective disorder has not been determined. Whole blood samples werecollected from 86 patients with either schizophrenia or schizoaffective disorder (56 people withschizophrenia and 30 people with schizoaffective disorder), and 77 healthy controls. Total RNA wasisolated, cDNA was synthesized, and stress-signalling mRNA levels (for NR3C1, FKBP5, FKBP4, PTGES3and BAG1) were determined. Stress and symptom severity scores were measured by the Depression,Anxiety and Stress Scale, and the Positive and Negative Syndrome Scale, respectively. We found increasedFKBP5 mRNA, Z(156) ¼ 2.5, p ¼ 0.01, decreased FKBP4 mRNA, t(155) ¼ 3.5, p 0.001, and decreasedPTGES3 mRNA, t(153) ¼ 3.0, p 0.01, in schizophrenia and schizoaffective disorder cohorts combinedcompared to healthy controls. Stress-related peripheral mRNA levels were differentially correlated withnegative emotional states and symptom severity in schizoaffective disorder (β's ¼ e0.45e0.56, p's ¼ 0.05e0.001) and schizophrenia (β's ¼ 0.34e0.38, p's ¼ 0.04e0.03), respectively. Therefore, molecules of thestress-signalling pathway appear to differentially contribute to clinical features of schizophrenia versusschizoaffective disorder.

Item Type: Article
Authors/Creators:Lee, CH and Sinclair, D and O'Donnell, M and Galletly, C and Liu, D and Weickert, CS and Weickert, TW
Keywords: schizophrenia, schizoaffective disorder, stress, symptoms, emotions, stress signalling transcripts
Journal or Publication Title: Schizophrenia Research
Publisher: Elsevier Science Publisher B. V.
ISSN: 0920-9964
DOI / ID Number: 10.1016/j.schres.2019.06.026
Copyright Information:

Copyright 2019 Crown Copyright

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