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

Altered levels of stress-signalling transcripts have been identified in post-mortem brains of people with schizophrenia, and since stress effects may be expressed throughout the body, there should be similar changes in peripheral cells. However, the extent to which these markers are altered in peripheral white blood cells of people with schizophrenia is not known. Furthermore, how peripheral cortisol and stress-related mRNA are associated with negative symptom severity and emotional states in people with schizophrenia versus schizoaffective disorder has not been determined. Whole blood samples were collected from 86 patients with either schizophrenia or schizoaffective disorder (56 people with schizophrenia and 30 people with schizoaffective disorder), and 77 healthy controls. Total RNA was isolated, cDNA was synthesized, and stress-signalling mRNA levels (for NR3C1, FKBP5, FKBP4, PTGES3 and 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 increased FKBP5 mRNA, Z(156) = 2.5, p = 0.01, decreased FKBP4 mRNA, t(155) = 3.5, p ≤ 0.001, and decreased PTGES3 mRNA, t(153) = 3.0, p ≤ 0.01, in schizophrenia and schizoaffective disorder cohorts combined compared to healthy controls. Stress-related peripheral mRNA levels were differentially correlated with negative emotional states and symptom severity in schizoaffective disorder (β's = -0.45-0.56, p's = 0.05-0.001) and schizophrenia (β's = -0.34-0.38, p's = 0.04-0.03), respectively. Therefore, molecules of the stress-signalling pathway appear to differentially contribute to clinical features of schizophrenia versus schizoaffective disorder.Cynthia H. Lee, Duncan Sinclair, Maryanne O'Donnell, Cherrie Galletly, Dennis Liu, Cynthia Shannon Weickert, Thomas W. Weicker