Objectives: There is growing evidence of both hypothalamic-pituitary-adrenal (HPA) axis and immune system dysfunction in schizophrenia. Additionally, accumulating evidence has linked dysfunction in the kynurenine pathway to schizophrenia as well as to stress and inflammation. The current pilot tested changes in immune, cortisol and kynurenine and kynurenic acid responses to a psychosocial stressor in people with schizophrenia and healthy controls. Methods: Ten people with schizophrenia/schizoaffective disorder and 10 healthy controls were included. Participants completed the Trier Social Stress Test (TSST) and cortisol, cytokines (IL-6 & TNF-α), kynurenine and kynurenic acid were measured in the plasma at baseline 15, 30, 60 and 90 minutes following the TSST. Results: Compared to baseline, at 30 minutes post TSST, mean cortisol levels had increased by 7.6 ng/ml (11%) in healthy controls but decreased by 16.3 ng/ml (25%) in schizophrenia (F=4.34, df=3,38.2, p=0.010). While people with schizophrenia had a lower TNF-α level at baseline (χ2(1)=10.14, p=0.001), no decreases or increases occurred after the TSST in either group. Both groups had a similar increase in IL-6 at 15 minutes post TSST (F=4.17, df=3, 16.3, p=0.023) demonstrating an immune response to the stress in both groups. A trend towards increased kynurenine from baseline was found immediately after the TSST followed by a decrease at 60 minutes in healthy controls but no change was found in people with schizophrenia (F=2.46, df=3, 49.1, p=0.074). Conclusion: People with schizophrenia showed a decrease in cortisol from baseline following the TSST as compared to an elevation from baseline seen in healthy controls, supporting HPA axis dysfunction in schizophrenia. An immediate inflammatory response with IL-6 was seen in both groups following the TSST. Larger studies should examine psychosocial stress response in schizophrenia and the relationship of immune function and kynurenine pathway.
Matthew Glassman, Heidi J Wehring, Ana Pocivavsek, Kelli M Sullivan, Laura M Rowland, Robert P McMahon, Joshua Chiappelli, Fang Liu and Deanna L Kelly