title: Disrupted glucocorticoid--Immune interactions during stress response in schizophrenia.
abstract: Glucocorticoid and immune pathways typically interact dynamically to optimize adaptation to stressful environmental challenges. We tested the hypothesis that a dysfunctional glucocorticoid-immune relationship contributes to abnormal stress response in schizophrenia. Saliva samples from 34 individuals with schizophrenia (20 male, 14 female) and 40 healthy controls (20 male, 20 female) were collected prior to and at 3 time points following completion of a computerized psychological challenge meant to be frustrating. Salivary concentrations of cortisol and interleukin-6 (IL-6) and their response to the challenge were examined. Both cortisol and IL-6 significantly increased in response to stress in the combined sample (both p<.05). In controls, the rise in cortisol following the challenge was negatively correlated to the subsequent changes in IL-6 (r=-.461, p=.003), such that rise of cortisol immediately after stress predicts subsequently lower IL-6 levels. In contrast, this relationship was positive in schizophrenia patients (r=.379, p=.027). The trends were significantly different (Z=3.7, p=.0002). This stress paradigm induces a rise in both cortisol and IL-6. In healthy controls, a more robust acute cortisol response was associated with a steeper decline of IL-6 levels following stress, corresponding to the expected anti-inflammatory effects of cortisol. Patients exhibited the opposite relationship, suggesting an inability to down-regulate inflammatory responses to psychological stress in schizophrenia; or even a paradoxical increase of IL-6 response. This finding may partially underlie abnormalities in inflammatory and stress pathways previously found in the illness, implicating dysregulated stress response in the chronic inflammatory state in schizophrenia.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States. Electronic address: jchiappelli@mprc.umaryland.edu.
authors.forename: Joshua
authors.initials: J
authors.lastname: Chiappelli
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Priyadurga
authors.initials: P
authors.lastname: Kodi
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Anya
authors.initials: A
authors.lastname: Savransky
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Rowland
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Nugent
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D003071:Cognition; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D011618:Psychotic Disorders / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000523:psychology; D012463:Saliva / Q000737:chemistry; D012559:Schizophrenia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D012565:Schizophrenic Psychology; D013315:Stress, Psychological / Q000276:immunology / Q000378:metabolism* / Q000523:psychology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D005938:Glucocorticoids; C508600:IL6 protein, human; D015850:Interleukin-6; D006854:Hydrocortisone
keywords: Cortisol; IL-6; Inflammation; Schizophrenia; Stress