OBJECTIVES: Although acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. METHODS: Acute and prolonged salivary cortisol response was measured outside the scanner at pretest and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n = 45) and controls (n = 53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n = 30) and controls (n = 33). RESULTS: Patients who did not tolerate the psychological stress task and quit had greater acute (t = 2.52 [p = .016] and t = 3.51 [p = .001] at 0 and 20 minutes) and prolonged (t = 3.62 [p = .001] at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r = -0.468, p = .009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. CONCLUSIONS: This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages.
OBJECTIVES: Although acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. METHODS: Acute and prolonged salivary cortisol response was measured outside the scanner at pretest and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n = 45) and controls (n = 53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n = 30) and controls (n = 33). RESULTS:Patients who did not tolerate the psychological stress task and quit had greater acute (t = 2.52 [p = .016] and t = 3.51 [p = .001] at 0 and 20 minutes) and prolonged (t = 3.62 [p = .001] at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r = -0.468, p = .009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. CONCLUSIONS: This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages.
Authors: S Muñoz Maniega; G K S Lymer; M E Bastin; D Marjoram; D E Job; T W J Moorhead; D G Owens; E C Johnstone; A M McIntosh; S M Lawrie Journal: Schizophr Res Date: 2008-10-11 Impact factor: 4.939
Authors: Kenneth L Davis; Daniel G Stewart; Joseph I Friedman; Monte Buchsbaum; Philip D Harvey; Patrick R Hof; Joseph Buxbaum; Vahram Haroutunian Journal: Arch Gen Psychiatry Date: 2003-05
Authors: Joseph I Friedman; Cheuk Tang; David Carpenter; Monte Buchsbaum; James Schmeidler; Lauren Flanagan; Shana Golembo; Isabella Kanellopoulou; Johnny Ng; Patrick R Hof; Philip D Harvey; Nicholas D Tsopelas; Daniel Stewart; Kenneth L Davis Journal: Am J Psychiatry Date: 2008-06-16 Impact factor: 18.112
Authors: Anya Savransky; Joshua Chiappelli; Laura M Rowland; Krista Wisner; Dinesh K Shukla; Peter Kochunov; L Elliot Hong Journal: Psychosom Med Date: 2017-09 Impact factor: 4.312
Authors: Brian R Barnett; Jacqueline M Anderson; Maribel Torres-Velázquez; Sue Y Yi; Paul A Rowley; John-Paul J Yu Journal: Magn Reson Imaging Date: 2019-05-16 Impact factor: 2.546
Authors: Krista M Wisner; Joshua Chiappelli; Anya Savransky; Feven Fisseha; Laura M Rowland; Peter Kochunov; L Elliot Hong Journal: Brain Imaging Behav Date: 2020-04 Impact factor: 3.978
Authors: Stephanie M Hare; Joshua Chiappelli; Anya Savransky; Bhim M Adhikari; Krista Wisner; Mark Kvarta; Eric Goldwaser; Xiaoming Du; Shuo Chen; Laura M Rowland; Peter Kochunov; L Elliot Hong Journal: Psychosom Med Date: 2020 Jul/Aug Impact factor: 4.312
Authors: Joshua Chiappelli; Teodor T Postolache; Peter Kochunov; Laura M Rowland; S Andrea Wijtenburg; Dinesh K Shukla; Malle Tagamets; Xiaoming Du; Anya Savransky; Christopher A Lowry; Adem Can; Dietmar Fuchs; L Elliot Hong Journal: Neuropsychopharmacology Date: 2016-05-04 Impact factor: 7.853
Authors: Eric L Goldwaser; Xiaoming Du; Bhim M Adhikari; Mark Kvarta; Joshua Chiappelli; Stephanie Hare; Wyatt Marshall; Anya Savransky; Kathleen Carino; Heather Bruce; Ashley Acheson; Peter Kochunov; L Elliot Hong Journal: J Neuropsychiatry Clin Neurosci Date: 2022-01-18 Impact factor: 2.891
Authors: Katarzyna Zalewska; Rebecca J Hood; Giovanni Pietrogrande; Sonia Sanchez-Bezanilla; Lin Kooi Ong; Sarah J Johnson; Kaylene M Young; Michael Nilsson; Frederick R Walker Journal: Int J Mol Sci Date: 2021-06-22 Impact factor: 5.923