title: Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia.
abstract: OBJECTIVE
  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.affiliation: From the Maryland Psychiatric Research Center, Department of Psychiatry (Nugent, Chiappelli, Sampath, Rowland, Thangavelu, Davis, Du, Muellerklein, Kochunov, Hong), University of Maryland School of Medicine, Baltimore, Maryland; and Department of Psychology (Daughters), The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Nugent
authors.forename: Joshua
authors.initials: J
authors.lastname: Chiappelli
authors.forename: Hemalatha
authors.initials: H
authors.lastname: Sampath
authors.forename: Laura M
authors.initials: LM
authors.lastname: Rowland
authors.forename: Kavita
authors.initials: K
authors.lastname: Thangavelu
authors.forename: Beshaun
authors.initials: B
authors.lastname: Davis
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Du
authors.forename: Florian
authors.initials: F
authors.lastname: Muellerklein
authors.forename: Stacey
authors.initials: S
authors.lastname: Daughters
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology*; D013315:Stress, Psychological / Q000378:metabolism*; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
chemical_list: D006854:Hydrocortisone