title: Allostatic load and reduced cortical thickness in schizophrenia.
abstract: Structural imaging studies have consistently found reduced gray matter thickness of the cerebral cortex in schizophrenia, a finding that is evident in first episode psychosis and may be progressive in some cases. Although genetic predisposition and medication effects may contribute to cortical thinning, we hypothesize that the cumulative effects of stress may represent an environmental factor impacting brain morphology in schizophrenia. We examined the relationship between allostatic load, an index of peripheral biomarkers representing the cumulative effects of stress, and cortical thickness. Allostatic load was calculated for 44 patients with schizophrenia spectrum disorders (SSD) and 33 normal controls (NC) based on 13 cardiovascular, neuroendocrine, immune, and metabolic measurements. Controlling for age, SSD had significantly elevated allostatic load as compared with NC (p=0.008). Controlling for age, whole brain average cortical thickness was lower in SSD patients compared to NC (p=0.008). However, once allostatic load was accounted for, the group difference in cortical thickness became marginal (p=0.058). Exploratory analyses on subcomponents of allostatic load suggested that elevated immune marker C-reactive protein, stress hormones, and cardiovascular indices within allostatic load were more strongly associated with reduced cortical thickness in SSD. In NC, only the association between immune marker C-reactive protein and cortical thickness was replicated. These results support the hypothesis that allostatic load may account for some of the gray matter deficits observed in schizophrenia. Among the allostatic indices, the inflammatory mechanism appears particularly relevant to cortical thickness in both schizophrenia patients and normal controls.
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: 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: 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: Feven
authors.initials: F
authors.lastname: Fisseha
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Krista
authors.initials: K
authors.lastname: Wisner
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Du
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: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D052636:Allostasis / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D002784:Cholesterol / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000502:physiology; D011618:Psychotic Disorders / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012559:Schizophrenia / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D002784:Cholesterol
keywords: Allostatic load; C-reactive protein; Cortical thickness; Schizophrenia; Stress