title: Impact of chronic hypercortisolemia on affective processing.
abstract: Cushing syndrome (CS) is the classic condition of cortisol dysregulation, and cortisol dysregulation is the prototypic finding in Major Depressive Disorder (MDD). We hypothesized that subjects with active CS would show dysfunction in frontal and limbic structures relevant to affective networks, and also manifest poorer facial affect identification accuracy, a finding reported in MDD. Twenty-one patients with confirmed CS (20 ACTH-dependent and 1 ACTH-independent) were compared to 21 healthy control subjects. Identification of affective facial expressions (Facial Emotion Perception Test) was conducted in a 3 Tesla GE fMRI scanner using BOLD fMRI signal. The impact of disease (illness duration, current hormone elevation and degree of disruption of circadian rhythm), performance, and comorbid conditions secondary to hypercortisolemia were evaluated. CS patients made more errors in categorizing facial expressions and had less activation in left anterior superior temporal gyrus, a region important in emotion processing. CS patients showed higher activation in frontal, medial, and subcortical regions relative to controls. Two regions of elevated activation in CS, left middle frontal and lateral posterior/pulvinar areas, were positively correlated with accuracy in emotion identification in the CS group, reflecting compensatory recruitment. In addition, within the CS group, greater activation in left dorsal anterior cingulate was related to greater severity of hormone dysregulation. In conclusion, cortisol dysregulation in CS patients is associated with problems in accuracy of affective discrimination and altered activation of brain structures relevant to emotion perception, processing and regulation, similar to the performance decrements and brain regions shown to be dysfunctional in MDD. This article is part of a Special Issue entitled 'Anxiety and Depression'.
authors.affiliation: Department of Psychiatry, University of Michigan Medical Center, 2101 Commonwealth Blvd., Suite C., Ann Arbor, MI 48105, USA. slangen@umich.edu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Langenecker
authors.forename: Sara L
authors.initials: SL
authors.lastname: Weisenbach
authors.forename: Bruno
authors.initials: B
authors.lastname: Giordani
authors.forename: Emily M
authors.initials: EM
authors.lastname: Briceño
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Guidotti Breting
authors.forename: Michael-Paul
authors.initials: MP
authors.lastname: Schallmo
authors.forename: Hadia M
authors.initials: HM
authors.lastname: Leon
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Noll
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
authors.forename: David E
authors.initials: DE
authors.lastname: Schteingart
authors.forename: Monica N
authors.initials: MN
authors.lastname: Starkman
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000473:pathology; D001931:Brain Mapping; D002908:Chronic Disease; D002940:Circadian Rhythm / Q000502:physiology; D003480:Cushing Syndrome / Q000150:complications*; D004644:Emotions / Q000502:physiology*; D005149:Facial Expression; D005260:Female; D007839:Functional Laterality; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000209:etiology* / Q000473:pathology*; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D055815:Young Adult
chemical_list: D000324:Adrenocorticotropic Hormone; D010100:Oxygen; D006854:Hydrocortisone