title: Altered neural processing of emotional faces in remitted Cushing's disease.
abstract: Patients with long-term remission of Cushing's disease (CD) demonstrate residual psychological complaints. At present, it is not known how previous exposure to hypercortisolism affects psychological functioning in the long-term. Earlier magnetic resonance imaging (MRI) studies demonstrated abnormalities of brain structure and resting-state connectivity in patients with long-term remission of CD, but no data are available on functional alterations in the brain during the performance of emotional or cognitive tasks in these patients. We performed a cross-sectional functional MRI study, investigating brain activation during emotion processing in patients with long-term remission of CD. Processing of emotional faces versus a non-emotional control condition was examined in 21 patients and 21 matched healthy controls. Analyses focused on activation and connectivity of two a priori determined regions of interest: the amygdala and the medial prefrontal-orbitofrontal cortex (mPFC-OFC). We also assessed psychological functioning, cognitive failure, and clinical disease severity. Patients showed less mPFC activation during processing of emotional faces compared to controls, whereas no differences were found in amygdala activation. An exploratory psychophysiological interaction analysis demonstrated decreased functional coupling between the ventromedial PFC and posterior cingulate cortex (a region structurally connected to the PFC) in CD-patients. The present study is the first to show alterations in brain function and task-related functional coupling in patients with long-term remission of CD relative to matched healthy controls. These alterations may, together with abnormalities in brain structure, be related to the persisting psychological morbidity in patients with CD after long-term remission.
authors.affiliation: Institute of Psychology, Leiden University, Leiden, The Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Janna Marie
authors.initials: JM
authors.lastname: Bas-Hoogendam
authors.affiliation: Leiden Institute for Brain and Cognition, Leiden, The Netherlands; Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: c.d.andela@lumc.nl.
authors.forename: Cornelie D
authors.initials: CD
authors.lastname: Andela
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Steven J A
authors.initials: SJ
authors.lastname: van der Werff
authors.affiliation: Leiden Institute for Brain and Cognition, Leiden, The Netherlands; Division of Brain Sciences, Centre for Neuropsychopharmacology, Imperial College London, United Kingdom.
authors.forename: J Nienke
authors.initials: JN
authors.lastname: Pannekoek
authors.affiliation: Institute of Psychology, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: van Steenbergen
authors.affiliation: Leiden Institute for Brain and Cognition, Leiden, The Netherlands; Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Onno C
authors.initials: OC
authors.lastname: Meijer
authors.affiliation: Leiden Institute for Brain and Cognition, Leiden, The Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: Institute of Psychology, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Serge A R B
authors.initials: SA
authors.lastname: Rombouts
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Roos C
authors.initials: RC
authors.lastname: van der Mast
authors.affiliation: Leiden Institute for Brain and Cognition, Leiden, The Netherlands; Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
authors.forename: Nic J A
authors.initials: NJ
authors.lastname: van der Wee
authors.affiliation: Leiden Institute for Brain and Cognition, Leiden, The Netherlands; Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000503:physiopathology; D001931:Brain Mapping; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004644:Emotions / Q000502:physiology; D005149:Facial Expression; D000066499:Facial Recognition / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology*; D047748:Pituitary ACTH Hypersecretion / Q000503:physiopathology* / Q000523:psychology*; D017397:Prefrontal Cortex / Q000503:physiopathology; D055815:Young Adult
keywords: Amygdala; Cushing's syndrome; Emotional processing; Functional magnetic resonance imaging; Hypercortisolism; Medial prefrontal cortex