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 controlsubjects. 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 CSgroup, greater activation in left dorsal anterior cingulatewas 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.

MECHANISMS IN ENDOCRINOLOGY: Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies

“…In fMRI studies in active disease, dorsal anterior cingulate activation during emotional task was positively associated with percent decline in ACTH from morning peak to afternoon nadir, but not with percent cortisol decline from morning peak to afternoon nadir (25). On the other hand, in adolescents with active disease left amygdala activation and right anterior hippocampal activation during a facial memory task was not correlated with 24-h UFC levels (26).…”

“…Increased activation of the left lateral posterior/pulvinar nuclei of the thalamus and the left middle frontal gyrus was positively correlated with accuracy of emotion identification in patients with active disease, whereas activation in the left superior parietal lobule was not significantly correlated with accuracy of emotion identification (25). In adolescents with active CS, left amygdala activation and right anterior hippocampal activation did not correlate with the performance of a facial memory task (26).…”

“…Using an emotional faces task, adult patients demonstrated less activation in the left anterior superior temporal gyrus, and higher activation in the frontal, medial, and subcortical regions during the identification of emotional faces. These findings indicated alterations in brain activity in regions used for emotion processing (25). Furthermore, adolescents with active CS demonstrated increased activation in the left amygdala and right anterior hippocampus in response to successful encoding during the performance of a facial memory task.…”

“…One study did neither describe diagnostic nor remission criteria (20). Described diagnostic criteria were clinical features (truncal obesity, skin and muscle arthophy, moon facies) (11,12,13,21), elevated urinary free cortisol (UFC) (11,12,13,21,22,23,24,25,26,27,28,29), elevated cortisol secretion rates (11,12,13,21,23,24,25,30), elevated midnight salivary cortisol (29,31), absence of blunted circadian rhythm of cortisol secretion (11,12,13,21,26,27,30,32,33), elevated ACTH levels (in CD only) (12,13,21,23,24), lack of suppression after low dose dexamethasone ((1 mg) (22,25,29,33), (2 mg) (12,13,21...…”

Stress Response to the Functional Magnetic Resonance Imaging Environment in Healthy Adults Relates to the Degree of Limbic Reactivity during Emotion Processing

“…Illustratively, exaggerated cortisol stress responses and elevated basal levels of endogenous cortisol have been implicated in the development and maintenance of depression and other mental disorders [4]. This relation may be partially mediated by enhanced activation and dendritic hypertrophy in the amygdala, as well as reduced dendritic arborization in the hippocampus [5]. …”