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'.
Bibliographical noteFunding Information:
This project was supported by a General Clinical Research Center pilot grant to MNS and SAL (for some control and all Cushing’s fMRI scans, from # MO1 RR00042 ), KL2 Career Development Award ( RR024987 , SAL), K23 Award ( MH074459 , SAL), NIMH grant (# MH 43372 , MNS), a Rachel Upjohn Clinical Scholars Award for screening of control subjects (SAL), and some pilot (control) fMRI scans from the University of Michigan functional MRI lab (SAL,SLW). Allison M. Kade, Kathleen E. Hazlett, Michael L. Brinkman, Benjamin D. Long, Lawrence S. Own, Thomas M. Hooven, and Karandeep D. Singh, are thanked for their assistance in data collection and analysis for this work. We gratefully acknowledge James L. Abelson, M.D., Ph.D. for his constructive comments in the integration and presentation of data. The staff and faculty at the University of Michigan fMRI lab are gratefully acknowledged for their assistance and support in completing this work.