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Cushing's Disease: a model for stress-related neuropsychiatric disorders? New evidences from MRI volumetric data

Cushing's disease (CD) frequently causes Major Depression and neural damages. These patients experience high levels of endogenous cortisol, the naturally occurring GC. More than 50% melancholic patients do not suppress HPA axis with a single dose of Dexamethasone and have "pseudo-Cushing" features. Hippocampal formation, limbic system, prefrontal cortex and caudate nucleus seem to be the most implicated structure in the supposed glucocorticoid neuronal damage in Major Depression. These observations underline why CD provides a unique opportunity to study the potential role of cortisol in the well documented structural alterations of CNS in humans. Twenty CD patients and matched controls were examined. MRI measurements were performed separately for the hippocampal head, body and tail, amygdala, caudate and prefrontal cortex areas. We studied the relationship of various brain structure's volumes with the degree of HPA hyperactivity. Group comparison showed that patients had left hippocampal atrophy, mainly involving the hippocampal head. Cortisol levels after DST were negatively correlated with whole brain volume and caudate volume bilaterally, revealing a neuroplastic modulation of these structures in dependence with cortisol hyperproduction.