Psychiatric and neurocognitive consequences of endogenous hypercortisolism

Abstract

Psychiatric and neurocognitive symptoms due to hypercortisolism were already described by Harvey Cushing in his original paper on patients with Cushing's syndrome (CS). Nowadays, it is well known that psychiatric and cognitive complaints are two of the most common, and most distressing, symptoms in patients with CS. Psychiatric symptoms are indeed a major clinical manifestation of CS. The most commonly observed psychiatric conditions are depression and anxiety, whilst mania and psychosis are less common. Several domains of cognitive function are impaired at diagnosis, including episodic and working memory, executive function and attention. Following treatment, onefourth of the patients still experience depressed mood, and the cognitive impairments are only partially restored. Consequently, quality of life in patients with CS is severely and persistently affected. Neuroimaging studies have also illustrated the deleterious effects of hypercortisolism on the brain by demonstrating reduced grey matter volumes and cortical thickness, altered restingstate functional responses and during cognitive tasks, as well as widespread reduced white matter integrity, especially in structures important for cognitive function and emotional processing, both before and after successful abrogation of hypercortisolism. In this paper, we summarize the current knowledge on the psychiatric and neurocognitive consequences of hypercortisolism in patients with CS, both before, and after successful treatment. In addition, we review the structural and functional brain abnormalities associated with hypercortisolism and discuss the influence of these factors on quality of life.

Psychotropic Drugs in Patients with Cushing’s Disease Before Diagnosis and at Long-Term Follow-Up: A Nationwide Study

“…Glucocorticoid excess has a major impact on the human brain with accompanying neuropsychiatric consequences ( 26 ). In patients with CD, the mental consequences of hypercortisolism have not been fully addressed, and the reversibility after cure is debated.…”

Brain Mineralocorticoid receptor in health and disease: from molecular signaling to cognitive and emotional function

“…Separating MR from GR mediated effects is also very challenging in Cushing's syndrome (CS), that is characterized by chronic glucocorticoid overproduction by the adrenal glands. Apart from a plethora of well-known metabolic and cardiovascular complications, there are several neuropsychiatric sequelae of increased endogenous glucocorticoid secretion (Piasecka et al , 2020), as already noted by Harvey Cushing himself (Cushing, 1994). Additionally, brain atrophy due to excessive cortisol secretion has been repeatedly described in CS.…”

Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

“…Unfortunately, low health-related quality of life and psychiatric symptoms are only partially reversible after hypercortisolism resolution [ 120 ]. Indeed, following successful treatment of Cushing’s syndrome, one-fourth of patients still experience depressed mood, and the cognitive impairments are only partially restored [ 121 ]. The central nervous system is rich in GR and chronic brain exposure to cortisol excess causes deep structural and functional changes in cerebral areas particularly rich in GR and therefore particularly vulnerable to GC excess, such as the hippocampus, which is critical for learning and memory [ 122 ].…”