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Neuropsychological and Emotional Functioning in Patients with Cushing's Syndrome.

ABSTRACT: Patients with Cushing's syndrome (CS) frequently report impairments in cognitive and emotional functioning. Given neuroimaging research that implicates alterations in structure and function in the brain in this population, goals of this study were to investigate neuropsychological and emotional functioning, with particular emphasis on complex attention and memory. In a clinical sample of 18 adults with CS referred for neuropsychological evaluation (age 41.6 ± 10.6, 72% Caucasian), patients' most common subjective complaints were in attention and increased irritability. On objective testing, patients exhibited significant declines in the consistency of their sustained attention and visual-spatial functioning compared to normative peers. Patients exhibited on average significantly reduced initial learning following first exposure to visual and verbal stimuli but intact retention of information learned. Patients with CS endorsed highly elevated levels of somatization, depression, and anxiety, and 59% of them scored in the clinically elevated range for somatization and depressive symptomatology. Exploratory analyses suggested that the 11 patients with active Cushing's exhibited lower processing speed, poorer sustained attention, naming, and cognitive flexibility compared to the 7 patients who achieved biochemical remission. Patients with active Cushing's also reported higher levels of somatization and anxiety compared to patients in biochemical remission. Overall, this study provides new insights into complex attention and memory deficits in patients with CS and concern regarding cognitive and emotional issues despite resolution of hypercortisolism. Our study opens several avenues for further exploration.

SUBMITTER: Na S

PROVIDER: S-EPMC7428886 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Neuropsychological and Emotional Functioning in Patients with Cushing's Syndrome.

Na Sabrina S Fernandes Mary A MA Ioachimescu Adriana G AG Penna Suzanne S

Behavioural neurology 20200807

Patients with Cushing's syndrome (CS) frequently report impairments in cognitive and emotional functioning. Given neuroimaging research that implicates alterations in structure and function in the brain in this population, goals of this study were to investigate neuropsychological and emotional functioning, with particular emphasis on complex attention and memory. In a clinical sample of 18 adults with CS referred for neuropsychological evaluation (age 41.6 ± 10.6, 72% Caucasian), patients' most ...[more]

PMID: 32831970

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Project description:PurposeImpairment of skeletal muscle mass and strength affects 40-70% of patients with active Cushing's syndrome (CS). Glucocorticoid excess sustains muscle atrophy and weakness, while muscle-specific microRNAs (myomiRs) level changes were associated with muscle organization and function perturbation. The aim of the current study is to explore changes in circulating myomiRs in CS patients compared to healthy controls and their involvement in IGFI/PI3K/Akt/mTOR pathway regulation in skeletal muscle.MethodsC2C12, mouse myocytes, were exposed to hydrocortisone (HC), and atrophy-related gene expression was investigated by RT-qPCR, WB and IF to assess HC-mediated atrophic signalling. miRNAs were evaluated in HC-treated C2C12 by PCR Arrays. MyomiRs significantly overexpressed in C2C12 were investigated in 37 CS patients and 24 healthy controls serum by RT-qPCR. The anti-anabolic role of circulating miRNAs significantly upregulated in CS patients was explored in C2C12 by investigating the IGFI/PI3K/Akt/mTOR pathway regulation.ResultsHC induced higher expression of atrophy-related genes, miR-133a-3p, miR-122-5p and miR-200b-3p in C2C12 compared to untreated cells. Conversely, the anabolic IGFI/PI3K/Akt/mTOR signalling was reduced and this effect was mediated by miR-133a-3p. In CS patients miR-133a-3p and miR-200b-3p revealed higher circulating levels (p < 0.0001, respectively) compared to controls. ROC curves for miR-133a-3p (AUC 0.823, p < 0.0001) and miR-200b-3p (AUC 0.850, p < 0.0001) demonstrated that both myomiRs represent potential biomarkers to discriminate between CS and healthy subjects. Pearson's correlation analysis revealed that circulating levels of miR-133a-3p are directly correlated with 24 h urinary-free cortisol level (r = 0.468, p = 0.004) in CS patients.ConclusionsHC induces atrophic signals by miR-133a-3p overexpression in mouse myocytes and humans. Circulating miR-133a-3p is promising biomarkers of hypercortisolism.

Project description:Introduction: Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant genetic illness, characterized by a progressive loss of strength. Important deficits in cognitive functioning and a significant prevalence of psychiatric disorders have been previously reported. Methods:A neuropsychological and psychological assessment was carried out in 31 DM1 patients (61% males) in order to measure the cognitive functioning and explore their personality profiles. The MMSE Mini-Mental State Examination, Frontal Assessment Battery (FAB), ENB-2 Battery assessing memory (short term, long term and working memory), integration capacities, visual-spatial ability, attention (selective, divided, shifting/switching) executive functions, praxis, discrimination and logic capabilities and psychopathology Symptom Check List 90-R (SCL-90-R) were administered. The neuropsychological and psychological evaluation of DM1 patients was carried out taking into consideration the clinical parameters (CTG repeat, age at onset, disease duration, Muscular Impairment Rate Scale (MIRS), Medical Research Council Scale (MRC) and the Epworth Sleepiness Scales (EPS)). Results: Regarding psychopathology 19.4% of patients scored a moderate or high level of symptoms intensity index (GSI), 12.9% reported a high number of symptoms (PST) and 16.1% reported a high intensity level of the perceived symptoms (PSDI). Fatigue and daytime sleepiness resulted as being associated with higher levels of psychoticism (PSY). Only 1 patient reported a severe impairment in the spatial and temporal orientation, memory, language, praxis, attention and calculation. Longer disease duration was also associated with cognitive impairment evaluated through ENB-2 (p < 0.05). Discussions and Conclusions:There are indications of the utility of neuropsychological and psychological screening and support for these patients and their families due to the link between disease duration and cognitive performances. A proposal of a clinical protocol, with an illustration of a clinical case report of a family is presented.

Dataset Information

Neuropsychological and Emotional Functioning in Patients with Cushing's Syndrome.

Publications

Neuropsychological and Emotional Functioning in Patients with Cushing's Syndrome.

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