| 1. |
- Glad, Camilla A M, 1981, et al.
(författare)
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Reduced DNA methylation and psychopathology following endogenous hypercortisolism- a genome-wide study
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Cushing's Syndrome (CS) in remission were used as a model to test the hypothesis that long-standing excessive cortisol exposure induces changes in DNA methylation that are associated with persisting neuropsychological consequences. Genome-wide DNA methylation was assessed in 48 women with CS in long-term remission (cases) and 16 controls matched for age, gender and education. The Fatigue impact scale and the comprehensive psychopathological rating scale were used to evaluate fatigue, depression and anxiety. Cases had lower average global DNA methylation than controls (81.2% vs 82.7%; p = 0.002). Four hundred and sixty-one differentially methylated regions, containing 3,246 probes mapping to 337 genes were identified. After adjustment for age and smoking, 731 probes in 236 genes were associated with psychopathology (fatigue, depression and/or anxiety). Twenty-four gene ontology terms were associated with psychopathology; terms related to retinoic acid receptor signalling were the most common (adjusted p = 0.0007). One gene in particular, COL11A2, was associated with fatigue following a false discovery rate correction. Our findings indicate that hypomethylation of FKBP5 and retinoic acid receptor related genes serve a potential mechanistic explanation for long-lasting GC-induced psychopathology.
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| 2. |
- Papakokkinou, Eleni, et al.
(författare)
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Mental Fatigue and Executive Dysfunction in Patients with Cushing's Syndrome in Remission
- 2015
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Ingår i: Behavioural Neurology. - : Hindawi Limited. - 0953-4180 .- 1875-8584.
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Cushing's syndrome (CS) in remission often suffer from impaired quality of life and cognitive dysfunction. The primary aim was to investigate the occurrence of mental fatigue, characterized by mental exhaustion and long recovery time following mentally strenuous tasks, in patients with CS in remission. The secondary aim was to examine whether the newly developed parts C and D of the trailmaking test (TMT) are more sensitive, compared to the conventional parts A and B, to evaluate attention and executive function. This was a cross-sectional study including 51 patients with CS in remission and 51 controls. All subjects completed the self-administrated mental fatigue scale (MFS) and performed all four parts of the TMT. The patients had worse outcome on all components of the MFS except for sensitivity to noise. After adjustment for mental fatigue, depression, and anxiety, the patients performed worse only on part D of the TMT (P < 0.05). Mental fatigue is common in patients with CS in remission and can be captured by using the MFS. The most demanding part of the TMT, part D, is more useful to capture cognitive deficits in patients with CS in remission compared to the conventional parts A and B.
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| 3. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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Common genetic variants in the glucocorticoid receptor and the 11β-Hydroxysteroid dehydrogenase type 1 genes influence long-term cognitive impairments in patients with Cushing's syndrome in remission.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:9
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Tidskriftsartikel (refereegranskat)abstract
- Context: Cognitive function is impaired in patients with Cushing's syndrome (CS) in remission. Objective: To study the effects of polymorphisms in genes associated with glucocorticoid (GC) sensitivity on cognitive function in patients with CS in long-term remission. Design: A cross-sectional, case-controlled, single center study. Patients: Fifty-three patients with Cushing's syndrome in remission and 53 controls matched for age, gender and educational level. Main Outcome Measures: Cognitive function, studied using standardized neuropsychological testing, and polymorphisms in the GC receptor (NR3C1; Bcl1 and A3669G), mineralocorticoid receptor (NR3C2; I180V), 11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1; rs11119328) and ATP binding cassette B1 (ABCB1; rs1045642) genes. The association between cognitive function and polymorphisms were analyzed using linear regression with adjustments for age and educational level. Results: The mean age in patients and controls was 53 ± 14 years. The median (interquartile range) duration of remission was 13 (5-18) years. In patients, SNP rs11119328 was associated with impairments in processing speed, auditory attention, auditory working memory and reading speed. This association was not seen in matched controls. The Bcl1 polymorphism was associated with fatigue and worse visual attention and working memory. The remaining SNPs were not associated with cognitive performance. Conclusion: In this study, polymorphisms in the 11βHSD1 and NR3C1 genes were associated with impaired cognitive function, indicating that GC sensitivity and pre-receptor regulation of GC action may play a role in the long-term consequences of CS. The study provides a novel insight into the etiology of cognitive dysfunction in patients with CS in remission.
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| 4. |
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| 5. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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Neurodegenerative and inflammatory biomarkers in cerebrospinal fluid in patients with Cushing's syndrome in remission.
- 2013
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 169:2, s. 211-5
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Cushing's syndrome (CS) in long-term remission have impaired cognitive function. Cerebrospinal fluid (CSF) biomarkers are important diagnostic tools in the work-up of patients with cognitive impairment. The aim of this study was to analyze neurodegenerative and inflammatory biomarkers in the CSF of patients with CS in remission.
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