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Biomarkers
H04 The relationship of hypothalamic pituitary adrenal axis dysfunction to mood and cognitive changes in the early stages of Huntington's disease
  1. C Shirbin1,
  2. J C Stout1,
  3. A Churchyard2,3,
  4. E Chiu2,4,
  5. A J Hannan5,
  6. T Pang5,
  7. A Komiti6,
  8. P Chua1,2,4
  1. 1School of Psychology and Psychiatry, Monash University, Australia
  2. 2Huntington's Disease Clinic, St George's Hospital, Kew, Australia
  3. 3Huntington's Disease Service, Calvary Health Care Bethlehem, Caulfield, Australia
  4. 4Academic Department of Old Age Psychiatry, University of Melbourne, St George's Hospital, Kew, Australia
  5. 5Howard Florey Institute, Florey Neuroscience Institutes, University of Melbourne, Australia
  6. 6Department of Psychiatry, University of Melbourne, Australia

Abstract

Background Hypothalamic-adrenal-pituitary (HPA)-axis dysfunction in Huntington's disease (HD) rodents has been linked to symptoms such as sleep disturbance, weight loss and depression. HPA axis dysfunction has also been associated with poor mood and cognitive decline in non-HD conditions. A few human studies have identified elevated blood serum and urine cortisol levels in HD gene positive patients. However, no data exist on salivary cortisol levels across the early clinical spectrum and how this relates to mood and cognition. HPA dysfunction could potentially be used as a biomarker in preclinical HD.

Aims A cross-sectional proof of concept study to determine: (1) the sensitivity of salivary cortisol testing as a marker of HPA axis dysfunction at the different stages of HD; (2) how these abnormalities relate to the presence of depressive and cognitive symptoms.

Methods HPA axis activity in participants (20 gene negative controls, 20 prediagnosed gene carriers (pre-HD), 20 early stage HD) will be evaluated by collecting four saliva samples over a 24 h period (day 1: 11pm; day 2: 8am, 4pm, 11pm). Mood, cognitive, stress, sleep quality and motor rating data will also be obtained.

Results Results are available for 10 controls, 10 pre-HD and five early stage HD patients. Preliminary analysis did not identify a significant difference in cortisol levels between participant groups across the four collection times. Higher cortisol levels were associated with poorer performance on several cognitive measures (p≤0.05, including California Verbal Learning Task-II, Symbol Digit Modalities Test, Ruff 2 and 7 Selective Attention Test) at various salivary cortisol time points. No significant correlation was noted for depression and cortisol levels at any time points.

Conclusions These results are currently preliminary. Participant recruitment and testing is still ongoing. Further results with a larger sample size will be reported and discussed.

  • Huntington's disease
  • hypothalamic pituitary adrenal axis (HPA axis)
  • cortisol
  • mood
  • cognition

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Footnotes

  • Funding This study was supported by a Pfizer Neuroscience Research Grant.

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