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Striosomes and mood dysfunction in Huntington's disease

Lynette J. Tippett, Henry J. Waldvogel, Sally J. Thomas, Virginia M. Hogg, Willeke van Roon-Mom, Beth J. Synek, Ann M. Graybiel, Richard L. M. Faull
DOI: http://dx.doi.org/10.1093/brain/awl243 206-221 First published online: 13 October 2006


Variable phenotype is common in neurological disorders with single-gene inheritance patterns. In Huntington's disease, mood and cognitive symptoms are variably co-expressed with motor symptoms. There is also variable degeneration of neurons in the two major neurochemical compartments of the striatum, the striosomes and the extrastriosomal matrix. To determine whether the phenotypic variability in Huntington's disease is related to this compartmental organization, we carried out a double-blind study in which we used GABAA receptor immunohistochemistry to analyse the status of striosomes and matrix in the brains of 35 Huntington's disease cases and 13 control cases, and collected detailed data on the clinical symptomatology expressed by the patients from family members and records. We report here a significant association between pronounced mood dysfunction in Huntington's disease patients and differential loss of the GABAA receptor marker in striosomes of the striatum. This association held for both clinical onset and end-stage assessments of symptoms. The cases with accentuated striosome abnormality further exhibited later onset age, lower disease grade and lower CAG repeat length in the HD gene. We found no independent association, however, between CAG repeat length or age of onset and mood dysfunction. We suggest that variation in clinical symptomatology in Huntington's disease is associated with variation in the relative abnormality of GABAA receptor expression in the striosome and matrix compartments of the striatum, and that striosome-related circuits may modulate mood functioning.

  • striosomes, striatum
  • neurological disorder
  • Huntington's disease
  • mood symptoms

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