Brain Advance Access originally published online on October 12, 2006
Brain 2007 130(1):206-221; doi:10.1093/brain/awl243
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Striosomes and mood dysfunction in Huntington's disease
1 Department of Psychology, The University of Auckland Auckland, New Zealand 2 Department of Anatomy with Radiology, The University of Auckland Auckland, New Zealand 3 Department of Forensic Pathology, Auckland City Hospital Auckland, New Zealand 4 Department of Brain and Cognitive Sciences and the McGovern Institute for Brain Research, Massachusetts Institute of Technology Cambridge, MA, USA
Correspondence to: Dr Lynette J. Tippett, Department of Psychology, The University of Auckland, Private Bag 92019, Auckland, New Zealand E-mail: l.tippett{at}auckland.ac.nz
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.
Key Words: striosomes, striatum; neurological disorder; Huntington's disease; mood symptoms
Abbreviations: NeuN, neuronal N; PBS, phosphate-buffered saline
Received May 5, 2006. Revised July 12, 2006. Accepted August 4, 2006.
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