HD Lighthouse Contributing Editor's Comment: One of the puzzling things about Huntington's Disease is the variability of symptoms. As the researchers note, some people with the disease have predominately movement symptoms, others psychological symptoms, and others cognitive symptoms, whereas some have all three types of symptoms.

The researchers looked for differences in the brains between deceased HD patients to see if they were associated with the symptoms and course of the disease, based on patient records and family acounts. They also looked at a control group of those who died from other causes. They considered anxiety, depression, irritability, delusions, compulsiveness, and repetitive behavior to be signs of mood dysfunction. The researchers who compiled the data about symptoms were unaware of the brain pathology data. The researchers divided the deceased patients into three groups, those with GABA (alpha) receptor loss occurring predominantly in the striosome compartment of the brain, those with this type of loss occurring predominately in the matrix compartment, and those with a mixed pattern of loss. They found that the striosome loss group had had more mood dysfunction throughout the disease and milder neuropathology at the time of death as compared to the matrix loss group. The mixed loss group fell in between. The three groups did not differ in disease duration.

On average, those with the mood disorders tended to have lower CAG repeats and later onset than the matrix group with the mixed group again falling inbetween. However CAG counts and age of onset weren't independently associated with mood disorder; in other words low CAG repeat, late onset patients who didn't exhibit the striosomal damage didn't exhibit the mood dysfunctions.

In animal studies, the striosome compartment of the brain has been linked to areas in the limbic forebrain which are associated with mood disorders and obsessive compulsive disorder in humans.

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 15 Jan 2007

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, and Richard M. L. Faull

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. # # #

Source: Brain 2007 130(1):206-221

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