Huntington's disease as a model for mood disorders - Clues from neuropathology and neurochemistry

Carol Efron Peyser, Susan E. Folstein

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Huntington's disease (HD) is an inherited neuropsychiatric degenerative process characterized by movement disorder, dementia, and, often, affective disorder (AfD) (seen in 38% of patients). Depression in HD is not just an understandable reaction to fatal illness: 10% of HD patients develop mania; AfD can occur 20 yr before neurological signs; and mood disorders are not randomly distributed, but occur in a subset of HD families. This evidence suggests that AfD in HD relates to brain pathophysiology. With its clear neuropathology, HD is proposed as one model for biological underpinnings of idiopathic AfD. There is striking atrophy and neuronal loss in HD neostriatum, particularly caudate. Caudate has rich connections to the limbic system. It is hypothesized that AfD in HD relates to dysfunction of the part of the neostriatum damaged earliest, dorsal medial caudate. Preliminary studies on neuropathological differences between HD patients with and without AfD are discussed. HD neurochemistry is reviewed, emphasizing the excitotoxin hypothesis, which involves dysfunction of the glutamate neurotransmitter system in HD (especially the NMDA receptor, which contains a channel with a phencyclidine (PCP) binding site). Based on the HD model, it is suggested that the glutamate system (particularly NMDA receptors) be examined in idiopathic AfD.

Original languageEnglish (US)
Pages (from-to)99-119
Number of pages21
JournalMolecular and Chemical Neuropathology
Issue number2
StatePublished - Mar 1990


  • affective disorder
  • excitoxin hypothesis
  • glutamate neurotransmitter system
  • Huntington's disease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Molecular Biology


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