Petersen Å and Gabery S.
Translational Neuroendocrine Research Unit, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Journal of Huntington's disease 1: 13-24 (2012)
Huntington’s disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Today, the clinical diagnosis of the disease requires unequivocal signs of typical motor disturbances, which is thought to be due to pathology in the striatum of the basal ganglia. Increasing numbers of studies have emphasized that also non-motor symptoms and signs are common and occur early in HD. These include psychiatric disturbances and cognitive impairment as well as sleep disturbances with disrupted circadian rhythm, autonomic dysfunction and metabolic changes. Several of the non-motor features may be results of dysfunction of the hypothalamus and the limbic system, which are interconnected structures central in the regulation of emotion, sleep and metabolism. In fact, recent studies using postmortem tissue, magnetic resonance imaging and positron emission tomography have shown that hypothalamic and limbic system changes occur early in clinical HD. This review summarizes the current state of knowledge in this area based on clinical studies as well as experiments in animal models of the disease and establishes that hypothalamic and limbic system changes are part of the HD pathology.