Early Psychiatric Manifestations of Huntington's Disease: More Than Just a Movement Disorder

Abstract

Huntington's disease (HD), a neurodegenerative condition of the central nervous system, poses a major challenge for clinicians. The clinical presentation is variable and consists of cognitive, psychiatric and motor symptoms. The psychiatric manifestations often appear many years before the movement disorder. Lack of recognition of the psychiatric mani-festations may lead to delays in diagnosis and multidisciplinary interventions. The aim of this article is to highlight the psychiatric aspects of HD, particularly focusing on the early presenta-tion. Two cases of HD with prominent psychiatric symptoms are used to illustrate the preva-lence of these aspects of the disease. In the absence of treatment directly influencing the course of HD, psychiatrists remain central to the multidisciplinary team diagnosing and treating this debilitating condition.Huntington's disease (HD), which was first described by George Huntington in 1872, is a neurodegenerative disorder which presents as a syndrome of motor abnormalities, cognitive decline and neuropsychiatric symptoms. HD has an autosomal dominant pattern of in-heritance with complete penetrance. The gene for the disease was identified in March, 1993 (1,2), enabling predictive and prenatal testing for those at risk of inheriting the disease (3). The disease affects 5 to 8 per 100,000 in North America (4,5). The average age of onset is be-tween 35 and 40 years of age, however, juve-nile forms of the disease can result in symp-toms as early as age 4 (6).The course of HD is progressive and is marked by increasing motor difficulties, in-cluding chorea, dystonia and athetosis, as well as bradykinesia, dysarthria, dysphagia, and urinary incontinence (7). Death results an average of 17 years after onset of the disease and is caused by cardiac and pulmonary complica-tions, suicide, nutritional deficiencies and self-destructive behaviours (8).The HD gene (referred to as IT15), found on the short arm of chromosome 4, partly consists of an unstable triplicate repeat (CAG) sequence. The number of triplicate repeats is higher (more than 38 repeats) in those with HD than in the normal population, which has 11-38 repeats. The mRNA transcribed from the HD gene can be found in all organs of an affected person and codes for a protein which has been called "huntingtin". The relationship between this protein and the development of the pathological changes in HD is still unclear, although several studies have attempted to define the neurophysiology and neuropathology. Neuropathology reveals early and promi-nent degeneration of the caudate nucleus. Later cell loss occur in the globus pallidus, subthalamic nucleus, nucleus accumbens, cerebellum and parts of the cortex (9). Within the caudate nucleus, abnormalities of small-to-medium sized spiny neurons result in loss of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) as well as substance P and enkephalins. There is relative sparing of somatostatin and dopamine (10).HD is generally considered a "neurologic" illness, falling ...