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Psychiatric symptoms are a common and debilitating manifestation of Huntington’s disease (HD), a progressive, inherited neurodegenerative disorder also characterized by chorea (involuntary, nonrepetitive movements) and cognitive decline. The prevalence of HD is 4 to 8 patients per 100,000 persons in most populations of European descent, with lower prevalence among non-Europeans.1 HD is caused by an abnormal expansion of a trinucleotide (CAG) repeat sequence on chromosome 4, and is inherited in an autosomal dominant fashion, meaning a HD patient’s child has a 50% chance of inheriting the mutation. The expansion is located in the gene that encodes the “huntingtin” protein, the normal function of which is not well understood.
There’s no cure for HD, and treatments primarily are directed at symptom control. Psychiatric symptoms include depression, apathy, anxiety, and psychosis (Table).2-4 Treating patients with HD can be challenging because most psychiatrists will see only a handful of patients with this multifaceted illness during their careers. See Box 1 for a case study of a patient with HD.
Table
Psychiatric symptoms of HD
| Anxiety |
| Apathy |
| Delusions |
| Disinhibitions, impulsivity, aggressive behavior |
| Dysphoria |
| Euphoria |
| Hallucinations |
| Irritability |
| Obsessions and compulsions |
| HD: Huntington’s disease Source: References 2-4 |
Frustrated by declining function
Mr. M, age 50, was diagnosed with Huntington’s disease (HD) 1 year ago. He returns to our psychiatric clinic for treatment of depressive symptoms and temper. Previously, he was prescribed citalopram, 40 mg/d; eventually low-dose olanzapine, 2.5 mg at night, was added. Mr. M reported better temper control, but his low mood, irritability, hopelessness, and amotivation were not significantly improved.
Mr. M left his job at a software company because he had difficulty completing tasks as the result of mood and cognitive changes. He wants to return to work, but feels that he would be unable to complete his job duties.
He begins a trial of bupropion, 150 mg/d, to improve the vegetative component of his mood symptoms to help him return to work. Mr. M now complains of worsening chorea, irritability, and insomnia, with continued difficulty completing tasks. He is intermittently tearful throughout the interview.
Mr. M continues to struggle with mood symptoms that likely are related to the stressful experience of declining function and the intrinsic evolution of HD. His chorea worsens on bupropion; this agent is discontinued and replaced with mirtazapine, 15 mg at night, for his depressive symptoms and insomnia. Citalopram and olanzapine are unchanged. Mr. M is advised to follow up with our HD psychiatry team in 1 month, and is referred for brief psychotherapy. We remind him—as we do for all of our HD patients—to call the HD clinic or 911 if he becomes suicidal. Ongoing treatment efforts likely will be complex, given the multifaceted and progressive nature of his disease.
Psychiatric sequelae
In general, psychiatric symptoms of HD become increasingly prevalent over time (Box 2).3,5 In a 2001 study of 52 HD patients by Paulsen et al,2 51 patients had ≥1 psychiatric symptom, such as dysphoria (69.2%), agitation (67.3%), irritability (65.4%), apathy (55.8%), and anxiety (51.9%); delusions (11.5%) and hallucinations (1.9%) were less prevalent.2 Similarly, Thompson et al3 followed 111 HD patients for ≥3 years and all experienced psychiatric symptoms.
Psychiatric symptoms of HD change over time
According to Thompson et al,3 the presence and severity of apathy, irritability, and depression trend differently across the course of Huntington’s disease (HD). Apathy worsens with disease progression, closely following cognitive and motor symptoms. Irritability increases significantly, but this effect seems confined to early stages of HD. Depressive symptoms appear to decline slightly as HD advances, although it is unclear if this is because of antidepressants’ effects, increasing emotional blunting, and waning insight in later stages of HD, or another unknown factor.3 This study did not examine psychotic symptoms over time because few patients were experiencing delusions or hallucinations.
Similar to Thompson et al, Naarding et al5 found that apathy and depression in HD follow distinct time courses. Depression is a feature of early HD and apathy worsens with overall disease progression.
Depressed mood and functional ability—not cognitive or motor symptoms6—are the 2 most critical factors linked to health-related quality of life in HD. Hamilton et al7 found that apathy or executive dysfunction in HD patients is strongly related to decline in ability to complete activities of daily living, and may be severely debilitating.
Apathy. Often mistaken for a symptom of depression, apathy’s presentation may resemble anhedonia or fatigue; however, research suggests that depression and apathy are distinct conditions. Naarding et al