Citalopram to Enhance Cognition in HD

This research plan proposes to conduct a double-blind, placebo-controlled pilot clinical trial in 36 adults with mild Huntington's disease (HD) to address the following research aims:

1. To determine the effect of citalopram compared to placebo in patients with early HD on executive function and other outcome variables including functional measures (health-related quality of life, work productivity, and self-reported attention), motor performance, and psychiatric status,
2. To study the relationship between executive function and functional status in patients with early HD after selective serotonin reuptake inhibitor (SSRI) treatment, and
3. To examine the effect of citalopram treatment on volumetric and metabolic (i.e, N-acetyl-aspartate concentration) measures in the neostriatum among patients with recently diagnosed Huntington's disease.

Specific Aims:

1. To examine the effects of sixteen weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram compared to placebo on executive function in patients with early Huntington's disease (HD).
2. To study the relationship between executive function and functional status in patients with early HD after SSRI treatment.
3. To determine the effect of sixteen weeks of citalopram compared to placebo on other outcome variables including functional measures (health-related quality of life, work productivity, and self-reported attention), motor performance, and psychiatric status.
4. To examine the effect of citalopram treatment on volumetric and metabolic (i.e, N-Acetyl-Aspartate concentration) measures in the neostriatum among patients with recently diagnosed Huntington's Disease.

Main Hypotheses:

1. At the end of the treatment protocol, patients receiving citalopram as compared with placebo will show a significantly greater improvement on tests of executive function.
2. Performance on measures of executive function will be significantly associated with measures of functional status.
3. At the end of the treatment protocol, patients receiving citalopram as compared with placebo will show a significantly greater improvement in functional status and psychiatric ratings; motor score is not expected to change as a result of citalopram therapy.
4. Using structural MRI and occipital proton magnetic resonance spectroscopy (1H-MRS), after treatment, patients with recently diagnosed Huntington's Disease will show greater changes from baseline on volumetric and metabolic (i.e., N-Acetyl-Aspartate concentration) neuroimaging measures in the neostriatum than those on placebo.

Eligibility Criteria:
Inclusion Criteria:

* Gene positive HD test (or, if untested, an HD diagnosis) with some abnormal motor signs (i.e., diagnostic confidence level of greater than or equal to 1 as measured by the UHDRS).
* Aged between 18 and 75
* Ability to provide written informed consent
* Mild stage HD (Shoulson and Fahn Scale Stage 1 or 2)
* Mild executive dysfunction: Participants must have complaints of poor cognition, mild functional decline, or demonstrate objective evidence of decline from their premorbid level
* Participants are able to complete all study assessments

Exclusion Criteria:

* Age under 18 or greater than 75
* Current major depression deemed significant by the investigator at the screening visit or current suicidal ideation.
* Any unstable or severe psychiatric disease including diagnoses of schizophrenia, bipolar affective disorder, dementia, delirium, severe anxiety and/or substance abuse/dependence.
* Current use of an SSRI or other treatment for depression (e.g., use of an MAOI) or treatment with an SSRI within the past 14 days.
* Current use of St. John's wort within the past 14 days.
* To ensure performance on cognitive measures are not affected by specific concomitant medications, participants taking methylphenidate, amphetamine/dextroamphetamine, atomoxetine, an acetyl cholinesterase inhibitor, an atypical antipsychotic, kava kava, Ginkgo Biloba, or an anxiolytic drug may be excluded unless their dose and dosing frequency have remained stable for 30 days prior to receiving study drug. Continued participation also requires the dose and dosing frequency remain stable throughout the study.
* Patients who are pregnant, nursing, or planning to become pregnant during the study.
* Patients who are unable to participate in the study assessments (cognitive, functional, psychiatric and motor scales) due to cognitive, motor, or sensory impairments (i.e., significant vision or hearing deficits).
* Other serious medical conditions such as cardiovascular or cerebrovascular disease; head injury deemed clinically significant by the PI; neurological disorder or insult other than HD.
* Learning disability or other medical condition that is likely to affect cognitive function; history of symptoms indicative of attention deficit hyperactivity disorder (ADHD) in childhood; or a diagnosis of ADHD.

It is important to note that participants who are unable to receive an MRI scan may still participate in this study