The purpose of this trial is to study early brain and behavioral changes in people who have the gene expansion for Huntington's disease, but are currently healthy and have no symptoms.

Huntington's Disease (HD) is an inherited disease that causes changes in a person's ability to control movements, thinking, and feelings. The intent of this study is to learn more about the beginning changes in thinking skills, emotional regulation, and brain structure and function as a person begins the transition from health to HD.

Preliminary studies indicate that people with HD may have marked decline before an actual diagnosis. This study will help reveal the earliest indicators of the disease and what factors influence the age at which a person carrying the gene develops the disease. It is necessary to get information on the early stages of HD in order to develop drugs that can slow or postpone the onset of HD. The investigators hope this study will provide essential information for future trials of experimental drugs for HD.

During this study, participants will undergo several detailed tests, including MRI scans of the brain, cognitive assessments, physical exams, bio specimen (blood, urine, cerebral spinal fluid) collection and neurological and psychiatric testing.

Inclusion Criteria:

• men and women at risk for HD, who have been tested for the HD gene mutation, and who have not been diagnosed with symptoms of HD (CAG ≥36 for CAG-expanded group or CAG <36 for CAG-norm group).

Exclusion Criteria:

• diagnosis of manifest HD (at least 50% confidence by neurologist that symptoms are present);
• clinical evidence of unstable medical or psychiatric illness (including substance abuse);
• history of sever learning disability or mental retardation;
• history of other CNS disease or event (e.g., seizures or head trauma);
• current treatment with antipsychotic medications, including the traditional neuroleptics such as haloperidol as well as the atypical antipsychotics risperidone, clozapine, quetiapine, and olanzapine;
• treatment with phenothiazine-derivative antiemetic medications such as prochlorperazine, metoclopramide, promethazine, and Inapsine on a regular basis (greater than 3 times per month);

Specific exclusion criteria for the lumbar puncture:

• Current use of anti-coagulants
• Current use of anti-platelets
• Unable to provide consent for him/herself

People at risk for HD, who have been tested for the HD gene mutation, and who have not been diagnosed with symptoms of HD.

All data have been de-identified and anonymized with the best possible methods to allow and facilitate data sharing with other investigators. Data has been shared to CHDI and dbGaP.

Data will be on dbGaP and at CHDI for data sharing with no anticipated endpoint.

NINDS monitors dbGaP and CHDI scientific staff monitors their data copy.