Acute D2 Receptor Blockade Induced Neuronal Network Changes in Human Volunteers

Not Applicable

Completed

Conditions: Imaging of the Brain and Antipsychotics
Neuronal Network Changes

Brief Summary: To detect the effect of second-generation antipsychotic drug on the neural activity.

Detailed Description: To detect functional correlation changes in the brain with anti-psychotic drug administration as compared to placebo, and b.) to measure if these changes correlate with the plasma level of anti-psychotic, and c.) to evaluate if these changes correlate with drug induced symptoms and changes in cognitive function.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Mini Mental Status Exam is less than 28
Past or current history of any psychotic illness in the subject or in first degree family members
Self report of illicit drug use (except marijuana) in the past. Use of marijuana during the last 3 month...
Any use of antipsychotic in the past.
Any neuro-anatomical lesions on previous brain imaging
Any use of D2 receptor blocking agent (such as antiemetics) in the last two weeks.
Any use of any psychotropic medications (SSRI, mood stabilizers, benzodiazepines, stimulants) in the last month.
MRI contraindications
Any cardiovascular or cerebrovascular diseases or conditions that predispose patients to hypotension (eg. dehydration, hypovolemia, antihypertensive medication)
Subjects with diabetes mellitus, metabolic syndrome, hepatic or renal impairment, seizure disorder and any neurological disorder
QTc interval longer than 450 ms for male and 470 ms for female
Subjects who used any medications in the last two weeks (to avoid any possible drug-drug interactions)
Pregnancy
Individuals who are illiterate and/or visually impaired

Arm && Interventions

Group	Intervention	Description
Risperidone then Placebo	Placebo	This group will receive 2 mg (\>200lbs), 1.5mg (150-200lbs.) or 1 mg (\< 150lbs. of risperidone oral solution on the first day and a placebo on the second day.
Placebo then Risperidone	Placebo	This group will receive a placebo on the first day and 2mg (\> 200lbs.), 1.5mg (150-200lbs), or 1 mg (\<150lbs.) of risperidone oral solution on the second day
Risperidone then Placebo	Risperidone	This group will receive 2 mg (\>200lbs), 1.5mg (150-200lbs.) or 1 mg (\< 150lbs. of risperidone oral solution on the first day and a placebo on the second day.
Placebo then Risperidone	Risperidone	This group will receive a placebo on the first day and 2mg (\> 200lbs.), 1.5mg (150-200lbs), or 1 mg (\<150lbs.) of risperidone oral solution on the second day

Primary Outcome Measures

Name	Time	Method
Repeatable Battery for the Assessment of Neuropsychological Status	The change of RBANS scores between placebo and treatment conditions on two consecutive days	This will measure the subject's cognitive performance. RBANS is a well-characterized repeatable battery to measure a wide array of cognitive performance in different cognitive domains. We will use Total Score in RBANS: five index scores are computed from the RBANS (immediate memory, language, visuospatial, attention, delayed memory) that are combined to provide the Total Score. The Total Score is expressed as a standardized score normalized to a population mean of 100, with a standard deviation of 15 (possible scores 40-135). Higher scores reflect better performance. More detailed information is available: Randolph C, Tierney MC, Mohr E, Chase TN (June 1998). "The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity". J Clin Exp Neuropsychol. 20 (3): 310-9. doi:10.1076/jcen.20.3.310.823. PMID 9845158. Here we calculated the difference of T-scaled total RBANS score between risperidone day and placebo day in all participants

Secondary Outcome Measures

Name	Time	Method
Simpson-Angus Extrapyramidal Side Effects Scale	2 times on risperidone day and on placebo day	The secondary outcome measures are the scores from side effect scales (Simpson-Angus Extrapyramidal Side Effects. It will measured in synchrony with Repeated Battery for the Assessment of Neuropsychological Status to explore if any of these measures would correlate with network changes in the brain. The Simpson-Angus scale is 0 if there is no extrapyramidal side effects, and is higher the worst the symptoms are.