Occupancy of Dopamine D3 Receptors by Aripiprazole in Treatment Resistant Late-Life Depressed Patients Depends on Length of Treatment as Evidenced by in vivo Imaging with [11C]-(+)-PHNO

Abstract

Introduction: Intriguing evidence suggests that antipsychotic medication exposure may potentially play a protective role in the process leading to amyloid deposition. In this study we examined brain amyloid imaging in persons with schizophrenia in late life using brain imaging with Pittsburg Compound-B (C-PIB). Methods: Subjects were recruited from the University of Iowa Carver College of Medicine Psychiatry outpatient clinic and inpatient neuropsychiatric unit. Inclusion criteria included patients from 55 to 75 years of age, at least 20 years of antipsychotic medication exposure, ability to undergo PET scan, and DSM-IV diagnosis of schizophrenia spectrum disorders: schizophrenia, schizoaffective disorder, delusional disorder. Exclusion criteria included unstable cardiovascular, cerebrovascular, neoplastic, serious systemic illness, Parkinson’s disease, epilepsy, head injury, or multiple sclerosis. Patients underwent PET imaging using C-PIB and neuropsychological testing using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The relationship between amyloid burden (C-PIB measured as standardized uptake ratio) and antipsychotic exposure, as well as cognitive performance were assessed. The standardized uptake value ratio (SUVR) of C-PIB uptake was calculated from predetermined regions of interest (ROI) (frontal, parietal, and temporal cortical regions) divided by the cerebellums C-PIB uptake. Results: There were 5 subjects, mean age 59, with 12-16 years of education, who completed the study. All had significant cognitive impairment on RBANS testing. No subjects had a SUVR (reflecting amyloid deposition) above a threshold that would be considered positive, only one subject had an SUVR that was in a questionably positive range. The relationship between amyloid deposition and cognition was non-significant. There also did not appear to be a relationship between amyloid deposition and years of antipsychotic medication use, except in respect to the patient with the greatest amount of antipsychotic use. This subject had the greatest amount of amyloid burden, although this was greatest in the occipital lobe. Conclusions: This is the first study to our knowledge, to study amyloid (C-PIB) imaging in schizophrenia. Our findings are consistent with previous Alzheimer’s literature demonstrating no clear association between amyloid deposition and cognitive testing, which was the case in our study. The oldest subject (66 years of age) in this study had the greatest amount of antipsychotic exposure (50 years) and highest SUVR, but when his data was combined with the remaining subjects there did not appear to be a relationship between antipsychotic exposure and amyloid burden. These findings suggest that amyloid deposition in persons with schizophrenia does have variance that may be attributable to antipsychotic medication exposure, but a larger sample of subjects will be needed to fully characterize the role of the exposure to medications.