The relationship between D2 occupancy of aripiprazole and working memory in patients with schizophrenia

Abstract

Rationale: Aripiprazole's effects on cognitive function for patients with schizophrenia are obscure with possible difficulty in disentangling specific effects on cognitive function from effects secondary to the improvement of other schizophrenic symptoms. This requires using an intermediate biomarker relating the drug effect on the brain to change in cognitive function.

Objectives: This study aims to find aripiprazole's effect on working memory by determining the correlation between D2 receptor occupancy and working memory of patients with schizophrenia.

Methods: Seven patients with schizophrenia participated in the study. Serial positron emission tomography (PET) scans with [11C]raclopride were conducted at 3, 24, and 72 hour-marks after the administration of aripiprazole. The subjects performed the N-back task just after the [11C]raclopride PET scan.

Results: The mean (±SD) D2 receptor occupancies were 66.9 ±6.7 % at 3 hours, 65.0±8.6% at 24, and 57.7±11.2 % at 72 hours after administering aripiprazole. As D2 receptor occupancy levels decreased, the mean reaction time of N-back tasks (1, 2, and 3) (1-back, ß=−1.023, t=−3.553, df=13.381, p=0.003; 2-back, ß=−2.523, t=−4.215, df=14.731, p=0.001; 3-back, ß=−1.709, t=−2.159, df=16.899, p=0.046) increased significantly compared to the baseline of 0-back task. The error rate increased as much as N-back tasks (1, 2, and 3) (1-back, ß=−1.785, t=−3.135, df=14.437, p=0.007; 2-back, ß=−3.107, t=−6.049, df=12.956, p=0.001; 3-back, ß=−1.427, t=−2.344, df=18.524, p=0.030)

Conclusions: As D2 receptor occupancy levels of aripiprazole increased, reaction time and error rate of N-back task decreased. These results indicate that aripiprazole can improve working memory in patients with schizophrenia under the clinical stable phase.