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. 2018 Apr 24;8(1):87.
doi: 10.1038/s41398-018-0134-6.

The Relationship Between Dopamine Receptor Blockade and Cognitive Performance in Schizophrenia: A [ 11 C]-raclopride PET Study With Aripiprazole

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Free PMC article

The Relationship Between Dopamine Receptor Blockade and Cognitive Performance in Schizophrenia: A [ 11 C]-raclopride PET Study With Aripiprazole

Sangho Shin et al. Transl Psychiatry. .
Free PMC article

Abstract

Aripiprazole's effects on cognitive function in patients with schizophrenia are unclear because of the difficulty in disentangling specific effects on cognitive function from secondary effects due to the improvement in other schizophrenic symptoms. One approach to address this is to use an intermediate biomarker to investigate the relationship between the drug's effect on the brain and change in cognitive function. This study aims to investigate aripiprazole's effect on working memory by determining the correlation between dopamine D2/3 (D2/3) receptor occupancy and working memory of patients with schizophrenia. Seven patients with schizophrenia participated in the study. Serial positron emission tomography (PET) scans with [11C]raclopride were conducted at 2, 26, and 74 h after the administration of aripiprazole. The subjects performed the N-back task just after finishing the [11C]raclopride PET scan. The mean (±SD) D2/3 receptor occupancies were 66.9 ± 6.7% at 2 h, 65.0 ± 8.6% at 26, and 57.7 ± 11.2% at 74 h after administering aripiprazole. Compared with performance on the zero-back condition, performance in memory-loaded conditions (one-, two-, and three-back conditions) was significantly related to D2/3 receptor occupancy by aripiprazole (error rate: ß = -2.236, t = -6.631, df = 53.947, and p = 0.001; reaction time: ß = -9.567, t = -2.808, df = 29.967, and p = 0.009). Although the sample size was relatively small, these results suggest that aripiprazole as a dopamine-partial agonist could improve cognitive function in patients with schizophrenia.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Diagram for the study protocol.
a Aripiprazole. b Positron emission tomomgraphy (PET) scan with [11C]raclopride. c N-back task performed within 30 min of the end of the PET scan
Fig. 2
Fig. 2. Dopamine D2/3 receptor occupancy and average plasma concentrations of aripiprazole according to time.
The error bar indicates standard deviation
Fig. 3
Fig. 3. The relationship between dopamine D2/3 receptor occupancy and mean error rates in the no-memory load and memory-load conditions of the N-back task after aripiprazole administration.
This shows an inverse relationship between dopamine D2/3 receptor occupancy and error rate, indicating that better performance is associated with higher D2/3 receptor blockade (memory load, ß = −2.236, t = −6.631, df = 53.947, and p = 0.001)
Fig. 4
Fig. 4. The relationship between dopamine D2/3 receptor occupancy and mean reaction times for correct responses in the no-memory load and memory-load conditions of the N-back task after aripiprazole administration.
This shows an inverse relationship between D2/3 receptor occupancy and reaction time, indicating that better performance is associated with higher D2/3 receptor blockade (memory load, ß = −9.567, t = −2.808, df = 29.967, and p = 0.009)

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