The relationship between antipsychotic D2 occupancy and change in frontal metabolism and working memory View Full Text


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Article Info

DATE

2012-12-28

AUTHORS

Euitae Kim, Oliver D. Howes, Federico E. Turkheimer, Bo-Hyung Kim, Jae Min Jeong, Ji Who Kim, Jae Sung Lee, In-Jin Jang, Sang-Goo Shin, Shitij Kapur, Jun Soo Kwon

ABSTRACT

RationaleThe effects of aripiprazole on cognitive function are obscure, possibly due to the difficulty in disentangling the specific effects on cognitive function from effects secondary to the improvement of other schizophrenic symptoms. This prompts the necessity of using an intermediate biomarker relating the drug effect on the brain to change in cognitive function.ObjectivesTo explore the effect of aripiprazole on cognitive function, we measured changes in frontal metabolism as an intermediate biomarker and sought to determine its relationship with D2 receptor occupancy and changes in working memory.MethodsFifteen healthy male volunteers participated in the study. Serial positron emission tomography (PET) scans with [11C]raclopride and [18 F]FDG were conducted 1 day before and 2 days after the administration of aripiprazole. The subjects performed the N-back task just after finishing the [18 F]FDG scan.ResultsThe mean (±SD) D2 receptor occupancies were 22.2 ± 16.0 % in the 2 mg group, 35.5 ± 3.6 % in the 5 mg group, 63.2 ± 9.9 % in the 10 mg group and 72.8 ± 2.1 % in the 30 mg group. The frontal metabolism was significantly decreased after the administration of aripiprazole (t = 2.705, df = 14, p = 0.017). Greater striatal D2 receptor occupancy was related to greater decrease in frontal metabolism (r = −0.659, p = 0.010), and greater reduction in frontal metabolism was associated with longer reaction times (r = −0.597, p = 0.019) under the greatest task load.ConclusionsAripiprazole can affect cognitive function and alter frontal metabolic function. The changes in these functions are linked to greater D2 receptor occupancy. This suggests that it may be important to find the lowest effective dose of aripiprazole in order to prevent adverse cognitive effects. More... »

PAGES

221-229

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00213-012-2953-0

DOI

http://dx.doi.org/10.1007/s00213-012-2953-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1010101910

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23271192


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35 schema:description RationaleThe effects of aripiprazole on cognitive function are obscure, possibly due to the difficulty in disentangling the specific effects on cognitive function from effects secondary to the improvement of other schizophrenic symptoms. This prompts the necessity of using an intermediate biomarker relating the drug effect on the brain to change in cognitive function.ObjectivesTo explore the effect of aripiprazole on cognitive function, we measured changes in frontal metabolism as an intermediate biomarker and sought to determine its relationship with D2 receptor occupancy and changes in working memory.MethodsFifteen healthy male volunteers participated in the study. Serial positron emission tomography (PET) scans with [11C]raclopride and [18 F]FDG were conducted 1 day before and 2 days after the administration of aripiprazole. The subjects performed the N-back task just after finishing the [18 F]FDG scan.ResultsThe mean (±SD) D2 receptor occupancies were 22.2 ± 16.0 % in the 2 mg group, 35.5 ± 3.6 % in the 5 mg group, 63.2 ± 9.9 % in the 10 mg group and 72.8 ± 2.1 % in the 30 mg group. The frontal metabolism was significantly decreased after the administration of aripiprazole (t = 2.705, df = 14, p = 0.017). Greater striatal D2 receptor occupancy was related to greater decrease in frontal metabolism (r = −0.659, p = 0.010), and greater reduction in frontal metabolism was associated with longer reaction times (r = −0.597, p = 0.019) under the greatest task load.ConclusionsAripiprazole can affect cognitive function and alter frontal metabolic function. The changes in these functions are linked to greater D2 receptor occupancy. This suggests that it may be important to find the lowest effective dose of aripiprazole in order to prevent adverse cognitive effects.
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41 schema:keywords ConclusionsAripiprazole
42 D2 occupancy
43 D2 receptor occupancy
44 ObjectivesTo
45 RationaleThe effects
46 administration
47 administration of aripiprazole
48 adverse cognitive effects
49 aripiprazole
50 biomarkers
51 brain
52 changes
53 cognitive effects
54 cognitive function
55 days
56 decrease
57 difficulties
58 dose
59 drug effects
60 effect
61 effective dose
62 effects of aripiprazole
63 emission tomography
64 frontal metabolism
65 function
66 greater decrease
67 greater reduction
68 group
69 healthy male volunteers
70 improvement
71 intermediate biomarkers
72 load
73 longer reaction times
74 lowest effective dose
75 male volunteers
76 mean D2 receptor occupancy
77 memory
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81 necessity
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83 order
84 positron emission tomography
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88 relationship
89 scans
90 schizophrenic symptoms
91 serial positron emission tomography
92 specific effects
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