Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5′-diphosphate choline: A longitudinal proton magnetic resonance spectroscopy study

Sujung J. Yoon; In Kyoon Lyoo; Hengjun J. Kim; Tae Suk Kim; Young Hoon Sung; Namkug Kim; Scott E. Lukas; Perry F. Renshaw

doi:10.1038/npp.2009.221

Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5′-diphosphate choline: A longitudinal proton magnetic resonance spectroscopy study

Sujung J. Yoon, In Kyoon Lyoo, Hengjun J. Kim, Tae Suk Kim, Young Hoon Sung, Namkug Kim, Scott E. Lukas, Perry F. Renshaw

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Abstract

Cytidine-5′-diphosphate choline (CDP-choline), as an important intermediate for major membrane phospholipids, may exert neuroprotective effects in various neurodegenerative disorders. This longitudinal proton magnetic resonance spectroscopy (1 H-MRS) study aimed to examine whether a 4-week CDP-choline treatment could alter neurometabolite levels in patients with methamphetamine (MA) dependence and to investigate whether changes in neurometabolite levels would be associated with MA use. We hypothesized that the prefrontal levels of N-acetyl-aspartate (NAA), a neuronal marker, and choline-containing compound (Cho), which are related to membrane turnover, would increase with CDP-choline treatment in MA-dependent patients. We further hypothesized that this increase would correlate with the total number of negative urine results. Thirty-one treatment seekers with MA dependence were randomly assigned to receive CDP-choline (n16) or placebo (n15) for 4 weeks. Prefrontal NAA and Cho levels were examined using 1 H-MRS before medication, and at 2 and 4 weeks after treatment. Generalized estimating equation regression analyses showed that the rate of change in prefrontal NAA (p0.005) and Cho (p0.03) levels were greater with CDP-choline treatment than with placebo. In the CDP-choline-treated patients, changes in prefrontal NAA levels were positively associated with the total number of negative urine results (p0.03). Changes in the prefrontal Cho levels, however, were not associated with the total number of negative urine results. These preliminary findings suggest that CDP-choline treatment may exert potential neuroprotective effects directly or indirectly because of reductions in drug use by the MA-dependent patients. Further studies with a larger sample size of MA-dependent patients are warranted to confirm a long-term efficacy of CDP-choline in neuroprotection and abstinence.

Original language	English
Pages (from-to)	1165-1173
Number of pages	9
Journal	Neuropsychopharmacology
Volume	35
Issue number	5
DOIs	https://doi.org/10.1038/npp.2009.221
State	Published - Apr 2010

Bibliographical note

Funding Information:
This study was supported in part by grants from the NIDA (1R01 DA024070-01A1, Drs Lyoo and Renshaw; 5 R01 DA 14178-05, Dr Renshaw), from the NIH (7K24DA015116, Dr Renshaw; 5K05-DA000343-12, Dr Lukas), from the Korean Ministry of Education, Science and Technology, (2009K001272, Dr Lyoo; Basic Science Research Program 20090066915, Dr Yoon), and from Seoul National University Hospital (03-2008-006-0, Dr Lyoo).

Keywords

Cytidine-50-diphosphate choline
Methamphetamine dependence
N-acetyl-aspartate
Proton magnetic resonance spectroscopy
Treatment

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10.1038/npp.2009.221

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title = "Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5′-diphosphate choline: A longitudinal proton magnetic resonance spectroscopy study",

abstract = "Cytidine-5′-diphosphate choline (CDP-choline), as an important intermediate for major membrane phospholipids, may exert neuroprotective effects in various neurodegenerative disorders. This longitudinal proton magnetic resonance spectroscopy (1 H-MRS) study aimed to examine whether a 4-week CDP-choline treatment could alter neurometabolite levels in patients with methamphetamine (MA) dependence and to investigate whether changes in neurometabolite levels would be associated with MA use. We hypothesized that the prefrontal levels of N-acetyl-aspartate (NAA), a neuronal marker, and choline-containing compound (Cho), which are related to membrane turnover, would increase with CDP-choline treatment in MA-dependent patients. We further hypothesized that this increase would correlate with the total number of negative urine results. Thirty-one treatment seekers with MA dependence were randomly assigned to receive CDP-choline (n16) or placebo (n15) for 4 weeks. Prefrontal NAA and Cho levels were examined using 1 H-MRS before medication, and at 2 and 4 weeks after treatment. Generalized estimating equation regression analyses showed that the rate of change in prefrontal NAA (p0.005) and Cho (p0.03) levels were greater with CDP-choline treatment than with placebo. In the CDP-choline-treated patients, changes in prefrontal NAA levels were positively associated with the total number of negative urine results (p0.03). Changes in the prefrontal Cho levels, however, were not associated with the total number of negative urine results. These preliminary findings suggest that CDP-choline treatment may exert potential neuroprotective effects directly or indirectly because of reductions in drug use by the MA-dependent patients. Further studies with a larger sample size of MA-dependent patients are warranted to confirm a long-term efficacy of CDP-choline in neuroprotection and abstinence.",

keywords = "Cytidine-50-diphosphate choline, Methamphetamine dependence, N-acetyl-aspartate, Proton magnetic resonance spectroscopy, Treatment",

author = "Yoon, {Sujung J.} and Lyoo, {In Kyoon} and Kim, {Hengjun J.} and Kim, {Tae Suk} and Sung, {Young Hoon} and Namkug Kim and Lukas, {Scott E.} and Renshaw, {Perry F.}",

note = "Funding Information: This study was supported in part by grants from the NIDA (1R01 DA024070-01A1, Drs Lyoo and Renshaw; 5 R01 DA 14178-05, Dr Renshaw), from the NIH (7K24DA015116, Dr Renshaw; 5K05-DA000343-12, Dr Lukas), from the Korean Ministry of Education, Science and Technology, (2009K001272, Dr Lyoo; Basic Science Research Program 20090066915, Dr Yoon), and from Seoul National University Hospital (03-2008-006-0, Dr Lyoo).",

year = "2010",

month = apr,

doi = "10.1038/npp.2009.221",

language = "English",

volume = "35",

pages = "1165--1173",

journal = "Neuropsychopharmacology",

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publisher = "Nature Publishing Group",

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T1 - Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5′-diphosphate choline

T2 - A longitudinal proton magnetic resonance spectroscopy study

AU - Yoon, Sujung J.

AU - Lyoo, In Kyoon

AU - Kim, Hengjun J.

AU - Kim, Tae Suk

AU - Sung, Young Hoon

AU - Kim, Namkug

AU - Lukas, Scott E.

AU - Renshaw, Perry F.

N1 - Funding Information: This study was supported in part by grants from the NIDA (1R01 DA024070-01A1, Drs Lyoo and Renshaw; 5 R01 DA 14178-05, Dr Renshaw), from the NIH (7K24DA015116, Dr Renshaw; 5K05-DA000343-12, Dr Lukas), from the Korean Ministry of Education, Science and Technology, (2009K001272, Dr Lyoo; Basic Science Research Program 20090066915, Dr Yoon), and from Seoul National University Hospital (03-2008-006-0, Dr Lyoo).

PY - 2010/4

Y1 - 2010/4

N2 - Cytidine-5′-diphosphate choline (CDP-choline), as an important intermediate for major membrane phospholipids, may exert neuroprotective effects in various neurodegenerative disorders. This longitudinal proton magnetic resonance spectroscopy (1 H-MRS) study aimed to examine whether a 4-week CDP-choline treatment could alter neurometabolite levels in patients with methamphetamine (MA) dependence and to investigate whether changes in neurometabolite levels would be associated with MA use. We hypothesized that the prefrontal levels of N-acetyl-aspartate (NAA), a neuronal marker, and choline-containing compound (Cho), which are related to membrane turnover, would increase with CDP-choline treatment in MA-dependent patients. We further hypothesized that this increase would correlate with the total number of negative urine results. Thirty-one treatment seekers with MA dependence were randomly assigned to receive CDP-choline (n16) or placebo (n15) for 4 weeks. Prefrontal NAA and Cho levels were examined using 1 H-MRS before medication, and at 2 and 4 weeks after treatment. Generalized estimating equation regression analyses showed that the rate of change in prefrontal NAA (p0.005) and Cho (p0.03) levels were greater with CDP-choline treatment than with placebo. In the CDP-choline-treated patients, changes in prefrontal NAA levels were positively associated with the total number of negative urine results (p0.03). Changes in the prefrontal Cho levels, however, were not associated with the total number of negative urine results. These preliminary findings suggest that CDP-choline treatment may exert potential neuroprotective effects directly or indirectly because of reductions in drug use by the MA-dependent patients. Further studies with a larger sample size of MA-dependent patients are warranted to confirm a long-term efficacy of CDP-choline in neuroprotection and abstinence.

AB - Cytidine-5′-diphosphate choline (CDP-choline), as an important intermediate for major membrane phospholipids, may exert neuroprotective effects in various neurodegenerative disorders. This longitudinal proton magnetic resonance spectroscopy (1 H-MRS) study aimed to examine whether a 4-week CDP-choline treatment could alter neurometabolite levels in patients with methamphetamine (MA) dependence and to investigate whether changes in neurometabolite levels would be associated with MA use. We hypothesized that the prefrontal levels of N-acetyl-aspartate (NAA), a neuronal marker, and choline-containing compound (Cho), which are related to membrane turnover, would increase with CDP-choline treatment in MA-dependent patients. We further hypothesized that this increase would correlate with the total number of negative urine results. Thirty-one treatment seekers with MA dependence were randomly assigned to receive CDP-choline (n16) or placebo (n15) for 4 weeks. Prefrontal NAA and Cho levels were examined using 1 H-MRS before medication, and at 2 and 4 weeks after treatment. Generalized estimating equation regression analyses showed that the rate of change in prefrontal NAA (p0.005) and Cho (p0.03) levels were greater with CDP-choline treatment than with placebo. In the CDP-choline-treated patients, changes in prefrontal NAA levels were positively associated with the total number of negative urine results (p0.03). Changes in the prefrontal Cho levels, however, were not associated with the total number of negative urine results. These preliminary findings suggest that CDP-choline treatment may exert potential neuroprotective effects directly or indirectly because of reductions in drug use by the MA-dependent patients. Further studies with a larger sample size of MA-dependent patients are warranted to confirm a long-term efficacy of CDP-choline in neuroprotection and abstinence.

KW - Cytidine-50-diphosphate choline

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KW - N-acetyl-aspartate

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KW - Treatment

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Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5′-diphosphate choline: A longitudinal proton magnetic resonance spectroscopy study

Abstract

Bibliographical note

Keywords

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