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 (n=16) or placebo (n=15) 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 (p=0.005) and Cho (p=0.03) 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 (p=0.03). 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.
authors.affiliation: Department of Psychiatry, Catholic University of Korea School of Medicine, Seoul, South Korea.
authors.forename: Sujung J
authors.initials: SJ
authors.lastname: Yoon
authors.forename: In Kyoon
authors.initials: IK
authors.lastname: Lyoo
authors.forename: Hengjun J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Tae-Suk
authors.initials: TS
authors.lastname: Kim
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Sung
authors.forename: Namkug
authors.initials: N
authors.lastname: Kim
authors.forename: Scott E
authors.initials: SE
authors.lastname: Lukas
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003566:Cytidine Diphosphate Choline / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D012044:Regression Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D001224:Aspartic Acid; D008694:Methamphetamine; D003566:Cytidine Diphosphate Choline; C000179:N-acetylaspartate