title: D-amino acid aberrations in cerebrospinal fluid and plasma of smokers.
abstract: The glutamatergic neurotransmission system and the N-methyl-D-aspartate receptor (NMDAR) have been implicated in smoking and alcohol consumption behavior. Preclinical studies have demonstrated that nicotine and ethanol influence NMDAR functionality, which may have a role in tendencies to consume these substances. Nonetheless, little is known about concentrations of NMDAR coagonists in the cerebrospinal fluid (CSF) and plasma of individuals who smoke or consume alcohol. Glycine and L- and D-stereoisomers of alanine, serine, and proline were therefore measured using ultra-high-performance liquid chromatography-tandem mass spectrometry in 403 healthy subjects. Nicotine and alcohol consumption were quantified using questionnaires. Possible differences in NMDAR coagonist concentrations in plasma and CSF were investigated using ANCOVA with age, body mass index, and storage duration as covariates. The significance threshold was Bonferroni corrected (α=0.00625). Compared with non-smokers, smokers displayed lower levels of D-proline in plasma (p=0.0027, Cohen's d=-0.41) and D-proline in CSF (p=0.0026, Cohen's d=-0.43). D-Serine in CSF was higher in smokers than in non-smokers (p=0.0052, Cohen's d=0.41). After subdividing participants based on smoking quantity, dose-dependent decreases were demonstrated in smokers for D-proline in plasma (F=5.65, p=0.0039) and D-proline in CSF (F=5.20, p=0.0060). No differences in NMDAR coagonist levels between alcohol consumption groups were detected. To our knowledge, this is the first report to implicate D-amino acids in smoking behavior of humans. Whether such concentration differences lie at the root of or result from smoking habits may be addressed in prospective studies.
authors.affiliation: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht (UMCU), Utrecht, the Netherlands.
authors.forename: Jurjen J
authors.initials: JJ
authors.lastname: Luykx
authors.forename: Steven C
authors.initials: SC
authors.lastname: Bakker
authors.forename: Loes
authors.initials: L
authors.lastname: van Boxmeer
authors.forename: Christiaan H
authors.initials: CH
authors.lastname: Vinkers
authors.forename: Hanne E
authors.initials: HE
authors.lastname: Smeenk
authors.forename: Wouter F
authors.initials: WF
authors.lastname: Visser
authors.forename: Nanda M
authors.initials: NM
authors.lastname: Verhoeven-Duif
authors.forename: Eric
authors.initials: E
authors.lastname: Strengman
authors.forename: Jacobine E
authors.initials: JE
authors.lastname: Buizer-Voskamp
authors.forename: Lizzy
authors.initials: L
authors.lastname: de Groene
authors.forename: Eric Pa
authors.initials: EP
authors.lastname: van Dongen
authors.forename: Paul
authors.initials: P
authors.lastname: Borgdorff
authors.forename: Peter
authors.initials: P
authors.lastname: Bruins
authors.forename: Tom J
authors.initials: TJ
authors.lastname: de Koning
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
mesh_terms: D000328:Adult; D000409:Alanine / Q000097:blood / Q000134:cerebrospinal fluid; D000428:Alcohol Drinking / Q000097:blood* / Q000134:cerebrospinal fluid*; D018690:Excitatory Amino Acid Agonists / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D005998:Glycine / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D011392:Proline / Q000097:blood / Q000134:cerebrospinal fluid; D057566:Self Report; D012694:Serine / Q000097:blood / Q000134:cerebrospinal fluid; D012907:Smoking / Q000097:blood* / Q000134:cerebrospinal fluid*; D013237:Stereoisomerism
chemical_list: D018690:Excitatory Amino Acid Agonists; D012694:Serine; D011392:Proline; D000409:Alanine; D005998:Glycine