PMID- 37146499
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20231116
IS  - 1879-0046 (Electronic)
IS  - 0376-8716 (Linking)
VI  - 248
DP  - 2023 Jul 1
TI  - BDNF rs6265 Met carriers with alcohol use disorder show greater age-related 
      decline of N-acetylaspartate in left dorsolateral prefrontal cortex.
PG  - 109901
LID - S0376-8716(23)00139-4 [pii]
LID - 10.1016/j.drugalcdep.2023.109901 [doi]
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is implicated in neuronal 
      and glial cell growth and differentiation, synaptic plasticity, and apoptotic 
      mechanisms. A single-nucleotide polymorphism of the BDNF rs6265 gene may 
      contribute to the pattern and magnitude of brain metabolite abnormalities 
      apparent in those with an Alcohol Use Disorder (AUD). We predicted that 
      methionine (Met) carriers would demonstrate lower magnetic resonance spectroscopy 
      (MRS) measures of N-acetylaspartate level (NAA) and greater age-related decline 
      in NAA than valine (Val) homozygotes. METHODS: Veterans with AUD (n=95; 46+/-12 
      years of age, min = 25, max = 71) were recruited from VA Palo Alto residential 
      treatment centers. Single voxel MRS, at 3 Tesla, was used to obtain NAA, choline 
      (Cho) and creatine (Cr) containing compounds from the left dorsolateral 
      prefrontal cortex (DLPFC). Metabolite spectra were fit with LC Model and NAA and 
      Cho were standardized to total Cr level and NAA was also standardized to Cho. 
      RESULTS: Val/Met (n=35) showed markedly greater age-related decline in left DLPFC 
      NAA/Cr level than Val/Val (n=60); no differences in mean metabolite levels were 
      observed between Val/Met and Val/Val. Val/Met demonstrated greater frequency of 
      history of MDD and higher frequency of cannabis use disorder over 12 months prior 
      to study. CONCLUSIONS: The greater age-related decline in left DLPFC NAA/Cr and 
      the higher frequency of MDD history and Cannabis Use disorder in BDNF rs6265 Met 
      carriers with AUD are novel and may have implications for non-invasive brain 
      stimulation targeting the left DLFPC and other psychosocial interventions 
      typically utilized in the treatment of AUD.
CI  - Published by Elsevier B.V.
FAU - Durazzo, Timothy C
AU  - Durazzo TC
AD  - Palo Alto Veterans Affairs Health Care System, Mental Illness Research and 
      Education Clinical Centers (MIRECC) Palo Alto, CA, USA; Department of Psychiatry 
      and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 
      USA. Electronic address: tdurazzo@stanford.edu.
FAU - McNerney, M Windy
AU  - McNerney MW
AD  - Palo Alto Veterans Affairs Health Care System, Mental Illness Research and 
      Education Clinical Centers (MIRECC) Palo Alto, CA, USA; Department of Psychiatry 
      and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Hansen, Annika M
AU  - Hansen AM
AD  - Palo Alto Veterans Affairs Health Care System, Mental Illness Research and 
      Education Clinical Centers (MIRECC) Palo Alto, CA, USA.
FAU - Gu, Meng
AU  - Gu M
AD  - Department of Radiology, Stanford University School of Medicine, Stanford, CA, 
      USA.
FAU - Sacchet, Matthew D
AU  - Sacchet MD
AD  - Meditation Research Program, Department of Psychiatry, Massachusetts General 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Padula, Claudia B
AU  - Padula CB
AD  - Palo Alto Veterans Affairs Health Care System, Mental Illness Research and 
      Education Clinical Centers (MIRECC) Palo Alto, CA, USA; Department of Psychiatry 
      and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20230428
PL  - Ireland
TA  - Drug Alcohol Depend
JT  - Drug and alcohol dependence
JID - 7513587
RN  - AE28F7PNPL (Methionine)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 997-55-7 (N-acetylaspartate)
RN  - 73JWT2K6T3 (Racemethionine)
RN  - MU72812GK0 (Creatine)
SB  - IM
MH  - Humans
MH  - Methionine/genetics
MH  - Dorsolateral Prefrontal Cortex
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - *Alcoholism/genetics
MH  - *Marijuana Abuse
MH  - Racemethionine
MH  - Creatine/metabolism
OTO - NOTNLM
OT  - Alcohol use disorder
OT  - Brain derived neurotrophic factor
OT  - Magnetic resonance spectroscopy
OT  - N-acetylaspartate
COIS- Declaration of Competing Interest The Authors have no actual or potential 
      conflicts of interest to report.
EDAT- 2023/05/06 09:42
MHDA- 2023/06/19 13:09
CRDT- 2023/05/05 18:06
PHST- 2022/12/01 00:00 [received]
PHST- 2023/04/04 00:00 [revised]
PHST- 2023/04/25 00:00 [accepted]
PHST- 2023/06/19 13:09 [medline]
PHST- 2023/05/06 09:42 [pubmed]
PHST- 2023/05/05 18:06 [entrez]
AID - S0376-8716(23)00139-4 [pii]
AID - 10.1016/j.drugalcdep.2023.109901 [doi]
PST - ppublish
SO  - Drug Alcohol Depend. 2023 Jul 1;248:109901. doi: 
      10.1016/j.drugalcdep.2023.109901. Epub 2023 Apr 28.