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.
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.
Drug Alcohol Depend. 2023 Jul 1;248:109901. doi: 10.1016/j.drugalcdep.2023.109901. Epub 2023 Apr 28.
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.
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.
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.
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.
脑源性神经营养因子（BDNF）参与神经元和神经胶质细胞的生长和分化、突触可塑性和细胞凋亡机制。BDNF rs6265 基因的单核苷酸多态性可能导致那些患有酒精使用障碍（AUD）的人的大脑代谢物异常模式和幅度。我们预测蛋氨酸（Met）携带者的 N-乙酰天冬氨酸（NAA）水平的磁共振波谱（MRS）测量值较低，且 NAA 随年龄的衰退程度大于缬氨酸（Val）纯合子。
从退伍军人事务部帕洛阿尔托住宅治疗中心招募 AUD 患者（n=95；年龄 46±12 岁，最小 25 岁，最大 71 岁）。使用 3T 单体素 MRS 从左背外侧前额叶皮质（DLPFC）获得 NAA、胆碱（Cho）和肌酸（Cr）化合物。用 LC Model 拟合代谢物谱，将 NAA 和 Cho 标准化为总 Cr 水平，将 NAA 也标准化为 Cho。
Val/Met（n=35）的左 DLPFC NAA/Cr 水平随年龄的衰退明显大于 Val/Val（n=60）；Val/Met 和 Val/Val 之间的平均代谢物水平没有差异。Val/Met 表现出更高的 MDD 病史发生率和更高的大麻使用障碍发生率在研究前 12 个月。
BDNF rs6265 Met 携带者 AUD 中左 DLPFC NAA/Cr 随年龄的衰退更大，MDD 病史和大麻使用障碍的频率更高，这是新的发现，可能对针对左 DLFPC 的非侵入性脑刺激和 AUD 治疗中常用的其他心理社会干预具有重要意义。
