Hou Wenpeng, Qin Xiangqin, Li Hang, Wang Qi, Ding Yushen, Chen Xiongying, Wang Ru, Dong Fang, Bo Qijing, Li Xianbin, Zhou Fuchun, Wang Chuanyue
Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
Schizophrenia (Heidelb). 2024 Aug 22;10(1):70. doi: 10.1038/s41537-024-00493-x.
Both the brain-derived neurotrophic factor (BDNF) valine (Val)/methionine (Met) polymorphism and mismatch negativity (MMN) amplitude are reportedly linked to working memory impairments in schizophrenia. However, there is evident scarcity of research aimed at exploring the relationships among the three factors. In this secondary analysis of a randomized, controlled, double-blind trial, we investigated these relationships. The trial assessed the efficacy of transcranial direct current stimulation for enhancing working memory in clinically stable schizophrenia patients, who were randomly divided into three groups: dorsolateral prefrontal cortex stimulation, posterior parietal cortex stimulation, and sham stimulation groups. Transcranial direct current stimulation was administered concurrently with a working memory task over five days. We assessed the BDNF genotype, MMN amplitude, working memory capacity, and interference control subdomains. These assessments were conducted at baseline with 54 patients and followed up post-intervention with 48 patients. Compared to BDNF Met-carriers, Val homozygotes exhibited fewer positive and general symptoms and increased working memory capacity at baseline. A correlation between MMN amplitude and working memory capacity was noted only in BDNF Val homozygotes. The correlations were significantly different in the two BDNF genotype groups. Furthermore, in the intervention group that showed significant improvement in MMN amplitude, BDNF Val homozygotes exhibited greater enhancement in working memory capacity than Met-carriers. This study provides in vivo evidence for the interaction between MMN and BDNF Val/Met polymorphism for working memory capacity. As MMN has been considered a biomarker of N-methyl-D-aspartate receptor (NMDAR) function, these data shed light on the complex interactions between BDNF and NMDAR in terms of working memory in schizophrenia.
据报道，脑源性神经营养因子（BDNF）缬氨酸（Val）/蛋氨酸（Met）多态性和失配负波（MMN）波幅均与精神分裂症的工作记忆损害有关。然而，旨在探索这三个因素之间关系的研究明显匮乏。在这项对一项随机、对照、双盲试验的二次分析中，我们调查了这些关系。该试验评估了经颅直流电刺激对改善临床稳定的精神分裂症患者工作记忆的疗效，这些患者被随机分为三组：背外侧前额叶皮层刺激组、顶叶后皮层刺激组和假刺激组。经颅直流电刺激在五天内与一项工作记忆任务同时进行。我们评估了BDNF基因型、MMN波幅、工作记忆能力和干扰控制子域。这些评估在基线时对54名患者进行，干预后对48名患者进行随访。与BDNF Met携带者相比，Val纯合子在基线时表现出更少的阳性和一般症状，工作记忆能力增强。仅在BDNF Val纯合子中观察到MMN波幅与工作记忆能力之间存在相关性。两个BDNF基因型组的相关性存在显著差异。此外，在MMN波幅有显著改善的干预组中，BDNF Val纯合子在工作记忆能力方面的增强比Met携带者更大。本研究为MMN与BDNF Val/Met多态性在工作记忆能力方面的相互作用提供了体内证据。由于MMN被认为是N-甲基-D-天冬氨酸受体（NMDAR）功能的生物标志物，这些数据揭示了BDNF与NMDAR在精神分裂症工作记忆方面的复杂相互作用。
