Bang-Kittilsen Gry, Egeland Jens, Ueland Thor, Andersen Eivind, Bigseth Therese Torgersen, Holmen Tom Langerud, Mordal Jon, Holst René, Engh John Abel
Division of Mental Health and Addiction, Vestfold Hospital Trust, Tonsberg, Norway.
Division of Mental Health and Addiction, Vestfold Hospital Trust, Tonsberg, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
Psychoneuroendocrinology. 2023 Nov;157:106356. doi: 10.1016/j.psyneuen.2023.106356. Epub 2023 Aug 3.
Physical exercise can improve neurocognition in individuals with schizophrenia, presumably by facilitating neuroplasticity. There is, however, large inter-individual variation in response. The brain-derived neurotrophic factor (BDNF) has been proposed to mediate these effects. The current aim was to investigate the sparsely studied relationship between peripheral resting BDNF and neurocognitive response to physical exercise in individuals with schizophrenia.
The current study reports secondary analyses of data from a randomized controlled trial (RCT), ClinicalTrials.gov number 02205684, recently reported according to the CONSORT guidelines. Eighty-two individuals with schizophrenia (mean age 37 ± 14 years old, 61% men) were randomly allocated to high-intensity interval training (HIIT) or a comparison group performing low-intensity active video gaming (AVG). Both interventions consisted of 2 sessions/week for 12 weeks. In previously published primary RCT analyses, HIIT and AVG showed comparable small to moderate improvements in neurocognition. We now address the inter-individual variability in neurocognitive response. We apply mediation and moderation analyses for repeated measures designs (MEMORE) and mixed effects models.
Baseline neurocognition was not significantly correlated with baseline levels of mature BDNF (baseline-mBDNF) or the precursor proBDNF. Nonetheless, baseline-mBDNF but not baseline proBDNF, moderated the effect of exercise on neurocognition (p = 0.025) and explained 7% of the variance. The neurocognitive improvement increased with increasing baseline-mBDNF values. The moderating effect of baseline-mBDNF remained significant in a more complex model adding the moderating effects of exercise mode, sex, age, duration of illness and baseline VOmax on the outcome (neurocognition). Mean baseline-mBDNF significantly decreased from baseline to post-intervention (p = 0.036), regardless of exercise mode, differing by sex and associated with improved VOmax but not with change in neurocognition. A mediating role of mBDNF on the effect of physical exercise on neurocognition was not supported. Values of proBDNF mainly remained stable from baseline to post-intervention.
We found that baseline-mBDNF moderated the effect of physical exercise on neurocognition in individuals with schizophrenia and explained a small part of the inter-individual variation in neurocognitive response. Mean mBDNF decreased from baseline to post-intervention, regardless of exercise mode. A mediating role of mBDNF on the effect of exercise on neurocognition was not supported. The inter-individual variation in neurocognitive response and the complex role of peripheral BDNF in physical exercise is still to be elucidated.
体育锻炼可能通过促进神经可塑性来改善精神分裂症患者的神经认知功能。然而，个体间的反应存在很大差异。有研究提出脑源性神经营养因子（BDNF）可介导这些效应。当前的研究目的是探讨精神分裂症患者外周静息BDNF与体育锻炼的神经认知反应之间鲜少被研究的关系。
本研究报告了一项随机对照试验（RCT）数据的二次分析，该试验在ClinicalTrials.gov上的编号为02205684，最近已按照CONSORT指南进行了报告。82名精神分裂症患者（平均年龄37±14岁，61%为男性）被随机分配至高强度间歇训练（HIIT）组或进行低强度主动视频游戏（AVG）的对照组。两种干预措施均为每周2次，共12周。在先前发表的主要RCT分析中，HIIT和AVG在神经认知方面均显示出相当的小至中度改善。我们现在探讨神经认知反应中的个体间差异。我们应用重复测量设计的中介和调节分析（MEMORE）以及混合效应模型。
基线神经认知与成熟BDNF（基线-mBDNF）或前体proBDNF的基线水平无显著相关性。尽管如此，基线-mBDNF而非基线proBDNF调节了锻炼对神经认知的影响（p = 0.025），并解释了7%的方差。神经认知改善随着基线-mBDNF值的增加而增加。在一个更复杂的模型中，加入锻炼模式、性别、年龄、病程和基线最大摄氧量对结果（神经认知）的调节作用后，基线-mBDNF的调节作用仍然显著。无论锻炼模式如何，从基线到干预后，平均基线-mBDNF显著降低（p = 0.036），存在性别差异，且与最大摄氧量的改善相关，但与神经认知的变化无关。不支持mBDNF在体育锻炼对神经认知的影响中起中介作用。从基线到干预后，proBDNF的值主要保持稳定。
我们发现基线-mBDNF调节了体育锻炼对精神分裂症患者神经认知的影响，并解释了神经认知反应中个体间差异的一小部分。无论锻炼模式如何，从基线到干预后，平均mBDNF降低。不支持mBDNF在锻炼对神经认知的影响中起中介作用。神经认知反应中的个体间差异以及外周BDNF在体育锻炼中的复杂作用仍有待阐明。
