Shkundin Anton, Wheeler Heather E, Sinacore James, Halaris Angelos
Department of Psychiatry and Behavioral Neurosciences, Loyola University Chicago, Maywood, IL 60153, USA.
Department of Biology, Loyola University Chicago, Chicago, IL 60660, USA.
J Pers Med. 2025 Feb 7;15(2):62. doi: 10.3390/jpm15020062.
Bipolar disorder (BD) is a chronic condition associated with treatment resistance, cognitive decline, structural brain changes, and an approximately 13-year reduction in life expectancy compared to the general population. Depression in BD substantially impairs quality of life, while neuroinflammation and excitotoxicity are thought to contribute to the recurrence of mood episodes and disease progression. Brain-derived neurotrophic factor (BDNF) plays a key role in neuronal growth and function, with its dysregulation being linked to various psychiatric disorders. This study is an extension of a previously published clinical trial and was conducted to assess the effects of three BDNF and BDNF-AS gene polymorphisms (rs1519480, rs6265, and rs10835210) on treatment outcomes and serum BDNF levels in patients with treatment-resistant bipolar disorder depression (TRBDD) over an eight-week period. This study included 41 participants from a previously conducted randomized clinical trial, all of whom had available BDNF serum samples and genotype data. The participants, aged 21 to 65, were diagnosed with bipolar disorder, and treatment-resistant depression was assessed using the Maudsley Staging Method. Participants were randomly assigned to receive either escitalopram plus a placebo (ESC+PBO) or escitalopram plus celecoxib (ESC+CBX) over an 8-week period. Statistical analyses included a mixed ANOVA and chi-square tests to compare the minor allele carrier status of three SNPs with treatment response and remission rates. Non-carriers of the rs6265 A allele ( = 0.005) and carriers of the rs10835210 A allele ( = 0.007) showed a significantly higher response to treatment with adjunctive celecoxib compared to escitalopram alone. Additionally, remission rates after adjunctive celecoxib were significantly higher in both carriers and non-carriers across all three SNPs compared to escitalopram alone. However, remission rates were notably higher in non-carriers of the rs1519480 G allele and rs10835210 A allele, as well as in carriers of the rs6265 A allele. This study suggests that genetic variations in BDNF and BDNF-AS genes significantly influence treatment response to and remission with escitalopram and celecoxib in bipolar disorder.
双相情感障碍（BD）是一种慢性疾病，与治疗抵抗、认知衰退、脑结构改变有关，与普通人群相比，预期寿命缩短约13年。双相情感障碍中的抑郁严重损害生活质量，而神经炎症和兴奋性毒性被认为是导致情绪发作复发和疾病进展的原因。脑源性神经营养因子（BDNF）在神经元生长和功能中起关键作用，其失调与多种精神疾病有关。本研究是之前发表的一项临床试验的扩展，旨在评估三种BDNF和BDNF-AS基因多态性（rs1519480、rs6265和rs10835210）在八周时间内对难治性双相情感障碍抑郁（TRBDD）患者治疗效果和血清BDNF水平的影响。本研究纳入了之前一项随机临床试验的41名参与者，他们都有可用的BDNF血清样本和基因型数据。参与者年龄在21至65岁之间，被诊断为双相情感障碍，并使用莫兹利分期法评估难治性抑郁。参与者在8周内被随机分配接受艾司西酞普兰加安慰剂（ESC+PBO）或艾司西酞普兰加塞来昔布（ESC+CBX）。统计分析包括混合方差分析和卡方检验，以比较三个单核苷酸多态性的次要等位基因携带者状态与治疗反应和缓解率。与单独使用艾司西酞普兰相比，rs6265 A等位基因的非携带者（P = 0.005）和rs10835210 A等位基因的携带者（P = 0.007）对辅助使用塞来昔布治疗的反应显著更高。此外，与单独使用艾司西酞普兰相比，所有三个单核苷酸多态性的携带者和非携带者在辅助使用塞来昔布后的缓解率均显著更高。然而，rs1519480 G等位基因和rs10835210 A等位基因的非携带者以及rs6265 A等位基因的携带者的缓解率明显更高。本研究表明，BDNF和BDNF-AS基因的遗传变异显著影响双相情感障碍患者对艾司西酞普兰和塞来昔布的治疗反应和缓解情况。
