Valproate is among the most prescribed drugs for bipolar disorder; however, 87% of patients do not report full long-term treatment response (LTTR) to this medication. One of valproate's suggested mechanisms of action involves the brain-derived neurotrophic factor (BDNF), expressed in the brain areas regulating emotions, such as the prefrontal cortex. Nonetheless, data about the role of BDNF in LTTR and its implications in the structure of the dorsolateral prefrontal cortex (dlPFC) is scarce. We explore the association of BDNF variants and dorsolateral cortical thickness (CT) with LTTR to valproate in bipolar disorder type I (BDI). Twenty-eight BDI patients were genotyped for BDNF polymorphisms rs1519480, rs6265, and rs7124442, and T1-weighted 3D brain scans were acquired. LTTR to valproate was evaluated with Alda's scale. A logistic regression analysis was conducted to evaluate LTTR according to BDNF genotypes and CT. We evaluated CT differences by genotypes with analysis of covariance. LTTR was associated with BDNF rs1519480 and right dlPFC thickness. Insufficient responders with the CC genotype had thicker right dlPFC than TC and TT genotypes. Full responders reported thicker right dlPFC in TC and TT genotypes. In conclusion, different patterns of CT related to BDNF genotypes were identified, suggesting a potential biomarker of LTTR to valproate in our population.

中文翻译：

---

BDNF 风险变异和背外侧皮质厚度与 I 型双相情感障碍丙戊酸盐长期治疗反应的关联：一项探索性研究

丙戊酸是治疗双相情感障碍最常用的药物之一；然而，87% 的患者并未报告对该药物的完全长期治疗反应 (LTTR)。丙戊酸建议的作用机制之一涉及脑源性神经营养因子（BDNF），该因子在调节情绪的大脑区域（例如前额皮质）中表达。尽管如此，有关BDNF在 LTTR 中的作用及其对背外侧前额叶皮层 (dlPFC) 结构的影响的数据很少。我们探讨了BDNF变异和背外侧皮质厚度 (CT) 与 I 型双相情感障碍 (BDI) 中丙戊酸 LTTR的关系。对 28 名 BDI 患者进行了BDNF多态性 rs1519480、rs6265 和 rs7124442 的基因分型，并获取了 T1 加权 3D 脑部扫描。使用 Alda 量表评估丙戊酸的 LTTR。根据BDNF基因型和 CT 进行逻辑回归分析来评估 LTTR。我们通过协方差分析评估了基因型的 CT 差异。LTTR 与BDNF rs1519480 和右侧 dlPFC 厚度相关。CC 基因型应答不足者的右侧 dlPFC 比 TC 和 TT 基因型更厚。完全缓解者报告 TC 和 TT 基因型的右侧 dlPFC 较厚。总之，确定了与BDNF基因型相关的不同 CT 模式，表明丙戊酸在我们人群中是 LTTR 的潜在生物标志物。