Córdova-Palomera Aldo, de Reus Marcel A, Fatjó-Vilas Mar, Falcón Carles, Bargalló Nuria, van den Heuvel Martijn P, Fañanás Lourdes
Unidad de Antropología, Departamento de Biología Animal, Facultad de Biología and Instituto de Biomedicina (IBUB), Universitat de Barcelona, Av. Diagonal, 643, 08028, Barcelona, Spain.
Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), C/Doctor Esquerdo, 46, 28007, Madrid, Spain.
Brain Imaging Behav. 2017 Feb;11(1):62-75. doi: 10.1007/s11682-015-9503-4.
The hippocampus is a key modulator of stress responses underlying depressive behavior. While FKBP5 has been found associated with a large number of stress-related outcomes and hippocampal features, its potential role in modifying the hippocampal communication transfer mechanisms with other brain regions remains largely unexplored. The putative genetic or environmental roots of the association between depression and structural connectivity alterations of the hippocampus were evaluated combining diffusion weighted imaging with both a quantitative genetics approach and molecular information on the rs1360780 single nucleotide polymorphism, in a sample of 54 informative monozygotic twins (27 pairs). Three main results were derived from the present analyses. First, graph-theoretical measures of hippocampal connectivity were altered in depression. Specifically, decreased connectivity strength and increased network centrality of the right hippocampus were found in depressed individuals. Second, these hippocampal alterations are potentially driven by familial factors (genes plus shared environment). Third, there is an additive interaction effect between FKBP5's rs1360780 variant and the graph-theoretical metrics of hippocampal connectivity to influence depression risk. Our data reveals alterations of the communication patterns between the hippocampus and the rest of the brain in depression, effects potentially driven by overall familial factors (genes plus shared twin environment) and modified by the FKBP5 gene.
海马体是抑郁行为背后应激反应的关键调节因子。虽然已发现FKBP5与大量应激相关结果及海马体特征有关，但其在改变海马体与其他脑区的通信传递机制中的潜在作用仍 largely unexplored。结合扩散加权成像、定量遗传学方法以及关于rs1360780单核苷酸多态性的分子信息，在54对有信息的同卵双胞胎（27对）样本中评估了抑郁症与海马体结构连接改变之间关联的假定遗传或环境根源。本次分析得出了三个主要结果。首先，抑郁症患者海马体连接的图论测量值发生了改变。具体而言，在抑郁个体中发现右侧海马体的连接强度降低且网络中心性增加。其次，这些海马体改变可能由家族因素（基因加共享环境）驱动。第三，FKBP5的rs1360780变体与海马体连接的图论指标之间存在累加交互作用，以影响抑郁风险。我们的数据揭示了抑郁症中海马体与大脑其他部分之间通信模式的改变，这些影响可能由整体家族因素（基因加共享双胞胎环境）驱动，并由FKBP5基因修饰。
