Psychiatric Clinic, Department of Neurosciences, University of Padova, Via Giustiniani 3, 35128 Padova, Italy; Centro di Neuroscienze Cognitive, Università di Padova, Italy.
Department of Medicine and Surgery, University of Salerno, Italy; IRCCS Istituto San Camillo, Venezia, Italy.
Psychiatry Res. 2014 Aug 30;223(2):157-63. doi: 10.1016/j.pscychresns.2014.05.006. Epub 2014 May 22.
A change in neural connectivity of brain structures implicated in the memory of negative life events has been hypothesized to explain the enhancement of memory encoding during the processing of negative stimuli in depressed patients. Here, we investigated the effects of the interaction between negative life events and the 5-HTTLPR genotype - a polymorphism of the serotonin transporter gene - on the functional and structural connectivity of the hippocampal area in 34 healthy women. All participants were genotyped for the presence of the 5-HTTLPR short variant and for the A/G single-nucleotide polymorphism; they underwent clinical assessment including structured diagnostic interviews to exclude the presence of psychiatric disorders and to assess the presence of stressful life events. Resting state functional magnetic resonance imaging and diffusion tensor imaging scans were performed. We found significant interactions between stressful events and the 5-HTTLPR genotype in both the functional connectivity of the parahippocampus with the posterior cingulate cortex and the structural connectivity between the hippocampus and both the amygdala and the putamen. In addition, we found several genotype-related differences in the relationship between functional/structural connectivity of the hippocampal area and the ability to update expectations or stress-related phenotypes, such as anxiety symptoms. If confirmed by future studies, these mechanisms may clarify the role of the 5HTTLPR genotype as a risk factor for depression, in interaction with negative events.
大脑结构中与消极生活事件记忆有关的神经连接变化，被假设可以解释抑郁患者在处理消极刺激时增强记忆编码的现象。在这里，我们研究了消极生活事件与 5-HTTLPR 基因座（血清素转运蛋白基因的多态性）之间的相互作用，对 34 名健康女性的海马区功能和结构连接的影响。所有参与者均进行了 5-HTTLPR 短变体和 A/G 单核苷酸多态性的基因分型；他们接受了临床评估，包括结构诊断访谈，以排除精神障碍的存在，并评估应激性生活事件的存在。进行了静息状态功能磁共振成像和弥散张量成像扫描。我们发现，应激性生活事件和 5-HTTLPR 基因型在旁海马区与后扣带皮层之间的功能连接以及海马区与杏仁核和壳核之间的结构连接方面均存在显著的相互作用。此外，我们发现，海马区功能/结构连接与期望更新或与应激相关的表型（如焦虑症状）之间的关系中存在几种与基因型相关的差异。如果未来的研究得到证实，这些机制可能会阐明 5-HTTLPR 基因型作为与消极事件相互作用的抑郁风险因素的作用。
