Neuroscience & Psychiatry Unit, Institute of Brain, Behaviour and Mental Health and Manchester Academic Health Sciences Centre, Stopford Building, University of Manchester, Manchester, M13 9PT, UK.
MTA-SE-NAP B Genetic Brain Imaging Migraine Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
Transl Psychiatry. 2019 Mar 15;9(1):116. doi: 10.1038/s41398-019-0447-0.
The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram. In MDD patients during saline infusion, in contrast with controls, the DMN (i) did not include the precuneus that was instead part of an anti-correlated network but (ii) did include amygdala that was part of the anti-correlated network in controls. Citalopram infusion in MDD patients restored the pattern seen in controls under saline. In healthy controls, citalopram infusion disengaged the precuneus from the DMN and engaged the amygdala, partially reproducing the abnormalities seen under saline in MDD. In exploratory analyses within the MDD group, greater rumination self-ratings were associated with greater intra-network connectivity of the anterior cingulate cortex with the DMN. We hypothesise that, in MDD, disengagement of the precuneus from the DMN relates to overgeneral memory bias in rumination. The opposite effect, with greater engagement of the amygdala in the DMN, reflects the negative valence of rumination. Reversal of these abnormalities by citalopram suggests that they may be related to impaired serotonin function. That citalopram engaged the amygdala in the DMN in controls may relate to the paradoxical effects on aversive processing seen with acute SSRIs in healthy subjects.
尚未研究重度抑郁症（MDD）中默认模式网络（DMN）连接改变与 5-羟色胺功能异常之间的关系。我们使用静脉给予西酞普兰和静息态 fMRI，研究了 77 名健康对照者和 MDD 患者的 DMN 内网络连接和 5-羟色胺功能。MDD 或西酞普兰对 DMN 内网络连接均无显著的主要影响；然而，显著的相互作用表明，盐水下的组间差异被西酞普兰所修饰。在盐水输注期间，与对照组相比，MDD 患者的 DMN（i）不包括被认为是相反相关网络一部分的楔前叶，而是包括被认为是对照组相反相关网络一部分的杏仁核；（ii）包括在对照组的相反相关网络中的杏仁核。在 MDD 患者中静脉输注西酞普兰恢复了盐水下对照组中所见的模式。在健康对照者中，西酞普兰输注使楔前叶与 DMN 脱离，并使杏仁核参与，部分再现了 MDD 患者在盐水下所见的异常。在 MDD 组内的探索性分析中，更大的反刍自评与前扣带皮层与 DMN 的内网络连接增加有关。我们假设，在 MDD 中，楔前叶与 DMN 的脱离与反刍中的过度概括记忆偏向有关。相反的效果，即杏仁核在 DMN 中的更大参与，反映了反刍的负性情绪。西酞普兰逆转这些异常提示它们可能与 5-羟色胺功能受损有关。西酞普兰在对照组中使杏仁核参与 DMN 可能与健康受试者中急性 SSRIs 对厌恶处理的矛盾作用有关。
