Department of Psychiatry, Yale School of Medicine, New Haven, CT, 06511, USA.
Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, 06511, USA.
Nat Commun. 2019 Apr 4;10(1):1529. doi: 10.1038/s41467-019-09562-7.
Synaptic loss and deficits in functional connectivity are hypothesized to contribute to symptoms associated with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The synaptic vesicle glycoprotein 2A (SV2A) can be used to index the number of nerve terminals, an indirect estimate of synaptic density. Here, we used positron emission tomography (PET) with the SV2A radioligand [C]UCB-J to examine synaptic density in n = 26 unmedicated individuals with MDD, PTSD, or comorbid MDD/PTSD. The severity of depressive symptoms was inversely correlated with SV2A density, and individuals with high levels of depression showing lower SV2A density compared to healthy controls (n = 21). SV2A density was also associated with aberrant network function, as measured by magnetic resonance imaging (MRI) functional connectivity. This is the first in vivo evidence linking lower synaptic density to network alterations and symptoms of depression. Our findings provide further incentive to evaluate interventions that restore synaptic connections to treat depression.
突触损失和功能连接缺陷被假设是导致与重度抑郁症（MDD）和创伤后应激障碍（PTSD）相关症状的原因。突触囊泡糖蛋白 2A（SV2A）可用于标记神经末梢的数量，这是突触密度的间接估计。在这里，我们使用正电子发射断层扫描（PET）与 SV2A 放射性配体 [C]UCB-J 检查了 26 名未经治疗的 MDD、PTSD 或 MDD/PTSD 共病患者的突触密度。抑郁症状的严重程度与 SV2A 密度呈负相关，与健康对照组（n=21）相比，抑郁程度高的个体 SV2A 密度较低。SV2A 密度还与磁共振成像（MRI）功能连接测量的异常网络功能有关。这是将较低的突触密度与网络改变和抑郁症状联系起来的第一个体内证据。我们的研究结果进一步激励人们评估恢复突触连接以治疗抑郁症的干预措施。
