Department of Neurology, University of California, San Francisco, San Francisco, California.
Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, California; San Francisco Veteran Affairs Health Care System, San Francisco, California.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Sep;8(9):928-939. doi: 10.1016/j.bpsc.2022.10.009. Epub 2022 Oct 31.
Treatment-resistant depression (TRD) refers to patients with major depressive disorder who do not remit after 2 or more antidepressant trials. TRD is common and highly debilitating, but its neurobiological basis remains poorly understood. Recent neuroimaging studies have revealed cortical connectivity gradients that dissociate primary sensorimotor areas from higher-order associative cortices. This fundamental topography determines cortical information flow and is affected by psychiatric disorders. We examined how TRD impacts gradient-based hierarchical cortical organization.
In this secondary study, we analyzed resting-state functional magnetic resonance imaging data from a mindfulness-based intervention enrolling 56 patients with TRD and 28 healthy control subjects. Using gradient extraction tools, baseline measures of cortical gradient dispersion within and between functional brain networks were derived, compared across groups, and associated with graph theoretical measures of network topology. In patients, correlation analyses were used to associate measures of cortical gradient dispersion with clinical measures of anxiety, depression, and mindfulness at baseline and following the intervention.
Cortical gradient dispersion was reduced within major intrinsic brain networks in patients with TRD. Reduced cortical gradient dispersion correlated with increased network degree assessed through graph theory-based measures of network topology. Lower dispersion among default mode, control, and limbic network nodes related to baseline levels of trait anxiety, depression, and mindfulness. Patients' baseline limbic network dispersion predicted trait anxiety scores 24 weeks after the intervention.
Our findings provide preliminary support for widespread alterations in cortical gradient architecture in TRD, implicating a significant role for transmodal and limbic networks in mediating depression, anxiety, and lower mindfulness in patients with TRD.
治疗抵抗性抑郁症（TRD）是指患有重性抑郁症的患者，在经过 2 次或更多次抗抑郁药物治疗后仍未缓解。TRD 较为常见且严重致残，但其神经生物学基础仍知之甚少。最近的神经影像学研究揭示了皮质连接梯度，将主要感觉运动区与高级联合皮质区分开。这种基本的拓扑结构决定了皮质信息流，并受到精神疾病的影响。我们研究了 TRD 如何影响基于梯度的分层皮质组织。
在这项二级研究中，我们分析了正念干预研究中的静息态功能磁共振成像数据，该研究纳入了 56 名 TRD 患者和 28 名健康对照者。使用梯度提取工具，我们在组内和组间得出了皮质梯度分散的静息状态功能磁共振成像数据，比较了两组之间的差异，并与网络拓扑的图论测量指标相关联。在患者中，我们使用相关分析将皮质梯度分散的测量值与焦虑、抑郁和正念的基线和干预后的临床测量值相关联。
TRD 患者的主要内在脑网络内的皮质梯度分散度降低。皮质梯度分散度的降低与网络拓扑的图论测量指标评估的网络度增加相关。默认模式、控制和边缘网络节点之间的低分散度与基线特质焦虑、抑郁和正念相关。患者的基线边缘网络分散度预测了干预 24 周后的特质焦虑评分。
我们的研究结果初步支持 TRD 中皮质梯度结构的广泛改变，表明跨模态和边缘网络在介导 TRD 患者的抑郁、焦虑和较低的正念水平方面具有重要作用。
