Khosravani Sanaz, Palm Stephan T, Drew William, Frandsen Summer B, Lin Christopher, Tirrell Eric, Hindley Lauren, Schineller Molly, Garimella Arun, Chiulli Nicole, Lawson David, Jones Emma, Press Daniel Z, Stern Adam P, Brown Joshua C, Barbour Tracy A, Taylor Joseph J, Carpenter Linda L, Siddiqi Shan H, Fox Michael D
Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Mol Psychiatry. 2025 Aug 22. doi: 10.1038/s41380-025-03153-3.
Small single-site studies found that transcranial magnetic stimulation (TMS) targets with better antidepressant response were more negatively functionally connected to the subgenual cingulate cortex (SGC). These led to "anti-subgenual" TMS targeting in recent clinical trials. We conducted a larger prospective multi-site observational study to test the robustness of this observation in more diverse clinical populations. Sixty-six treatment-seeking individuals with major depressive disorder (MDD) received 3-8 weeks of daily rTMS to the left dorsolateral prefrontal cortex using scalp-based targeting as part of standard clinical care. Stimulation sites were recorded with MRI neuronavigation on multiple days. Our primary outcome was the correlation between change in Beck Depression Inventory (BDI-II) score and connectivity of each individual's TMS site to the SGC, computed using resting-state functional connectivity data from 1000 healthy individuals. Secondary (post hoc) analyses incorporated additional clinical covariates. No relationship was found between antidepressant response and normative connectivity of TMS site to SGC (r = 0.1, p = 0.39). This was not due to inconsistency in the location of the TMS sites, which showed smaller within- than between-individual variance (p < 0.0001). Post hoc analyses showed significant associations when adding clinical covariates (r = -0.27, p = 0.014). Baseline anxiety (p < 0.0001) and comorbid psychiatric conditions (p < 0.001) accounted for the most variance in response. Atlas-based connectivity of TMS site to the SGC accounted for minimal variance in antidepressant response in this diverse sample. The "anti-subgenual" target derived based on normative connectome may be suboptimal for MDD patients with high baseline anxiety or psychiatric comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03276793.
小型单中心研究发现，具有更好抗抑郁反应的经颅磁刺激（TMS）靶点与膝下扣带回皮质（SGC）的功能连接更负相关。这些发现促使在近期的临床试验中采用“抗膝下”TMS靶点。我们开展了一项更大规模的前瞻性多中心观察性研究，以检验这一观察结果在更多样化临床人群中的稳健性。66名寻求治疗的重度抑郁症（MDD）患者作为标准临床护理的一部分，使用基于头皮的靶点，接受了为期3 - 8周的每日左侧背外侧前额叶皮质重复经颅磁刺激（rTMS）。在多个日期使用MRI神经导航记录刺激部位。我们的主要结局是贝克抑郁量表（BDI-II）评分的变化与每个个体的TMS部位与SGC的连接性之间的相关性，使用来自1000名健康个体的静息态功能连接数据进行计算。次要（事后）分析纳入了其他临床协变量。未发现抗抑郁反应与TMS部位与SGC的标准连接性之间存在关联（r = 0.1，p = 0.39）。这并非由于TMS部位位置不一致所致，TMS部位的个体内差异小于个体间差异（p < 0.0001）。事后分析显示，加入临床协变量后存在显著关联（r = -0.27，p = 0.014）。基线焦虑（p < 0.0001）和共病精神疾病（p < 0.001）在反应中占最大方差。在这个多样化样本中，基于图谱的TMS部位与SGC的连接性在抗抑郁反应中占最小方差。基于标准连接组得出的“抗膝下”靶点对于基线焦虑高或有精神疾病共病情况的MDD患者可能并非最优。试验注册：ClinicalTrials.gov标识符：NCT03276793
