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<p>Transcranial magnetic stimulation (TMS) is effective for major depressive disorder (MDD) and anxious depression despite imprecise scalp-based targeting. Retrospective connectomics analyses suggest that targeting one brain circuit preferentially improves “dysphoric” symptoms, while targeting a different brain circuit preferentially improves “anxiosomatic” symptoms. Here, we tested this hypothesis prospectively by randomizing adults with MDD (n = 40, age 18-65) who had moderate-to-severe symptoms of depression (Beck Depression Inventory (BDI) ≥ 20) and anxiety (Beck Anxiety Inventory (BAI) ≥ 16) to a 30-treatment TMS course at the dysphoric circuit target (MNI coordinates [-32, 44, 34], close to the conventional left dorsolateral prefrontal cortex target for MDD), or at the anxiosomatic circuit target (MNI coordinates [0, 48, 46], a dorsomedial target not routinely used). As hypothesized, dysphoric circuit targeting (n = 16) improved BDI more than BAI (ratio 1.08, IQR 0.69-2.02), while anxiosomatic circuit targeting (n = 20) improved BAI more than BDI (ratio 0.70, IQR 0.01-1.01) (Wilcoxon rank-sum test p = 0.0195). Both targets improved BDI (55 vs 54%), but BAI improved significantly more with anxiosomatic circuit targeting (58 vs 36%, p = 0.0301), even when controlling for BDI (p &lt; 0.001). Thus, TMS targeting different connectome-derived brain circuits differentially modulates anxiety that is comorbid with major depressive disorder. Future studies could target according to baseline symptom profile, a step toward precision psychiatry. <b>Trial Registration Number</b> NCT04604210.</p>

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Circuit-targeted modulation of anxiety symptoms in individuals with major depression: A randomized head-to-head TMS trial

  • 期刊论文

  • 发表日期：

    2026年3月30日

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  • Joseph J. Taylor,
  • Jing Li,
  • Christopher Lin,
  • Emma Jones,
  • Summer Frandsen,
  • Claudia R. Becker,
  • William Drew,
  • Dania Haj-Darwish,
  • Sandrine Jabbour,
  • Jessica Leach,
  • Stephan Palm,
  • Lauren Sanderson,
  • Emanuella Santos,
  • Lera Sterina,
  • Nicole Chiulli,
  • John Miller,
  • Sheena Barantono,
  • Irene Gonsalvez,
  • Stanley Lyndon,
  • Samuel B. Snider,
  • Michael D. Fox,
  • Shan H. Siddiqi

摘要

Transcranial magnetic stimulation (TMS) is effective for major depressive disorder (MDD) and anxious depression despite imprecise scalp-based targeting. Retrospective connectomics analyses suggest that targeting one brain circuit preferentially improves “dysphoric” symptoms, while targeting a different brain circuit preferentially improves “anxiosomatic” symptoms. Here, we tested this hypothesis prospectively by randomizing adults with MDD (n = 40, age 18-65) who had moderate-to-severe symptoms of depression (Beck Depression Inventory (BDI) ≥ 20) and anxiety (Beck Anxiety Inventory (BAI) ≥ 16) to a 30-treatment TMS course at the dysphoric circuit target (MNI coordinates [-32, 44, 34], close to the conventional left dorsolateral prefrontal cortex target for MDD), or at the anxiosomatic circuit target (MNI coordinates [0, 48, 46], a dorsomedial target not routinely used). As hypothesized, dysphoric circuit targeting (n = 16) improved BDI more than BAI (ratio 1.08, IQR 0.69-2.02), while anxiosomatic circuit targeting (n = 20) improved BAI more than BDI (ratio 0.70, IQR 0.01-1.01) (Wilcoxon rank-sum test p = 0.0195). Both targets improved BDI (55 vs 54%), but BAI improved significantly more with anxiosomatic circuit targeting (58 vs 36%, p = 0.0301), even when controlling for BDI (p < 0.001). Thus, TMS targeting different connectome-derived brain circuits differentially modulates anxiety that is comorbid with major depressive disorder. Future studies could target according to baseline symptom profile, a step toward precision psychiatry. Trial Registration Number NCT04604210.