Cognitive-Affective Variability in TMS for Depression: Investigating Anxiety Exacerbation as a Treatment Outcome

Poster Session D - Monday, March 31, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Morgan Healey¹, Lamaan Haq¹, Joshua Brown^1,2; ¹Division of Depression and Anxiety Disorders, McLean Hospital, ²Department of Psychiatry, Harvard Medical School

Transcranial Magnetic Stimulation (TMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a well-established treatment for major depressive disorder (MDD), with evidence suggesting it enhances cognitive control over emotion by modulating the cognitive control network (CCN). While TMS has been demonstrated to have anxiolytic effects, clinical reports suggest some patients experience increases in anxiety, raising questions about individual differences in treatment response and the neural mechanisms underlying emotional variability. Despite these observations, TMS-emergent anxiety remains poorly characterized, limiting its integration into treatment optimization. This retrospective study examined 23 adults with MDD who completed ≥29 sessions of high-frequency (18Hz) TMS targeting the left DLPFC. Anxiety severity was assessed using the Generalized Anxiety Disorder-7 (GAD-7) scale at baseline and post-treatment, with percentage change analyzed to assess symptom trajectories. While anxiety improved on average, 9 of 23 patients (39%) experienced increased GAD-7 scores post-treatment, with 4 patients of these patients showing a >30% worsening and 3 exhibiting a 100% increase. Baseline anxiety severity was weakly negatively correlated with percentage change in GAD-7 (r = -0.21), suggesting that TMS-induced anxiety changes may not be solely explained by initial symptom severity. These findings highlight variability in the emotional response to TMS, suggesting that some individuals may be more prone to anxiety worsening during treatment. Future research should examine whether baseline symptom patterns, cognitive-affective profiles, or alternative TMS parameters (e.g., right low-frequency stimulation) could help predict and mitigate anxiety exacerbation. Identifying these predictors could improve treatment personalization and optimize patient outcomes in TMS for depression.

Topic Area: EMOTION & SOCIAL: Other