Testing a Neurobiological Model of Depersonalization Disorder Using Repetitive Transcranial Magnetic Stimulation☆

BACKGROUND Depersonalization disorder (DPD) includes changes in subjective experiencing of self, encompassing emotional numbing. Functional magnetic resonance imaging (fMRI) has pointed to ventrolateral prefrontal cortex (VLPFC) inhibition of insula as a neurocognitive correlate of the disorder. OBJECTIVE We hypothesized that inhibition to right VLPFC using repetitive transcranial magnetic stimulation (rTMS) would lead to increased arousal and reduced symptoms. METHODS Patients with medication-resistant DSM-IV DPD (N = 17) and controls (N = 20) were randomized to receive one session of right-sided rTMS to VLPFC or temporo-parietal junction (TPJ). 1 Hz rTMS was guided using neuronavigation and delivered for 15 min. Co-primary outcomes were: (a) maximum skin conductance capacity, and (b) reduction in depersonalization symptoms (Cambridge Depersonalisation Scale (CDS) [state version]). Secondary outcomes included spontaneous fluctuations (SFs) and event-related skin conductance responses. RESULTS In patients with DPD, rTMS to VLPFC led to increased electrodermal capacity, namely maximum skin conductance deflections. Patients but not controls also showed increased SFs post rTMS. Patients who had either VLPFC or TPJ rTMS showed a similar significant reduction in symptoms. Event-related electrodermal activity did not change. CONCLUSIONS A single session of right-sided rTMS to VLPFC (but not TPJ) significantly increased physiological arousal capacity supporting our model regarding the relevance of increased VLPFC activity to emotional numbing in DPD. rTMS to both sites led to reduced depersonalization scores but since this was independent of physiological arousal, this may be a non-specific effect. TMS is a potential therapeutic option for DPD; modulation of VLPFC, if replicated, is a plausible mechanism.