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.
Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, King's College London, Denmark Hill, London SE5 8AF, UK.
Emma-Louise
EL
Jay
Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, King's College London, Denmark Hill, London SE5 8AF, UK.
Mauricio
M
Sierra
MRC Human Movement and Balance Unit, Institute of Cognitive Neuroscience, University College London, UK.
Frederique
F
Van den Eynde
Institut Universitaire en Santé Mentale, Douglas McGill University, Montreal, Canada.
John C
JC
Rothwell
Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, King's College London, Denmark Hill, London SE5 8AF, UK. Electronic address: anthony.david@kcl.ac.uk.
Anthony S
AS
David
D000328:Adult; D001143:Arousal / Q000502:physiology*; D003861:Depersonalization / Q000503:physiopathology / Q000628:therapy*; D004644:Emotions / Q000502:physiology*; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D038361:Neuronavigation; D017397:Prefrontal Cortex / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
Depersonalization disorder; Neuronavigation-guided TMS; Prefrontal cortex; Repetitive transcranial magnetic stimulation; Skin conductance responses; Temporal parietal cortex