Ventrolateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of depersonalization disorder: A consecutive case series.

Case reports and an open trial have reported promising responses to repetitive transcranial magnetic stimulation (rTMS) to prefrontal and temporo-parietal sites in patients with depersonalization disorder (DPD). We recently showed that a single session of rTMS to the ventrolateral prefrontal cortex (VLPFC) was associated with a reduction in symptoms and increase in physiological arousal. Seven patients with medication-resistant DSM-IV DPD received up to 20 sessions of right-sided rTMS to the VLPFC for 10 weeks. Stimulation was guided using neuronavigation software based on participants' individual structural MRIs, and delivered at 110% of resting motor threshold. A session consisted of 1Hz repetitive TMS for 15min. The primary outcome measure was reduction in depersonalization symptoms on the Cambridge Depersonalization Scale (CDS). Secondary outcomes included scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). 20 sessions of rTMS treatment to right VLPFC significantly reduced scores on the CDS by on average 44% (range 2-83.5%). Two patients could be classified as "full responders", four as "partial" and one a non-responder. Response usually occurred within the first 6 sessions. There were no significant adverse events. A randomized controlled clinical trial of VLPFC rTMS for DPD is warranted.

Symptom profiles in depersonalization and anxiety disorders: an analysis of the Beck Anxiety Inventory.

BACKGROUND: Depersonalization disorder (DPD) entails distressing alterations in self-experiencing. However, it has long been recognized that depersonalisation symptoms occur in other disorders, particularly anxiety and panic. One strand of research proposes that depersonalization phenomenology arises through altered autonomic arousal in response to stress. SAMPLING AND METHODS: We sought to examine profiles of anxiety symptoms through a secondary data analysis of individual items and factor subscales on the Beck Anxiety Inventory (BAI), comparing two relatively large patient samples with DPD or with a variety of anxiety conditions, respectively. The DPD sample (n = 106) had a lower overall BAI score than the combined anxiety disorders group (n = 525). RESULTS: After controlling for this as well as for potential confounders such as age and gender, the DPD group presented significantly lower scores on the panic subscale, marginally lower scores on the autonomic subscale and significantly higher scores on the neurophysiological subscale of the BAI. CONCLUSIONS: These differences imply similarities between the cognitive components of DPD and anxiety disorders while physiological experiences diverge. The findings encourage future research looking at direct physiological measures and longitudinal designs to confirm the mechanisms underlying different clinical manifestations of anxiety.

A structural MRI study of cortical thickness in depersonalisation disorder.

Depersonalisation disorder (DPD) is characterised by a sense of unreality about the self and the world. Research suggests altered autonomic responsivity and dysfunction in prefrontal and temporal lobe areas in this condition. We report the first structural magnetic resonance imaging study of 20 patients with DPD and 21 controls using the FreeSurfer analysis tool employing both region-of-interest and vertex-based methods. DPD patients showed significantly lower cortical thickness in the right middle temporal region according to both methods of analysis. The vertex-based method revealed additional differences in bilateral temporal lobes, inferior frontal regions, the right posterior cingulate, and increased thickness in the right gyrus rectus and left precuneus. Clinical severity scores were negatively correlated with cortical thickness in middle and right inferior frontal regions. In sum, grey matter changes in the frontal, temporal, and parietal lobes are associated with DPD. Further research is required to specify the functional significance of the findings and whether they are vulnerability or disease markers.

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.