Antoine Pelissolo

Subthalamic nucleus stimulation in severe obsessive-compulsive disorder.

BACKGROUND Severe, refractory obsessive-compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option. METHODS In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests. RESULTS After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [+/-SD], 19+/-8 vs. 28+/-7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56+/-14 vs. 43+/-8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events. CONCLUSIONS These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377.)

Tourette’s syndrome and deep brain stimulation

In this prospective double blind randomised “N of 1” study, a patient with a severe form of Tourette’s syndrome was treated with bilateral high frequency stimulation of the centromedian-parafascicular complex (Ce-Pf) of the thalamus, the internal part of the globus pallidus (GPi), or both. Stimulation of either target improved tic severity by 70%, markedly ameliorated coprolalia, and eliminated self injuries. Severe forms of Tourette’s syndrome may benefit from stimulation of neuronal circuits within the basal ganglia, thus confirming the role of the dysfunction of limbic striato-pallido-thalamo-cortical systems in this disorder.

Stimulation of subterritories of the subthalamic nucleus reveals its role in the integration of the emotional and motor aspects of behavior

Two parkinsonian patients who experienced transient hypomanic states when the subthalamic nucleus (STN) was stimulated during postoperative adjustment of the electrical parameters for antiparkinsonian therapy agreed to have the mood disorder reproduced, in conjunction with motor, cognitive, and behavioral evaluations and concomitant functional neuroimaging. During the experiment, STN stimulation again induced a hypomanic state concomitant with activation of cortical and thalamic regions known to process limbic and associative information. This observation suggests that the STN plays a role in the control of a complex behavior that includes emotional as well as cognitive and motor components. The localization of the four contacts of the quadripolar electrode was determined precisely with an interactive brain atlas. The results showed that (i) the hypomanic state was caused only by stimulation through one contact localized in the anteromedial STN; (ii) both this contact and the contact immediately dorsal to it improved the parkinsonian motor state; (iii) the most dorsal and ventral contacts, located at the boundaries of the STN, neither induced the behavioral disorder nor improved motor performance. Detailed analysis of these data led us to consider a model in which the three functional modalities, emotional, cognitive, and motor, are not processed in a segregated manner but can be subtly combined in the small volume of the STN. This nucleus would thus serve as a nexus that integrates the motor, cognitive, and emotional components of behavior and might consequently be an effective target for the treatment of behavioral disorders that combine emotional, cognitive, and motor impairment.

Compulsions, Parkinson's disease, and stimulation

Pathophysiological models suggest that obsessive compulsive disorder (OCD) might be associated with dysfunctions in cortico-striato-pallido-thalamo-cortical neuronal circuits. We implanted subthalamic electrodes to alleviate parkinsonian symptoms in two patients who had Parkinsons disease and a history of severe OCD. Parkinsonian disability improved postoperatively in both patients, and 2 weeks after the procedure, their compulsions had disappeared and obsessive symptoms improved (58% improvement for patient 1 on the Yale-Brown obsessive compulsive scale, 64% for patient 2). The improvements in these two patients suggest that high-frequency stimulation could improve function in the subcortical-limbic circuitry in patients with severe OCD.

Size and burden of social phobia in Europe

This paper provides a critical review of the prevalence of social phobia in European countries, a description of associated disability and burden and of clinical correlates and risk factors associated with social phobia. On the basis of a comprehensive literature search we identified 21 community studies and two primary care studies. The median lifetime and 12-month prevalence rates of social phobia in community samples referring to DSM-III-R and DSM-IV criteria were 6.65% and 2.0%, respectively. Younger individuals showed the highest rates, and women were more frequently affected than men. Social phobia was shown to be a persistent condition with a remarkably high degree of comorbid conditions, associated impairment and disability. Research deficits lie in a lack of data for most EU countries and in a lack of studies in children and the elderly. No data are available addressing met and unmet needs for intervention and costs, and data for vulnerability and risk factors of malignant course are scarce.

Pathological gambling in Parkinson's disease improves on chronic subthalamic nucleus stimulation.

Pathological gambling (PG) related to dopaminergic treatment in Parkinsons disease (PD) is part of a spectrum of behavioral disorders called the dopamine dysregulation syndrome (DDS). We describe a series of PD patients with preoperative active PG due to dopaminergic treatment from a total of 598 patients who have undergone surgery for subthalamic nucleus stimulation for disabling motor fluctuations. The patients had systematic open assessment of behavioral symptoms and standardized assessments of motor symptoms, mood, and apathy. Seven patients (6 men, 1 woman; age, 54 ± 9 years; levodopa equivalent dose, 1,390 ± 350 mg/day) had preoperative PG over a mean of 7 years, intolerant to reduction in medication. Six had nonmotor fluctuations and four had other behavioral symptoms consistent with a diagnosis of the DDS. After surgery, motor symptoms improved, allowing for 74% reduction of dopaminergic treatment, below the dosage of gambling onset. In all patients, PG resolved postoperatively after 18 months on average (range, 0–48), although transient worsening occurred in two. Improvement paralleled the time course and degree of reduction in dopaminergic treatment. Nonmotor fluctuations, off period dysphoria, and other symptoms of the DDS improved. Two patients developed persistent apathy. In conclusion, PG and other symptoms of the DDS‐associated dopaminergic treatment improved in our patients following surgery. Dopaminergic dysregulation commonly attributed to pulsatile overstimulation of the limbic dopaminergic system may be subject to desensitization on chronic subthalamic stimulation, which has a relative motor selectivity and allows for decrease in dopaminergic treatment.

Normative data and factor structure of the Temperament and Character Inventory (TCI) in the French version.

We explored the psychometric features of the French Temperament and Character Inventory (TCI) in a 602-subject community sample (263 men and 339 women), representative of the French population. The factor structures of the temperament and character dimensions, explored separately, were in agreement with the hypothesized constructs, except for the scales Novelty Seeking NS1 (exploratory excitability), Persistence, and Self-Directedness SD4 (self-acceptance). The internal consistency of the main dimensions was good (Cronbach alpha coefficients between 0.68 and 0.82), but weak for Persistence (0.49). The mean scores of the temperament dimensions were notably different from those published in other normative data - especially lower for Novelty Seeking (16.4+/-5.6) and higher for Harm Avoidance (16.1+/-7.2) when compared with US data - suggesting cross-cultural differences in personality assessment, and the necessity to use specific normative values with each translated instrument.

Negative affectivity, self-referential processing and the cortical midline structures

The neural bases of the association between negative affectivity and self-focus remain unknown in healthy subjects. Building on the role of the cortical midline structures (CMS) in self-referential processing, we hypothesized that negative affectivity in healthy subjects would be associated with an increased activation of the CMS during self-referential processing. We presented positive and negative pictures to 45 healthy subjects during fMRI and asked them to judge whether the pictures were related to themselves or not (self condition), or whether the pictures were positive or negative (general condition). Negative affectivity was measured by the level of harm avoidance (HA) with the Temperament and Character Inventory. Self-referential processing activated the CMS, including the dorsal and ventral medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC). A higher HA score was associated with a greater activation of the dorsal MPFC and PCC during self-referential processing, this greater activation being more pronounced for negative pictures in the dorsal MPFC. This increased activation of the CMS may embody the association between negative affectivity and self-focus in healthy subjects, as previously observed in major depression. Within the CMS, the dorsal MPFC may play a key role in negative affectivity, integrating an increased attention to negative stimuli with an increased attention to the self.

The Temperament and Character Inventory-Revised (TCI-R): psychometric characteristics of the French version

Objective:  To explore the psychometric characteristics of a modified version of the Cloningers personality questionnaire, the Temperament and Character Inventory‐Revised (TCI‐R).

Gaze avoidance in social phobia: Objective measure and correlates

Gaze aversion could be a central component of the physiopathology of social phobia. The emotions of the people interacting with a person with social phobia seem to model this gaze aversion. Our research consists of testing gaze aversion in subjects with social phobia compared to control subjects in different emotional faces of men and women using an eye tracker. Twenty-six subjects with DSM-IV social phobia were recruited. Twenty-four healthy subjects aged and sex-matched constituted the control group. We looked at the number of fixations and the dwell time in the eyes area on the pictures. The main findings of this research are: confirming a significantly lower amount of fixations and dwell time in patients with social phobia as a general mean and for the 6 basic emotions independently from gender; observing a significant correlation between the severity of the phobia and the degree of gaze avoidance. However, no difference in gaze avoidance according to subject/picture gender matching was observed. These findings confirm and extend some previous results, and suggest that eye avoidance is a robust marker of persons with social phobia, which could be used as a behavioral phenotype for brain imagery studies on this disorder.