Nematollah Jaafari

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.)

Gray matter alterations in obsessive-compulsive disorder: an anatomic likelihood estimation meta-analysis.

Many voxel-based morphometry (VBM) studies have found abnormalities in gray matter density (GMD) in obsessive–compulsive disorder (OCD). Here, we performed a quantitative meta-analysis of VBM studies contrasting OCD patients with healthy controls (HC). A literature search identified 10 articles that included 343 OCD patients and 318 HC. Anatomic likelihood estimation meta-analyses were performed to assess GMD changes in OCD patients relative to HC. GMD was smaller in parieto-frontal cortical regions, including the supramarginal gyrus, the dorsolateral prefrontal cortex, and the orbitofrontal cortex, and greater in the basal ganglia (putamen) and the anterior prefrontal cortex in OCD patients relative to HC. No significant differences were found between children and adults. Our findings indicate differences in GMD in parieto-frontal areas and the basal ganglia between OCD patients and HC. We conclude that structural abnormalities within the prefrontal-basal ganglia network are involved in OCD pathophysiology.

Safety and efficacy of repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: A review

Abstract Objectives. Obsessive-compulsive disorder (OCD) is a chronic, often severe, neuropsychiatric disorder leading to a dramatic impairment in interpersonal and occupational functions. rTMS has been tried out in several studies in patients with OCD with different characteristics. In this paper, we review the safety and efficacy of rTMS in the treatment of mostly severe resistant OCD. Methods. A review of the English literature from 1966 to 2010 pertaining to rTMS in the treatment of OCD was conducted using MEDLINE by selectively entering the search terms “transcranial magnetic stimulation”, “repetitive transcranial magnetic stimulation”, “obsessive-compulsive disorder” and “OCD”. Twelve studies including open and randomized, sham-controlled trials were included in this review. Results. Although available data about the use of rTMS in OCD treatment are quite heterogeneous in terms of sample size, study design, stimulus parameters used and stimulation areas targeted, promising findings regarding rTMS efficacy appeared for two structures based on recent controlled studies: the supplementary motor area and the orbitofrontal cortex. On the other hand, rTMS of the dorsolateral prefrontal cortex is not significantly effective when compared to sham rTMS. Conclusions. Three target areas have already been selected of which the supplementary motor area in particular and the orbitofrontal cortex seem to be the most promising in terms of potential efficacy and could more accurately be targeted with the help of neuronavigational techniques. Larger randomized controlled trials should be conducted in order to better clarify the therapeutic role of rTMS in OCD.

A challenging task for assessment of checking behaviors in obsessive-compulsive disorder

Objective:  The present study concerns the objective and quantitative measurement of checking activity, which represents the most frequently observed compulsions in obsessive–compulsive disorder (OCD). To address this issue, we developed an instrumental task producing repetitive checking in OCD subjects.

Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia.

Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case–control study, we examine whether these gene variants are associated with schizophrenia and ultra-resistant schizophrenia (URS) in a population of French Caucasian patients. The URS phenotype is characterized according to stringent criteria as patients who experience no clinical, social and/or occupational remission in spite of treatment with clozapine and at least two periods of treatment with distinct conventional or atypical antipsychotic drugs. We find a significant association between DISC1 missense variants and URS. The association with rs3738401 remains significant after appropriate correction for multiple testing. These results suggest that the DISC1 rs3738401 missense variant is statistically linked with ultra-resistance to antipsychotic treatment.

Alzheimer's disease and impairment of the Self.

UNLABELLED Impairment of the Self has been described in frontal-temporal dementia but little research has been carried out in patients with Alzheimers disease (AD). OBJECTIVE The aim of this study was to explore changes in the self in patients with AD. METHOD Forty-seven patients with mild to moderate AD were examined using a semi-structured scale designed to assess the self-concept along three dimensions, namely, the Material Self, the Social Self and the Spiritual Self. RESULTS The majority of patients (43 out of 47) presented impairment of at least one dimension of the Self. When only one dimension was affected, it was always the Social Self. The severity of impairment of the Self was correlated to the impairment of the semantic autobiographical memory and apathy. CONCLUSION The Self is impaired in AD and the Social Self dimension appears to be more vulnerable in AD than other dimensions.

Obsessive Compulsive Disorder Networks: Positron Emission Tomography and Neuropsychology Provide New Insights

Background Deep brain stimulation has shed new light on the central role of the prefrontal cortex (PFC) in obsessive compulsive disorder (OCD). We explored this structure from a functional perspective, synchronizing neuroimaging and cognitive measures. Methods and Findings This case-control cross-sectional study compared 15 OCD patients without comorbidities and not currently on serotonin reuptake inhibitors or cognitive behavioural therapy with 15 healthy controls (matched for age, sex and education level) on resting-state 18FDG-PET scans and a neuropsychological battery assessing executive functions. We looked for correlations between metabolic modifications and impaired neuropsychological scores. Modifications in glucose metabolism were found in frontal regions (orbitofrontal cortex and dorsolateral cortices), the cingulate gyrus, insula and parietal gyrus. Neuropsychological differences between patients and controls, which were subtle, were correlated with the metabolism of the prefrontal, parietal, and temporal cortices. Conclusion As expected, we confirmed previous reports of a PFC dysfunction in OCD patients, and established a correlation with cognitive deficits. Other regions outside the prefrontal cortex, including the dorsoparietal cortex and the insula, also appeared to be implicated in the pathophysiology of OCD, providing fresh insights on the complexity of OCD syndromes.

Empathy Is a Protective Factor of Burnout in Physicians: New Neuro-Phenomenological Hypotheses Regarding Empathy and Sympathy in Care Relationship

Burnout is a multidimensional work-related syndrome that is characterized by emotional exhaustion, depersonalization—or cynicism—and diminution of personal accomplishment. Burnout particularly affects physicians. In medicine as well as other professions, burnout occurrence depends on personal, developmental-psychodynamic, professional, and environmental factors. Recently, it has been proposed to specifically define burnout in physicians as “pathology of care relationship.” That is, burnout would arise, among the above-mentioned factors, from the specificity of the care relationship as it develops between the physician and the patient. Accordingly, experimental studies and theoretical approaches have suggested that burnout and empathy, which is one of the most important skills in physicians, are closely linked. However, the nature of the relation between burnout and empathy remains not yet understood, as reflected in the variety of theoretical and contradictory hypotheses attempting to causally relate these two phenomena. Firstly, we here question the epistemological problem concerning the modality of the burnout-empathy link. Secondly, we hypothesize that considering the multidimensional features of both burnout and empathy, on one hand, and on the other hand, the distinction between empathy and sympathy enables to overcome these contradictions and, consequently, gives a better understanding of the relationship between burnout and empathy in physicians. Thirdly, we propose that clarifying the link between burnout, empathy and sympathy would enable developing specific training in medical students and continuous professional formation in senior physicians and would potentially contribute to the prevention of burnout in medical care.

Contextual and behavioral influences on uncertainty in obsessive-compulsive disorder

INTRODUCTION Behavioral adaptation generally follows the contextual changes arising from the consequences (rewards and punishments) of an action. According to the reciprocal determinism model, there is a mutual influence between external context, cognitive processes and behavior. The maladaptive behaviors observed in obsessive-compulsive disorder (OCD) have been hypothesized to result from the disruption of the interactions between these three entities. For this, we assessed the influence of error signals and checking behavior on prefrontal cortical functions during decision-making in 14 OCD patients and 14 matched healthy participants. METHODS We used a behavioral task designed to elicit intolerance of uncertainty (IU) followed by the free expression of checking behaviors, which was coupled with functional magnetic resonance imaging. RESULTS At the behavioral level, IU intensity was correlated to the number of checking behaviors in both checking OCD patients and healthy controls during decision-making. However, external error signals did not influence checking behaviors in OCD patients, whereas they appeared to trigger checking behaviors in healthy subjects. At the neural level, IU intensity was positively correlated with activation in the orbitofrontal cortex (OFC) in both the OCD and control groups. At the region of interest (ROI) level, error signals increased IU-related OFC activations; in contrast, checking behaviors contributed to decreasing these neural activations in the healthy subjects, but no such modulation was observed in the OCD patients. CONCLUSIONS Our results show that IU-related OFC dysfunctions are not under the influence of the context and the behavioral response in OCD, suggesting that alterations of the dynamic features for this neural network may contribute to the expression of OCD symptoms.

Limbic versus cognitive target for deep brain stimulation in treatment-resistant depression: accumbens more promising than caudate.

High-frequency deep brain stimulation (DBS) represents a major stake for treatment for treatment-resistant depression (TRD). We describe a preliminary trial of DBS of two potential brain targets in chronic TRD: the nucleus accumbens (Acb) and, in the event of failure, the caudate nucleus. Patients were followed for 6 months before surgery (M0). From M1 to M5, they underwent stimulation of the Acb target. PET scans allowed us to track metabolic modifications resulting from this stimulation. The caudate target of nonresponders was stimulated between M5 and M9. Patients then entered an extension phase, in which it was possible to adapt stimulation parameters and treatments. Six patients were included and four were operated on. At M5, none of the patients were either responders or remitters, but we did observe a decrease in Hamilton Depression Rating Scale (HDRS) scores. Three patients were switched to caudate stimulation, but no improvement was observed. During the extension phase, the Acb target was stimulated for all patients, three of whom exhibited a significant response. A decrease in glucose metabolism was observed after Acb stimulation, in the posterior cingulate gyrus, left frontal lobe, superior and medial gyrus, and bilateral cerebellum. An increase in metabolism was observed in the bilateral frontal lobe (superior gyrus), left frontal lobe (medial gyrus), and right limbic lobe (anterior cingulate gyrus). The results of this trial suggest that Acb is a more promising target than the caudate. NCT01569711.