Jean Tignol

Meta-analysis of brain volume changes in obsessive-compulsive disorder.

BACKGROUND Many neuroimaging studies exploring the volumes of brain structures in obsessive-compulsive disorder (OCD) have been published in the past 2 decades. In this study, we attempted to provide a complete overview of structural alterations in OCD by meta-analyzing magnetic resonance imaging (MRI) data. METHODS We conducted a systematic search of MRI studies that reported volumetric measurements in both OCD patients and healthy subjects. Data were entered into the meta-analysis through calculation of the standardized mean differences (SMDs) between the volumes of cerebral regions in OCD patients and the corresponding volumes in control subjects. We then performed a meta-regression to explore the influence of clinical covariates on effect sizes. RESULTS Although no volumetric differences were found for the whole brain, intracranial region, gray matter, or prefrontal cortex, OCD patients did show a reduced volume of the left anterior cingulate cortex (ACC) and the left and right orbitofrontal cortex (OFC). No significant volumetric differences within the basal ganglia were observed, although the left and right thalamic volumes were significantly increased in OCD patients. The severity of obsessive or compulsive symptoms correlated significantly with the effect sizes for the left and right thalamus. CONCLUSIONS Our findings indicate volumetric differences between OCD patients and control subjects in the cortical and thalamic regions, suggesting that structural alteration of the thalamocortical pathways may contribute to the functional disruptions of frontosubcortical circuits observed in OCD.

French Field Experience with Buprenorphine

In most European countries, methadone treatment is provided to only 20-30% of opiate abusers who need treatment due to regulations and concerns about safety. To address this need in France, all registered medical doctors since 1995 have been allowed to prescribe buprenorphine (BUP) without any special education or licensing. This led to treating approximately 65,000 patients per year with BUP, about ten times more than with more restrictive methadone policies. French physician compensation mechanisms, pharmacy services, and medical insurance funding all minimized barriers to BUP treatment. About 20% of all physicians in France are using BUP to treat about half of the estimated 150,000 problem heroin users. Daily supervised dosing by a pharmacist for the first six months resulted in significantly better treatment retention (80% vs 46%) and lower heroin use. Intravenous diversion of BUP may occur in up to 20% of BUP patients and has led to various infections and relatively rare overdoses in combination with sedatives. Opiate overdose deaths have declined substantially (by 79%) since BUP was introduced in 1995. Newborn opiate withdrawal in mothers treated with buprenorphine compared to methadone was reported to be less frequent, less severe, and of shorter duration. Although some of the public health benefits seen during the time of buprenorphine expansion in France might be contingent upon characteristics of the French health and social services system, the French model raises questions about the value of tight regulations on prescribing BUP imposed by many countries throughout the world.

Distinct striatal targets in treating obsessive-compulsive disorder and major depression.

The ventral striatum, including the head of the caudate nucleus and the nucleus accumbens, is a putative target for deep brain stimulation (DBS) in the treatment of obsessive-compulsive disorder (OCD) and major depression (MD). However, the respective roles of these structures in the pathophysiology of OCD and MD remain to be clarified. To address this issue, DBS of the ventral striatum was tested in 2 patients with severely distressing and intractable forms of OCD and MD. Comparisons of clinical outcomes and anatomical data on electrode positioning showed that caudate nucleus stimulation preferentially alleviated OCD manifestations, whereas nucleus accumbens stimulation improved depressive symptoms. These findings suggest that the caudate nucleus and nucleus accumbens participate differently in the pathogenesis of both of these psychiatric conditions.

Neuronal Correlates of Obsessions in the Caudate Nucleus

BACKGROUND Metabolic overactivity of corticosubcortical loops including the caudate nucleus (CN) has been reported in obsessive-compulsive disorder (OCD) using functional imaging techniques. However, direct proof of a modification of neuronal activity within the CN of OCD patients is still lacking. We tested the hypothesis that obsessions or compulsions might be associated with particular features of neuronal activity in the CN of OCD patients. METHODS Single unit recordings were performed peroperatively in the CN of three patients with severe forms of obsessive-compulsive disorder (OCD) who were candidates for deep brain stimulation of the CN. Severity of obsessions was assessed preoperatively with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and peroperatively with a subjective obsession score based on a visual analog scale (VAS). RESULTS Frequency of CN discharge and variability of interspike intervals were found to be abnormally high in two patients with a high VAS score during surgery but not in one with a low VAS score. Lateralization and depth of recording influenced neuronal activity variably among patients. CONCLUSIONS Because the three patients had high Y-BOCS scores before surgery, these findings suggest that caudate hyperactivity in OCD is concomitant with the occurrence of the obsession process.

Transcranial electrical stimulation with high frequency intermittent current (Limoge's) potentiates opiate-induced analgesia: blind studies

&NA; Transcutaneous cranial electrical stimulation (TCES) with high frequency (166 kHz) intermittent current (100 Hz; Limoge current) has been used for several years in cardiac, thoracic, abdominal, urological and micro‐surgery. The main benefits are a reduced requirement for analgesic drugs, especially opiates, and a long‐lasting postoperative analgesia. We have confirmed these clinical observations in rats using the tail‐flick latency (TFL) test to measure pain threshold. TCES was not found to modify the pain threshold in drug‐free rats, but it potentiated morphine‐induced analgesia (systemic injection). To obtain a maximal effect, the stimulation must be initiated 3 h before the drug injection and be maintained throughout the duration of its pharmacological action. TCES potentiation was found to depend on the dose of the drug, the intensity of the current and the polarity of electrodes. These findings were confirmed by blind tests of the efficiency of TCES on several opiate analgesic drugs currently used in human surgery (morphine, fentanyl, alfentanil and dextromoramide). The analgesic effect of these 4 opiates (TFL as % of baseline without or with TCES) were respectively: 174%, 306%; 176%, 336%; 160%, 215%; and 267%, 392%. The results were obtained not only after systemic opiate treatment, but also after intracerebroventricular injection of morphine (10 &mgr;g; analgesic effect 152%, 207% with TCES) suggesting that TCES potentiation of opiate‐induced analgesia is centrally mediated.

Transcutaneous electrical stimulation with limoge current potentiates morphine analgesia and attenuates opiate abstinence syndrome

Transcutaneous electrostimulation is a somewhat controversial technique used in the management of the opiate withdrawal syndrome. We report an animal study of a particular transcutaneous electrostimulation called transcutaneous cranial electrostimulation, based on a technique used for many years on heroin addicts for the rapid severance of their addiction, which has been validated in a clinical setting by a double-blind trial. This technique involves the application of an intermittent high-frequency current (Limoges current). Our experimental data show that this transcutaneous cranial electrostimulation increases morphine analgesia by threefold on the tail flick latency measure and produces a 48% attenuation of the abstinence syndrome observed after abrupt cessation of morphine administration. These results were obtained using a double-blind paradigm.

[Deep brain stimulation of the ventral striatum in the treatment of obsessive-compulsive disorder and major depression].

> Le trouble obsessionnel-compulsif (TOC) est une affection psychiatrique relativement frequente avec une prevalence « vie entiere » de l’ordre de 2 % a 3 % en population generale [1]. Il est souvent associe a la depression majeure et represente un des troubles anxieux les plus invalidants [2] de par l’intensite des symptomes qui le caracterise et la gene fonctionnelle qu’il entraine. Heureusement, la recherche et notamment l’enrichissement permanent de nos connaissances sur les relations structurefonction, ainsi que l’apport recent de la neuro-imagerie, permettent actuellement de mieux apprehender la physiopathologie de ce trouble et de proposer une hypothese essentiellement fondee sur l’approche anatomo-fonctionnelle.

Post-ECT agitation and plasma lactate concentrations

This prospective study evaluated the hypothesis that emergence agitation after electroconvulsive therapy (ECT) could be caused by lactate-induced panic secondary to insufficient neuromuscular blockade. Plasma lactate levels were measured before and after 245 consecutive ECT sessions in 37 patients monitored for evidence of post-ECT agitation. ECT was administered using a brief-pulse, rectangular, constant-current device through bilaterally placed electrodes under general anesthesia and neuromuscular blockade. Agitation was observed in 7% of all ECT sessions. No significant difference could be found in pre-ECT lactate levels. However, mean post-ECT lactate levels in agitated sessions were significantly greater than those in nonagitated sessions (4.77 versus 2.54 mmol/l, p < 0.05). An increase (+27%) in the pre-ECT succinylcholine dose for those patients who previously had repeated post-ECT agitation resulted in cessation of post-ECT agitation and return of the formerly high post-ECT lactate levels to normal (1.61 versus 2.07 mmol/l). Although the number of patients who had post-ECT agitation was small, the data support the hypothesis that post-ECT agitation might be a manifestation of lactate-induced panic.

Childhood history of behavioral inhibition and comorbidity status in 256 adults with social phobia

BACKGROUND Behavioral inhibition (BI), a heritable temperament, predisposes one to an increased risk of social phobia. Recent investigations have reported that BI may also be a precursor to anxiety as well as depressive and alcohol-related disorders, which are frequently comorbid with social phobia. In the present study, we explored the relationship between BI and psychiatric disorders in 256 adults with a primary diagnosis of social phobia. METHODS BI severity was retrospectively assessed with the Retrospective Self-Report of Inhibition (RSRI). The severity of social phobia and the presence of comorbid diagnoses were evaluated with the Liebowitz Social Anxiety Scale (LSAS) and the Mini-International Neuropsychiatric Interview, respectively. RESULTS The RSRI score was significantly and positively correlated with both the LSAS score and the occurrence of a major depressive disorder. No significant association was found with other anxiety and substance-related disorders. LIMITATION The assessment of BI was retrospective and self-reported. CONCLUSION A childhood history of BI was associated with an increased risk of depressive comorbidity in social phobia.

The Relationship between Insight and Uncertainty in Obsessive-Compulsive Disorder

Background: The aim of this study was to investigate the relationship between the levels of insight and checking-related uncertainty in patients with obsessive-compulsive disorder (OCD). Sampling and Methods: Twenty OCD patients with checking compulsions and without current comorbidity were recruited. We used an experimental paradigm that gave subjects the opportunity to check during a decision-making task, thereby allowing for the calculation of a response time index (RTI) as the ‘uncertainty cost’ during decision-making. The level of insight was assessed with the Brown Assessment of Beliefs Scale (BABS). Results: Regression analyses indicated a significant positive correlation between RTI and BABS scores (r = 0.49). Conclusions: The level of insight is related to cognitive characteristics underlying OCD symptoms, in particular, checking-related uncertainty in checking OCD patients. Study Limitations: The absence of a comparison group and the low number of included patients are the main limitations of the present study.