Brain regional α-[11C]methyl-L-tryptophan trapping in medication-free patients with obsessive-compulsive disorder.

CONTEXT: The hypothesis of a serotonin (5-hydroxytryptamine [5-HT]) dysfunction in obsessive-compulsive disorder (OCD) stems largely from the clinical efficacy of 5-HT reuptake inhibitors. Serotonergic abnormalities in the unmedicated symptomatic state, however, remain to be fully characterized. OBJECTIVE: To investigate brain regional 5-HT synthesis, as indexed by positron emission tomography and the α-[(11)C]methyl-L-tryptophan trapping constant (K*), in treatment-free adults meeting criteria for OCD. DESIGN: Between-group comparison. SETTING: Department of Psychiatry and Montreal Neurological Institute, McGill University, and Department of Psychology, McGill University Health Centre, Quebec, Canada. PARTICIPANTS: Twenty-one medication-free patients with OCD (15 men with a mean [SD] age of 33.2 [9.3] years and 6 women with a mean [SD] age of 35.8 [7.1] years) and 21 healthy controls matched for age and sex (15 men with a mean [SD] age of 32.9 [10.1] years and 6 women with a mean [SD] age of 36.5.5 [8.6] years). Main Outcome Measure The α-[(11)C]methyl-L-tryptophan brain trapping constant K*, which was analyzed with Statistical Parametric Mapping (SPM8) and with proportional normalization (extent threshold of 100 voxels with a peak threshold of P ≤ .005). RESULTS: Compared with healthy controls, the patients with OCD exhibited significantly greater α-[(11)C]methyl-L-tryptophan trapping in the right hippocampus and left temporal gyrus (Brodmann area 20). In the larger subsample of all men, these same differences were also evident, as well as higher K* values in the caudate nucleus. Individual differences in symptom severity correlated positively with K* values sampled from the caudate and temporal lobe of the patients with OCD, respectively. There were no regions where the patients exhibited abnormally low K* values. Volumetric analyses found no morphometric alterations that would account for the group differences. CONCLUSION: The results support previous reports of greater striatal and temporal lobe activity in patients with OCD than in healthy controls and suggest that these disturbances include a serotonergic component. Previously reported glucose metabolic disturbances in OCD involving the orbitofrontal and cingulate cortices, in comparison, might reflect postsynaptic changes in the serotonergic system.

Treatment of panic disorder with agoraphobia: randomized placebo-controlled trial of four psychosocial treatments combined with imipramine or placebo.

Few randomized controlled trials have included panic disorder patients with moderate to severe agoraphobia. Therefore, this population was studied using pharmacotherapy as well as psychotherapy. At the time of the study, imipramine was widely used as a pharmacological treatment. Also, current practice guidelines for patients with panic disorder find selective serotonin reuptake inhibitors and tricyclic antidepressants roughly comparable in terms of efficacy. Therefore, the main objective of this study is to compare four psychosocial treatments-cognitive and graded in vivo exposure treatments, graded in vivo exposure, cognitive treatment, and supportive therapy-to evaluate the benefits of combining cognitive therapy with exposure in vivo. These treatments were combined with imipramine or placebo for a total of eight experimental conditions. Participants presented moderate to severe agoraphobia. The method involved a randomized, double-blind, placebo-controlled trial with 137 participants who completed a 14-session protocol involving the treatments just mentioned. Measures were taken at baseline and posttreatment and at 3-, 6-, and 12-month follow-up. All treatment conditions were statistically and clinically effective in reducing self-reported panic-agoraphobia symptoms over the 1-year follow-up. No statistical differences were observed between imipramine and placebo conditions. This study found that all treatment modalities helped reduce panic and agoraphobic symptomatology over a 1-year follow-up period. These surprising results support the need to document the relations among the various components of an intervention. This would make it possible to assess the relative efficacy of the treatment components rather than of the intervention as a whole.

Influence of comorbid obsessive-compulsive symptoms on brain event-related potentials in Gilles de la Tourette syndrome.

Approximately 30 to 50% of people suffering from Gilles de la Tourette Syndrome (GTS) also fulfill diagnostic criteria for obsessive-compulsive disorder (OCD). Despite this high degree of comorbidity, very few studies have addressed the question of obsessive-compulsive symptoms (OCS) in GTS patients using specific brain event-related potentials (ERP) responses. The aim of the current study was to quantify neurocognitive aspects of comorbidity, using ERPs. Fourteen adults with GTS (without OCD) were compared to a group of 12 participants with GTS and comorbid obsessive-compulsive symptoms (GTS+OCS), to a group of 15 participants with OCD and to a group of 14 control participants without neurological or psychiatric problems. The P200 and P300 components were recorded during a visual counting oddball task. Results showed intact P200 amplitude in all groups, whilst the P300 amplitude was affected differentially across groups. The P300 oddball effect was reduced in participants in both OCD and GTS+OCS groups in the anterior region. However, the P300 oddball effect was significantly larger in participants of the GTS group compared to all other groups, mostly in the parietal region. These findings suggest that adults with GTS are characterized by enhanced working memory updating processes and that the superimposition of OCS can lead to a reduction of these processes. The discrepancy between our findings and results obtained in previous studies on GTS could reflect the modulating effect of OCS on late ERP components.

Are there common mechanisms in sensation seeking and reality distortion in schizophrenia? A study using memory event-related potentials.

A growing literature suggests that the characteristics of sensation seeking and reality distortion expressed in schizophrenia share several mechanisms. In a previous study, the comparison of patients with high vs. low reality distortion using event-related potentials (ERPs) recorded in a recognition memory task for unfamiliar faces identified neural and cognitive anomalies specifically related to the expression of these symptoms. As a follow-up, this study investigated the ERP correlates of sensation seeking in schizophrenia using the same recognition memory protocol. ERPs have been recorded in controls (N=21) and schizophrenia patients separated into high (HSS; N=13) and low (LSS; N=17) scorers according to Zuckerman's Sensation Seeking Scale. The results show a reduced P2a that was found unrelated to reality distortion in the previous study of reality distortion. It identifies interference inhibition impairment as being specifically related to sensation seeking. On the other hand, HSS scorers display enhanced fronto-central and normal P600 effects also found in high reality distortion patients. These results indicate inappropriate context processing and mnemonic binding common to sensation seeking and reality distortion. LSS scorers also display a reduced temporal N300 similar to that found in low reality distortion patients. This anomaly could reflect the lower reactivity to emotionally significant stimuli that underlies anhedonia symptoms. Finally, the N400 effect and a late frontal effect are found in both HSS and LSS. Since they were unrelated to reality distortion, these indices have been related to basic aspects of schizophrenia, e.g., deficient knowledge integration, or other mechanisms, e.g. anxiety or impulsivity. In summary, the present study examines the strategy of investigating variables, such as temperamental characteristics, in addition to symptoms, to show how discrete impairments may contribute to the expression of the illness.

The relationships between symptom dimensions and dysphoria in schizophrenia.

Previous studies have suggested that qualitatively distinct aspects of dysphoria (anxiety and depression) are related to specific dimension of schizophrenia symptomatology. Most of these studies used simple dimensions and dysphoria models, although finer distinctions could help defining specific relationships. This study examined the relationships of distinctive aspects of depression and anxiety (both state and trait) with symptom dimensions. Forty patients with a DSM-IV diagnosis of schizophrenia were assessed for symptoms (SAPS-SANS), trait and state anxiety (STAI) and depression (CDS). Symptoms ratings were summarized as dimensional scores according to a two-, three- or five-dimensional models proposed in the literature. The correlation analysis replicates previous observations that distinct aspects of dysphoria are associated with specific dimensions of schizophrenia, with the exception of disorganization. Moreover, controlling for intercorrelated variables revealed that schizophrenia and dysphoric symptoms might act in combination and/or through indirect links to contribute to illness expression. Our data further suggested that these associations may be best understood in terms of interactions between various processing biases alluded in the most recent cognitive accounts of schizophrenia symptoms.

Inferential confusion in obsessive-compulsive disorder: the inferential confusion questionnaire.

The current article represents the further validation of the construct of inferential confusion amongst clinical samples. Inferential confusion is proposed to be a meta-cognitive confusion particularly relevant to obsessive compulsive disorder (OCD) that leads a person to confuse an imagined possibility with an actual probability. As such, it conceptualizes OCD as a form of belief disorder similar to a delusion or overvalued idea that is a product of distorted reasoning processes. In contrast, other cognitive models of OCD emphasize a phobic model of development in OCD, and thus consider the exaggerated interpretation of intrusions as an essential element in OCD. The present study administered a revised version of the Inferential Confusion Questionnaire, and the Obsessive Belief Questionnaire (OBQ), to a total of 183 participants in three clinical groups and a non-clinical control group. Results suggest that OCD, at least in part, follows a non-phobic model of development with inferential confusion significantly related to obsessive-compulsive symptoms independently of cognitive domains as measured by the OBQ, and mood states. Further, scores on inferential confusion were particularly high in those with OCD and delusional disorder as compared to anxious and non-clinical controls.

[Is there a specific pharmacological treatment for anxiety disorders? Summary of a controversy]. / Le traitement pharmacologique des troubles anxieux est-il spécifique? Résumé d'une controverse.

The acute pharmacological treatment of anxiety disorders is barely specific with the exception of the obsessive-compulsive disorder: it responds preferentially to potent serotoninergic antidepressants only. For all other anxiety disorders all antidepressants regardless of their mechanism of action could be equally efficient thanks to their common class effect and are considered to be the pharmacological treatment of first choice. Benzodiazepines that also share a common class effect are recommended as possible and temporary adjuvants. Augmentation strategies for the cases of refractory anxiety disorders are also non-specific: lithium, antipsychotics, anticonvulsants.

The cognitive and anatomo-functional basis of reality distortion in schizophrenia: a view from memory event-related potentials.

This study investigated the neural and cognitive correlates of reality distortion in schizophrenia by using event-related potentials (ERPs) recorded in a recognition memory task for face. This task has been chosen because previous studies have shown that it provides distinct indices related to specific cognitive processes and to the functioning of specific brain regions. ERPs have been recorded in controls and schizophrenia patients separated into high scorers (RD+) and low-scorers (RD-) according to their Reality Distortion score (hallucination and delusion SAPS subscales). The results indicate that RD+ presents abnormalities on various cognitive processes. First, RD+ are deficient at interference inhibition and knowledge integration (reduced P2a and N400 effect). The similar impairments found in RD- suggest that they represent basic traits of the illness. Second, RD+ showed inappropriate stimulus categorization and contextual integration (larger N300 and fronto-central effect). Third, RD+ showed a late index (P600 effect) not different from controls, but larger than in RD-. This result is consistent with a qualitative, rather than quantitative, impairment of mnemonic binding processes (inappropriate binding) in RD+. Since each of the ERP abnormalities observed represents associated with distinct brain dysfunction, the results are further discussed in regard of the respective contribution of the parietal, frontal and hippocampal structures to reality distortion symptoms.