Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates

To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.Obsessive Compulsive FoundationTourette Syndrome AssociationAnxiety Disorders Association of AmericaAmerican Academy of Child and Adolescent Psychiatr

Dysfunctional belief-based subgroups and inferential confusion in obsessive-compulsive disorder

Cognitive-behavioural models emphasize the mediating role of dysfunctional beliefs in obsessive-compulsive disorder (OCD). However, recent studies indicated that beliefs related to responsibility and threat-estimation, Importance and Control of Thoughts, and perfectionism and intolerance of uncertainty were not elevated in a substantial proportion of patients suffering from OCD. This study attempts to replicate these findings, and, in addition, explores the role of a cognitive process characteristic of OCD, i.e., inferential confusion. Participants suffering from OCD (n = 174), completed cognitive- and symptom measures. Cluster-analysis revealed a 2- and a 6-cluster solution, both which contained substantial low belief subgroups. The Perfectionism and Certainty beliefs cluster in the 6-cluster solution was distinct from the other high beliefs clusters, which is in line with the recently proposed distinction between harm related versus 'just right' related OC symptoms. Finally, the assessment of cognitive processes seems to have complimentary value in addition to assessing belief content, and therefore could further our understanding of OCD within a cognitive framework. (C) 2010 Elsevier Ltd. All rights reserved

Covert neutralization in the treatment of OCD with overt compulsions

The objective of the study was to compare two forms of exposure and response prevention for obsessive-compulsive disorder (OCD): one in which response prevention targeted both mental (covert) and behavioral (overt) neutralization; the other in which it targeted only overt neutralization. Treatment lasted 20 weeks in both programs, and OCD symptoms, neutralization, self esteem, quality of life, and psychosocial functioning were measured pre- and post-treatment and at six-month follow-up. Fifty participants (37 completers) were randomly assigned to each condition. Both groups demonstrated significant and equivalent improvement on the Yale-Brown Obsessive-Compulsive Scale at post-treatment; and these gains were maintained at six-month follow-up. There were no significant differences between groups on outcome measures at post-treatment or at follow-up. The group that received treatment targeting both overt and covert neutralization reported less need to engage in neutralization behavior at post-treatment. These results suggest that cognitive behavioral treatment can generate significant and lasting change in OCD symptoms without addressing all types of neutralization. (C) 2012 Elsevier Ltd. All rights reserved

Processes of Change in Cognitive-Behavioural Treatment of Obsessive-Compulsive Disorder: Current Status and Some Future Directions

The present paper discusses theoretical and methodological issues involved in the processes of change in cognitive-behavioural treatment (CBT) of obsessive-compulsive disorder (OCD). Treatment outcome studies showed that CBT is effective in reducing obsessive-compulsive symptoms. However, why and how CBT works cannot be corroborated by comparing pre- and post-assessment. Recently, there has been a resurgence of interest in theory driven process studies. By showing patterns of change over time, process studies can contribute to our insight into the actual mechanisms of change during treatment. We review process research in the field of OCD and discuss methodological issues involved in process studies for this particular disorder. It is concluded that studying the processes of change harbours promising possibilities for bridging the gap between theory and clinical practice. Copyright (C) 2009 John Wiley & Sons, Ltd

Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo

Two humanized IgG4 antibodies, natalizumab and gemtuzumab, are approved for human use, and several others, like TGN1412, are or have been in clinical development. Although IgG4 antibodies can dynamically exchange half-molecules(1), Fab-arm exchange with therapeutic antibodies has not been demonstrated in humans. Here, we show that natalizumab exchanges Fab arms with endogenous human IgG4 in natalizumab-treated individuals. Gemtuzumab, in contrast, contains an IgG4 core-hinge mutation that blocks Fab-arm exchange to undetectable levels both in vitro and in a mouse model. The ability of IgG4 therapeutics to recombine with endogenous IgG4 may affect their pharmacokinetics and pharmacodynamics. Although pharmacokinetic modeling lessens concerns about undesired cross-linking under normal conditions, unpredictability remains and mutations that completely prevent Fab-arm exchange in vivo should be considered when designing therapeutic IgG4 antibodies