Pathways to inflated responsibility beliefs in adolescent obsessive-compulsive disorder: a preliminary investigation

Background: An inflated sense of responsibility is characteristic of obsessive-compulsive disorder (OCD). No previous studies have investigated its origins. Five potential pathways to inflated responsibility beliefs have been proposed; these are tested in this study. Method: A novel measure, the Origins Questionnaire for Adolescents (OQA), was developed to assess experiences on these five pathways. Reliability of the OQA was investigated. The experiences on the five pathways to inflated responsibility beliefs of sixteen adolescents with a history of OCD were compared to sixteen adolescents with no history of OCD. Parents also reported on adolescents’ experiences on the five pathways. Results: Inter-rater reliability was high. The internal consistency of the subscales were only partly satisfactory. The groups differed on one pathway; the clinical group reported a higher sense of responsibility for significant incidents with a negative outcome prior to onset of OCD. Conclusions: An inflated sense of responsibility, in combination with the occurrence of specific incidents, might act as a vulnerability factor for development of OCD. Future research should consider how to measure the subtle effects of experiences of responsibility over the course of development.

Randomized controlled trial of full and brief cognitive-behaviour therapy and wait-list for paediatric obsessive-compulsive disorder

Background: Reviews and practice guidelines for paediatric obsessive-compulsive disorder (OCD) recommend cognitive-behaviour therapy (CBT) as the psychological treatment of choice, but note that it has not been sufficiently evaluated for children and adolescents and that more randomized controlled trials are needed. The aim of this trial was to evaluate effectiveness and optimal delivery of CBT, emphasizing cognitive interventions. Methods: A total of 96 children and adolescents with OCD were randomly allocated to the three conditions each of approximately 12 weeks duration: full CBT (average therapist contact: 12 sessions) and brief CBT (average contact: 5 sessions, with use of therapist-guided workbooks), and wait-list/delayed treatment. The primary outcome measure was the child version of the semi-structured interviewer-based Yale-Brown Obsessive Compulsive Scale. Clinical Trial registration: http://www.controlled-trials.com/ISRCTN/; unique identifier: ISRCTN29092580. Results: There was statistically significant symptomatic improvement in both treatment groups compared with the wait-list group, with no significant differences in outcomes between the two treatment groups. Controlled treatment effect sizes in intention-to-treat analyses were 2.2 for full CBT and 1.6 for brief CBT. Improvements were maintained at follow-up an average of 14 weeks later. Conclusions: The findings demonstrate the benefits of CBT emphasizing cognitive interventions for children and adolescents with OCD and suggest that relatively lower therapist intensity delivery with use of therapist-guided workbooks is an efficient mode of delivery.

Are the NICE guidelines for Obsessive Compulsive Disorder being used in primary care?

This study aims to: 1) assess the proportion of General Practioners (GPs) who are aware of or who have read the National Institute for Health and Clinical Excellence (NICE; 2005a) guidelines for Obsessive Compulsive Disorder (OCD), 2) compare this with the proportion of other mental health disorders found by previous research and 3) establish the prevalence of OCD in primary care. Questionnaires were sent to all GPs (n = 795) and practice managers (n = 157) in Berkshire and Buckinghamshire, South East England. These contained 19 questions and took 5 min to complete. After the first set of responses, larger practices were visited and telephoned to encourage further responses. The response rates were 10.1% from GPs and 19.1% from practice managers. In all, 48.7% of the GPs were aware of the NICE guidelines for OCD and 30.3% reported that they had read them – higher than for Post-Traumatic Stress Disorder, but lower than for depression. Of registered patients, 0.2% were diagnosed with OCD, lower than the 1.1% found in epidemiological studies.

Adjuvant-free immunization with hemagglutinin-Fc fusion proteins as an approach to influenza vaccines

The hemagglutinins (HAs) of human H1 and H3 influenza viruses and avian H5 influenza virus were produced as recombinant fusion proteins with the human immunoglobulin Fc domain. Recombinant HA-human immunoglobulin Fc domain (HA-HuFc) proteins were secreted from baculovirus-infected insect cells as glycosylated oligomer HAs of the anticipated molecular mass, agglutinated red blood cells, were purified on protein A, and were used to immunize mice in the absence of adjuvant. Immunogenicity was demonstrated for all subtypes, with the serum samples demonstrating subtype-specific hemagglutination inhibition, epitope specificity similar to that seen with virus infection, and neutralization. HuFc-tagged HAs are potential candidates for gene-to-vaccine approaches to influenza vaccination.

An experimental manipulation of responsibility in children: a test of the inflated responsibility model of obsessive-compulsive disorder

The objective of this study was to investigate whether Salkovskis (1985) inflated responsibility model of obsessive-compulsive disorder (OCD) applied to children. In an experimental design, 81 children aged 9– 12 years were randomly allocated to three conditions: an inflated responsibility group, a moderate responsibility group, and a reduced responsibility group. In all groups children were asked to sort sweets according to whether or not they contained nuts. At baseline the groups did not differ on children’s self reported anxiety, depression, obsessive-compulsive symptoms or on inflated responsibility beliefs. The experimental manipulation successfully changed children’s perceptions of responsibility. During the sorting task time taken to complete the task, checking behaviours, hesitations, and anxiety were recorded. There was a significant effect of responsibility level on the behavioural variables of time taken, hesitations and check; as perceived responsibility increased children took longer to complete the task and checked and hesitated more often. There was no between-group difference in children’s self reported state anxiety. The results offer preliminary support for the link between inflated responsibility and increased checking behaviours in children and add to the small but growing literature suggesting that cognitive models of OCD may apply to children.

The shape and tempo of language evolution

There are approximately 7000 languages spoken in the world today. This diversity reflects the legacy of thousands of years of cultural evolution. How far back we can trace this history depends largely on the rate at which the different components of language evolve. Rates of lexical evolution are widely thought to impose an upper limit of 6000-10,000 years on reliably identifying language relationships. In contrast, it has been argued that certain structural elements of language are much more stable. Just as biologists use highly conserved genes to uncover the deepest branches in the tree of life, highly stable linguistic features hold the promise of identifying deep relationships between the world's languages. Here, we present the first global network of languages based on this typological information. We evaluate the relative evolutionary rates of both typological and lexical features in the Austronesian and Indo-European language families. The first indications are that typological features evolve at similar rates to basic vocabulary but their evolution is substantially less tree-like. Our results suggest that, while rates of vocabulary change are correlated between the two language families, the rates of evolution of typological features and structural subtypes show no consistent relationship across families.

Hypoxia suppresses glutamate transport in astrocytes

Glutamate uptake by astrocytes is fundamentally important in the regulation of CNS function. Disruption of uptake can lead to excitotoxicity and is implicated in various neurodegenerative processes as well as a consequence of hypoxic/ischemic events. Here, we investigate the effect of hypoxia on activity and expression of the key glutamate transporters excitatory amino acid transporter 1 (EAAT1) [GLAST (glutamate-aspartate transporter)] and EAAT2 [GLT-1 (glutamate transporter 1)]. Electrogenic, Na+-dependent glutamate uptake was monitored via whole-cell patch-clamp recordings from cortical astrocytes. Under hypoxic conditions (2.5 and 1% O2 exposure for 24 h), glutamate uptake was significantly reduced, and pharmacological separation of uptake transporter subtypes suggested that the EAAT2 subtype was preferentially reduced relative to the EAAT1. This suppression was confirmed at the level of EAAT protein expression (via Western blots) and mRNA levels (via real-time PCR). These effects of hypoxia to inhibit glutamate uptake current and EAAT protein levels were not replicated by desferrioxamine, cobalt, FG0041, or FG4496, agents known to mimic effects of hypoxia mediated via the transcriptional regulator, hypoxia-inducible factor (HIF). Furthermore, the effects of hypoxia were not prevented by topotecan, which prevents HIF accumulation. In stark contrast, inhibition of nuclear factor-kappaB (NF-kappaB) with SN50 fully prevented the effects of hypoxia on glutamate uptake and EAAT expression. Our results indicate that prolonged hypoxia can suppress glutamate uptake in astrocytes and that this effect requires activation of NF-kappaB but not of HIF. Suppression of glutamate uptake via this mechanism may be an important contributory factor in hypoxic/ischemic triggered glutamate excitotoxicity.

The treatment of mental contamination: a case series

The recommended treatment for obsessive-compulsive disorder (OCD) is cognitive behavior therapy (CBT) incorporating exposure and response prevention (ERP), which is effective for approximately 50% of patients. However, there has been little advance in treatment outcomes since the introduction of ERP in 1979. It has been suggested that some progress can be made in treating contamination obsessions and washing compulsions by addressing feelings of dirtiness and contamination that arise without physical contact with a tangible contaminant. To date, the treatment of these “mental contamination” fears in OCD has not been systematically explored. This paper reports on a case series of 12 participants with OCD who received 10 to 20 sessions of a CBT-based treatment for mental contamination. At the end of treatment, 7 participants no longer met the diagnostic criteria for OCD and mental contamination and these gains were maintained at 6-month follow-up. The clinical implications of these findings are discussed.

Mental contamination in obsessive–compulsive disorder

It was recently proposed that feelings of contamination can arise in the absence of physical contact with a contaminant. Currently, there are limited data regarding this construct of ‘mental contamination’ although it is hypothesised to be relevant to obsessive compulsive disorder(OCD) where compulsive washing in response to contamination fear is a common presentation (Rachman,2006). This research examined the presence of mental contamination in OCD. Participants (N=177) with obsessive compulsive symptoms completed questionnaires to assess mental contamination, OCD symptoms and thought-action fusion (TAF). Findings indicated that 46% of participants experienced mental contamination, and severity was associated with severity of OCD symptoms and TAF. Mental contamination in the absence of contact contamination was reported by 10.2% of participants. Similar findings were reported in a sub-sample of participants who had received a formal diagnosis of OCD (N=54). These findings suggest that mental contamination is a distinct construct that overlaps with, but is separate from, contact contamination, and provide preliminary empirical support for the construct.

The induction of mental and contact contamination

Background: Extreme fear of contamination within Obsessive Compulsive Disorder is traditionally conceptualised as a physical phenomenon. More recent research has supported the notion of ‘mental’ contamination, in which people feel contaminated in the absence of physical contact. The current research sought to determine whether feelings of contact and mental contamination could be induced within a non-clinical sample, whether the impact of mental and contact contamination was comparable in terms of associated feelings and behaviour and whether related psychopathology related to the impact of the tasks. Methods: Undergraduate students (n=60) completed OCD relevant measures and were randomly assigned to either a contact contamination condition (CC: moving a bucket of fake vomit) or a mental contamination condition (MC: thinking about a bucket of vomit). Results: Both manipulations induced feelings of contamination. Participants in the contact condition had significantly greater urges to wash than those in the mental condition. Neutralising behaviour did not differ across conditions. Conclusions: Feelings of contamination can be induced in the absence of physical contact and for those in the MC group, some aspects of OCD-relevant psychopathology were related to the impact of the manipulation. These findings have implications for the understanding and treatment of contamination-related fears in OCD.

Randomized controlled trial of parent-enhanced CBT compared with individual CBT for obsessive-compulsive disorder in young people

Objective: Obsessive-compulsive disorder (OCD) in young people can be effectively treated with Cognitive Behavior Therapy (CBT). Practice guidelines in the United Kingdom recommend that CBT be delivered with parental or family involvement; however, there is no evidence from randomized trials that this enhances effectiveness. The aim of this trial was to assess if CBT with high parental involvement was more effective than CBT with low parental involvement (individual CBT) in reducing symptoms of OCD. Method: Fifty young people ages 12–17 years with OCD were randomly allocated to individual CBT or parent-enhanced CBT. In parent-enhanced CBT parents attended all treatment sessions; in individual CBT, parents attended only Sessions 1, 7, and the final session. Participants received up to 14 sessions of CBT. Data were analyzed using intent-to-treat and per-protocol methods. The primary outcome measure was the Children’s Yale-Brown Obsessive Compulsion Scale (Scahill et al., 1997). Results: Both forms of CBT significantly reduced symptoms of OCD and anxiety. Change in OCD symptoms was maintained at 6 months. Per-protocol analysis suggested that parent-enhanced CBT may be associated with significantly larger reductions in anxiety symptoms. Conclusions: High and low parental involvement in CBT for OCD in young people were both effective, and there was no evidence that 1 method of delivery was superior on the primary outcome measure. However, this study was small. Future trials should be adequately powered and examine interactions with the age of the young person and comorbid anxiety disorders.

An epigenetic signature of developmental potential in neural stem cells and early neurons.

A cardinal property of neural stem cells (NSCs) is their ability to adopt multiple fates upon differentiation. The epigenome is widely seen as a read-out of cellular potential and a manifestation of this can be seen in embryonic stem cells (ESCs), where promoters of many lineage-specific regulators are marked by a bivalent epigenetic signature comprising trimethylation of both lysine 4 and lysine 27 of histone H3 (H3K4me3 and H3K27me3, respectively). Bivalency has subsequently emerged as a powerful epigenetic indicator of stem cell potential. Here, we have interrogated the epigenome during differentiation of ESC-derived NSCs to immature GABAergic interneurons. We show that developmental transitions are accompanied by loss of bivalency at many promoters in line with their increasing developmental restriction from pluripotent ESC through multipotent NSC to committed GABAergic interneuron. At the NSC stage, the promoters of genes encoding many transcriptional regulators required for differentiation of multiple neuronal subtypes and neural crest appear to be bivalent, consistent with the broad developmental potential of NSCs. Upon differentiation to GABAergic neurons, all non-GABAergic promoters resolve to H3K27me3 monovalency, whereas GABAergic promoters resolve to H3K4me3 monovalency or retain bivalency. Importantly, many of these epigenetic changes occur before any corresponding changes in gene expression. Intriguingly, another group of gene promoters gain bivalency as NSCs differentiate toward neurons, the majority of which are associated with functions connected with maturation and establishment and maintenance of connectivity. These data show that bivalency provides a dynamic epigenetic signature of developmental potential in both NSCs and in early neurons. Stem Cells 2013;31:1868-1880.

Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal rTMS in major depression

Background Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brain’s emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes. Methods Here, we applied 20 sessions of magnetic resonance imaging-guided repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex in 47 unipolar or bipolar patients with a medication-resistant major depressive episode. Results Treatment response was strongly bimodal, with individual patients showing either minimal or marked improvement. Compared with responders, nonresponders showed markedly higher baseline anhedonia symptomatology (including pessimism, loss of pleasure, and loss of interest in previously enjoyed activities) on item-by-item examination of Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology ratings. Congruently, on baseline functional magnetic resonance imaging, nonresponders showed significantly lower connectivity through a classical reward pathway comprising ventral tegmental area, striatum, and a region in ventromedial prefrontal cortex. Responders and nonresponders also showed opposite patterns of hemispheric lateralization in the connectivity of dorsomedial and dorsolateral regions to this same ventromedial region. Conclusions The results suggest distinct depression subtypes, one with preserved hedonic function and responsive to dorsomedial rTMS and another with disrupted hedonic function, abnormally lateralized connectivity through ventromedial prefrontal cortex, and unresponsive to dorsomedial rTMS. Future research directly comparing the effects of rTMS at different targets, guided by neuroimaging and clinical presentation, may clarify whether hedonia/reward circuit integrity is a reliable marker for optimizing rTMS target selection.

Obsessive–compulsive disorder in young people

Obsessive–compulsive disorder (OCD) is one of the most debilitating psychiatric conditions in young people. In DSM-5 it is no longer characterised as an anxiety disorder, but instead is part of a group of ‘obsessive–compulsive and related disorders’. In the past 10 years, cognitive–behavioural therapy (CBT) has become well established as the first-choice treatment. This article explains some of the elements of CBT and describes new directions in research which might improve interventions.

Obsessive Compulsive Treatment Efficacy Trial (OCTET) comparing the clinical and cost effectiveness of self-managed therapies: study protocol for a randomised controlled trial

Background: UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required. Methods/Design: Our proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments. Discussion: This study will provide more robust evidence of efficacy, cost effectiveness and acceptability of self-help treatments for OCD. If cCBT and/or GSH prove effective, it will provide additional, more accessible treatment options for people with OCD.