Examining Cognitive Models of Obsessive Compulsive Disorder in Adolescents

Abstract. Three influential theoretical models of OCD focus upon the cognitive factors of inflated responsibility (Salkovskis, 1985), thought-action fusion (Rachman, 1993) and meta-cognitive beliefs (Wells and Matthews, 1994). Little is known about the relevance of these models in adolescents or about the nature of any direct or mediating relationships between these variables and OCD symptoms. This was a cross-sectional correlational design with 223 non-clinical adolescents aged 13 to 16 years. All participants completed questionnaires measuring inflated responsibility, thought-action fusion, meta-cognitive beliefs and obsessive-compulsive symptoms. Inflated responsibility, thought-action fusion and metacognitive beliefs were significantly associated with higher levels of obsessive-compulsive symptoms. These variables accounted for 35% of the variance in obsessive-compulsive symptoms, with inflated responsibility and meta-cognitive beliefs both emerging as significant independent predictors. Inflated responsibility completely mediated the effect of thoughtaction fusion and partially mediated the effect of meta-cognitive beliefs. Support for the downward extension of cognitive models to understanding OCD in a younger population was shown. Findings suggest that inflated responsibility and meta-cognitive beliefs may be particularly important cognitive concepts in OCD. Methodological limitations must be borne in mind and future research is needed to replicate and extend findings in clinical samples. Keywords: Obsessive compulsive disorder, adolescents, cognitive models.

The effect of targeting tolerance of children's negative emotions among anxious parents of children with anxiety disorders: a pilot randomised controlled trial

Following cognitive behavioural therapy for child anxiety a significant minority of children fail to lose their diagnosis status. One potential barrier is high parental anxiety. We designed a pilot RCT to test claims that parental intolerance of the child’s negative emotions may impact treatment outcomes. Parents of 60 children with an anxiety disorder, who were themselves highly anxious, received either brief parent-delivered treatment for child anxiety or the same treatment with strategies specifically targeting parental tolerance of their child’s negative emotions. Consistent with predictions, parental tolerance of the child’s negative emotions significantly improved from pre- to post-treatment. However, there was no evidence to inform the direction of this association as improvements were substantial in both groups. Moreover, while there were significant improvements in child anxiety in both conditions, there was little evidence that this was associated with the improvement in parental tolerance. Nevertheless, findings provide important clinical insight, including that parent-led treatments are appropriate even when the parent is highly anxious and that it may not be necessary to adjust interventions for many families.

Beneficial Effects of Physical Training on the Cardio-Inflammatory Disorder Induced by Lung Ischemia/Reperfusion in Rats

Our laboratory demonstrated that training program attenuated the inflammatory responses in lung ischemia/reperfusion (IR). Considering the importance of the inflammatory responses on the cardiovascular system, we evaluate the effect of physical training on the vascular responsiveness and its underlying mechanism after lung IR. Male Wistar rats were submitted to run training and lung IR. Concentration-response curves for relaxing and contracting agents were obtained. Protein expressions of SOD-1 and p47(phox), plasma nitritre/nitrate (NO (x) (-) ) and interleukin 6 (IL-6) were evaluated. A decreased in the potency for acetylcholine and phenylephrine associated with an upregulation of the p47(phox) expression were found after Lung IR as well as an increase in IL-6 and NO (x) (-) levels. Run training attenuated the vascular dysfunction that was accompanied by reduction of the p47(phox) protein expression and IL-6 levels. Our findings show the beneficial effect of training on the vascular function that was associated with reduction in inflammatory response in lung IR.

Disorder-based graphene spintronics

The use of the spin of the electron as the ultimate logic bit-in what has been dubbed spintronics-can lead to a novel way of thinking about information flow. At the same time single-layer graphene has been the subject of intense research due to its potential application in nanoscale electronics. While defects can significantly alter the electronic properties of nanoscopic systems, the lack of control can lead to seemingly deleterious effects arising from the random arrangement of such impurities. Here we demonstrate, using ab initio density functional theory and non-equilibrium Green`s functions calculations, that it is possible to obtain perfect spin selectivity in doped graphene nanoribbons to produce a perfect spin filter. We show that initially unpolarized electrons entering the system give rise to 100% polarization of the current due to random disorder. This effect is explained in terms of different localization lengths for each spin channel which leads to a new mechanism for the spin filtering effect that is disorder-driven.

Effects of torsional disorder on poly-para-phenylene

We study the effect of thermal disorder on the electronic structure of one-dimensional poly-para-phenylene (PPP). In a real chain the torsion angles between rings are bound to be distributed over a range of values, which depend on temperature, and thus the chain is intrinsically disordered. In this study we simulated this kind of thermally induced off-diagonal disorder through the simple Huckel method. We base our Hamiltonian on ab initio results for the effect of temperature on torsion angles, and the effect of torsion angles on the energy gap. We analyze the electronic structure of 200-monomer-long chains focusing on the density of states, and the associated localization character (measured by the inverse participation ratio). Our results contrast with the usually assumed Gaussian-shaped density of localized states for disordered systems. (C) 2009 Elsevier B.V. All rights reserved.

PL spectroscopy of Fermi electrons in regime of the quantum Hall effect

The influence of the interlayer coupling on formation of the quantized Hall phase at the filling factor v = 2 was studied in the multilayer GaAs/AlGaAs heterostructures The disorder broaden Gaussian photoluminescence line due to the localized electrons was found in the quantized Hall phase of the isolated multi-quantum well structure On the other hand. the quantized Hall phase of the weakly-coupled multilayers emitted an asymmetrical line similar to that one observed in the metallic electron systems. We demonstrated that the observed asymmetry indicates a formation of the Fermi Surface in the quantized Hall phase of the multilayer electron system due to the interlayer peicolation. A sharp decrease of the single-particle scattering time associated with the extended states oil the Fermi surface was observed at the filling factor v = 2. (C) 2009 Elsevier B.V All rights reserved

Effect of the toxic milk mutation (tx) on the function and intracellular localization of Wnd, the murine homologue of the Wilson copperATPase

Wilson disease is an autosomal recessive copper transport disorder resulting from defective biliary excretion of copper and subsequent hepatic copper accumulation and liver failure if not treated. The disease is caused by mutations in the ATP7B (WND) gene, which is expressed predominantly in the liver and encodes a copper-transporting P-type ATPase that is structurally and functionally similar to the Menkes protein (MNK), which is defective in the X-linked copper transport disorder Menkes disease. The toxic milk (tx) mouse has a clinical phenotype similar to Wilson disease patients and, recently, the tx mutation within the murine WND homologue (Wnd) of this mouse was identified, establishing it as an animal model for Wilson disease. In this study, cDNA constructs encoding the wild-type (Wnd-wt) and mutant (Wnd-tx) Wilson proteins (Wnd) were generated and expressed in Chinese hamster ovary (CHO) cells. The tx mutation disrupted the copper-induced relocalization of Wnd in CHO cells and abrogated Wnd-mediated copper resistance of transfected CHO cells. In addition, co-localization experiments demonstrated that while Wnd and MNK are located in the trans-Golgi network in basal copper conditions, with elevated copper, these proteins are sorted to different destinations within the same cell. Ultrastructural studies showed that with elevated copper levels, Wnd accumulated in large multi-vesicular structures resembling late endosomes that may represent a novel compartment for copper transport. The data presented provide further support for a relationship between copper transport activity and the copper-induced relocalization response of mammalian copper ATPases, and an explanation at a molecular level for the observed phenotype of tx mice

Cost-effectiveness of psychological and pharmacological interventions for generalized anxiety disorder and panic disorder

Objective: To assess from a health sector perspective the incremental cost-effectiveness of interventions for generalized anxiety disorder (cognitive behavioural therapy [CBT] and serotonin and noradrenaline reuptake inhibitors [SNRIs]) and panic disorder (CBT, selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]).

Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analyses of randomised controlled trials. An assessment on second stage filters ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are calculated for a period of one year for the eligible population (prevalent cases of generalized anxiety disorder/panic disorder identified in the National Survey of Mental Health and Wellbeing, extrapolated to the Australian population in the year 2000 for those aged 18 years and older). Simulation modelling techniques are used to present 95% uncertainty intervals (UI) around the incremental cost-effectiveness ratios (ICERs).

Results: Compared to current practice, CBT by a psychologist on a public salary is the most cost-effective intervention for both generalized anxiety disorder (A$6900/DALY saved; 95% UI A$4000 to A$12 000) and panic disorder (A$6800/DALY saved; 95% UI A$2900 to A$15 000). Cognitive behavioural therapy results in a greater total health benefit than the drug interventions for both anxiety disorders, although equity and feasibility concerns for CBT interventions are also greater.

Conclusions: Cognitive behavioural therapy is the most effective and cost-effective intervention for generalized anxiety disorder and panic disorder. However, its implementation would require policy change to enable more widespread access to a sufficient number of trained therapists for the treatment of anxiety disorders.

Parenting style as a moderator of the effect of temperament on adolescent externalising and internatlising behaviour problems

The direct and interactive effects of temperament and parenting were examined in the prediction of early adolescent externalising behaviour problems (conduct disorder and hyperactivity), internalising problems (depression and anxiety), and substance use, using data on 1,402 13- and 14-year-olds. Significant direct effects were found for four temperament factors (negative reactivity, task persistence, activity, and approach), and four parenting factors (warmth, power assertion, physical punishment, and monitoring). For those high in persistence, low in negative reactivity, or low in activity, problem outcomes were generally very rare, regardless of parenting. Prevalence of behaviour problems was generally elevated among those low in persistence, high in negative reactivity, or high in activity, even in cases where parenting was high in positive qualities such as warmth and monitoring. Prevalence of certain behaviour problems was substantially elevated when low persistence, high negative reactivity, or high activity occurred in combination with lower parental warmth or lower monitoring. The results suggest that parenting can play an important moderating role in the relationship of particular temperament characteristics to behavioural problems. [Author abstract]

Cost-effectiveness of dexamphetamine and methylphenidate for the treatment of childhood attention deficit hyperactivity disorder

Objective: To analyze from a health sector perspective the cost-effectiveness of dexamphetamine (DEX) and methylphenidate (MPH) interventions to treat childhood attention deficit hyperactivity disorder (ADHD), compared to current practice.

Method: Children eligible for the interventions are those aged between 4 and 17 years in 2000, who had ADHD and were seeking care for emotional or behavioural problems, but were not receiving stimulant medication. To determine health benefit, a meta-analysis of randomized controlled trials was performed for DEX and MPH, and the effect sizes were translated into utility values. An assessment on second stage filter criteria ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Simulation modelling techniques are used to present a 95% uncertainty interval (UI) around the incremental costeffectiveness ratio (ICER), which is calculated in cost (in A$) per DALY averted.

Results: The ICER for DEX is A$4100/DALY saved (95% UI: negative to A$14 000) and for MPH is A$15 000/DALY saved (95% UI: A$9100-22 000). DEX is more costly than MPH for the government, but much less costly for the patient.

Conclusions: MPH and DEX are cost-effective interventions for childhood ADHD. DEX is more cost-effective than MPH, although if MPH were listed at a lower price on the Pharmaceutical Benefits Scheme it would become more cost-effective. Increased uptake of stimulants for ADHD would require policy change. However, the medication of children and wider availability of stimulants may concern parents and the community.

The effect of Shamanic-like stimulus conditions and the cognitive-perceptual factor of schizotypy on phenomenology

Shamanism has remained an integral part of indigenous healing rituals since ancient times and is currently attracting interest as a complementary therapeutic technique in psychology. Recently, shamanic-like techniques have been used to facilitate changes in the phenomenology of nonshamans. However, such research has largely been delimited to a single shamanic-like technique (i.e., drumming), and the role of personality traits with regards to receptivity to this technique has been neglected. The purpose of the present study was to investigate experimentally the effect of different shamanic-like techniques and the cognitive-perceptual factor of the schizotypy construct on phenomenology. One hundred and four non-shamans were randomly assigned to one of three conditions: Drumming, Ganzfeld, or Sitting Quietly with Eyes Open. Participants' phenomenology was assessed using the Phenomenology of Consciousness Inventory, Phenomenology associated with shamanic-like techniques appeared to be statistically significantly different from phenomenology associated with sitting quietly with eyes open. Furthermore, high cognitive-perceptual participants reported significant alterations in phenomenology compared to their low cognitive-perceptual counterparts. Methodological shortcomings of the present study are discussed and suggestions for future research are advanced.

Origins of inflated responsibility in obsessive compulsive disorder

The pivotal role of inflated responsibility beliefs in the maintenance and treatment of obsessive-compulsive disorder (OCD) has been clearly demonstrated (Rachman, 1993; Salkovskis, 1998; Shafran, 1997; van Oppen & Arntz, 1994). Yet little is known about the origins of these beliefs, their contribution to a sense of inflated responsibility or the symptoms of OCD, or the contribution of personality to inflated responsibility and to OCD, The aims of this thesis were to investigate a model of the inter-relationships among the personality dimensions of neuroticism and psychoticism, inflated responsibility and OCD, and the origins of inflated responsibility to inflated responsibility and to OCD. In order to achieve these aims, a scale was developed to assess the origins of inflated responsibility based upon the five pathways proposed by Salkovskis, Shafran, Rachman, and Freeston (1999) and the additional domains of guilt, vigilance and thought-action fusion (Shafran, Thordarson, & Rachman, 1996; Shafran, Watkins & Charman, 1996; Tallis, 1994). Eighty-four participants with OCD (age M = 43.36) and 74 control participants (age M =37.14) volunteered to participate in the two studies of this thesis. The aim of Study 1 was to develop and validate a measure of the Origins of Inflated Responsibility (OIR). The results of the first study yielded a 25-ttem scale, the Origins of Inflated Responsibility Questionnaire (OIRQ) with five independent factors: responsibility, strictness, protection from responsibility, critical incidents, and peer blame which demonstrated both internal reliability and temporal stability over a 2-week period. In Study 2, participants also completed the Responsibility Attitudes Scale (Salkovskis, Wroe, Gledhill, Morrison, Forrester, Richards, ct al. (2000) (a measure of inflated responsibility), the Padua Inventory (Sanavio, 1988) (to measure of the symptoms of OCD)y and the Eysenck Personality Inventory-Revised (Eysenck & Eysenck, 1991). Multivariatc Analysis of Variance revealed that the OCD group scored higher on all variables than the control group except for strictness where the groups were not different, and psychoticism where the OCD group scored lower. A series of Multiple Regression analyses revealed that both group and the OIR contributed to inflated responsibility (R2 = .56). When all variables, OIR, inflated responsibility and neuroticism were entered as predictors of OCD, 60% of the variance in OCD was explained however, 49% of the variance was shared by the independent variables suggesting the presence of some underlying construct. Structural Equation Modelling, where all the constructs in the model were examined simultaneously, revealed that neuroticism contributed to the OIR, inflated responsibility and OCD. The OIR were also significant predictors of inflated responsibility and indirectly through inflated responsibility predictive of OCD. The OIR also directly predicted OCD and when the total effects are considered, their contribution was greater than the total effect for inflated responsibility alone. The results of these studies provide good support for the origins of inflated responsibility proposed by Salkovskis et al. (1999), as measured by the OIRQ developed for use in the current thesis. The results also support the contribution of inflated responsibility and neuroticism, as well as the OIR, to OCD, The large amount of variance shared by the OIR, inflated responsibility and neuroticism suggest that there might be some underlying construct, perhaps of a biopsychosocial nature, that requires further investigation for its role in the onset and maintenance of OCD. The clinical relevance of these findings is discussed in terms of early prevention strategies and interventions.

N-acetyl cysteine for depressive symptoms in bipolar disorder - a double blind, randomized, placebo-controlled trial

Background: Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorderare complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder.

Methods: A randomized, double-blind, multicenter, placebo-controlled study of individuals (n 75) with bipolar disorder in the maintenance phase treated with NAC (1 g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning.

Results: NAC treatment caused a significant improvement on the MADRS (least squares mean difference [95% confidence interval]: 8.05 [13.16, 2.95], p .002) a n d most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p .968) and no significant between-group differences inadverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts.

Conclusions: NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar  disorder.

Nail-biting stuff? The effect of N-acetyl cysteine on nail-biting

N-acetyl cysteine (NAC) is a widely available nutraceutical with a variety of actions. As a precursor of cysteine and glutathione, it has antioxidant properties that may impact on mood and contribute to an effect on impulsivity and obsessive behaviour. Via its additional effect on glutamate via the cystine-glutamate exchange system, NAC has been shown to mediate impulsivity in preclinical models of addiction, reduce craving, and cue extinction. Further, by boosting glutathione, NAC acts as a potent antioxidant and has been shown in two positive, large-scale randomized placebo-controlled trials to affect negative symptoms in schizophrenia and depression in bipolar disorder. We describe three cases in which its actions specifically on nail-biting and associated anxiety may offer a potential treatment. The spontaneous findings are reported as part of an ongoing treatment trial examining the utility of NAC in bipolar disorder. Its actions, if robustly replicated, also point to potential treatment targets in glutathione or glutamate pathways in the brain.

Efficacy of atypical antipsychotics in bipolar disorder

Bipolar disorder is a severe and recurrent disorder. Atypical antipsychotics have emerged as both an alternative and adjunct to conventional mood stabilisers. The manic phase of the illness is the best studied, and it appears that a class effect with regards to efficacy is present in both monotherapy and augmentation studies. Evidence for efficacy of atypical antipsychotics in depression is emerging. At this stage controlled data are available for both olanzapine and quetiapine. Maintenance data demonstrating efficacy are available for olanzapine. Atypical antipsychotics have utility in treating acute agitation and aggression in manic episodes of bipolar disorder. Subgroup analyses from trials treating manic phase bipolar disorder, and an open-label study of rapid cycling, have suggested that atypical antipsychotics may be useful for the treatment of mixed states and rapid cycling. Several studies have suggested that atypical antipsychotics may be useful in treatment-refractory episodes of bipolar disorder. The current available data suggest greater efficacy of the atypical antipsychotics in mania than in depression, although the data are fairly clear that induction of depression is not an issue with the atypical antipsychotics. A number of trials are underway that will hopefully address many of the questions still pending.