The moderating and mediating role of telepresence and cognitive change in cognitive behaviour therapy delivered via videoconference.

In this study, we combined the results of two controlled trials and examined the relationships between working alliance, telepresence, cognitive change and treatment outcome. Sixty-five participants with a primary diagnosis of generalized anxiety disorder (GAD) or panic disorder with agoraphobia (PDA) received cognitive behaviour therapy delivered via videoconference. Participants completed measures of working alliance and telepresence after three psychotherapy sessions. They also completed measures of treatment outcome and dysfunctional beliefs (cognitive change) specific to PDA and GAD at pretreatment and posttreatment. Results revealed that telepresence at the fifth session moderated the relationship between the working alliance at the first and fifth sessions. As telepresence increased, its impact on the working alliance diminished. Cognitive change mediated the relationship between the working alliance at the fifth session and treatment outcome.

The ARF tumor suppressor controls ribosome biogenesis by regulating the RNA polymerase I transcription factor TTF-I.

The p14/p19(ARF) (ARF) product of the CDKN2A gene displays tumor suppressor activity both in the presence and absence of p53/TP53. In p53-negative cells, ARF arrests cell proliferation, at least in part, by suppressing ribosomal RNA synthesis. We show that ARF does this by controlling the subnuclear localization of the RNA polymerase I transcription termination factor, TTF-I. TTF-I shuttles between nucleoplasm and nucleolus with the aid of the chaperone NPM/B23 and a nucleolar localization sequence within its N-terminal regulatory domain. ARF inhibits nucleolar import of TTF-I by binding to this nucleolar localization sequence, causing the accumulation of TTF-I in the nucleoplasm. Depletion of TTF-I recapitulates the effects of ARF on ribosomal RNA synthesis and is rescued by the introduction of a TTF-I transgene. Thus, our data delineate the pathway by which ARF regulates ribosomal RNA synthesis and provide a compelling explanation for the role of NPM.

Loss of human ribosomal gene CpG methylation enhances cryptic RNA polymerase II transcription and disrupts ribosomal RNA processing.

Epigenetic methyl-CpG silencing of the ribosomal RNA (rRNA) genes is thought to downregulate rRNA synthesis in mammals. In contrast, we now show that CpG methylation in fact positively influences rRNA synthesis and processing. Human HCT116 cells, inactivated for DNMT1 and DNMT3b or treated with aza-dC, lack CpG methylation and reactivate a large fraction of normally silent rRNA genes. Unexpectedly, these cells display reduced rRNA synthesis and processing and accumulate unprocessed 45S rRNA. Reactivation of the rRNA genes is associated with their cryptic transcription by RNA polymerase II. Ectopic expression of cryptic rRNA gene transcripts recapitulates the defects associated with loss of CpG methylation. The data demonstrate that rRNA gene silencing prevents cryptic RNA polymerase II transcription of these genes. Lack of silencing leads to the partial disruption of rRNA synthesis and rRNA processing, providing an explanation for the cytotoxic effects of loss of CpG methylation.

Reduction in Costs after Treating Comorbid Panic Disorder with Agoraphobia and Generalized Anxiety Disorder.

BACKGROUND: Panic disorder with agoraphobia (PDA) and generalized anxiety disorder (GAD) are impairing and costly disorders that are often misdiagnosed and left untreated despite multiple consultations. These disorders frequently co-occur, but little is known about the costs associated with their comorbidity and the impact of cognitive-behavioral therapy (CBT) on cost reduction. AIMS OF THE STUDY: The first objective of this study was to assess the mental health-related costs associated with the specific concomitance of PDA and GAD. The second aim was to determine whether there is a reduction in direct and indirect mental health-related costs following conventional CBT for the primary disorder only (PDA or GAD) or combined CBT adapted to the comorbidity (PDA and GAD). METHODS: A total of 123 participants with a double diagnosis of PDA and GAD participated in this study. Direct and indirect mental health-related costs were assessed and calculated from a societal perspective at the pre-test, the post-test, and the three-month, six-month and one-year follow-ups. RESULTS: At the pre-test, PDA-GAD comorbidity was found to generate a mean total cost of CADUSD 2,000.48 (SD = USD 2,069.62) per participant over a three-month period. The indirect costs were much higher than the direct costs. Both treatment modalities led to significant and similar decreases in all cost categories from the pre-test to the post-test. This reduction was maintained until the one-year follow-up. DISCUSSION: Methodological choices may have underestimated cost evaluations. Nonetheless, this study supports the cost offset effects of both conventional CBT for primary PDA or GAD and combined CBT for PDA-GAD comorbidity. IMPLICATIONS FOR HEALTHCARE PROVISION AND USE: Treatment of comorbid and costly disorders with evidence-based treatments such as CBT may lead to considerable economic benefits for society. IMPLICATIONS FOR HEALTH POLICIES: Considering the limited resources of healthcare systems, it is important to make choices that will lead to better accessibility of quality services. The application of CBT for PDA, GAD or both disorders and training mental health professionals in this therapeutic approach should be encouraged. Additionally, it would be favorable for insurance plans to reimburse employees for expenses associated with psychological treatment for anxiety disorders. IMPLICATIONS FOR FURTHER RESEARCH: In addition to symptom reduction, it would be of great pertinence to explore which factors can contribute to reducing direct and indirect mental health-related costs.

Insomnia Symptoms Following Treatment for Comorbid Panic Disorder With Agoraphobia and Generalized Anxiety Disorder.

Patients with panic disorder with agoraphobia (PDA) or generalized anxiety disorder (GAD) frequently also suffer from insomnia. However, the impact of cognitive-behavioral therapy (CBT) for anxiety disorders on insomnia has been understudied. Furthermore, comorbidity between anxiety disorders is common. Our main objective was to assess the impact of CBT for PDA or GAD on insomnia. In a quasi-experimental design, 86 participants with PDA and GAD received conventional CBT for their primary disorder or combined CBT for both disorders. Overall, CBTs had a significant impact on reducing insomnia symptoms (η = 0.58). However, among people with insomnia at pretest (67%), 33% still had an insomnia diagnosis, and the majority (63%) had clinically significant residual insomnia following treatment. In conclusion, the CBTs had a positive effect on the reduction of insomnia, but a significant proportion of participants still had insomnia problems following treatment. Clinicians should address insomnia during CBT for PDA and GAD.

A Multisite Non-Inferiority Randomized Controlled Trial of the Efficacy of Cognitive-Behavior Therapy for Generalized Anxiety Disorder Delivered by Videoconference.

Delivering psychotherapy by videoconference has been studied in a number of clinical trials, but no large controlled trial has involved generalized anxiety disorder (GAD). This multicenter randomized controlled non-inferiority trial was conducted to test if cognitive-behavior psychotherapy delivered by videoconference (VCP) is as effective as cognitive-behavior psychotherapy delivered face-to-face, using a strict margin of tolerance for non-inferiority. A total of 148 adults received a 15-session weekly manualized program. The treatment was based on the intolerance of uncertainty model of GAD. The impact of treatment was assessed using primary (GAD severity), secondary (worry, anxiety, and intolerance of uncertainty) and tertiary (general functioning) variables measured before and after treatment and at 6-month and 12-month follow-ups. Results showed that: (a) the treatment was effective; (b) VCP for GAD was statistically non-inferior to face-to-face psychotherapy on primary, secondary and tertiary measures at all assessment points; (c) change in intolerance of uncertainty significantly predicted change in the primary outcome measure over and above important clinical factors common to all psychotherapies (motivation, working alliance, perceived therapist competence, and client satisfaction). These findings support the use of VCP as a promising treatment option for adults with GAD. Clinical trial registry: ISRCTN#12662027.

Translation and Validation of a State-Measure of Body Image Satisfaction: The Body Image State Scale.

The aim of the present study is to test the validity and reliability of the French Body Image State Scale (F-BISS). The scale was translated using a back-translation technique, with discrepancies being settled through consensus. Three hundred and twelve female participants were recruited. Convergent validity was assessed using eating disorder evaluation and social comparison. Exploratory and confirmatory factor analyses were also conducted. The translated Body Image State Scale (BISS) demonstrated good psychometric properties, with good internal consistency (α = 0.83), and adequate goodness-of-fit. The translated BISS presented a unifactorial structure, with one factor explaining 56% of the variance. The exploratory factor analysis led to the removal of a single item due to insufficient factor loading (<0.45). Its convergent validity seems consistent with previous literature. Discriminant analyses showed a significant difference in F-BISS score between participants relative to eating disorder symptomatology (t = 11.65; p < 0.001). This translation could prove useful in both research and clinical settings to assess state body satisfaction in French populations.

The Role of Intolerance of Uncertainty and Working Alliance in the Outcome of Cognitive Behavioral Therapy for Generalized Anxiety Disorder Delivered by Videoconference: Mediation Analysis.

BACKGROUND: Previous meta-analyses have shown a significant relationship between working alliance and treatment outcome in general. Some studies have examined the relationship between working alliance and treatment outcome during telepsychotherapy, but to the best of our knowledge, no study has examined the mediating role of individual components of the working alliance. OBJECTIVE: As part of a clinical trial of cognitive behavioral therapy (CBT) for generalized anxiety disorder (GAD) delivered by videoconference (VC), the aim of this study is to examine the mediating role of intolerance of uncertainty on the relationship between the components of the working alliance and treatment outcome. METHODS: A sample of 46 adults with primary GAD received 15 sessions of CBT for GAD delivered over VC. Participants completed the measure of working alliance immediately after the fifth therapy session. The degree of change in intolerance of uncertainty (a key psychological process) was assessed from pre- to posttreatment. Treatment outcome was assessed via changes in GAD symptoms from pretreatment to the 6-month follow-up. RESULTS: The results revealed that the therapeutic bond did not predict treatment outcome (r=-0.23; P=.12). However, agreement on therapeutic goals and tasks did predict treatment outcome (r=-0.42; P=.004 and r=-0.37; P=.01, respectively). In addition, the relationship between consensus on therapeutic tasks and treatment outcome was completely mediated by changes in intolerance of uncertainty (unstandardized ß=-0.03; r2=0.12), whereas consensus relative to treatment goals had a direct impact on treatment outcome. CONCLUSIONS: These results provide a better understanding of the differential role of the components of the working alliance in telepsychotherapy as a facilitative factor for changes in key cognitive processes, leading to therapeutic change. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 12662027; http://www.isrctn.com/ISRCTN12662027.

Specificity of belief domains in OCD: validation of the French version of the Obsessive Beliefs Questionnaire and a comparison across samples.

This paper assesses the psychometric properties of the French version of the Obsessive Beliefs Questionnaire (OBQ-44) and investigates whether the questionnaire discriminates between obsessive-compulsive disorder (OCD), anxious control (AC), and non-clinical control (NCC) participants. A confirmatory factor analysis suggested a poor fit of the model. An exploratory factor analysis replicated the original factor structure. The subscales were moderately intercorrelated and highly correlated with the total score. There was partial support for convergent/divergent validity of the OBQ-44. In analyses of variance comparing the three samples, the participants in the OCD sample scored significantly higher than the participants in the AC and NCC samples on all of the OBQ-44 scores. In analyses of covariance comparing the OCD and NCC samples while controlling for general distress and age, the participants with OCD scored significantly higher than the NCC participants on all of the OBQ-44 scores. Implications of the current study are discussed.

Cognitive variables related to worry among adolescents: avoidance strategies and faulty beliefs about worry.

Studies aiming to better understand worry have neglected children and adolescents. This constitutes an important limitation considering that excessive worry is frequent among adolescents and that patients suffering from excessive worries associate the beginning of their disorder with adolescence. This study evaluates the cognitive variables associated with worry in a sample of 777 adolescents. It attempts to determine whether cognitive avoidance and false beliefs about the usefulness of worries are present and associated with worries in adolescence. The results showed that participants with a high level of worry used more avoidance strategies and held more beliefs about worry. The results also revealed that avoidance of stimuli that trigger unpleasant thoughts and thought substitution were the major avoidance strategies related to worry among adolescents. The belief that worry helps to avoid future negative events was also related to worry. These findings may suggest that adolescents' worries are maintained by processes similar to those observed among adults.

Group cognitive-behavioral therapy for generalized anxiety disorder: treatment outcome and long-term follow-up.

A recently developed cognitive-behavioral treatment for generalized anxiety disorder (GAD) targets intolerance of uncertainty by the reevaluation of positive beliefs about worry, problem-solving training, and cognitive exposure. As previous studies have established the treatment's efficacy when delivered individually, the present study tests the treatment in a group format as a way to enhance its cost-benefit ratio. A total of 52 GAD patients received 14 sessions of cognitive-behavioral therapy in small groups of 4 to 6 participants. A wait-list control design was used, and standardized clinician ratings and self-report questionnaires assessed GAD symptoms, intolerance of uncertainty, anxiety, depression, and social adjustment. Results show that the treatment group, relative to the wait-list group, had greater posttest improvement on all dependent variables and that treated participants made further gains over the 2-year follow-up phase of the study.

Characteristics of illness intrusions in a non-clinical sample.

This study examines whether illness intrusions can be distinguished from obsessional intrusions and worries. It also assesses the relationship between strategies, thought characteristics, and appraisal of illness intrusions. Two hundred and forty-three non-clinical participants identified an obsessive intrusive thought, a worry, and an illness intrusion. They evaluated each thought using items from the Cognitive Intrusions Questionnaire. The comparisons of intrusions showed that illness intrusions share characteristics of worries and obsessional intrusions, but also have their own characteristics. Illness intrusions seem to be particularly egosyntonic. The relationships between the strategies used to counter illness intrusions and their appraisal were also tested. Results support the idea that there are specific links between the evaluation of cognitive intrusions and the way they are processed. It demonstrated that escape/avoidance strategies are associated with the egodystonic nature of the thought and that problem-focused strategies are associated with the thought's basis in reality. Illness intrusions may be conceptualised as either obsessions or worries. This study demonstrated that the category of an intrusive thought might not be as important as the way it is processed. It seems more important to consider appraisal of the disturbing thought and the way in which the person subsequently reacts and behaves.

Insomnia and generalized anxiety disorder: effects of cognitive behavior therapy for gad on insomnia symptoms.

Although clinical practice suggests that sleep complaints are frequent among patients with generalized anxiety disorder (GAD), frequency, severity, types of insomnia complaints, and relationship to GAD diagnosis severity in patients diagnosed using Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria are not well documented. Clinical data about the impact on insomnia symptoms of treating GAD worries are also lacking. The present study examined these aspects in 44 GAD patients who participated in a treatment study specifically addressing excessive worries through CBT interventions. All patients were assessed using a structured clinical interview and the Anxiety Disorder Interview Schedule-IV (ADIS-IV). They also completed anxiety and insomnia inventories, including the Insomnia Severity Index (ISI), a self-report measure which assesses insomnia type, severity and interference with daily life. Among this sample, 47.7% reported difficulties initiating sleep, 63.6% reported difficulties maintaining sleep, and 56.8% complained of waking too early in the morning. The majority of these patients (86.5%) reported never having experienced insomnia without having excessive worries. However, insomnia severity and GAD severity were not correlated. In this sample, patients with severe GAD did not necessarily report more severe insomnia symptoms. Regarding treatment impact on insomnia complaints, ISI post-treatment scores were significantly lower after treatment. Mean post-treatment scores almost reached ISI's "absence of clinical insomnia" category. Results indicate that this CBT package for GAD does have a significant impact on sleep quality even if sleep disturbances were not specifically addressed during treatment.

The effect of a combined versus a conventional cognitive-behavioral therapy on quality of life for comorbid panic disorder with agoraphobia and generalized anxiety disorder: preliminary results.

Concurrent panic disorder with agoraphobia (PDA) and generalized anxiety disorder (GAD) are the most common diagnostic occurrences among anxiety disorders. This particular comorbidity is associated with significant impairments in quality of life (QOL). The current study sought to investigate the efficacy of a combined cognitive-behavioral psychotherapy that addressed both conditions compared with a conventional psychotherapy, which attends solely to the primary disorder. The hypotheses postulated firstly, that both treatment conditions would lead to improvements in participants' QOL and secondly, that the combined therapy would lead to greater QOL ameliorations. Twenty-five participants with comorbid PDA/GAD diagnoses were evaluated with a number of clinical interviews and self-report questionnaires, and were provided with either conventional or combined cognitive-behavioral psychotherapy, which consisted of 14 one-hour weekly sessions. Participants were once again evaluated in the same fashion 2-weeks after the completion of the psychotherapy. The results revealed that both conditions led to significant improvements in participants' QOL, but that the two groups did not significantly differ in terms of the effect on QOL. The results also reveal that the two conditions did not significantly differ in terms of their effect on PDA and GAD symptomatology or psychiatric comorbidity. The results demonstrate that the combined psychotherapy, which addresses both conditions simultaneously, is similar to the conventional psychotherapy employed for the primary disorder in terms of QOL enhancement, symptom severity, and comorbidity reduction.

Attentional bias, distractibility and short-term memory in anxiety.

Cognitive effects of anxiety have been amply documented. Anxiety has been linked with an attentional bias toward threat, distractibility, and reductions in short-term memory (STM) capacity. These three functions have rarely been investigated jointly and permeability may account for some of the effects documented. In this experiment, we examine these three cognitive functions using one verbal and one visuospatial task. In the irrelevant speech paradigm, participants had to remember strings of letters while irrelevant neutral or threatening speech was presented. In the visuospatial sandwich paradigm, participants were asked to remember sequences of visuospatial targets sometimes presented within irrelevant distracters. We examined the links between state anxiety, worry, and indices of attentional bias toward threat, distractibility from neutral stimuli, and STM capacity. Results show that state anxiety was uniquely linked with impairments in STM while worry was more particularly related to distractibility, independently from permeability between the different cognitive functions. Attentional bias toward threat was linked with variance common to both anxiety and worry. An examination of clinical and non-clinical subgroups suggests that subjective threat perception and attentional bias toward threat are features that are particularly characteristic of clinical levels of anxiety. Our findings confirm the important links between anxiety and basic cognitive functions.

Dig1 protects against cell death provoked by glyphosate-based herbicides in human liver cell lines.

BACKGROUND: Worldwide used pesticides containing different adjuvants like Roundup formulations, which are glyphosate-based herbicides, can provoke some in vivo toxicity and in human cells. These pesticides are commonly found in the environment, surface waters and as food residues of Roundup tolerant genetically modified plants. In order to know their effects on cells from liver, a major detoxification organ, we have studied their mechanism of action and possible protection by precise medicinal plant extracts called Dig1. METHODS: The cytotoxicity pathways of four formulations of glyphosate-based herbicides were studied using human hepatic cell lines HepG2 and Hep3B, known models to study xenobiotic effects. We monitored mitochondrial succinate dehydrogenase activity and caspases 3/7 for cell mortality and protection by Dig1, as well as cytochromes P450 1A1, 1A2, 3A4 and 2C9 and glutathione-S-transferase to approach the mechanism of actions. RESULTS: All the four Roundup formulations provoke liver cell death, with adjuvants having stronger effects than glyphosate alone. Hep3B are 3-5 times more sensitive over 48 h. Caspases 3/7 are greatly activated in HepG2 by Roundup at non-cytotoxic levels, and some apoptosis induction by Roundup is possible together with necrosis. CYP3A4 is specifically enhanced by Roundup at doses 400 times less than used in agriculture (2%). CYP1A2 is increased to a lesser extent together with glutathione-S-transferase (GST) down-regulation. Dig 1, non cytotoxic and not inducing caspases by itself, is able to prevent Roundup-induced cell death in a time-dependant manner with an important efficiency of up to 89%, within 48 h. In addition, we evidenced that it prevents Caspases 3/7 activation and CYP3A4 enhancement, and not GST reduction, but in turn it slightly inhibited CYP2C9 when added before Roundup. CONCLUSION: Roundup is able to provoke intracellular disruption in hepatic cell lines at different levels, but a mixture of medicinal plant extracts Dig1 can protect to some extent human cell lines against this pollutants. All this system constitutes a tool for studying liver intoxication and detoxification.

ERK modulates DNA bending and enhancesome structure by phosphorylating HMG1-boxes 1 and 2 of the RNA polymerase I transcription factor UBF.

Transcription of the ribosomal RNA genes of mammals by RNA polymerase I is rapidly activated by epidermal growth factor via the MAP-kinase (ERK) signaling cascade. This activation is mediated by direct phosphorylation of the HMG box DNA binding domains of the architectural transcription factor UBF. Mutation of the ERK sites of UBF inhibits its normal function and blocks growth factor activation of ribosomal transcription. UBF has little or no DNA sequence selectivity and binds throughout the ribosomal genes, defining a specialized chromatin. Indeed, the HMG boxes of UBF induce looping of the ribosomal DNA to create the enhancesome, a structure somewhat reminiscent of the nucleosome. Here, we show that both ERK phosphorylation and mutations that simulate this phosphorylation decrease the affinity of the individual HMG boxes of UBF for linear ribosomal DNA but have little or no effect on the capacity of these HMG boxes to bind to pre-bent DNA and do not affect the overall binding constant of UBF for the DNA. Electron spectroscopic imaging showed that ERK site UBF mutants do not induce the characteristic DNA looping of the enhancesome and associate with no more than half of the enhancesomal DNA. The data demonstrate that ERK phosphorylation of UBF prevents DNA bending by its first two HMG boxes, leading to a cooperative unfolding of the enhancesome.

Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling.

Synthesis of the 45S rRNA by RNA polymerase I limits cell growth. Knowledge of the mechanism of its regulation is therefore key to understanding growth control. rRNA transcription is believed to be regulated solely at initiation/promoter release. However, we found that stimulation of endogenous 45S rRNA synthesis by epidermal growth factor (EGF) and serum failed to induce an increase in RNA polymerase I engagement on the rRNA genes, despite robust enhancement of 45S rRNA synthesis. Further, endogenous transcription elongation rates were measured and found to be directly proportional to 45S rRNA synthesis. Thus, elongation is a rate-limiting step for rRNA synthesis in vivo. ERK phosphorylation of the HMG boxes of UBF, an RNA polymerase I factor essential for transcription enhancement, was shown to directly regulate elongation by inducing the remodeling of ribosomal gene chromatin. The data suggest a mechanism for coordinating the cotranscriptional assembly of preribosomal particles.