Moderators and Predictors of Response to Behavior Therapy for Tics in Tourette Syndrome

Objective: To examine moderators and predictors of response to behavior therapy for tics in children and adults with Tourette syndrome and chronic tic disorders. Methods: Data from 2 10-week, multisite studies (1 in children and 1 in adults; total n = 248) comparing comprehensive behavioral intervention for tics (CBIT) to psychoeducation and supportive therapy (PST) were combined for moderator analyses. Participants (177 male, 71 female) had a mean age of 21.5 ± 13.9 years (range 9–69). Demographic and clinical characteristics, baseline tic-suppressing medication, and co-occurring psychiatric disorders were tested as potential moderators for CBIT vs PST or predictors of outcome regardless of treatment assignment. Main outcomes measures were the Yale Global Tic Severity Scale Total Tic score and the Clinical Global Impression–Improvement score assessed by masked evaluators. Results: The presence of tic medication significantly moderated response to CBIT vs PST (p = 0.01). Participants showed tic reduction after CBIT regardless of tic medication status, but only participants receiving tic medication showed reduction of tics after PST. Co-occurring psychiatric disorders, age, sex, family functioning, tic characteristics, and treatment expectancy did not moderate response. Across both treatments, greater tic severity (p = 0.005) and positive participant expectancy (p = 0.01) predicted greater tic improvement. Anxiety disorders (p = 0.042) and premonitory urge severity (p = 0.005) predicted lower tic reduction. Conclusions: Presence of co-occurring attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, or anxiety disorders did not moderate response to CBIT. Although participants on tic medication showed improvement after CBIT, the difference between CBIT and PST was greater for participants who were not on tic-suppressing medication. ClinicalTrials.gov identifiers: The child and adult CBIT studies are listed on clinical trials.gov (NCT00218777 and NCT00231985, respectively). Classification of evidence: This study provides Class I evidence that CBIT is effective in reducing tic severity across subgroups of patients with chronic tic disorders, although the difference between treatments was smaller for participants on tic-suppressing medications, suggesting reduced efficacy in this subgroup

Neurocognitive Correlates of Treatment Response in Children with Tourette\u27s Disorder

This paper examined neurocognitive functioning and its relationship to behavior treatment response among youth with Tourette\u27s Disorder (TD) in a large randomized controlled trial. Participants diagnosed with TD completed a brief neurocognitive battery assessing inhibitory functions, working memory, and habit learning pre- and post-treatment with behavior therapy (CBIT, Comprehensive Behavioral Intervention for Tics) or psychoeducation plus supportive therapy (PST). At baseline, youth with tics and Attention Deficit Hyperactivity Disorder (ADHD) exhibited some evidence of impaired working memory and simple motor inhibition relative to youth with tics without ADHD. Additionally, a small negative association was found between antipsychotic medications and youth\u27s performance speed. Across treatment groups, greater baseline working memory and aspects of inhibitory functioning were associated with a positive treatment response; no between-group differences in neurocognitive functioning at post-treatment were identified. Within the behavior therapy group, pre-treatment neurocognitive status did not predict outcome, nor was behavior therapy associated significant change in neurocognitive functioning post-treatment. Findings suggest that co-occurring ADHD is associated with some impairments in neurocognitive functioning in youth with Tourette\u27s Disorder. While neurocognitive predictors of behavior therapy were not found, participants who received behavior therapy exhibited significantly reduced tic severity without diminished cognitive functioning

A Multicenter Examination and Strategic Revisions of the Yale Global Tic Severity Scale

Objective To examine the internal consistency and distribution of the Yale Global Tic Severity Scale (YGTSS) scores to inform modification of the measure. Methods This cross-sectional study included 617 participants with a tic disorder (516 children and 101 adults), who completed an age-appropriate diagnostic interview and the YGTSS to evaluate tic symptom severity. The distributions of scores on YGTSS dimensions were evaluated for normality and skewness. For dimensions that were skewed across motor and phonic tics, a modified Delphi consensus process was used to revise selected anchor points. Results Children and adults had similar clinical characteristics, including tic symptom severity. All participants were examined together. Strong internal consistency was identified for the YGTSS Motor Tic score (α = 0.80), YGTSS Phonic Tic score (α = 0.87), and YGTSS Total Tic score (α = 0.82). The YGTSS Total Tic and Impairment scores exhibited relatively normal distributions. Several subscales and individual item scales departed from a normal distribution. Higher scores were more often used on the Motor Tic Number, Frequency, and Intensity dimensions and the Phonic Tic Frequency dimension. By contrast, lower scores were more often used on Motor Tic Complexity and Interference, and Phonic Tic Number, Intensity, Complexity, and Interference. Conclusions The YGTSS exhibits good internal consistency across children and adults. The parallel findings across Motor and Phonic Frequency, Complexity, and Interference dimensions prompted minor revisions to the anchor point description to promote use of the full range of scores in each dimension. Specific minor revisions to the YGTSS Phonic Tic Symptom Checklist were also proposed

Atomic Tunneling from a STM/AFM tip: Dissipative Quantum Effects from Phonons

We study the effects of phonons on the tunneling of an atom between two surfaces. In contrast to an atom tunneling in the bulk, the phonons couple very strongly, and qualitatively change the tunneling behavior. This is the first example of {\it ohmic} coupling from phonons for a two-state system. We propose an experiment in which an atom tunnels from the tip of an STM, and show how its behavior would be similar to the Macroscopic Quantum Coherence behavior predicted for SQUIDS. The ability to tune and calculate many parameters would lead to detailed tests of the standard theories. (For a general intro to this work on the on the World-Wide-Web: http://www.lassp.cornell.edu. Click on ``Entertaining Science Done Here'' and ``Quantum Tunneling of Atoms'')Comment: 12 pages, ReVTex3.0, two figures (postscript). This is a (substantially) revised version of cond-mat/9406043. More info (+ postscript text) at : http://www.lassp.cornell.edu/ardlouis/publications.htm

Comparative study of in situ N2 rotational Raman spectroscopy methods for probing energy thermalisation processes during spin-exchange optical pumping

Spin-exchange optical pumping (SEOP) has been widely used to produce enhancements in nuclear spin polarisation for hyperpolarised noble gases. However, some key fundamental physical processes underlying SEOP remain poorly understood, particularly in regards to how pump laser energy absorbed during SEOP is thermalised, distributed and dissipated. This study uses in situ ultra-low frequency Raman spectroscopy to probe rotational temperatures of nitrogen buffer gas during optical pumping under conditions of high resonant laser flux and binary Xe/N2 gas mixtures. We compare two methods of collecting the Raman scattering signal from the SEOP cell: a conventional orthogonal arrangement combining intrinsic spatial filtering with the utilisation of the internal baffles of the Raman spectrometer, eliminating probe laser light and Rayleigh scattering, versus a new in-line modular design that uses ultra-narrowband notch filters to remove such unwanted contributions. We report a ~23-fold improvement in detection sensitivity using the in-line module, which leads to faster data acquisition and more accurate real-time monitoring of energy transport processes during optical pumping. The utility of this approach is demonstrated via measurements of the local internal gas temperature (which can greatly exceed the externally measured temperature) as a function of incident laser power and position within the cell

Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

<p>Abstract</p> <p>Objective</p> <p>To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents.</p> <p>Methods</p> <p>Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described.</p> <p>Results</p> <p>CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance.</p> <p>Conclusions</p> <p>CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00052078.</p

Genome-wide association study of Tourette Syndrome

Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder

Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n&nbsp;=&nbsp;151) and male (n&nbsp;=&nbsp;143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model

Self-control interventions for children under age 10 for improving self-control and delinquency and problem behaviors

Self-control improvement programs are intended to serve many purposes, most notably improving self-control. Yet, interventions such as these often aim to reduce delinquency and problem behaviors. However, there is currently no summary statement available regarding whether or not these programs are effective in improving self-control and reducing delinquency and problem behaviors. The main objective of this review is to assess the available research evidence on the effect of self-control improvement programs on self-control and delinquency and problem behaviors. In addition to investigating the overall effect of early selfcontrol improvement programs, this review will examine, to the extent possible, the context in which these programs may be most successful. The studies included in this systematic review indicate that self-control improvement programs are an effective intervention for improving self-control and reducing delinquency and problem behaviors, and that the effect of these programs appears to be rather robust across various weighting procedures, and across context, outcome source, and based on both published and unpublished data

Depression treatment and healthcare expenditures among elderly Medicare beneficiaries with newly diagnosed depression and incident breast, colorectal, or prostate cancer

Objectives—Depression is associated with high healthcare expenditures, and depression treatment may reduce healthcare expenditures. However, to date, there have not been any studies on the effect of depression treatment on healthcare expenditures among cancer survivors. Therefore, this study examined the association between depression treatment and healthcare expenditures among elderly with depression and incident cancer. Methods—The current study used a retrospective longitudinal study design, the linked Surveillance, Epidemiology, and End Results–Medicare database. Elderly (≥66 years) fee-forservice Medicare beneficiaries with newly diagnosed depression and incident breast, colorectal, or prostate cancer (N = 1502) were followed for a period of 12 months after depression diagnosis. Healthcare expenditures were measured every month for a period of 12-month follow-up period. Depression treatment was identified during the 6-month follow-up period. The adjusted associations between depression treatment and healthcare expenditures were analyzed with generalized linear mixed model regressions with gamma distribution and log link after controlling for other factors. Results—The average 1-year total healthcare expenditures after depression diagnosis were $38 219 for those who did not receive depression treatment;$42 090 for those treated with antidepressants only; $46 913 for those treated with psychotherapy only; and$51 008 for those treated with a combination of antidepressants and psychotherapy. As compared to no depression treatment, those who received antidepressants only, psychotherapy only, or a combination of antidepressants and psychotherapy had higher healthcare expenditures. However, second-year expenditures did not significantly differ among depression treatment categories. Conclusions—Among cancer survivors with newly diagnosed depression, depression treatment did not have a significant effect on expenditures in the long term