James McCracken | Semel Institute of Neuroscience and Human Behavior at UCLA (original) (raw)

Papers by James McCracken

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53, Jan 27, 2017

Cognitive behavioral therapy (CBT) for anxiety disorders is effective, but nonadherence with trea... more Cognitive behavioral therapy (CBT) for anxiety disorders is effective, but nonadherence with treatment may reduce the benefits of CBT. This study examined (a) four baseline domains (i.e., demographic, youth clinical characteristics, therapy related, family/parent factors) as predictors of youth adherence with treatment and (b) the associations between youth adherence and treatment outcomes. Data were from 279 youth (7-17 years of age, 51.6% female; 79.6% White, 9% African American), with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) diagnoses of separation anxiety disorder, generalized anxiety disorder, and/or social phobia, who participated in CBT in the Child/Adolescent Anxiety Multimodal Study. Adherence was defined in three ways (session attendance, therapist-rated compliance, and homework completion). Multiple regressions revealed several significant predictors of youth adherence with CBT, but predictors varied according to the definition of adheren...

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53, Jan 26, 2017

Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors are effective trea... more Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors are effective treatments for pediatric anxiety disorders. However, the mechanisms of these treatments are unknown. Previous research indicated that somatic symptoms are reduced following treatment, but it is unclear if their reductions are merely a consequence of treatment gains. This study examined reductions in somatic symptoms as a potential mediator of the relationship between treatment and anxiety outcomes. Participants were 488 anxious youth ages 7-17 (M = 10.7), 50.4% male, 78.9% Caucasian, enrolled in Child/Adolescent Anxiety Multimodal Study, a large randomized control trial comparing 12-week treatments of CBT, sertraline, a combination of CBT and sertraline, and a pill placebo. Causal mediation models were tested in R using data from baseline, 8-, and 12-week evaluations. Somatic symptoms were assessed using the Panic/Somatic subscale from the Screen for Child Anxiety Related Emotional Disorders...

Journal of Child and Adolescent Psychopharmacology, 2016

Objectives: The characterization and prediction of placebo response in clinical trials of youth w... more Objectives: The characterization and prediction of placebo response in clinical trials of youth with anxiety disorders have received little attention, despite the critical effects of placebo response rate on the success or failure of clinical trials. With this in mind, we sought to examine the factors that predict or influence placebo response in randomized controlled trials of youth with anxiety disorders. Methods: Prospective, randomized, parallel-group controlled trials of psychopharmacologic interventions in pediatric patients with anxiety disorders were identified using a search of PubMed/Medline (1966-2015). Weighted least squares regression models and z-tests were utilized to examine the impact of continuous and categorical variables, respectively, on placebo response. These variables included demographic (e.g., age, percent white, percent female), clinical (e.g., baseline symptom severity), and trial characteristics (sample size, duration, funding). Finally, the relationship between the class of comparator medication and placebo response rate was examined using a multiple comparison for proportions test. Results: The analyses of data from 14 trials involving 2230 patients and 9 medications reveal that higher placebo response rates were associated with a greater number of study sites (p = 0.013) and fewer patients per site (p < 0.008), while placebo dropout rates increased with more recent publication (p = 0.01) and were positively associated with the number of study visits (p < 0.02). Lower placebo response rates were associated with federally funded studies (z =-4.61, p < 0.001), studies conducted in the United States (z = 1.81, p < 0.035), and with an increased likelihood of detecting a significant effect on the primary outcome (z = 4.58, p < 0.0001). Additionally, studies, in which the majority of patients (>60%) had a diagnosis of social anxiety disorder, exhibited lower placebo response rates (p < 0.001). Finally, for trials, effect size has decreased over time (p = 0.004). Conclusions: Important trial-specific factors affect placebo response and placebo dropout in youth with anxiety disorders and have pragmatic implications for the conduct and design of clinical trials and raise the possibility that limiting the number of sites while maximizing the number of patients per site could enhance the ability to detect medication-placebo differences.

Journal of Consulting and Clinical Psychology, 2015

Objective-To evaluate changes in the trajectory of youth anxiety following the introduction of sp... more Objective-To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive behavior therapy (CBT) components: relaxation training, cognitive restructuring, and exposure tasks. Methods-488 youths ages 7-17 years (50% female; 74% ≤ 12 years) were randomly assigned to receive either CBT, sertraline (SRT), their combination (COMB), or pill placebo (PBO) as part of their participation in the Child/Adolescent Anxiety Multimodal Study (CAMS). Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity (CGI-S; Guy, 1976) and the Children's Global Assessment Scale (CGAS; Schaffer et al., 1983) and every four weeks by blind independent evaluators (IEs) using the Pediatric Anxiety Ratings Scale (PARS; Rupp Study Group, 2002). Youths in SRT and PBO were included as controls. Results-Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring (e.g., changing self-talk) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment; the introduction of relaxation training had limited impact. Counter to expectations, no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target (i.e., somatic symptoms, anxious self-talk, avoidance behavior).

Journal of the American Academy of Child & Adolescent Psychiatry, 2011

Objective-We previously reported that a history of abuse was associated with a poorer response to... more Objective-We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings. Method-Youth who did not benefit from an adequate selective serotonin re-uptake inhibitor (SSRI) trial (N=334) were randomized to: an alternative SSRI; an alternative SSRI plus cognitive behavior therapy (CBT); venlafaxine; or venlafaxine plus CBT. Analyses examined the effect of history of abuse on response to the pharmacotherapy and combination therapy. Results-Those without a history of physical abuse (PA) or sexual abuse (SA) had a higher 12week response rate to combination therapy compared to medication mono-therapy (62.8% vs. 37.6%; OR=2.8, 95% CI: 1.6-4.7, p<0.001). Those with a history of SA had similar response rates to combination vs. medication monotherapy (48.3% vs. 42.3%; OR=1.3, 95% CI: 0.4-3.7; p=0.66), while those with history of PA had a much lower rate of response to combination therapy (18.4% vs. 52.4%, OR=0.1; 95% CI: 0.02-0.43). Even after adjusting for other clinical predictors, a history of PA moderated treatment outcome. Conclusion-These results should be considered within the limitations of a post-hoc analysis, lack of detailed assessment of abuse and other forms of trauma, and neuropsychological status. Depressed patients with history of abuse, especially PA may require specialized clinical approaches. Further work is needed to understand by what mechanisms a history of abuse affects treatment response.

Journal of Anxiety Disorders, 2010

Reports the characteristics of a large, representative sample of treatment seeking anxious youth ... more Reports the characteristics of a large, representative sample of treatment seeking anxious youth (N =488). Participants, aged 7-17 years (mean 10.7 yrs), had a principal DSM-IV diagnosis of separation anxiety disorder (SAD), generalized anxiety disorder (GAD), or social phobia (SP). Although youth with a co-primary diagnosis for which a different disorder-specific treatment would be indicated (e.g., major depressive disorder, substance abuse) were not included, there were few other exclusion criteria. Participants and their parent/guardian underwent an extensive baseline assessment using a broad array of measures capturing diagnostic status, anxiety symptoms and severity, and areas of functional impairment. Means and standard deviations of the measures of psychopathology and data on diagnostic status are provided. The sample had moderate to severe anxiety disorder and was highly comorbid, with 55.3% of participants meeting criteria for at least one non-targeted DSM-IV disorder. Anxiety disorders in youth often do not present as a single/focused disorder: such disorders in youth overlap in symptoms and are highly comorbid among themselves. Keywords anxiety; anxiety in children and adolescence; comorbidities Anxiety disorders are among the most common conditions affecting youth (Costello, Egger, & Angold, 2005). Epidemiological reports based on large and/or nationally representative samples estimate the prevalence of anxiety disorders in youth to range between 10% and 20% (Achenbach, et al., 1995; Shaffer, Fisher, Dulcan, & Davies, 1996). In general, anxiety disorders are often comorbid among themselves and with other disorders. If left untreated, pediatric anxiety disorders predict adult anxiety disorders and depression; and other childhood sequelae, such as substance use problems, suicide attempts, and hospitalization (Ferdinand &

Journal of Clinical Psychopharmacology, 2011

This paper examines the relationship between plasma concentration of antidepressant and both clin... more This paper examines the relationship between plasma concentration of antidepressant and both clinical response and adverse effects in treatment-resistant depressed adolescents. Adolescents (n = 334) with major depression who had not responded to a selective serotonin reuptake inhibitor (SSRI) were randomized to 1 of 4 treatments: switch to another SSRI (fluoxetine, citalopram, or paroxetine), switch to venlafaxine, switch to SSRI plus cognitive behavior therapy, or switch to

Journal of the American Academy of Child & Adolescent Psychiatry, 2014

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Autism : the international journal of research and practice, Jan 16, 2015

Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two f... more Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder to detect change with treatment. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. In Study 2, 49 subjects received risperidone only and 75 subjects received risperidone plus parent training. The combined sample consisted of 187 boys and 38 girls (aged 4-17 years). At the medication-free baseline, the internal consistency on the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder total score was excellent (Cronbach's alpha = 0.84) and the mean scores were similar across the four groups. Compared to placebo in Study 1, all...

Psychological medicine, 2009

Obsessive-compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many pa... more Obsessive-compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes. Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated. Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive di...

Free Radical Biology and Medicine, 2013

Type 2 Diabetes (T2D) has been associated with deleterious changes in multiple stem cell populati... more Type 2 Diabetes (T2D) has been associated with deleterious changes in multiple stem cell populations; however, the effects of T2D on cardiac stem cells (CSCs) remain unknown. This is important because T2D is associated with increased mortality and progression to heart failure. We examined the effects of diabetes on mouse CSC metabolism and function. Under basal conditions, c-kit + /lin -CSCs expressed both the Glut1 and Glut4 transporters, displayed insulin-independent glucose utilization, and showed highly coupled mitochondrial respiratory activity. CSCs isolated from diabetic (db/db) mice showed a 50 75% decrease in basal and maximal mitochondrial respiratory capacity, decreased cytochrome oxidase activity, and an increase in glycolysis compared with non-diabetic CSCs. Mitochondrial content, as assessed by qPCR of mitochondrial:nuclear DNA, was not significantly different between wild-type and db/db CSCs. Diabetic CSCs, although resistant to insulin, demonstrated a 3-fold increase in basal Akt phosphorylation and a 4-fold increase in phosphofructokinase/bisphosphatase-2 isoform 3 (PFKFB3) an isoform of PFK2 that sustains high rates of glycolysis. the diabetic CSCs showed a decreased capacity to attain Nkx2.5 positivity upon differentiation and an inability to increase additional markers of differentiation. in vivo, even mild conditions of metabolic syndrome decreased CSC reparative capacity. Mice fed a highfat-diet for 12 weeks showed no improvement in myocardial infarction-induced heart failure after CSC transplantation, whereas infarcted, normal chow-fed mice responded normally to CSC therapy. These data indicate that diabetes induces a dormant CSC phenotype associated with high rates of glycolysis and decreased mitochondrial function. This metabolic phenotype appears to mirror the Warburg glycolytic feature of cancer cells and may underlie deficits in reparative capacity in diabetes.

Brain and Behavior, 2013

Introduction Understanding the relationship between brain and complex latent behavioral construct... more Introduction Understanding the relationship between brain and complex latent behavioral constructs like cognitive control will require an inordinate amount of data. Internet-based methods can rapidly and efficiently refine behavioral measures in very large samples that are needed for genetics and behavioral research. Cognitive control is a multifactorial latent construct that is considered to be an endophenotype in numerous neuropsychiatric disorders, including attention deficit/hyperactivity disorder (ADHD). While previous studies have demonstrated high correlations between Web- and lab-based scores, skepticism remains for its broad implementation. Methods Here, we promote a different approach by characterizing a completely Web-recruited and tested community family sample on measures of cognitive control. We examine the prevalence of attention deficit symptoms in an online community sample of adolescents, demonstrate familial correlations in cognitive control measures, and use construct validation techniques to validate our high-throughput assessment approach. Results A total of 1214 participants performed Web-based tests of cognitive control with over 200 parent-child pairs analyzed as part of the primary study aims. The data show a wide range of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;subclinical&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; symptomatology in a web community sample of adolescents that supports a dimensional view of attention and also provide preliminary narrow-sense heritability estimates for commonly used working memory and response inhibition tests. Conclusions Finally, we show strong face and construct validity for these measures of cognitive control that generally exceeds the evidence required of new lab-based measures. We discuss these results and how broad implementation of this platform may allow us to uncover important brain-behavior relationships quickly and efficiently.

Background: Multiple epidemiological investigations have established that roadway proximity is as... more Background: Multiple epidemiological investigations have established that roadway proximity is associated with adverse cardiovascular conditions. Recent literature indicates circulating angiogenic cells (CACs), types vascular progenitor cells, may be indicators of exposure to roadway-generated pollutants. Our study advances cardiovascular science by describing associations between CACs and geographic roadway exposure metrics. Methods: Peripheral blood CAC levels of participants in the Louisville, KY Healthy Heart Study (n=240) were quantified using flow cytometry. Roadway exposure was assessed by utilizing GIS to measure distance to nearest roadway, total length of major roadways, total length of all roadways, and vehicle distance travelled, all within buffer areas between 50 and 300 meter intervals from subject residences. Generalized Linear Modeling was used to assess associations between roadway exposure and CAC levels. Results: CACs positive for early progenitor cell marker, AC1...

Background: Benzene is an aromatic hydrocarbon found in high amounts in vehicular exhaust and tob... more Background: Benzene is an aromatic hydrocarbon found in high amounts in vehicular exhaust and tobacco smoke. Exposure to traffic pollutants or chronic tobacco smoke exposure induces cardiovascular injury, suppresses circulating angiogenic cells (CACs), and increases thrombosis and atherogenesis. The purpose of this study was to examine whether benzene exposure is associated with CAC levels and cardiovascular injury in humans. Methods: Benzene exposure was assessed in 240 participants of the Louisville Healthy Heart Study with cardiovascular disease (CVD) risk by measuring the urinary levels of the benzene metabolite – trans, trans-muconic acid (t,t-MA). Because benzene is both environmental pollutant and a tobacco smoke constituent, urine cotinine levels were also measured. Generalized linear models were used to assess the association between benzene exposure and parameters of CVD risk and injury and adjusted for potential confounders. Results: The study population was 51±10 years o...

Journal of Child and Adolescent Psychopharmacology, 2003

This research aimed to increase understanding regarding functional impairment in children and ado... more This research aimed to increase understanding regarding functional impairment in children and adolescents with Obsessive-Compulsive Disorder (OCD). Eight South African children and adolescents with OCD participated in the study. The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), the Children's Global Assessment Scale (CGAS), the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Child Obsessive-Compulsive Impact Scale-Revised (COIS-R) were used to assess the children and adolescents' past and current psychopathology, OCD symptom severity and OCD-related functional impairment. Children and adolescents rated more problems as being significant than did their parents. In addition, parents reported that the most significant domain of impairment was in the school domain; child reports, in contrast, showed that the most significant impairments occurred in the school and social domains. Parents and children differed in terms of their ratings regarding the most significant individual functional problems. These findings differ from those of previous North American and European studies in this domain, and thus provide the rationale for future research that will examine the effect of culture on childhood OCD-related functional impairment. This future research will have important implications for the diagnosis and treatment of children with OCD in South Africa.

Journal of the American Academy of Child & Adolescent Psychiatry, 2014

To evaluate the frequency of adverse events (AEs) across 4 treatment conditions in the Child/Adol... more To evaluate the frequency of adverse events (AEs) across 4 treatment conditions in the Child/Adolescent Anxiety Multimodal Study (CAMS), and to compare the frequency of AEs between children and adolescents. Participants ages 7 to 17 years (mean = 10.7 years) meeting the DSM-IV criteria for 1 or more of the following disorders: separation anxiety disorder, generalized anxiety disorder, or social phobia were randomized (2:2:2:1) to cognitive-behavioral therapy (CBT, n = 139), sertraline (SRT, n = 133), a combination of both (COMB, n = 140), or pill placebo (PBO, n = 76). Data on AEs were collected via a standardized inquiry method plus a self-report Physical Symptom Checklist (PSC). There were no differences between the double-blinded conditions (SRT versus PBO) for total physical and psychiatric AEs or any individual physical or psychiatric AEs. The rates of total physical AEs were greater in the SRT-alone treatment condition when compared to CBT (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01) and COMB (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). Moreover, those who received SRT alone reported higher rates of several physical AEs when compared to COMB and CBT. The rate of total psychiatric AEs was higher in children (≤12 years) across all arms (31.7% versus 23.1%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). Total PSC scores decreased over time, with no significant differences between treatment groups. The results support the tolerability/safety of selective serotonin reuptake inhibitor (SSRI) treatment for anxiety disorders even after adjusting for the number of reporting opportunities, leading to no differences in overall rates of AEs. Few differences occurred on specific items. Additional monitoring of psychiatric AEs is recommended in children (≤12 years). Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); http://clinicaltrials.gov; NCT00052078.

Journal of Consulting and Clinical Psychology, 2014

To evaluate changes in the trajectory of youth anxiety following the introduction of specific cog... more To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive-behavior therapy (CBT) components: relaxation training, cognitive restructuring, and exposure tasks. Four hundred eighty-eight youths ages 7-17 years (50% female; 74% ≤ 12 years) were randomly assigned to receive either CBT, sertraline (SRT), their combination (COMB), or pill placebo (PBO) as part of their participation in the Child/Adolescent Anxiety Multimodal Study (CAMS). Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity (CGI-S; Guy, 1976) and the Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Global Assessment Scale (CGAS; Shaffer et al., 1983) and every 4 weeks by blind independent evaluators (IEs) using the Pediatric Anxiety Ratings Scale (PARS; RUPP Anxiety Study Group, 2002). Youths in SRT and PBO were included as controls. Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring (e.g., changing self-talk) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment; the introduction of relaxation training had limited impact. Counter to expectations, no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target (i.e., somatic symptoms, anxious self-talk, avoidance behavior). Findings support CBT theory and suggest that cognitive restructuring and exposure tasks each make substantial contributions to improvement in youth anxiety. Implications for future research are discussed. (PsycINFO Database Record

Journal of the American Heart Association, 2014

Acrolein is a reactive aldehyde present in high amounts in coal, wood, paper, and tobacco smoke. ... more Acrolein is a reactive aldehyde present in high amounts in coal, wood, paper, and tobacco smoke. It is also generated endogenously by lipid peroxidation and the oxidation of amino acids by myeloperoxidase. In animals, acrolein exposure is associated with the suppression of circulating progenitor cells and increases in thrombosis and atherogenesis. The purpose of this study was to determine whether acrolein exposure in humans is also associated with increased cardiovascular disease (CVD) risk. Acrolein exposure was assessed in 211 participants of the Louisville Healthy Heart Study with moderate to high (CVD) risk by measuring the urinary levels of the major acrolein metabolite-3-hydroxypropylmercapturic acid (3-HPMA). Generalized linear models were used to assess the association between acrolein exposure and parameters of CVD risk, and adjusted for potential demographic confounders. Urinary 3-HPMA levels were higher in smokers than nonsmokers and were positively correlated with urina...

Frontiers in Human Neuroscience, 2015

Journal of obsessive-compulsive and related disorders, 2014

Compared to studies in adults, there have been few studies of hoarding in children and adolescent... more Compared to studies in adults, there have been few studies of hoarding in children and adolescents with obsessive-compulsive disorder (OCD). In the current study, we evaluated OCD clinical features, Axis I disorders, and social reciprocity scores in 641 children and adolescents with OCD, of whom 163 (25%) had hoarding compulsions and 478 did not. We found that, as a group, youth with hoarding had an earlier age at onset and more severe lifetime OCD symptoms, poorer insight, more difficulty making decisions and completing tasks, and more overall impairment. The hoarding group also had a greater lifetime prevalence of panic disorder, specific phobia, Tourette disorder, and tics. As measured with the Social Reciprocity Scale, the hoarding group had more severe deficits in parent-rated domains of social communication, social motivation, and restricted interests and repetitive behavior. In a multivariable model, the overall social reciprocity score, age at onset of OCD symptoms, symmetry...

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53, Jan 27, 2017

Cognitive behavioral therapy (CBT) for anxiety disorders is effective, but nonadherence with trea... more Cognitive behavioral therapy (CBT) for anxiety disorders is effective, but nonadherence with treatment may reduce the benefits of CBT. This study examined (a) four baseline domains (i.e., demographic, youth clinical characteristics, therapy related, family/parent factors) as predictors of youth adherence with treatment and (b) the associations between youth adherence and treatment outcomes. Data were from 279 youth (7-17 years of age, 51.6% female; 79.6% White, 9% African American), with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) diagnoses of separation anxiety disorder, generalized anxiety disorder, and/or social phobia, who participated in CBT in the Child/Adolescent Anxiety Multimodal Study. Adherence was defined in three ways (session attendance, therapist-rated compliance, and homework completion). Multiple regressions revealed several significant predictors of youth adherence with CBT, but predictors varied according to the definition of adheren...

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53, Jan 26, 2017

Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors are effective trea... more Cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors are effective treatments for pediatric anxiety disorders. However, the mechanisms of these treatments are unknown. Previous research indicated that somatic symptoms are reduced following treatment, but it is unclear if their reductions are merely a consequence of treatment gains. This study examined reductions in somatic symptoms as a potential mediator of the relationship between treatment and anxiety outcomes. Participants were 488 anxious youth ages 7-17 (M = 10.7), 50.4% male, 78.9% Caucasian, enrolled in Child/Adolescent Anxiety Multimodal Study, a large randomized control trial comparing 12-week treatments of CBT, sertraline, a combination of CBT and sertraline, and a pill placebo. Causal mediation models were tested in R using data from baseline, 8-, and 12-week evaluations. Somatic symptoms were assessed using the Panic/Somatic subscale from the Screen for Child Anxiety Related Emotional Disorders...

Journal of Child and Adolescent Psychopharmacology, 2016

Objectives: The characterization and prediction of placebo response in clinical trials of youth w... more Objectives: The characterization and prediction of placebo response in clinical trials of youth with anxiety disorders have received little attention, despite the critical effects of placebo response rate on the success or failure of clinical trials. With this in mind, we sought to examine the factors that predict or influence placebo response in randomized controlled trials of youth with anxiety disorders. Methods: Prospective, randomized, parallel-group controlled trials of psychopharmacologic interventions in pediatric patients with anxiety disorders were identified using a search of PubMed/Medline (1966-2015). Weighted least squares regression models and z-tests were utilized to examine the impact of continuous and categorical variables, respectively, on placebo response. These variables included demographic (e.g., age, percent white, percent female), clinical (e.g., baseline symptom severity), and trial characteristics (sample size, duration, funding). Finally, the relationship between the class of comparator medication and placebo response rate was examined using a multiple comparison for proportions test. Results: The analyses of data from 14 trials involving 2230 patients and 9 medications reveal that higher placebo response rates were associated with a greater number of study sites (p = 0.013) and fewer patients per site (p < 0.008), while placebo dropout rates increased with more recent publication (p = 0.01) and were positively associated with the number of study visits (p < 0.02). Lower placebo response rates were associated with federally funded studies (z =-4.61, p < 0.001), studies conducted in the United States (z = 1.81, p < 0.035), and with an increased likelihood of detecting a significant effect on the primary outcome (z = 4.58, p < 0.0001). Additionally, studies, in which the majority of patients (>60%) had a diagnosis of social anxiety disorder, exhibited lower placebo response rates (p < 0.001). Finally, for trials, effect size has decreased over time (p = 0.004). Conclusions: Important trial-specific factors affect placebo response and placebo dropout in youth with anxiety disorders and have pragmatic implications for the conduct and design of clinical trials and raise the possibility that limiting the number of sites while maximizing the number of patients per site could enhance the ability to detect medication-placebo differences.

Journal of Consulting and Clinical Psychology, 2015

Objective-To evaluate changes in the trajectory of youth anxiety following the introduction of sp... more Objective-To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive behavior therapy (CBT) components: relaxation training, cognitive restructuring, and exposure tasks. Methods-488 youths ages 7-17 years (50% female; 74% ≤ 12 years) were randomly assigned to receive either CBT, sertraline (SRT), their combination (COMB), or pill placebo (PBO) as part of their participation in the Child/Adolescent Anxiety Multimodal Study (CAMS). Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity (CGI-S; Guy, 1976) and the Children's Global Assessment Scale (CGAS; Schaffer et al., 1983) and every four weeks by blind independent evaluators (IEs) using the Pediatric Anxiety Ratings Scale (PARS; Rupp Study Group, 2002). Youths in SRT and PBO were included as controls. Results-Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring (e.g., changing self-talk) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment; the introduction of relaxation training had limited impact. Counter to expectations, no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target (i.e., somatic symptoms, anxious self-talk, avoidance behavior).

Journal of the American Academy of Child & Adolescent Psychiatry, 2011

Objective-We previously reported that a history of abuse was associated with a poorer response to... more Objective-We previously reported that a history of abuse was associated with a poorer response to combination treatment in the Treatment of Resistant Depression in Adolescents study (TORDIA). We now report on the nature and correlates of abuse that might explain these findings. Method-Youth who did not benefit from an adequate selective serotonin re-uptake inhibitor (SSRI) trial (N=334) were randomized to: an alternative SSRI; an alternative SSRI plus cognitive behavior therapy (CBT); venlafaxine; or venlafaxine plus CBT. Analyses examined the effect of history of abuse on response to the pharmacotherapy and combination therapy. Results-Those without a history of physical abuse (PA) or sexual abuse (SA) had a higher 12week response rate to combination therapy compared to medication mono-therapy (62.8% vs. 37.6%; OR=2.8, 95% CI: 1.6-4.7, p<0.001). Those with a history of SA had similar response rates to combination vs. medication monotherapy (48.3% vs. 42.3%; OR=1.3, 95% CI: 0.4-3.7; p=0.66), while those with history of PA had a much lower rate of response to combination therapy (18.4% vs. 52.4%, OR=0.1; 95% CI: 0.02-0.43). Even after adjusting for other clinical predictors, a history of PA moderated treatment outcome. Conclusion-These results should be considered within the limitations of a post-hoc analysis, lack of detailed assessment of abuse and other forms of trauma, and neuropsychological status. Depressed patients with history of abuse, especially PA may require specialized clinical approaches. Further work is needed to understand by what mechanisms a history of abuse affects treatment response.

Journal of Anxiety Disorders, 2010

Reports the characteristics of a large, representative sample of treatment seeking anxious youth ... more Reports the characteristics of a large, representative sample of treatment seeking anxious youth (N =488). Participants, aged 7-17 years (mean 10.7 yrs), had a principal DSM-IV diagnosis of separation anxiety disorder (SAD), generalized anxiety disorder (GAD), or social phobia (SP). Although youth with a co-primary diagnosis for which a different disorder-specific treatment would be indicated (e.g., major depressive disorder, substance abuse) were not included, there were few other exclusion criteria. Participants and their parent/guardian underwent an extensive baseline assessment using a broad array of measures capturing diagnostic status, anxiety symptoms and severity, and areas of functional impairment. Means and standard deviations of the measures of psychopathology and data on diagnostic status are provided. The sample had moderate to severe anxiety disorder and was highly comorbid, with 55.3% of participants meeting criteria for at least one non-targeted DSM-IV disorder. Anxiety disorders in youth often do not present as a single/focused disorder: such disorders in youth overlap in symptoms and are highly comorbid among themselves. Keywords anxiety; anxiety in children and adolescence; comorbidities Anxiety disorders are among the most common conditions affecting youth (Costello, Egger, & Angold, 2005). Epidemiological reports based on large and/or nationally representative samples estimate the prevalence of anxiety disorders in youth to range between 10% and 20% (Achenbach, et al., 1995; Shaffer, Fisher, Dulcan, & Davies, 1996). In general, anxiety disorders are often comorbid among themselves and with other disorders. If left untreated, pediatric anxiety disorders predict adult anxiety disorders and depression; and other childhood sequelae, such as substance use problems, suicide attempts, and hospitalization (Ferdinand &

Journal of Clinical Psychopharmacology, 2011

This paper examines the relationship between plasma concentration of antidepressant and both clin... more This paper examines the relationship between plasma concentration of antidepressant and both clinical response and adverse effects in treatment-resistant depressed adolescents. Adolescents (n = 334) with major depression who had not responded to a selective serotonin reuptake inhibitor (SSRI) were randomized to 1 of 4 treatments: switch to another SSRI (fluoxetine, citalopram, or paroxetine), switch to venlafaxine, switch to SSRI plus cognitive behavior therapy, or switch to

Journal of the American Academy of Child & Adolescent Psychiatry, 2014

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Autism : the international journal of research and practice, Jan 16, 2015

Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two f... more Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder to detect change with treatment. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. In Study 2, 49 subjects received risperidone only and 75 subjects received risperidone plus parent training. The combined sample consisted of 187 boys and 38 girls (aged 4-17 years). At the medication-free baseline, the internal consistency on the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder total score was excellent (Cronbach's alpha = 0.84) and the mean scores were similar across the four groups. Compared to placebo in Study 1, all...

Psychological medicine, 2009

Obsessive-compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many pa... more Obsessive-compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes. Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated. Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive di...

Free Radical Biology and Medicine, 2013

Type 2 Diabetes (T2D) has been associated with deleterious changes in multiple stem cell populati... more Type 2 Diabetes (T2D) has been associated with deleterious changes in multiple stem cell populations; however, the effects of T2D on cardiac stem cells (CSCs) remain unknown. This is important because T2D is associated with increased mortality and progression to heart failure. We examined the effects of diabetes on mouse CSC metabolism and function. Under basal conditions, c-kit + /lin -CSCs expressed both the Glut1 and Glut4 transporters, displayed insulin-independent glucose utilization, and showed highly coupled mitochondrial respiratory activity. CSCs isolated from diabetic (db/db) mice showed a 50 75% decrease in basal and maximal mitochondrial respiratory capacity, decreased cytochrome oxidase activity, and an increase in glycolysis compared with non-diabetic CSCs. Mitochondrial content, as assessed by qPCR of mitochondrial:nuclear DNA, was not significantly different between wild-type and db/db CSCs. Diabetic CSCs, although resistant to insulin, demonstrated a 3-fold increase in basal Akt phosphorylation and a 4-fold increase in phosphofructokinase/bisphosphatase-2 isoform 3 (PFKFB3) an isoform of PFK2 that sustains high rates of glycolysis. the diabetic CSCs showed a decreased capacity to attain Nkx2.5 positivity upon differentiation and an inability to increase additional markers of differentiation. in vivo, even mild conditions of metabolic syndrome decreased CSC reparative capacity. Mice fed a highfat-diet for 12 weeks showed no improvement in myocardial infarction-induced heart failure after CSC transplantation, whereas infarcted, normal chow-fed mice responded normally to CSC therapy. These data indicate that diabetes induces a dormant CSC phenotype associated with high rates of glycolysis and decreased mitochondrial function. This metabolic phenotype appears to mirror the Warburg glycolytic feature of cancer cells and may underlie deficits in reparative capacity in diabetes.

Brain and Behavior, 2013

Introduction Understanding the relationship between brain and complex latent behavioral construct... more Introduction Understanding the relationship between brain and complex latent behavioral constructs like cognitive control will require an inordinate amount of data. Internet-based methods can rapidly and efficiently refine behavioral measures in very large samples that are needed for genetics and behavioral research. Cognitive control is a multifactorial latent construct that is considered to be an endophenotype in numerous neuropsychiatric disorders, including attention deficit/hyperactivity disorder (ADHD). While previous studies have demonstrated high correlations between Web- and lab-based scores, skepticism remains for its broad implementation. Methods Here, we promote a different approach by characterizing a completely Web-recruited and tested community family sample on measures of cognitive control. We examine the prevalence of attention deficit symptoms in an online community sample of adolescents, demonstrate familial correlations in cognitive control measures, and use construct validation techniques to validate our high-throughput assessment approach. Results A total of 1214 participants performed Web-based tests of cognitive control with over 200 parent-child pairs analyzed as part of the primary study aims. The data show a wide range of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;subclinical&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; symptomatology in a web community sample of adolescents that supports a dimensional view of attention and also provide preliminary narrow-sense heritability estimates for commonly used working memory and response inhibition tests. Conclusions Finally, we show strong face and construct validity for these measures of cognitive control that generally exceeds the evidence required of new lab-based measures. We discuss these results and how broad implementation of this platform may allow us to uncover important brain-behavior relationships quickly and efficiently.

Background: Multiple epidemiological investigations have established that roadway proximity is as... more Background: Multiple epidemiological investigations have established that roadway proximity is associated with adverse cardiovascular conditions. Recent literature indicates circulating angiogenic cells (CACs), types vascular progenitor cells, may be indicators of exposure to roadway-generated pollutants. Our study advances cardiovascular science by describing associations between CACs and geographic roadway exposure metrics. Methods: Peripheral blood CAC levels of participants in the Louisville, KY Healthy Heart Study (n=240) were quantified using flow cytometry. Roadway exposure was assessed by utilizing GIS to measure distance to nearest roadway, total length of major roadways, total length of all roadways, and vehicle distance travelled, all within buffer areas between 50 and 300 meter intervals from subject residences. Generalized Linear Modeling was used to assess associations between roadway exposure and CAC levels. Results: CACs positive for early progenitor cell marker, AC1...

Background: Benzene is an aromatic hydrocarbon found in high amounts in vehicular exhaust and tob... more Background: Benzene is an aromatic hydrocarbon found in high amounts in vehicular exhaust and tobacco smoke. Exposure to traffic pollutants or chronic tobacco smoke exposure induces cardiovascular injury, suppresses circulating angiogenic cells (CACs), and increases thrombosis and atherogenesis. The purpose of this study was to examine whether benzene exposure is associated with CAC levels and cardiovascular injury in humans. Methods: Benzene exposure was assessed in 240 participants of the Louisville Healthy Heart Study with cardiovascular disease (CVD) risk by measuring the urinary levels of the benzene metabolite – trans, trans-muconic acid (t,t-MA). Because benzene is both environmental pollutant and a tobacco smoke constituent, urine cotinine levels were also measured. Generalized linear models were used to assess the association between benzene exposure and parameters of CVD risk and injury and adjusted for potential confounders. Results: The study population was 51±10 years o...

Journal of Child and Adolescent Psychopharmacology, 2003

This research aimed to increase understanding regarding functional impairment in children and ado... more This research aimed to increase understanding regarding functional impairment in children and adolescents with Obsessive-Compulsive Disorder (OCD). Eight South African children and adolescents with OCD participated in the study. The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), the Children's Global Assessment Scale (CGAS), the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Child Obsessive-Compulsive Impact Scale-Revised (COIS-R) were used to assess the children and adolescents' past and current psychopathology, OCD symptom severity and OCD-related functional impairment. Children and adolescents rated more problems as being significant than did their parents. In addition, parents reported that the most significant domain of impairment was in the school domain; child reports, in contrast, showed that the most significant impairments occurred in the school and social domains. Parents and children differed in terms of their ratings regarding the most significant individual functional problems. These findings differ from those of previous North American and European studies in this domain, and thus provide the rationale for future research that will examine the effect of culture on childhood OCD-related functional impairment. This future research will have important implications for the diagnosis and treatment of children with OCD in South Africa.

Journal of the American Academy of Child & Adolescent Psychiatry, 2014

To evaluate the frequency of adverse events (AEs) across 4 treatment conditions in the Child/Adol... more To evaluate the frequency of adverse events (AEs) across 4 treatment conditions in the Child/Adolescent Anxiety Multimodal Study (CAMS), and to compare the frequency of AEs between children and adolescents. Participants ages 7 to 17 years (mean = 10.7 years) meeting the DSM-IV criteria for 1 or more of the following disorders: separation anxiety disorder, generalized anxiety disorder, or social phobia were randomized (2:2:2:1) to cognitive-behavioral therapy (CBT, n = 139), sertraline (SRT, n = 133), a combination of both (COMB, n = 140), or pill placebo (PBO, n = 76). Data on AEs were collected via a standardized inquiry method plus a self-report Physical Symptom Checklist (PSC). There were no differences between the double-blinded conditions (SRT versus PBO) for total physical and psychiatric AEs or any individual physical or psychiatric AEs. The rates of total physical AEs were greater in the SRT-alone treatment condition when compared to CBT (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01) and COMB (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .01). Moreover, those who received SRT alone reported higher rates of several physical AEs when compared to COMB and CBT. The rate of total psychiatric AEs was higher in children (≤12 years) across all arms (31.7% versus 23.1%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). Total PSC scores decreased over time, with no significant differences between treatment groups. The results support the tolerability/safety of selective serotonin reuptake inhibitor (SSRI) treatment for anxiety disorders even after adjusting for the number of reporting opportunities, leading to no differences in overall rates of AEs. Few differences occurred on specific items. Additional monitoring of psychiatric AEs is recommended in children (≤12 years). Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); http://clinicaltrials.gov; NCT00052078.

Journal of Consulting and Clinical Psychology, 2014

To evaluate changes in the trajectory of youth anxiety following the introduction of specific cog... more To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive-behavior therapy (CBT) components: relaxation training, cognitive restructuring, and exposure tasks. Four hundred eighty-eight youths ages 7-17 years (50% female; 74% ≤ 12 years) were randomly assigned to receive either CBT, sertraline (SRT), their combination (COMB), or pill placebo (PBO) as part of their participation in the Child/Adolescent Anxiety Multimodal Study (CAMS). Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity (CGI-S; Guy, 1976) and the Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Global Assessment Scale (CGAS; Shaffer et al., 1983) and every 4 weeks by blind independent evaluators (IEs) using the Pediatric Anxiety Ratings Scale (PARS; RUPP Anxiety Study Group, 2002). Youths in SRT and PBO were included as controls. Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring (e.g., changing self-talk) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment; the introduction of relaxation training had limited impact. Counter to expectations, no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target (i.e., somatic symptoms, anxious self-talk, avoidance behavior). Findings support CBT theory and suggest that cognitive restructuring and exposure tasks each make substantial contributions to improvement in youth anxiety. Implications for future research are discussed. (PsycINFO Database Record

Journal of the American Heart Association, 2014

Acrolein is a reactive aldehyde present in high amounts in coal, wood, paper, and tobacco smoke. ... more Acrolein is a reactive aldehyde present in high amounts in coal, wood, paper, and tobacco smoke. It is also generated endogenously by lipid peroxidation and the oxidation of amino acids by myeloperoxidase. In animals, acrolein exposure is associated with the suppression of circulating progenitor cells and increases in thrombosis and atherogenesis. The purpose of this study was to determine whether acrolein exposure in humans is also associated with increased cardiovascular disease (CVD) risk. Acrolein exposure was assessed in 211 participants of the Louisville Healthy Heart Study with moderate to high (CVD) risk by measuring the urinary levels of the major acrolein metabolite-3-hydroxypropylmercapturic acid (3-HPMA). Generalized linear models were used to assess the association between acrolein exposure and parameters of CVD risk, and adjusted for potential demographic confounders. Urinary 3-HPMA levels were higher in smokers than nonsmokers and were positively correlated with urina...

Frontiers in Human Neuroscience, 2015

Journal of obsessive-compulsive and related disorders, 2014

Compared to studies in adults, there have been few studies of hoarding in children and adolescent... more Compared to studies in adults, there have been few studies of hoarding in children and adolescents with obsessive-compulsive disorder (OCD). In the current study, we evaluated OCD clinical features, Axis I disorders, and social reciprocity scores in 641 children and adolescents with OCD, of whom 163 (25%) had hoarding compulsions and 478 did not. We found that, as a group, youth with hoarding had an earlier age at onset and more severe lifetime OCD symptoms, poorer insight, more difficulty making decisions and completing tasks, and more overall impairment. The hoarding group also had a greater lifetime prevalence of panic disorder, specific phobia, Tourette disorder, and tics. As measured with the Social Reciprocity Scale, the hoarding group had more severe deficits in parent-rated domains of social communication, social motivation, and restricted interests and repetitive behavior. In a multivariable model, the overall social reciprocity score, age at onset of OCD symptoms, symmetry...