Myocardial ischemic disease is the major cause of death worldwide. After myocardial infarction, reperfusion of infracted heart has been an important objective of strategies to improve outcomes. ...However, cardiac ischemia/reperfusion (I/R) is characterized by inflammation, arrhythmias, cardiomyocyte damage, and, at the cellular level, disturbance in Ca²⺠and redox homeostasis. In this study, we sought to determine how acute inflammatory response contributes to reperfusion injury and Ca²⺠homeostasis disturbance after acute ischemia. Using a rat model of I/R, we show that circulating levels of TNF-α and cardiac caspase-8 activity were increased within 6 h of reperfusion, leading to myocardial nitric oxide and mitochondrial ROS production. At 1 and 15 d after reperfusion, caspase-8 activation resulted in S-nitrosylation of the RyR2 and depletion of calstabin2 from the RyR2 complex, resulting in diastolic sarcoplasmic reticulum (SR) Ca²⺠leak. Pharmacological inhibition of caspase-8 before reperfusion with Q-LETD-OPh or prevention of calstabin2 depletion from the RyR2 complex with the Ca²⺠channel stabilizer S107 ("rycal") inhibited the SR Ca²⺠leak, reduced ventricular arrhythmias, infarct size, and left ventricular remodeling after 15 d of reperfusion. TNF-α-induced caspase-8 activation leads to leaky RyR2 channels that contribute to myocardial remodeling after I/R. Thus, early prevention of SR Ca²⺠leak trough normalization of RyR2 function is cardioprotective.
We report active treatment group differences on response and remission rates and changes in anxiety severity at weeks 24 and 36 for the Child/Adolescent Anxiety Multimodal Study (CAMS).
CAMS youth (N ...= 488; 74% ≤ 12 years of age) with DSM-IV separation, generalized, or social anxiety disorder were randomized to 12 weeks of cognitive-behavioral therapy (CBT), sertraline (SRT), CBT+SRT (COMB), or medication management/pill placebo (PBO). Responders attended 6 monthly booster sessions in their assigned treatment arm; youth in COMB and SRT continued on their medication throughout this period. Efficacy of COMB, SRT, and CBT (n = 412) was assessed at 24 and 36 weeks postrandomization. Youth randomized to PBO (n = 76) were offered active CAMS treatment if nonresponsive at week 12 or over follow-up and were not included here. Independent evaluators blind to study condition assessed anxiety severity, functioning, and treatment response. Concomitant treatments were allowed but monitored over follow-up.
The majority (>80%) of acute responders maintained positive response at both weeks 24 and 36. Consistent with acute outcomes, COMB maintained advantage over CBT and SRT, which did not differ, on dimensional outcomes; the 3 treatments did not differ on most categorical outcomes over follow-up. Compared to COMB and CBT, youth in SRT obtained more concomitant psychosocial treatments, whereas those in SRT and CBT obtained more concomitant combined (medication plus psychosocial) treatment.
COMB maintained advantage over CBT and SRT on some measures over follow-up, whereas the 2 monotherapies remained indistinguishable. The observed convergence of COMB and monotherapy may be related to greater use of concomitant treatment during follow-up among youth receiving the monotherapies, although other explanations are possible. Although outcomes were variable, most CAMS-treated youth experienced sustained treatment benefit. Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); URL: http://clinicaltrials.gov. Unique identifier: NCT00052078.
Objective: To review the literature on the cognitive-behavioral treatment of children and adolescents with anxiety and depressive disorders within the conceptual framework of evidence-based medicine. ...Method: The psychiatric and psychological literature was systematically searched for controlled trials applying cognitive-behavioral treatment to pediatric anxiety and depressive disorders. Results: For both anxiety and depression, substantial evidence supports the efficacy of problem-specific cognitive-behavioral interventions. Comparisons with wait-list, inactive control, and active control conditions suggest medium to large effects for symptom reduction in primary outcome domains. Conclusions: From an evidence-based perspective, cognitive-behavioral therapy is currently the treatment of choice for anxiety and depressive disorders in children and adolescents. Future research in this area will need to focus on comparing cognitive-behavioral psychotherapy with other treatments, component analyses, and the application of exportable protocol-driven treatments to divergent settings and patient populations.
In this randomized study, children and adolescents with primary diagnoses of separation anxiety or generalized anxiety disorders or social phobia received cognitive behavioral therapy, sertraline, a ...combination of these treatments, or placebo for 12 weeks. The results indicate that both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders, and a combination of the two therapies had superior response rates.
The results of this study indicate that both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders, and a combination of the two therapies had superior response rates.
Anxiety disorders are common in children and cause substantial impairment in school, in family relationships, and in social functioning.
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Such disorders also predict adult anxiety disorders and major depression.
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Despite a high prevalence (10 to 20%
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) and substantial morbidity, anxiety disorders in childhood remain underrecognized and undertreated.
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An improvement in outcomes for children with anxiety disorders would have important public health implications.
In clinical trials, separation and generalized anxiety disorders and social phobia are often grouped together because of the high degree of overlap in symptoms and the distinction from other anxiety disorders (e.g., . . .
Objective: We sought to examine predictors and moderators of treatment outcomes among 488 youths ages 7-17 years (50% female; 74% ≤ 12 years) meeting Diagnostic and Statistical Manual of Mental ...Disorders (4th ed., text rev.; American Psychiatric Association, 2000) criteria for diagnoses of separation anxiety disorder, social phobia, or generalized anxiety disorder who were randomly assigned to receive either cognitive behavioral therapy (CBT), sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) in the Child/Adolescent Anxiety Multimodal Study (CAMS). Method: Six classes of predictor and moderator variables (22 variables) were identified from the literature and examined using continuous (Pediatric Anxiety Ratings Scale; PARS) and categorical (Clinical Global Impression Scale-Improvement; CGI-I) outcome measures. Results: Three baseline variables predicted better outcomes (independent of treatment condition) on the PARS, including low anxiety severity (as measured by parents and independent evaluators) and caregiver strain. No baseline variables were found to predict Week 12 responder status (CGI-I). Participants' principal diagnosis moderated treatment outcomes but only on the PARS. No baseline variables were found to moderate treatment outcomes on Week 12 responder status (CGI-I). Discussion: Overall, anxious children responded favorably to CAMS treatments. However, having more severe and impairing anxiety, greater caregiver strain, and a principal diagnosis of social phobia were associated with less favorable outcomes. Clinical implications of these findings are discussed.
Objective: Social phobia typically develops during the adolescent years, yet no nationally representative studies in the United States have examined the rates and features of this condition among ...youth in this age range. The objectives of this investigation were to: (1) present the lifetime prevalence, sociodemographic and clinical correlates, and comorbidity of social phobia in a large, nationally representative sample of U.S. adolescents; and (2) examine differences in the rates and features of social phobia across the proposed "DSM-5" social phobia subtypes. Method: The National Comorbidity Survey Replication-Adolescent Supplement is a nationally representative face-to-face survey of 10,123 adolescents 13 to 18 years of age in the continental United States. Results: Approximately 9% of adolescents met criteria for any social phobia in their lifetime. Of these adolescents, 55.8% were affected with the generalized subtype and 44.2% exhibited nongeneralized social phobia. Only 0.7% met criteria for the proposed DSM-5 performance-only subtype. Generalized social phobia was more common among female adolescents and risk for this subtype increased with age. Adolescents with generalized social phobia also had a younger age of onset, higher levels of disability and clinical severity, and a greater degree of comorbidity relative to adolescents with nongeneralized forms of the disorder. Conclusions: This study indicates that social phobia is a highly prevalent, persistent, and impairing psychiatric disorder among adolescent youth. Results of this study also provide evidence for the clinical utility of the generalized subtype and highlight the importance of considering the heterogeneity of social phobia in this age group. (Contains 1 figure and 3 tables.)
Anorexia nervosa (AN) is a serious mental illness characterized by reduced caloric intake that often persists after acute weight restoration. This preliminary study assesses the relationship between ...pre-meal anxiety and food intake in recently weight-restored individuals with AN. We hypothesized that pre-meal anxiety is inversely related to caloric intake in AN. Caloric intake and pre-meal anxiety were measured in three laboratory-based assessments (yogurt snack, multi-item lunch, macaroni and cheese lunch). Anxiety was measured by Spielberger State-Trait Anxiety Inventory (STAI-S) administered prior to the meal. Acutely weight-restored patients with AN were compared with healthy controls (HCs). Associations between anxiety and intake were analyzed first within each meal type separately and then using a model to combine the sample. In the multi-item lunch and the macaroni and cheese lunch, AN ate significantly less than HC (p=0.01, p<0.001). Pre-meal anxiety was significantly correlated with intake among AN, but not HC. In the yogurt snack, there was no significant association between anxiety and intake among patients or controls, and the groups did not differ in caloric intake. The association between pre-meal anxiety and intake among weight-restored individuals with AN suggests a potential target for relapse prevention treatment.
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