Background Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. Methods In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. Results The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. Conclusions Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.)

Context Tourette disorder is a chronic and typically impairing childhood-onset neurological condition. Antipsychotic medications, the first-line treatments for moderate to severe tics, are often associated with adverse effects. Behavioral interventions, although promising, have not been evaluated in large-scale controlled trials. Objective To determine the efficacy of a comprehensive behavioral intervention for reducing tic severity in children and adolescents. Design, Setting, Participants Randomized, observer-blind, controlled trial of 126 youngsters recruited from December, 2004 through May, 2007 and aged 9–17 years with impairing Tourette or chronic tic disorder as primary diagnosis randomized to 8 sessions over 10 weeks of behavior therapy (n=61) or a control treatment consisting of supportive therapy and education (n=65). Responders received 3 monthly treatment booster sessions and were reassessed at 3- and 6-months post-treatment. Intervention Comprehensive behavioral intervention. Main Outcome Measures Yale Global Tic Severity Scale (range 0–40, score >15 indicating clinically significant tics), Clinical Global Impression-Improvement Scale (range 1-very much improved to 8-very much worse). Results Behavioral intervention led to a significantly greater decrease on the Yale Global Tic Severity Scale (24.7; CI:23.1,26.3) to 17.1 CI:15.1,19.1) from baseline to endpoint compared to the control treatment (24.6 CI:23.2,26.0) to 21.1 CI:19.2,23.0) (P<.001; 95% CI for difference between groups: 6.2, 2.0); (effect size=0.68). Compared to children in control treatment, significantly more children receiving behavioral intervention were rated as “very much” or “much improved” on the Clinical Global Impression-Improvement scale (52.5% to 18.5%, respectively; P<0.001; number-needed-to-treat=3). Attrition was low (12/126 or 9.5%); tic worsening was reported by 4% of children (5/126). Treatment gains were durable with 87% of available responders to behavior therapy showing continued benefit 6 months post-treatment. Conclusions A comprehensive behavioral intervention, compared with supportive therapy and education, resulted in greater improvement in symptom severity among children with Tourette and chronic tic disorder.

Obsessive-compulsive disorder is a familial disorder. Obsessions are more specific to the phenotype than are compulsions. Age at onset of OCD is valuable in characterizing a familial subtype.

Context Tics in Tourette syndrome begin in childhood, peak in early adolescence, and often decline by early adulthood. However, some adult patients continue to have impairing tics. Medications for tics are often effective but can cause adverse effects. Behavior therapy may offer an alternative but has not been examined in a large-scale controlled trial in adults. Objective To test the efficacy of a comprehensive behavioral intervention for tics in adults with Tourette syndrome of at least moderate severity. Design A randomized, controlled trial with posttreatment evaluations at 3 and 6 months for positive responders. Setting Three outpatient research clinics. Subjects Subjects (N = 122; 78 males, age 16 to 69 years) with Tourette syndrome or chronic tic disorder. Interventions Eight sessions of Comprehensive Behavioral Intervention for Tics or 8 sessions of supportive treatment delivered over 10 weeks. Subjects showing a positive response were given 3 monthly booster sessions. Main Outcome Measures Total Tic score of the Yale Global Tic Severity Scale and the Improvement scale of the Clinical Global Impression rated by a clinician blind to treatment assignment. Results Behavior therapy was associated with a significantly greater decrease on the Yale Global Tic Severity Scale (24.0 ± 6.47 to 17.8 ± 7.32) from baseline to endpoint compared to the control treatment (21.8 ± 6.59 to 19.3 ± 7.40) (P < .001; effect size = 0.57). Twenty-four of 63 subjects (38.1%) in CBIT were rated as Much Improved or Very Much Improved on the Clinical Global Impression-Improvement scale compared to 6.8% (4 of 63) in the control group (P < .0001). Attrition was 13.9% with no difference across groups. Subjects in behavior therapy available for assessment at 6 months posttreatment showed continued benefit. Conclusions Comprehensive behavior therapy is a safe and effective intervention for adults with Tourette syndrome.

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.

Objective To report on remission rates in anxious youth who participated in the Child/Adolescent Anxiety Multimodal Study (CAMS). The CAMS, a multisite clinical trial, randomized 488 children and adolescents (ages 7–17 years; 79% Caucasian; 50% female) with separation, social, and/or generalized anxiety disorder to a 12-week treatment of sertraline (SRT), cognitive behavioral therapy (CBT), their combination (COMB), or clinical management with pill placebo (PBO). Method The primary definition of remission was loss of all study-entry anxiety disorder diagnoses; additional definitions of remission were used. All outcomes were rated by independent evaluators blind to treatment assignment. Predictors of remission were also examined. Results Remission rates after 12 weeks of treatment ranged from 46% to 68% for COMB, 34% to 46% for SRT, 20% to 46% for CBT, and 15% to 27% for PBO. Rates of remission (i.e., achieving a nearly symptom-free state) were significantly lower than rates of response (i.e., achieving a clinically meaningful improvement relative to baseline) for the entire sample. Youth who received COMB had significantly higher rates of remission compared to all other treatment groups. Both monotherapies had higher remission rates compared to PBO, but rates were not different from each other. Predictors of remission were younger age, nonminority status, lower baseline anxiety severity, absence of other internalizing disorders (e.g., anxiety, depression), and absence of social phobia. Conclusions For the majority of children, some symptoms of anxiety persisted, even among those showing improvement after 12 weeks of treatment, suggesting a need to augment or extend current treatments for some children.

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.

Objective-To identify the predictors of suicidal events and attempts in depressed adolescent suicide attempters treated in an open treatment trial.Method-Adolescents who had made a recent suicide attempt and had unipolar depression (n=124) were either randomized (n=22) or given a choice (n=102) among three conditions. Two participants withdrew prior to treatment assignment. The remaining 124 youth received either: a specialized psychotherapy for suicide attempting adolescents (n=17), a medication algorithm (n=14), or the combination (n=93). The participants were followed up 6 months after intake with respect to rate, timing, and predictors of a suicidal event (attempt or acute suicidal ideation necessitating emergency referral).Results-The morbid risks of suicidal events and attempts upon 6-month follow-up were 0.19 and 0.12, respectively, with a median time to event of 44 days. Higher self-rated depression, suicidal ideation, family income, greater number of previous suicide attempts, lower maximum lethality of previous attempt, history of sexual abuse, and lower family cohesion predicted the occurrence, and earlier time to event, with similar findings for the outcome of attempts. A slower decline in suicidal ideation was associated with the occurrence of a suicidal event.Conclusions-In this open trial, the 6-month morbid risks for suicidal events and for re-attempts were lower than in other comparable samples, suggesting that this intervention should be studied further. Important treatment targets include suicidal ideation, family cohesion, and sequelae of previous abuse. Because 40% of events occurred with 4 weeks of intake, an emphasis on safety planning and increased therapeutic contact early in treatment may be warranted.