Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal dopamine (DA) levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. Dopamine D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm HDC deficiency as a rare cause of TS and identify histamine-dopamine interactions in the basal ganglia as an important locus of pathology.

Objective Family accommodation refers to ways in which family members assist the proband in the performance of rituals, avoidance of anxiety provoking situations, or modification of daily routines to assist a relative with obsessive-compulsive disorder. The purpose of this review was to analyze and integrate the available data on the role of family accommodation in pediatric obsessive compulsive disorder including its prevalence and its relationship the course of the disorder. Method A search of available peer reviewed English language papers was conducted through PubMed and PsycINFO cross-referencing the keyword OCD, with accommodation, family relations, and parents. Resulting papers were individually evaluated for relevance to the scope of the review. Results Accommodation is common in pediatric OCD and is strongly associated with symptom severity. Levels of accommodation have been also associated with treatment outcomes for both cognitive behavioral and pharmacological treatment. Significant improvement with treatment in OCD is often associated with reductions in family accommodation.. Conclusion Family accommodation represents important clinical data that is worth measuring, monitoring and tracking in clinical care. Therapies targeting family accommodation may be successful in improving treatment outcomes in pediatric OCD.

BACKGROUND: Anxiety is a common and impairing problem in children and adolescents with autism spectrum disorder (ASD). There is emerging evidence that cognitive-behavioral therapy (CBT) could reduce anxiety in children with high-functioning ASD.OBJECTIVE: To systematically review the evidence of using CBT to treat anxiety in children and adolescents with ASD. Methods for this review were registered with PROSPERO (CRD42012002722). METHODS:We included randomized controlled trials published in English in peer-reviewed journals comparing CBT with another treatment, no treatment control, or waitlist control. Two authors independently screened 396 records obtained from database searches and hand searched relevant journals. Two authors independently extracted and reconciled all data used in analyses from study reports.RESULTS: Eight studies involving 469 participants (252 treatment, 217 comparison) met our inclusion criteria and were included in metaanalyses. Overall effect sizes for clinician-and parent-rated outcome measures of anxiety across all studies were d = 1.19 and d = 1.21, respectively. Five studies that included child self-report yielded an average d = 0.68 across self-reported anxiety.CONCLUSIONS: Parent ratings and clinician ratings of anxiety are sensitive to detecting treatment change with CBT for anxiety relative to waitlist and treatment-as-usual control conditions in children with high-functioning ASD. Clinical studies are needed to evaluate CBT for anxiety against attention control conditions in samples of children with ASD that are well characterized with regard to ASD diagnosis and co-occurring anxiety symptoms. Pediatrics 2013;132: e1341-e1350 AUTHORS:

Objective To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of hairpulling as measured by the Massachusetts General Hospital–Hairpulling Scale (MGH-HPS). Secondary measures assessed hairpulling severity, automatic versus focused pulling, clinician-rated improvement, and comorbid anxiety and depression. Outcomes were examined using linear mixed models to test the treatment × time interaction in an intention-to-treat population. Results No significant difference between N-acetylcysteine and placebo was found on any of the primary or secondary outcome measures. On several measures of hairpulling, subjects significantly improved with time regardless of treatment assignment. In the NAC group, 25% of subjects were judged as treatment responders, compared to 21% in the placebo group. Conclusions We observed no benefit of NAC for the treatment of children with trichotillomania. Our findings stand in contrast to a previous, similarly designed trial in adults with TTM, which demonstrated a very large, statistically significant benefit of NAC. Based on the differing results of NAC in pediatric and adult TTM populations, the assumption that pharmacological interventions demonstrated to be effective in adults with TTM will be as effective in children, may be inaccurate. This trial highlights the importance of referring children with TTM to appropriate behavioral therapy before initiating pharmacological interventions, as behavioral therapy has demonstrated efficacy in both children and adults with trichotillomania.

Objective The Food and Drug Administration currently requires the package inserts of most psychostimulant medications to list the presence of a tic disorder as a contraindication to their use. Approximately half of children with Tourette’s syndrome experience comorbid attention-deficit/hyperactivity disorder (ADHD). We sought to determine the relative efficacy of different medications in treating ADHD and tic symptoms in children with both Tourette’s syndrome and ADHD. Method We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of medications in the treatment of ADHD in the children with comorbid tics. We used a random effects meta-analysis with standardized mean difference as our primary outcome to estimate the effect size of pharmaceutical agents in the treatment of ADHD symptoms and tics. Results Our meta-analysis included nine studies involving 477 subjects. We assessed the efficacy of six medications—dextroamphetamine, methylphenidate, alpha-2 agonists (clonidine and guanfacine), desipramine, atomoxetine, and deprenyl. Methylphenidate, alpha-2 agonists, desipramine, and atomoxetine demonstrated efficacy in improving ADHD symptoms in children with comorbid tics. Alpha-2 agonists and atomoxetine significantly improved comorbid tic symptoms. Although there was evidence that supratherapeutic doses of dextroamphetamine worsens tics, there was no evidence that methylphenidate worsened tic severity in the short term. Conclusions Methylphenidate seems to offer the greatest and most immediate improvement of ADHD symptoms and does not seem to worsen tic symptoms. Alpha-2 agonists offer the best combined improvement in both tic and ADHD symptoms. Atomoxetine and desipramine offer additional evidence-based treatments of ADHD in children with comorbid tics. Supratherapeutic doses of dextroamphetamine should be avoided.

Background Treatments for obsessive-compulsive disorder (OCD) usually lead to incomplete symptom relief and take a long-time to reach full effect. Convergent evidence suggests that glutamate abnormalities contribute to the pathogenesis of OCD. Ketamine is a potent noncompetitive antagonist of the N-methyl-D-aspartate glutamate receptor. Trials have reported rapid antidepressant effects after low-dose ketamine infusion. Methods We conducted an open-label trial of ketamine (0.5mg/kg IV over 40 minutes) in 10 subjects with treatment-refractory OCD. Response was defined as a greater than 35% improvement in OCD symptoms and greater than a 50% improvement in depression symptoms from baseline at any time between 1–3 days following infusion. Results None of 10 subjects experienced a response in OCD symptoms in the first 3 days following ketamine. Four of 7 patients with comorbid depression experienced an antidepressant response to ketamine in the first 3 days following infusion. Both OCD and depression symptoms demonstrated a statistically significant improvement in the first 3 days following infusion compared to baseline, but the OCD response was <12%. The percentage reduction in depressive symptoms in the first 3 days following ketamine infusion was significantly greater than the reduction in OCD symptoms. Discussion Ketamine effects on OCD symptoms, in contrast to depressive symptoms, did not appear to persist or progress after the acute effects of ketamine had dissipated. Trial Registration Ketamine Infusion for Obsessive-Compulsive Disorder, http://clinicaltrials.gov/ct2/show/NCT01349231, NCT01349231.

OBJECTIVE The aim of this study was to determine the childhood clinical predictors of early adult outcomes in pediatric-onset obsessive-compulsive disorder (OCD) and to assess whether dimensional subtypes of OCD and the presence of comorbid tic symptoms influence long-term outcomes. METHODS We conducted a longitudinal cohort study in which 45 of 62 eligible children with OCD were reassessed an average of 9 years later, in early adulthood. Main outcome measures included expert-rated, obsessive-compulsive (OC) symptom severity and time to remission of OC symptoms. Baseline clinical characteristics were evaluated in terms of their influence on OCD severity in adulthood and time to remission of OC symptoms. RESULTS Forty-four percent of subjects were determined to have subclinical OC symptoms at the follow-up evaluation. The absence of a comorbid tic disorder and the presence of prominent hoarding symptoms were associated with the persistence of OCD symptoms. Female gender, earlier age at childhood assessment, later age of OCD onset, more-severe childhood OCD symptoms, and comorbid oppositional defiant disorder also were associated with persistence of OCD symptoms into adulthood. CONCLUSIONS These results confirm that a significant proportion of treated children with OCD experience remission by adulthood. The presence of comorbid tics heralds a positive outcome, whereas primary hoarding symptoms are associated with persistent OCD.

Family accommodation describes changes that individuals make to their behavior, to help their relative who is dealing with a psychiatric and/or psychological disorder(s), avoid or alleviate distress related to the disorder. Research on family accommodation has advanced rapidly. In this update we aim to provide a synthesis of findings from the past five years. A search of available, peer-reviewed, English language papers was conducted through PubMed and PsycINFO, cross referencing psychiatric disorders with accommodation and other family-related terms. The resulting 121 papers were individually reviewed and evaluated and the main findings were discussed. Family accommodation is common in obsessive-compulsive disorder (OCD) and in anxiety disorders, and manifests similarly across these disorders. Family accommodation is associated with more severe psychopathology and poorer clinical outcomes. Treatments have begun to focus on the reduction of family accommodation as a primary therapeutic goal and finally, neurobiological underpinnings of family accommodation are beginning to be investigated.