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Tics peak in late childhood and decline during adolescence. Yet, for some with Tourette's disorder, tics persist into adulthood. We evaluated childhood predictors of adult tic severity and tic impairment, and change over time. Eighty adolescents/adults were evaluated 11 years following a randomized-controlled trial of behavior therapy. An independent evaluator rated tic severity and tic impairment at baseline, posttreatment, and long-term follow-up. At baseline, parents completed demographics/medical history, and youth tic, internalizing, and externalizing symptom ratings. Youth rated premonitory urge severity and family functioning. After controlling for prior tic treatment effects, female sex and higher tic severity predicted higher tic severity in adulthood; and female sex, no stimulant medication use, higher tic severity, and poorer family functioning predicted higher tic impairment. Higher tic severity and premonitory urge severity predicted smaller reductions in tic severity, whereas higher externalizing symptoms predicted greater reduction in tic severity. Female sex predicted smaller reduction in tic impairment, and externalizing symptoms predicted greater reduction in tic impairment. Female sex and childhood tic severity are important predictors of tic severity and tic impairment in adulthood. Family functioning, premonitory urge severity, and tic severity are important modifiable targets for early or targeted intervention to improve long-term outcomes.

OBJECTIVE: Treatment guidelines for Tourette’s Disorder (TD) are based on patients’ degree of tic severity and impairment. However, clear benchmarks for determining tic severity and impairment have not been established. This study examined benchmarks of tic severity and tic impairment using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impression of Severity (CGI-S). METHOD: Individuals with TD or another Tic Disorder (N = 519) recruited across nine sites were administered a diagnostic interview, the YGTSS, and the CGI-S. Correlations and trend analyses contrasted YGTSS scores across CGI-S ratings. A logistic regression model examined predictive benchmarks for tic severity, tic impairment, and global severity. Model classifications were compared against CGI-S ratings, and agreement was examined using kappa. RESULTS: Spearman correlations between the CGI-S and YGTSS scores ranged from 0.54 to 0.63 (p < 0.001). Greater CGI-S ratings were associated with a linear stepwise increase in YGTSS Total Tic scores, Impairment scores, and Global Severity scores. Despite moderate-to-strong associations (ρ = 0.45–0.56, p < 0.001) between the CGI-S and predictive logistical regression models, only fair agreement was achieved when applying classification benchmarks (κ = 0.21–0.32, p < 0.001). CONCLUSIONS: CGI-S ratings are useful to characterize benchmarks for tic severity, tic impairment, and global severity on the YGTSS. Logistic regression model benchmarks had only fair agreement with the CGI-S and underscore the heterogeneity of TD symptoms. Collectively, findings offer guidance on the delineation of tic severity categorizations to apply evidence-based treatment recommendations.

The Comprehensive Behavioral Intervention for Tic Disorders (CBIT) has demonstrated efficacy in large randomized controlled trials for children (≥9 yrs), adolescents and adults with Tourette Syndrome and Chronic Tic Disorders. Given the early age of onset for tic disorders, a large portion of affected individuals with chronic tic disorders are less than 9 years of age and appropriate developmental adaptations of behavioral treatment have not yet been tested. The goal of this study was to adapt and evaluate the acceptability and utility of a family-based adaptation of CBIT for children under 9 years of age. Children 5–8 years of age (N = 15) with chronic tics were recruited from three study sites. CBIT was adapted for use with young children and included habit reversal strategies introduced in a developmentally appropriate game format and function-based interventions to reduce family accommodation of and attention to tic symptoms. Children and parents described high level of treatment satisfaction and study retention rate was 100%. Treatment response rate was 54% (CGI-I = 1 or 2) with a significant decrease in the YGTSS total score (Cohen’s d = 0.73) that was largely maintained at 3-month and 1-year follow-up assessments. Treatment was associated with reduction of some symptoms of tic-related comorbid syndromes and with changes in parental accommodation and attention to tics. Future research should determine if parental attention to tics and symptom accommodation are important mediators of treatment outcome, or if participating in this intervention at a younger age may prevent the chronic course of tic symptoms.

Background Cognitive control processes are implicated in the behavioral treatment of Tourette's disorder (TD). However, the influence of these processes on treatment outcomes has received minimal attention. This study examined whether cognitive control processes and/or tic suppression predicted reductions in tic severity and treatment response to behavior therapy. Method Fifty-three youth with TD or a pervasive tic disorder participated in a randomized wait list-controlled trial of behavior therapy. Following a baseline assessment to evaluate psychiatric diagnoses, tic severity, and cognitive control processes (e.g., response selection, inhibition, and suppression), youth were randomly assigned to receive eight sessions of behavior therapy (n = 23) or a wait list of equal duration (n = 28). Youth receiving immediate treatment completed a post-treatment assessment to determine improvement in tic severity. Meanwhile, youth in the wait list condition completed another assessment to re-evaluate tic severity and cognitive control processes, and subsequently received 8 sessions of behavior therapy followed by a post-treatment assessment to determine improvement. Results A multiple linear regression model found that pretreatment inhibition/switching on the Delis-Kaplan Executive Function System Color-Word Interference Test predicted reductions in tic severity after behavior therapy (β = -.36, t = -2.35, p = .025, ƞ2 = .15). However, other cognitive control processes and tic suppression did not predict treatment response and/or reductions in tic severity. Small nonsignificant effects were observed in cognitive control processes after behavior therapy. Conclusion Cognitive control processes may influence tic severity reductions in behavior therapy. Notably, even when other cognitive control processes are impaired and youth are initially unable to voluntarily suppress their tics, youth with TD can still benefit from behavior therapy. Findings offer implications for clinical practice and research for TD.

Objective To determine the long-term durability of behavior therapy for tics among youth with Tourette disorder and persistent (chronic) motor or vocal tic disorders. Method Of the 126 youth who participated in a randomized controlled trial of behavior therapy 11 years prior, 80 were recruited for this longitudinal follow-up. Consenting participants were interviewed in person or remotely (Web-based video) by trained evaluators to determine the course of tics, current tic severity, and tic-related impairment. Recruitment and data collection occurred between 2014 and 2019, with an average follow-up duration of 11.2 years. Results Treatment responders to both conditions in the original trial achieved partial, but not full, tic remission. Tic severity also decreased significantly across the sample, with 40% reporting partial remission. Behavior therapy responders (n = 21) in the original trial were more likely (67%) to achieve remission at follow-up (Total Tic Score = 12.52, SD = 10.75) compared to psychoeducation/supportive therapy responders (n = 6, 0%) at follow-up (Total Tic Score = 20.67, SD = 6.92) on the Yale Global Tic Severity Scale. Tic-related impairment decreased across the sample, with no significant differences between treatment groups or responders. Conclusion Despite limitations of unmeasured variables and veracity of self-report at follow-up, this study supports guidelines recommending behavior therapy as the first-line intervention for tics. Further investigation of behavior therapy as an early preventive intervention also merits attention.

Anxiety severity in youth is associated with a host of negative outcomes including poor response to treatment. Thus, a better understanding of factors that contribute to anxiety severity is needed. Such factors may include parental anxiety as well as anxiety-related approach and avoidance behaviors in both children and parents. In this study, we examined automatic behavioral tendencies as a method of quantifying anxiety-related approach and avoidance behaviors in children and their parents. Clinically anxious youth (N= 19) with mixed anxiety diagnoses and their parents completed an approach-avoidance task (AAT) comprising different emotional expressions. Our results suggest that in addition to parent report of youth anxiety, both youth and parent automatic avoidance biases predict clinician-rated youth anxiety severity accounting for 62% of the variance in clinician-rated youth anxiety. These results suggest that the AAT may be a useful measure of automatic behavioral tendencies in clinically anxious youth and their parents and that these factors may be relevant to youth anxiety severity.

The present study investigated inhibitory control deficits in Tourette's Disorder (TD)-only, Attention Deficit/Hyperactivity Disorder (ADHD)-only, and TD+ADHD and explored the degree to which measures of inhibitory control, and tic and ADHD severity predicted objective tic suppressibility. Participants were youth ages 9 to 14 (M=11.15) with TD-only (n=24), TD+ADHD (n=19), ADHD-only (n=139), and typically-developing controls (n=59) drawn from a larger study. Groups were compared on computer-based and paper and pencil neurocognitive inhibitory control tasks. Among youth with TD, neurocognitive measures of inhibitory control, subjective tic-suppressibility (Premonitory Urge for Tics Scale, item 10), and ADHD symptom severity were evaluated as predictors of objective tic suppressibility (i.e., laboratory-based tic suppression task), controlling for total tic severity. There were significant group differences on Color-Word inhibition/switching performance, though post-hoc comparisons yielded no significant pairwise group contrasts. Subjective tic suppressibility was the only significant predictor of objective tic suppressibility. The evident intact neurocognitive inhibitory control among youth with TD suggests that individuals with TD may use compensatory neural mechanisms to support typical speed and accuracy of response. The role of cognitive flexibility in mechanisms of tic suppression should also be further explored.

There is a dearth of studies examining the underlying mechanisms of blink suppression and the effects of urge and reward, particularly those measuring subsecond electroencephalogram (EEG) brain dynamics. To address these issues, we designed an EEG study to ask 3 questions: 1) How does urge develop? 2) What are EEG-correlates of blink suppression? 3) How does reward change brain dynamics related to urge suppression? This study examined healthy children (N = 26, age 8–12 years) during blink suppression under 3 conditions: blink freely (i.e., no suppression), blink suppressed, and blink suppressed for reward. During suppression conditions, children used a joystick to indicate their subjective urge to blink. Results showed that 1) half of the trials were associated with clearly defined urge time course of ~7 s, which was accompanied by EEG delta (1–4 Hz) power reduction localized at anterior cingulate cortex (ACC); 2) the EEG correlates of blink suppression were found in left prefrontal theta (4–8 Hz) power elevation; and 3) reward improved blink suppression performance while reducing the EEG delta power observed in ACC. We concluded that the empirically supported urge time course and underlying EEG modulations provide a subsecond chronospatial model of the brain dynamics during urge- and reward-mediated blink suppression.

Background Childhood obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric condition, with varied symptom presentations that have been differentially associated with clinical characteristics and treatment response. One OCD symptom cluster of particular interest is religious symptoms, including fears of offending religious figures/objects; patients affected by these symptoms have been characterized as having greater overall OCD severity and poorer treatment response. However, the extant literature primarily examines this symptom subtype within adults, leaving a gap in our understanding of this subtype in youth. Method Consequently, this study examined whether presence of religious symptoms in OCD-affected children and adolescents (N = 215) was associated with greater clinical impairments across OCD symptoms and severity, insight, other psychiatric comorbidity, family variables, or worse treatment response. Results Results found that youth with religious OCD symptoms presented with higher OCD symptom severity and exhibited more symptoms in the aggressive, sexual, somatic, and checking symptom cluster, as well as the symmetry, ordering, counting, and repeating cluster. Religious OCD symptoms were also significantly associated with poorer insight and higher family expressiveness. No differences in treatment response were observed in youths with versus without religious OCD symptoms. Conclusion Ultimately, youths with religious OCD symptoms only differed from their OCD-affected counterparts without religious symptoms on a minority of clinical variables; this suggests they may be more comparable to youths without religious OCD symptoms than would be expected based on the adult OCD literature and highlights the importance of examining these symptoms within a pediatric OCD sample.

A growing evidence base supports attention bias modification (ABM) as a novel intervention for anxiety. However, research has been largely conducted with adults and analogue samples, leaving the impact of ABM for child anxiety be fully elucidated. Thus, we conducted a double-blind, randomized controlled trial testing ABM efficacy versus an attention control condition (CC) in 31 children diagnosed with anxiety disorder. Youth were assigned to 4 weeks of ABM where attention was trained away from threat, or a sham CC in which no bias training occurred. Findings indicate that significantly more youth in the ABM versus CC group were considered treatment responders post training. The ABM versus CC group also demonstrated a greater decrease in anxiety severity, with this difference being marginally significant. Findings lend support for the potential of ABM in reducing youth anxiety. Further work regarding mechanisms of action is warranted to advance ABM research.

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

Evidence of associations between obsessive compulsive disorder (OCD) and alterations in neural indices of performance monitoring, i.e., elevated neural activity following errors, have accelerated interest in the error-related negativity (ERN) as a biomarker for pediatric OCD. The study investigates the degree to which attention bias training is linked to changes in neural measures of performance monitoring (ERN, correct response negativity or CRN) and whether pre-to-post training changes in these neural indices are associated with symptom changes in youth with OCD. The sample included 36 youth (8-17 years) diagnosed with OCD who completed a 12-session attention training program and pre- and post-training EEG assessment of performance monitoring using cognitive and emotional flanker tasks. The emotional flanker task was individualized to each participant's negative ratings of stimuli at pre-treatment to enhance salience of threat-related stimuli across youth. Results indicated that unlike participants who received attentional control protocol (CON), those who received attentional bias modification protocol (ABM) showed significant attenuations in neural activity following erroneous and correct responses in the emotional flanker task. The ERN amplitude during the cognitive flanker task was unchanged in both ABM and CON groups. Attenuations in the ERN were also linked to decreases in social anxiety and depressive symptoms. Findings highlight the relevance of including emotionally-salient tasks when investigating potential neural mechanisms of treatments and suggest that alterations in neural processes underlying performance monitoring can be targeted via attention training programs in pediatric OCD.

Objective To date, few studies of childhood obsessive compulsive disorder (OCD) have been adequately powered to examine patterns and predictors of comorbidity, despite the frequency with which it occurs. We address this gap, drawing on a large sample of youth with OCD who were systematically assessed through research and clinical programs in a university-based specialty program for children and adolescents with OCD. We examine patterns of comorbidity across different epochs of development and predict specific classes of OCD (comorbidity internalizing/externalizing/both) from key demographic and clinical variables that may be useful in guiding individualized treatment. Method A total of 322 youths (mean age = 12.28, 53% male) were assessed using the Anxiety Disorders Interview Schedule (ADIS; Silverman and Albano, 1996), the Children's Yale Brown Obsessive Compulsive Scale (CYBOCS; Scahill et al., 1997) and other standardized measures. Results Consistent with prior research, 50% of youth met criteria for a co-occurring anxiety or depressive disorder. Rates of externalizing disorders were lower (16%). Developmental differences emerged such that older youth met criteria for a higher number of co-occurring disorders. As expected, adolescents in particular were more likely to have a co-occurring internalizing disorder compared to early or pre-adolescent peers. Surprisingly, they were also more likely to have a comorbid externalizing disorder. Developmental trends were particularly striking with respect to depression, with adolescents with OCD demonstrating a six-fold greater likelihood of co-occurring depressive disorder compared to younger counterparts. Discussion Clinical implications are discussed with eye toward tailoring interventions, particularly during the transition to adolescence when youth are at heightened risk for depression.

Cognitive-behavioral therapy (CBT) is effective for pediatric obsessive-compulsive disorder (OCD), but non-response is common. Brain glutamate (Glu) signaling may contribute to OCD pathophysiology and moderate CBT outcomes. We assessed whether Glu measured with magnetic resonance spectroscopy (MRS) was associated with OCD and/or CBT response. Youths aged 7–17 years with DSM-IV OCD and typically developing controls underwent 3 T proton echo-planar spectroscopic imaging (PEPSI) MRS scans of pregenual anterior cingulate cortex (pACC) and ventral posterior cingulate cortex (vPCC)—regions possibly affected by OCD—at baseline. Controls returned for re-scan after 8 weeks. OCD youth—in a randomized rater-blinded trial—were re-scanned after 12–14 weeks of CBT or after 8 weeks of minimal-contact waitlist; waitlist participants underwent a third scan after crossover to 12–14 weeks of CBT. Forty-nine children with OCD (mean age 12.2±2.9 years) and 29 controls (13.2±2.2 years) provided at least one MRS scan. At baseline, Glu did not differ significantly between OCD and controls in pACC or vPCC. Within controls, Glu was stable from scan-to-scan. Within OCD subjects, a treatment-by-scan interaction (p=0.034) was observed, driven by pACC Glu dropping 19.5% from scan-to-scan for patients randomized to CBT, with minor increases (3.8%) for waitlist participants. The combined OCD participants (CBT-only plus waitlist-CBT) also showed a 16.2% (p=0.004) post-CBT decrease in pACC Glu. In the combined OCD group, within vPCC, lower pre-CBT Glu predicted greater post-CBT improvement in symptoms (CY-BOCS; r=0.81, p=0.00025). Glu may be involved in the pathophysiology of OCD and may moderate response to CBT.

Pediatric obsessive-compulsive disorder (OCD) co-occurs frequently with other mental health conditions, adding to the burden of disease and complexity of treatment. Cognitive behavioral therapy (CBT) is efficacious for both OCD and two of its most common comorbid conditions, anxiety and depression. Therefore, treating OCD may yield secondary benefits for anxiety and depressive symptomatology. This study examined whether anxiety and/or depression symptoms declined over the course of OCD treatment and, if so, whether improvements were secondary to reductions in OCD severity, impairment, and/or global treatment response. The sample consisted of 137 youths who received 12 sessions of manualized CBT and were assessed by independent evaluators. Mixed models analysis indicated that youth-reported anxiety and depression symptoms decreased in a linear fashion over the course of CBT, however these changes were not linked to specific improvements in OCD severity or impairment but to global ratings of treatment response. Results indicate that for youth with OCD, CBT may offer benefit for secondary anxiety and depression symptoms distinct from changes in primary symptoms. Understanding the mechanisms underlying carryover in CBT techniques is important for furthering transdiagnostic and/or treatment-sequencing strategies to address co-occurring anxiety and depression symptoms in pediatric OCD.

Background Little is known about the neural underpinnings of pediatric trichotillomania (TTM). We examined error-related negativity (ERN)-amplitude and theta-EEG power differences among youth with TTM, OCD, and healthy controls (HC). Methods Forty channel EEG was recorded from 63 pediatric participants (22 with TTM, 22 with OCD, and 19 HC) during the Eriksen Flanker Task. EEG data from inhibitory control were used to derive estimates of ERN amplitude and event-related spectral power associated with motor inhibition. Results TTM and HC were similar in brain activity patterns in frontal and central regions and TTM and OCD were similar in the parietal region. Frontal ERN-amplitude was significantly larger in OCD relative to TTM and HC, who did not differ from each other. The TTM group had higher theta power compared to OCD in frontal and central regions, and higher theta than both comparison groups in right motor cortex and superior parietal regions. Within TTM, flanker task performance was correlated with EEG activity in frontal, central, and motor cortices whereas global functioning and impairment were associated with EEG power in bilateral motor and parietal cortices. Conclusions Findings are discussed in terms of shared and unique neural mechanisms in TTM and OCD and treatment implications.

Prior research has identified OCD subtypes or "clusters" of symptoms that differentially relate to clinical features of the disorder. Given the high comorbidity between OCD and anxiety, OCD symptom clusters may more broadly associate with fear and/or distress internalizing constructs. This study examines fear and distress dimensions, including physical concerns (fear), separation anxiety (fear), perfectionism (distress), and anxious coping (distress), as predictors of previously empirically-derived OCD symptom clusters in a sample of 215 youth diagnosed with primary OCD (ages 7-17, mean age=12.25). Self-reported separation fears predicted membership in Cluster 1 (aggressive, sexual, religious, somatic obsessions, and checking compulsions) while somatic/autonomic fears predicted membership in Cluster 2 (symmetry obsessions and ordering, counting, repeating compulsions). Results highlight the diversity of pediatric OCD symptoms and their differential association with fear, suggesting the need to carefully assess both OCD and global fear constructs that might be directly targeted in treatment.

Objective The pathophysiology of Chronic Tic Disorders (CTDs), including Tourette Syndrome, remains poorly understood. The goal of this study was to compare neural activity and connectivity during a voluntary movement (VM) paradigm that involved cued eye blinks among children with and without CTDs. Using the precise temporal resolution of electroencephalography (EEG), we used the timing and location of cortical source resolved spectral power activation and connectivity to map component processes such as visual attention, cue detection, blink regulation and response monitoring. We hypothesized that neural activation and connectivity during the cued eye blink paradigm would be significantly different in regions typically associated with effortful control of eye blinks, such as frontal, premotor, parietal, and occipital cortices between children with and without CTD. Method Participants were 40 children (23 with CTD, 17 age-matched Healthy Control [HC]), between the ages of 8–12 (mean age = 9.5) years old. All participants underwent phenotypic assessment including diagnostic interviews, behavior rating scales and 128-channel EEG recording. Upon presentation of a cue every 3 s, children were instructed to make an exaggerated blink. Results Behaviorally, the groups did not differ in blink number, latency, or ERP amplitude. Within source resolved clusters located in left dorsolateral prefrontal cortex, posterior cingulate, and supplemental motor area, children with CTD exhibited higher gamma band spectral power relative to controls. In addition, significant diagnostic group differences in theta, alpha, and beta band power in inferior parietal cortex emerged. Spectral power differences were significantly associated with clinical characteristics such as tic severity and premonitory urge strength. After calculating dipole density for 76 anatomical regions, the CTD and HC groups had 70% overlap of top regions with the highest dipole density, suggesting that similar cortical networks were used across groups to carry out the VM. The CTD group exhibited significant information flow increase and dysregulation relative to the HC group, particularly from occipital to frontal regions. Conclusion Children with CTD exhibit abnormally high levels of neural activation and dysregulated connectivity among networks used for regulation and effortful control of voluntary eye blinks., Highlights • First cortical source level EEG study on brain activity and connectivity in CTD. • Children with CTD exhibit aberrant levels of neural activation and connectivity. • Neural activation was significantly associated with tic severity and premonitory urge.

Deficits in social communication are a core feature of autism spectrum disorder (ASD), yet significant social problems have been observed in youth with many neurodevelopmental disorders. In this preliminary investigation, we aimed to explore whether domains of social reciprocity (i.e., social communication, social cognition, social awareness, social motivation, and restricted and repetitive behaviors) represent transdiagnostic traits. These domains were compared across youth ages 7–17 with obsessive-compulsive disorder (OCD; N = 32), tic disorders (TD; N = 20), severe mood dysregulation (N = 33) and autism spectrum disorder (N = 35). While the ASD group was rated by parents as exhibiting the greatest social reciprocity deficits across domains, a high proportion of youth with severe mood dysregulation also exhibited pronounced deficits in social communication, cognition, and awareness. The ASD and severe mood dysregulation groups demonstrated comparable scores on the social awareness domain. In contrast, social motivation and restricted and repetitive behaviors did not appear to be transdiagnostic domains in severe mood dysregulation, OCD, or TD groups. The present work provides preliminary support that social awareness, and to a lesser extent social communication and cognition, may represent features of social reciprocity that are transdiagnostic across ASD and severe mood dysregulation.

This study assessed the psychometric properties of a parent-reported tic severity measure, the Parent Tic Questionnaire (PTQ), and used the scale to establish guidelines for delineating clinically significant tic treatment response. Participants were 126 children ages 9 to 17 who participated in a randomized controlled trial of Comprehensive Behavioral Intervention for Tics (CBIT). Tic severity was assessed using the Yale Global Tic Severity Scale (YGTSS), Hopkins Motor/Vocal Tic Scale (HMVTS) and PTQ; positive treatment response was defined by a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions - Improvement (CGI-I) scale. Cronbach's alpha and intraclass correlations (ICC) assessed internal consistency and test-retest reliability, with correlations evaluating validity. Receiver- and Quality-Receiver Operating Characteristic analyses assessed the efficiency of percent and raw-reduction cutoffs associated with positive treatment response. The PTQ demonstrated good internal consistency (α = 0.80 to 0.86), excellent test-retest reliability (ICC = .84 to .89), good convergent validity with the YGTSS and HM/VTS, and good discriminant validity from hyperactive, obsessive-compulsive, and externalizing (i.e., aggression and rule-breaking) symptoms. A 55% reduction and 10-point decrease in PTQ Total score were optimal for defining positive treatment response. Findings help standardize tic assessment and provide clinicians with greater clarity in determining clinically meaningful tic symptom change during treatment.

Cognitive models of anxiety suggest that threat-related attentional biases are associated with youth anxiety disorders. Although meta-analyses suggest that anxious youths display a bias toward threat, there is variability among studies, with youths displaying either an attention bias toward or away from threat. One possibility that may account for these discrepancies is the effect of youth age. Previous studies have found an effect of age on attentional biases in non-clinical samples. In this study, we examined the effects of age on attentional biases in youths diagnosed with an anxiety disorder. Clinically anxious youths (N 5 33) completed the probe detection task using threat-related word stimuli. Our results revealed a significant effect of age, with older youths (11-17 years) displaying a significant bias away from threat and younger youths (8-10 years) displaying a nonsignificant bias toward threat. These findings suggest that anxious youth may have either an attentional bias toward or away from threat-related words depending on age.Keywords: youth anxiety; age; probe detection task; information processing; attentional biasAnxiety disorders collectively are the most common psychiatric condition in youth (Albano, Chorpita, & Barlow, 1996), with a prevalence rate of 12% (Costello, Egger, & Angold, 2005). Moreover, youth anxiety disorders are characterized by an early age of onset (between 6 and 8 years; Costello et al., 2005; Merikangas et al., 2010), enhancing the potential for significant impairments typically associated with anxiety disorders across multiple domains including family and peer relationships (Kashani & Orvaschel, 1990), sleep (Alfano, Ginsburg, & Kingery, 2007), and school functioning (Mychailyszyn, Mendez, & Kendall, 2010). Finally, early onset of anxiety has been shown to be a predictor of anxiety and depression in adulthood (Copeland, Shanahan, Costello, & Angold, 2009). Thus, there is a need for an improved understanding of factors involved in the etiology and maintenance of youth anxiety across the age spectrum of childhood and adolescence.Cognitive models of youth anxiety suggest that information processing biases are involved in its etiology and maintenance (Pine et al., 2005; Vasey, Daleiden, Williams, & Brown, 1995). For example, threat-related attentional biases (i.e., the allocation of attention to threat-related information, when this information competes for processing resources with neutral information) may play a prominent role in anxiety disorders (Bar-Haim, Lamy, Pergamin, Bakermans-Kranenburg, & van IJzendoorn, 2007; Vasey et al., 1995). Although meta-analyses as a whole suggest that anxious youth show an attentional bias toward threat (Bar-Haim et al., 2007), there is variability across studies. Some studies show that anxious youth have an attentional bias toward threat-related information (e.g., Dalgleish et al., 2003; Roy et al., 2008; Shechner et al., 2012; Vasey et al., 1995; Waters, Henry, Mogg, Bradley, & Pine, 2010; Waters, Mogg, Bradley, & Pine, 2008, 2011), whereas other studies indicate that anxious youth demonstrate an attentional avoidance of threat-related information (e.g., Monk et al., 2006; Pine et al., 2005; Stirling, Eley, & Clark, 2006). Puliafico and Kendall (2006) summarized these discrepancies in the youth attention and anxiety literature suggesting that variability in methodology used to assess attentional bias (e.g., emotional Stroop task vs. probe detection task), stimuli type (picture vs. word stimuli), stimuli presentation times (500 ms vs. 1,000 ms), and demographic differences (e.g., age) between studies may account for these results.Regarding methodological differences, the emotional Stroop task requires participants to indicate the font color in which emotional words are printed while ignoring the meaning of the words, whereas the probe detection task requires participants to indicate the identity of a probe (e. …

The neurophysiological bases of cognitive-behavioral therapy (CBT) for obsessive–compulsive disorder (OCD) are incompletely understood. Previous studies, though sparse, implicate metabolic changes in pregenual anterior cingulate cortex (pACC) and anterior middle cingulate cortex (aMCC) as neural correlates of response to CBT. The goal of this pilot study was to determine the relationship between levels of the neurochemically interlinked metabolites glutamate + glutamine (Glx) and N -acetyl-aspartate + N -acetyl-aspartyl-glutamate (tNAA) in pACC and aMCC to pretreatment OCD diagnostic status and OCD response to CBT. Proton magnetic resonance spectroscopic imaging ( 1 H MRSI) was acquired from pACC and aMCC in 10 OCD patients at baseline, 8 of whom had a repeat scan after 4 weeks of intensive CBT. pACC was also scanned (baseline only) in 8 age-matched healthy controls. OCD symptoms improved markedly in 8/8 patients after CBT. In right pACC, tNAA was significantly lower in OCD patients than controls at baseline and then increased significantly after CBT. Baseline tNAA also correlated with post-CBT change in OCD symptom severity. In left aMCC, Glx decreased significantly after intensive CBT. These findings add to evidence implicating the pACC and aMCC as loci of the metabolic effects of CBT in OCD, particularly effects on glutamatergic and N -acetyl compounds. Moreover, these metabolic responses occurred after just 4 weeks of intensive CBT, compared to 3 months for standard weekly CBT. Baseline levels of tNAA in the pACC may be associated with response to CBT for OCD. Lateralization of metabolite effects of CBT, previously observed in subcortical nuclei and white matter, may also occur in cingulate cortex. Tentative mechanisms for these effects are discussed. Comorbid depressive symptoms in OCD patients may have contributed to metabolite effects, although baseline and post-CBT change in depression ratings varied with choline-compounds and myo -inositol rather than Glx or tNAA.

Objective: To review the evidence for using intravenous (IV) epoprostenol to treat Raynaud’s phenomenon (RP). Data Sources: The databases MEDLINE (1946 to March 2016), PubMed, and International Pharmaceutical Abstracts were searched using the terms epoprostenol, Flolan, Raynaud’s disease, and CREST syndrome. Further literature sources were identified by reviewing article citations. Study Selection and Data Extraction: All English-language, clinical trials and case series evaluating IV epoprostenol for the management or treatment of RP were included. Lower-quality evidence were incorporated due to limited information. Data Synthesis: Seven small uncontrolled studies/case series, 1 small placebo controlled study, and 1 larger randomized trial were identified and included. There was no consistent measurement of efficacy utilized, but improvements in hand temperature, RP attack duration and frequency were commonly associated with IV epoprostenol treatment (5 trials). There were conflicting data regarding effect sustainability, with 5 trials showing long-term effects and 3 showing immediate effects. Fewer ischemic ulcers developed during treatment with IV epoprostenol in 1 trial compared to conventional treatment. Ulcer healing ocurred in 2 trials. Common adverse effects included hypotension, headache, flushing, gastrointestinal symptoms, and jaw pain. Conclusions: Available evidence supports the use of IV epoprostenol for treatment of severe RP in patients refractory or intolerant to standard therapies. The dose, titration schedule, and duration of IV epoprostenol utilized in studies varied, but a conservative approach to initiation should be considered. Patients who do not respond to intermittent infusions and have severe digital ischemia may require more aggressive regimens.

Background The brain mechanisms of cognitive–behavioral therapy (CBT), a highly effective treatment for pediatric obsessive–compulsive disorder (OCD), are unknown. Neuroimaging in adult OCD indicates that CBT is associated with metabolic changes in striatum, thalamus, and anterior cingulate cortex. We therefore probed putative metabolic effects of CBT on these brain structures in pediatric OCD using proton magnetic resonance spectroscopic imaging ( 1 H MRSI). Method Five unmedicated OCD patients (4 ♀, 13.5 ± 2.8) and 9 healthy controls (7 ♀, 13.0 ± 2.5) underwent MRSI (1.5 T, repetition-time/echo-time = 1500/30 ms) of bilateral putamen, thalamus and pregenual anterior cingulate cortex (pACC). Patients were rescanned after 12 weeks of exposure-based CBT. The Children's Yale–Brown Obsessive–Compulsive Scale (CY-BOCS) of OCD symptoms was administered before and after CBT. Results Four of 5 patients responded to CBT (mean 32.8% CY-BOCS reduction). Multiple metabolite effects emerged. Pre-CBT, N -acetyl-aspartate + N -acetyl-aspartyl-glutamate (tNAA) in left pregenual anterior cingulate cortex (pACC) was 55.5% higher in patients than controls. Post-CBT, tNAA (15.0%) and Cr (23.9%) in left pACC decreased and choline compounds (Cho) in right thalamus increased (10.6%) in all 5 patients. In left thalamus, lower pre-CBT tNAA, glutamate + glutamine (Glx), and myo -inositol (mI) predicted greater post-CBT drop in CY-BOCS ( r = 0.98) and CY-BOCS decrease correlated with increased Cho. Conclusions Interpretations are offered in terms of the Glutamatergic Hypothesis of Pediatric OCD. Similar to 18 FDG-PET in adults, objectively measurable regional MRSI metabolites may indicate pediatric OCD and predict its response to CBT.

Objective To examine the efficacy of exposure-based cognitive-behavioral therapy (CBT) plus a structured family intervention (FCBT) versus psychoeducation plus relaxation training (PRT) for reducing symptom severity, functional impairment, and family accommodation in youths with obsessive-compulsive disorder (OCD). Method A total of 71 youngsters 8 to 17 years of age (mean 12.2 years; range, 8–17 years, 37% male, 78% Caucasian) with primary OCD were randomized (70:30) to 12 sessions over 14 weeks of FCBT or PRT. Blind raters assessed outcomes with responders followed for 6 months to assess treatment durability. Results FCBT led to significantly higher response rates than PRT in ITT (57.1% vs 27.3%) and completer analyses (68.3% vs. 35.3%). Using HLM, FCBT was associated with significantly greater change in OCD severity and child-reported functional impairment than PRT and marginally greater change in parent-reported accommodation of symptoms. These findings were confirmed in some, but not all, secondary analyses. Clinical remission rates were 42.5% for FCBT versus 17.6% for PRT. Reduction in family accommodation temporally preceded improvement in OCD for both groups and child functional status for FCBT only. Treatment gains were maintained at 6 months. Conclusions FCBT is effective for reducing OCD severity and impairment. Importantly, treatment also reduced parent-reported involvement in symptoms with reduced accommodation preceding reduced symptom severity and functional impairment. Clinical Trials Registry Information Behavior Therapy for Children and Adolescents with Obsessive-Compulsive Disorder (OCD); http://www.clinicaltrials.gov; NCT00000386.

Children (n = 126) ages 9 to 17 years with chronic tic or Tourette disorder were randomly assigned to receive either behavior therapy or a control treatment over 10 weeks. This study examined acute effects of behavior therapy on secondary psychiatric symptoms and psychosocial functioning and long-term effects on these measures for behavior therapy responders only. Baseline and end point assessments conducted by a masked independent evaluator assessed several secondary psychiatric symptoms and measures of psychosocial functioning. Responders to behavior therapy at the end of the acute phase were reassessed at 3-month and 6-month follow-up. Children in the behavior therapy and control conditions did not differentially improve on secondary psychiatric or psychosocial outcome measures at the end of the acute phase. At 6-month posttreatment, positive response to behavior therapy was associated with decreased anxiety, disruptive behavior, and family strain and improved social functioning. Behavior therapy is a tic-specific treatment for children with tic disorders.

The clinical characteristics and rates of co-occurring psychiatric conditions in youth seeking treatment for a chronic tic disorder (CTD) were examined. Children and adolescents (N = 126) with a primary CTD diagnosis were recruited for a randomized controlled treatment trial. An expert clinician established diagnostic status via semi-structured interview. Participants were male (78.6%), Caucasians (84.9%), mean age 11.7 years (SD = 2.3) with moderate-to-severe tics who met criteria for Tourette’s disorder (93.7%). Common co-occurring conditions included attention-deficit/hyperactivity disorder (ADHD; 26%), social phobia (21%), generalized anxiety disorder (20%), and obsessive-compulsive disorder (OCD; 19%). Motor and vocal tics with greater intensity, complexity, and interference were associated with increased impairment. Youth with a CTD seeking treatment for tics should be evaluated for non-OCD anxiety disorders in addition to ADHD and OCD. Despite the presence of co-occurring conditions, children with more forceful, complex, and/or directly interfering tics may seek treatment to reduce tic severity.

The comorbidity of tic disorders (TD) and obsessive-compulsive disorder (OCD) has long been recognized in the clinical literature and appears to be bidirectional, affecting 20-60% of individuals with each disorder. Coffey et al. (1998) found that adults with TD+OCD had a more severe comorbidity profile than adults with OCD or TD alone. This exploratory study in children attempts to evaluate whether heightened diagnostic severity, increased comorbidity load, and lower functioning is more commonplace in youth with TD+OCD in comparison to either syndrome alone. Participants were 306 children (seeking clinical evaluation) with TD, OCD, or TD+OCD. Assessment consisted of a diagnostic battery (including structured diagnostic interviews and standardized parent-report inventories) to evaluate diagnostic severity, comorbid psychopathology, behavioral and emotional correlates, and general psychosocial functioning. Data from this study sample were not supportive of the premise that youth with both a tic disorder and OCD present with elevated diagnostic severity, higher risk-for or intensity-of comorbidity, increased likelihood of externalizing/internalizing symptomatology, or lower broad-based adaptive functioning. The OCD group had elevated rates of comorbid anxiety disorders and attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) were more prevalent among youth in the TD group. The three groups also differed on key demographic variables. Our findings suggest that, in contrast to adults, TD+OCD in children and adolescents does not represent a more severe condition than either disorder alone on the basis of diagnostic comorbidity, symptom severity, or functional impairment.

Obsessive-Compulsive Disorder (OCD) is a chronic, impairing condition that affects between 1–4% of children and adolescents (Zohar, 1999). Its presentation is characterized by the presence of obsessions (i.e., recurrent, intrusive and typically distressing thoughts, ideas, or mental images) and compulsions (i.e., repetitive behaviors or mental acts designed to prevent, mitigate or attenuate anxiety) that yield substantial distress and functional impairment (American Psychiatric Association, 2000). The importance of early intervention has been emphasized (American Academy of Child and Adolescent Psychiatry, 1998; Geller, 2006), especially given that as many as 80% of adult OCD cases have an onset during childhood (Millet et al., 2004) and childhood OCD is itself associated with significant multi-domain impairment (Piacentini, Bergman, Keller, & McCracken, 2003). Although pharmacological and psychosocial treatments have yielded promising results (Lewin, Storch, Geffken, Goodman, & Murphy, 2006), many youngsters fail to benefit from these interventions (Barrett, Farrell, Pina, Peris, & Piacentini, 2008). Indeed, in the largest clinical trial to date, only 39% of youth with OCD entered remission following cognitive behavioral therapy (CBT; Pediatric OCD Treatment Study, 2004) and only 54% entered remission following combined CBT and pharmacotherapy. Thus, efforts have turned toward understanding factors that may influence treatment outcome for youth with OCD (Lewin & Piacentini, 2009). There are a number of features (e.g., comorbidity, symptom severity, poor insight) that may explain why certain youth with OCD fail to benefit from CBT (Lewin, Storch, Adkins, Murphy, & Geffken, 2005). Although current diagnostic criteria for OCD in adults requires patient recognition that the obsessions and compulsions are excessive and unreasonable (APA 2000), experts have noted that it is not uncommon for patients to lack insight into the bizarre or excessive nature of their thoughts and behaviors (Carmin, Wiegartz, & Wu, 2008; (Foa, Kozak, Goodman, Hollander, Jenike, & Rasmussen, 1995; Kozak & Foa, 1994). It is estimated that as many as 36% of adults with OCD have poor insight (Alonso et al., 2008). The degree to which a patient possesses insight into the irrational nature of his/her obsessional beliefs and compulsive rituals may contribute to both clinical presentation and treatment outcome (Bellino, Patria, Ziero, & Bogetto, 2005; Catapano, Sperandeo, Perris, Lanzaro, & Maj, 2001; Kozak et al., 1994; Vogel, Hansen, Stiles, & Gotestam, 2006). Several studies have examined correlates of insight among adults with OCD. Poor insight has been associated with increased OCD symptom severity (Bellino et al., 2005; Catapano et al., 2001; Ravi Kishore, Samar, Janardhan Reddy, Chandrasekhar, & Thennarasu, 2004) and psychiatric comorbidity (Bellino et al., 2005; Ravi Kishore et al., 2004). Other studies suggest that diminished insight is related to longer duration of illness, early onset of symptoms (Kishore et al., 2004), chronic course and increased family history of OCD (Bellino et al., 2005). Others studies have demonstrated that patients with worse insight (1) endorsed greater symptoms of depression and anxiety, (2) were more likely to have a comorbid depressive disorder, and (3) were less likely to resist obsessive and compulsive symptoms (Alonso et al., 2008; Turksoy, Tukel, Ozdemir, & Karali, 2002). One analysis, conducted by Matgunga et al. (2001), found that limited insight was linked to specific OCD symptoms (washing and checking compulsions) (Matsunaga et al., 2002). Studies also suggest that poor insight might contribute to failed responses to CBT and SRI treatment (Alonso et al., 2008; Basoglu, Lax, Kasvikis, & Marks, 1988; Catapano et al., 2001; Erzegovesi et al., 2001; Foa, 1979; Foa et al., 1983; Lax, Basoglu, & Marks, 1992; Neziroglu, Stevens, McKay, & Yaryura-Tobias, 2001; Salkovskis & Warwick, 1985; Shetti et al., 2005). Despite these findings, clinical correlates of insight among youth with OCD remain understudied. Unlike diagnostic requirements for adults with OCD, intact insight into obsessive-compulsive symptoms is not required for a diagnosis of childhood OCD (APA, 2000); however, youngsters can be diagnosed with the qualifier, “with poor insight” as needed (APA, 2000, pg 463). However, to date, the development of insight across different age groups is not documented. It is plausible that insight develops with age, consistent with higher-order cognitive processes such as abstract reasoning (Indelder & Piaget, 1958). Notably, insight into OC symptoms likely falls on a continuum (Insel & Akiskal, 1986), with severe deficits often bearing resemblance to delusional beliefs associated with Schizophrenia Spectrum Disorders (Rodowski, Cagande, & Riddle, 2008). Whereas clinical observation indicates that most children and adolescents have reasonable level of awareness that their symptoms are unusual and excessive, there are a subset of youth with OCD who deny that their symptoms are problematic or unreasonable (Geller, 2006). These youth often experience difficulties with CBT and outcomes may be diminished (Lewin et al., 2006; Storch et al., 2008a; Storch et al., 2008b). To date, only one other study has examined correlates of insight among youth with OCD (Storch et al., 2008b). The authors dichotomized youth into two groups (high and low insight) based on and Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) item 11, a clinician-rated assessment of the child’s insight (Scahill et al., 1997). Children with low insight had higher levels of OCD symptom severity and had more repeating compulsions. Parents rated children with low insight as having more internalizing symptoms and reported higher levels of family accommodation compared to parents of youth with high insight. Although one might expect insight to improve with age, no group differences in age. Similarly, despite (or gender and comorbidity) were identified. Jensen and colleagues (1996) listed demographics, IQ, externalizing/internalizing symptoms, OCD-spectrum severity, parental psychopathology, and family functioning as factors for conceptualizing child psychiatric treatment outcomes (Jensen et al., 1996). Although Storch et al. (2008b) evaluated many of these factors, relations between insight and child intellectual functioning, perceived control, parental psychopathology, and other demographic characteristics that have been shown to relate to treatment outcome (e.g., family history, duration of OCD illness) remain unstudied. This is unfortunate given adult studies suggesting increased insight may bolster treatment outcome. Building on this work, the present study aimed to provide an initial examination of insight with regard to cognitive and developmental factors. First, we examined the relationship of insight to intellectual functioning and perceived control. In addition, we were also interested in providing an initial, albeit cross-sectional description of insight across age groups. Finally, we aimed to provide the initial replication of findings by Storch et al. (2008b) examining differences in insight across demographic characteristics, clinical symptoms, adaptive functioning, and psychiatric comorbidity. We hypothesized that higher intellectual functioning and older age would predict higher insight. Based on the limited extant literature in this area, we also hypothesized that youth with poor insight would be younger, have a longer duration of illness, greater family history of OCD, increased OCD symptom severity, greater likelihood of psychiatric comorbidity, and lower adaptive functioning.

This article describes the development and initial psychometric properties of the Parent Tic Questionnaire (PTQ)—a new measure assessing the number, frequency, and intensity of motor and vocal tics in children and adolescents with Chronic Tic Disorder (CTD). Parents of 40 children with a CTD completed the PTQ as part of a larger assessment battery. Results show the PTQ to have excellent internal consistency and good to excellent 2-week test-retest reliability. The motor tic severity subscale, vocal tic severity subscale, and total severity score of the PTQ correlated highly with the corresponding scales of the gold-standard clinician-rated Yale Global Tic Severity Scale (YGTSS), indicating excellent convergent validity. Correlations between the YGTSS and PTQ remained strong after controlling for measures of obsessive-compulsive disorder and inattention, suggesting good discriminant validity. The PTQ is a promising supplement to current methods for assessing tic severity and further research on the validit...

Cook and Blacher (2007) provide the most comprehensive review to date of psychosocial treatments for patients with tic disorders and are to be congratulated for their fine effort. The authors’ conclusion that habit reversal treatment warrants designation as well established based on the American Psychological Association's Division 12 Task Force criteria should spur increased clinical and research interest in this treatment. However, to fully realize the promise of Cook and Blacher's findings, it is first necessary to understand the broad historical context surrounding the conceptualization and treatment of Tourette syndrome (TS), including fluctuating perceptions within the TS community about the efficacy and utility of psychosocial interventions. In related fashion, this commentary also addresses several barriers, some methodological and others based on historical misconceptions about psychological treatments, that have constrained greater acceptance of such interventions in the past. Finally, we present a model approach for the development and dissemination of evidence-based psychosocial treatments designed to facilitate maximal understanding and acceptance of these interventions by the TS treatment community.

Children with chronic tic disorders (CTD), including Tourette’s Disorder (TD), demonstrate a higher incidence of comorbid conditions, including attention-deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD). The relative contributions of tics versus ADHD and OCD symptoms for predicting impaired functioning in children with TD is unknown and existing studies on the topic are inconsistent. This study evaluated the unique contributions of tic severity, ADHD diagnostic status, and OCD symptom severity in predicting competence scores on the Child Behavior Checklist (CBCL) in a sample of children with CTD. Results of a hierarchical regression analysis show that both ADHD and OCD symptoms predicted decreased CBCL competence scores. When tic complexity was added, however, only ADHD and tic complexity continued to predict CBCL competence scores. These findings begin to resolve inconsistencies in existing literature and have important implications for understanding and treating children with CTD.

Focal brain metabolic effects detected by proton magnetic resonance spectroscopy (MRS) in obsessive-compulsive disorder (OCD) represent prospective indices of clinical status and guides to treatment design. Sampling bilateral pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and thalamus in 40 adult patients and 16 healthy controls, we examined relationships of the neurometabolites glutamate+glutamine (Glx), creatine+phosphocreatine (Cr), and choline-compounds (Cho) with OCD diagnosis and multiple symptom types. The latter included OC core symptoms (Yale-Brown Obsessive-Compulsive Scale - YBOCS), depressive symptoms (Montgomery-Åsberg Depression Rating Scale - MADRS), and general functioning (Global Assessment Scale - GAS). pACC Glx was 9.7% higher in patients than controls. Within patients, Cr and Cho correlated negatively with YBOCS and MADRS, while Cr correlated positively with the GAS. In aMCC, Cr and Cho correlated negatively with MADRS, while Cr in thalamus correlated positively with GAS. These findings present moderate support for glutamatergic and cingulocentric perspectives on OCD. Based on our prior metabolic model of OCD, we offer one possible interpretation of these group and correlational effects as consequences of a corticothalamic state of elevated glutamatergic receptor activity alongside below-normal glutamatergic transporter activity.

Tourette's Disorder and other chronic tic disorders are common neurodevelopmental conditions. One characteristic of tic disorders is the premonitory urge, an aversive or unpleasant sensory phenomenon that may precede tics. Initial examination of premonitory urge in pediatric tic disorders suggests that awareness and experience of sensations preceding tics may be related to anxiety and OCD. However, it may be possible that specific anxiety-related symptoms, such as anxious physiologic arousal, are particularly relevant to the experience of premonitory urge. The current study examines relationships between tic-related premonitory urge and anxiety-related symptom clusters in treatment-seeking youths with a primary diagnoses of Tourette's or other chronic tic disorder. The sample consisted of 124 youth, ages 9 to 17, who participated in the multi-site Comprehensive Behavioral Intervention for Tics randomized controlled trial (CBIT; Piacentini et al., 2010). Specific anxiety-related subtypes, including generalized worry, separation, social, and panic/somatic symptoms, as well as severity of obsessions and compulsions, were assessed as potential correlates of premonitory urge. Findings indicated that age, global tic-related impairment, and specific panic/somatic symptoms accounted for a substantial proportion of variance in youth report of premonitory urge. These findings provide information about the characteristics of premonitory urge in pediatric tic disorders, and have implications for the treatment of pediatric tic syndromes.

fMRI graph theory reveals resting-state brain networks, but has never been used in pediatric OCD.Whole-brain resting-state fMRI was acquired at 3T from 21 children with OCD and 20 age-matched healthy controls. BOLD connectivity was analyzed yielding global and local graph-theory metrics across 100 child-based functional nodes. We also compared local metrics between groups in frontopolar, supplementary motor, and sensorimotor cortices, regions implicated in recent neuroimaging and/or brain stimulation treatment studies in OCD.As in adults, the global metric small-worldness was significantly (P0.05) lower in patients than controls, by 13.5% (%mean difference=100%X(OCD mean - control mean)/control mean). This suggests less efficient information transfer in patients. In addition, modularity was lower in OCD (15.1%, P0.01), suggesting less granular - or differently organized - functional brain parcellation. Higher clustering coefficients (23.9-32.4%, P0.05) were observed in patients in frontopolar, supplementary motor, sensorimotor, and cortices with lower betweenness centrality (-63.6%, P0.01) at one frontopolar site. These findings are consistent with more locally intensive connectivity or less interaction with other brain regions at these sites.Relatively large node size; relatively small sample size, comorbidities in some patients.Pediatric OCD patients demonstrate aberrant global and local resting-state network connectivity topologies compared to healthy children. Local results accord with recent views of OCD as a disorder with sensorimotor component.

Behavior analysis has been at the forefront in establishing effective treatments for children and adults with chronic tic disorders. As is customary in behavior analysis, the efficacy of these treatments has been established using direct-observation assessment methods. Although behavior-analytic treatments have enjoyed acceptance and integration into mainstream health care practices for tic disorders (e.g., psychiatry and neurology), the use of direct observation as a primary assessment tool has been neglected in favor of less objective methods. Hesitation to use direct observation appears to stem largely from concerns about the generalizability of clinic observations to other settings (e.g., home) and a lack of consensus regarding the most appropriate and feasible techniques for conducting and scoring direct observation. The purpose of the current study was to evaluate and establish a reliable, valid, and feasible direct-observation protocol capable of being transported to research and clinical settings. A total of 43 children with tic disorders, collected from two outpatient specialty clinics, were assessed using direct (videotape samples) and indirect (Yale Global Tic Severity Scale; YGTSS) methods. Videotaped observation samples were collected across 3 consecutive weeks and two different settings (clinic and home), were scored using both exact frequency counts and partial-interval coding, and were compared to data from a common indirect measure of tic severity (the YGTSS). In addition, various lengths of videotaped segments were scored to determine the optimal observation length. Results show that (a) clinic-based observations correspond well to home-based observations, (b) brief direct-observation segments scored with time-sampling methods reliably quantified tics, and (c) indirect methods did not consistently correspond with the direct methods.

Tic frequency was assessed and compared across home and clinic as well as three experimentally-manipulated situations in order to assess the phenomenon of tic reactivity. Forty-three youngsters with chronic tic disorder recruited from two geographically-distinct sites were videotaped over three weekly laboratory visits under each of the following conditions: (1) alone/camera present, (2) other present/camera present, and (3) alone/camera hidden. Contrary to expectation, more tics were observed during overt as compared to covert observation, while the presence of another person had no overall impact on tic expression. Mean tic counts obtained from clinic observation did not significantly differ from those obtained at home collected either one day before or after. Tic frequency counts were remarkably stable over the three weekly assessments both at home and clinic. Study findings are consistent with past observations that tic expression can be influenced by environmental factors and suggest the stability of tic frequency may exhibit greater temporal and setting stability than previously thought. The clinical and research implications of these results are discussed.

The aim of this study was to establish a scoring system, Neonatal Facial Image Scoring System (NFISS), for investigating the pain responses in neonates during routine venipuncture. We collected 1998 facial images from 19 infants during the first phase of this study and identified twelve features of the facial image: normalized scale for NFISS (scale from 0-15), including brow bulge (0-2), vertical brow furrowing (0-1) and short distance (0-1), brow lowering (0-1), eyes close (0-1), bulging eyes (0-2), eye-eye furrowing (0-1), cheek bulge (0-1), nasal-labial furrowing (0-2), mouth open and stretch (0-1), lip purse (0-1) and taut tongue (0-1). During the second evaluation phase, with 2770 images from 31 newborn infants (average age: 2.85°”.027 days), the pain responses were graded on the NFISS scale. Two peak score values during a time course of baseline-venipuncture-recovery (3-3-10 min) were found with needle piercing and needle withdrawal. The reliability of the score analysis was evaluated using 492 randomly selected images out of the 2770 images. The results for intra-scorer (author, one week interval) and inter-scorer (author and one experienced nurse) has correlation coefficients of 0.916 and 0.826, respectively.

Although tics are the defining feature of chronic tic disorders (CTD), many children experience comorbid internalizing and externalizing problems that contribute to impairment across several domains, including family functioning. The current study examined clinical correlates and predictors of caregiver strain in parents of children with CTD. Participants were 123 children and adolescents diagnosed with a CTD who participated in a randomized-controlled trial of behavior therapy for reducing tics. Results showed that a combination of disruptive behavior, inattention/hyperactivity, and tic intensity best explained objective strain and a combination of inattention/hyperactivity and tic intensity were the best predictors of subjective caregiver strain. Implications of these findings for care providers are discussed.

Research has shown that motor and vocal tics fluctuate in frequency, intensity, and form in response to environmental and contextual cues. Behavioral models have proposed that some of the variation in tics may reflect context-dependent interactive learning processes such that once tics are performed, they are influenced by environmental contingencies. The current study describes the results of a function-based assessment of tics (FBAT) from a recently completed study comparing Comprehensive Behavioral Intervention for Tics (CBIT) with supportive psychotherapy. The current study describes the frequency with which antecedent and consequence variables were reported to exacerbate tics and the relationships between these functional variables and sample baseline characteristics, comorbidities, and measures of tic severity. Results showed that tic-exacerbating antecedents and consequences were nearly ubiquitous in a sample of children with chronic tic disorder. In addition, functional variables were related to baseline measures of comorbid internalizing symptoms and specific measures of tic severity.

Background Recent data suggest a serum vancomycin (vanc) trough (VT) of 11mg/L correlates with an AUC/MIC24 > 400 which has shown to be the optimal concentration to eradicate MRSA infection and improve mortality. There are currently limited published recommendations on how to achieve such a VT in children. This study validates a vancomycin nomogram used to achieve a VT of 10–15 mg/L in pediatric inpatients (pts) at a quaternary care children’s hospital. Methods This is an 18 month (mo) prospective analysis beginning in September 2015. Included pts were ≥2 mo of age and had ≥2 consecutive VT. Pts receiving renal replacement therapy or those with a serum creatinine (Scr) of ≥0.5 mg/dL from a prior admission or within 48 hours of vanc initiation were excluded. The starting dose (SD) of vanc was determined by age and creatinine clearance (CrCl) (Tables 1 and 2). CrCl was measured by Bedside Schwartz equation for patients ≤18 years old (yo) and Cockcroft-Gault equation for patients >18 yo. The maximum CrCl was set to 120 ml/minute. Patients who were on vanc and experienced a Scr increase of ≥0.5 mg/dL were considered to have acute kidney injury (AKI). The study had a 6 mo evaluation period which led to a revised version (RVN) on March 2016. The primary endpoint (PE) was achievement of 10–15 mg/L by the Second VT for patients with the First trough outside of this range, using our RVN (Table 3). Results Overall, a total of 276 patients received vanc, 17 and 29 patients were dosed according to the initial and RVN, respectively. For young children (Table 1), the SD for patients with a CrCL ≥90 ml/minute was therapeutic, sub-, and supra-therapeutic in 43.75%, 47.5% and 8.75%, respectively. For older children (Table 2), the SD for patients with a CrCl ≥100 ml/minute was therapeutic, sub-, and supra-therapeutic in 41.1%, 35.7% and 23.2%, respectively. The initial VN was successful 12/17 (70.6%) in achieving the PE. Success in achieving the PE after the RVN was 26/29 (89.7%). In the RVN group, the most common initial troughs were 5–7 mg/L (33.3%), followed by >18 mg/L (27.6%). The mean VT using the RVN was 13.7 mg/L. The overall AKI incidence throughout the study was 3.2% (9/276) and 0% using the RVN. Conclusion Our RVN led to a Second VT within a target range of 10–15 mg/L for 89.7% of patients, allowing for more accurate and safer use of vancomycin in our institution. Disclosures All authors: No reported disclosures.

Tic disorders are heterogeneous, with symptoms varying widely both within and across patients. Exploration of symptom clusters may aid in the identification of symptom dimensions of empirical and treatment import. This article presents the results of two studies investigating tic symptom clusters using a sample of 99 youth (M age = 10.7, 81% male, 77% Caucasian) diagnosed with a primary tic disorder (Tourette’s disorder or chronic tic disorder), across two university-based outpatient clinics specializing in tic and related disorders. In Study 1, a cluster analysis of the Yale Global Tic Severity Scale (YGTSS) identified four symptom dimensions: predominantly complex tics; simple head/face tics; simple body tics; and simple vocal/facial tics. In Study 2, these clusters were shown to be differentially associated with demographic and clinical characteristics. Findings lend support to prior research on tic phenomenology, help to organize treatment goals, and suggest symptom dimensions of tic disorders for further evaluation.

Tourette disorder is a chronic and typically impairing childhood-onset neurologic 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.To determine the efficacy of a comprehensive behavioral intervention for reducing tic severity in children and adolescents.Randomized, observer-blind, controlled trial of 126 children recruited from December 2004 through May 2007 and aged 9 through 17 years, with impairing Tourette or chronic tic disorder as a primary diagnosis, randomly assigned to 8 sessions during 10 weeks of behavior therapy (n = 61) or a control treatment consisting of supportive therapy and education (n = 65). Responders received 3 monthly booster treatment sessions and were reassessed at 3 and 6 months following treatment.Comprehensive behavioral intervention.Yale Global Tic Severity Scale (range 0-50, score15 indicating clinically significant tics) and Clinical Global Impressions-Improvement Scale (range 1 [very much improved] to 8 [very much worse]).Behavioral intervention led to a significantly greater decrease on the Yale Global Tic Severity Scale (24.7 [95% confidence interval {CI}, 23.1-26.3] to 17.1 [95% CI, 15.1-19.1]) from baseline to end point compared with the control treatment (24.6 [95% CI, 23.2-26.0] to 21.1 [95% CI, 19.2-23.0]) (P.001; difference between groups, 4.1; 95% CI, 2.0-6.2) (effect size = 0.68). Significantly more children receiving behavioral intervention compared with those in the control group were rated as being very much improved or much improved on the Clinical Global Impressions-Improvement scale (52.5% vs 18.5%, respectively; P.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 exhibiting continued benefit 6 months following treatment.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.clinicaltrials.gov Identifier: NCT00218777.