Anxiety Disorders: Scahill L

White SW, Oswald D, Ollendick T, Scahill L. · Virginia Polytechnic Institute and State University, Department of Psychology, 109 Williams Hall (0436), Blacksburg, VA 24061, United States. · Clin Psychol Rev. · Pubmed #19223098 No free full text.

Abstract: Anxiety and poor stress management are common concerns in clinical samples of children with autism spectrum disorders (ASD). Anxiety may worsen during adolescence, as young people face an increasingly complex social milieu and often become more aware of their differences and interpersonal difficulties. This review summarizes the state of research on the prevalence, phenomenology, and treatment of anxiety in youth with autism and related conditions such as Asperger's Disorder. Using search words autism, asperger(s), or pervasive developmental disorder and anxiety or anxious to find reports published between 1990 and 2008, this review identified 40 papers. The results of the review suggest that anxiety, whether measured categorically or dimensionally, is indeed common in children and adolescents with autism spectrum disorders and may be a source of additional morbidity. The assessment of anxiety disorders in ASD should be conducted using multiple informants and modalities, as children with ASD often do not display age-typical symptoms of anxiety. To date, relatively few controlled intervention studies using well-characterized samples have been conducted despite preliminary evidence for efficacy of select pharmacological and psychosocial approaches. Recommendations for future applied research are presented and clinical implications are explored.

Lombroso PJ, Scahill L. · Child Study Center, Yale University School of Medicine, New Haven, CT 06520, United States. · Brain Dev. · Pubmed #17937978 links to  free full text

Abstract: Tourette syndrome and obsessive-compulsive disorder are neuropsychiatric disorders that have sparked considerable interest over the decades. They are the focus of research for a remarkable diversity of disciplines, ranging from neuroimagers and prenatal epidemiologists to experts in the neural circuits that connect the cortex with the basal ganglia, as well as neuroimmunologists focusing on brain-based autoimmune phenomena. Several hypotheses have been put forward to explain the onset and exacerbation of these illnesses. Here, we discuss the clinical phenomenology and treatment options that are currently available. New psychopharmacological agents are being used that are based on a greater understanding of the neurobiology and are being used in combination with behavioral interventions. Longitudinal clinical investigations into clinical symptoms and the natural course are providing additional clues on the underlying pathophysiology. Recent advances in research models are also reviewed in an attempt to clarify some of the molecular etiologies that lead to these disorders.

Swain JE, Scahill L, Lombroso PJ, King RA, Leckman JF. · Child Study Center of Yale University, New Haven, CT, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #17667475 No free full text.

Abstract: OBJECTIVE: This is a review of progress made in the understanding of Tourette syndrome (TS) during the past decade including models of pathogenesis, state-of-the-art assessment techniques, and treatment. METHOD: Computerized literature searches were conducted under the key words "Tourette syndrome," "Tourette disorder," and "tics." Only references from 1996-2006 were included. RESULTS: Studies have documented the natural history of TS and the finding that tics usually improve by the end of the second decade of life. It has also become clear that TS frequently co-occurs with attention-deficit/hyperactivity disorder), obsessive-compulsive disorder, and a range of other mood and anxiety disorders. These comorbid conditions are often the major source of impairment for the affected child. Advances have also been made in understanding the underlying neurobiology of TS using in vivo neuroimaging and neurophysiology techniques. Progress on the genetic front has been less rapid. Proper diagnosis and education (involving the affected child and his or her parents, teachers, and peers) are essential prerequisites to the successful management of children with TS. When necessary, modestly effective antitic medications are available, although intervening to treat the comorbid attention-deficit/hyperactivity disorder and/or obsessive-compulsive disorder is usually the place to start. CONCLUSIONS: Prospective longitudinal studies and randomized clinical trials have led to the refinement of several models of pathogenesis and advanced our evidence base regarding treatment options. However, fully explanatory models are needed that would allow for more accurate prognosis and the development of targeted and efficacious treatments.

Leckman JF, Bloch MH, Scahill L, King RA. · Yale Child Study Center, New Haven, CT 06510, USA. · J Child Neurol. · Pubmed #16970864 No free full text.

Abstract: Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics--rapid, repetitive, stereotyped movements or vocalizations. Tourette syndrome typically has a prepubertal onset, and boys are more commonly affected than girls. Symptoms usually begin with transient bouts of simple motor tics. By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. These urges likely reflect a defect in sensorimotor gating because they intrude into the child's conscious awareness and become a source of distraction and distress. A momentary sense of relief typically follows the completion of a tic. Over the course of hours, tics occur in bouts, with a regular intertic interval. Tics increase during periods of emotional excitement and fatigue. Tics can become "complex" in nature and appear to be purposeful. Tics can be willfully suppressed for brief intervals and can be evoked by the mere mention of them. Tics typically diminish during periods of goal-directed behavior, especially those that involve both heightened attention and fine motor or vocal control, as occur in musical and athletic performances. Over the course of months, tics wax and wane. New tics appear, often in response to new sources of somatosensory irritation, such as the appearance of a persistent vocal tic (a cough) following a cold. Over the course of years, tic severity typically peaks between 8 and 12 years of age. By the end of the second decade of life, many individuals are virtually tic free. Less than 20% of cases continue to experience clinically impairing tics as adults. Tics rarely occur in isolation, and other coexisting conditions--such as behavioral disinhibition, hypersensitivity to a broad range of sensory stimuli, problems with visual motor integration, procedural learning difficulties, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depression, anxiety, and emotional instability--are often a greater source of impairment than the tics themselves. Emerging behavioral treatments of Tourette syndrome are based in part on an understanding of the moment-to-moment experience of somatosensory urges and motor response. With identification of specific genes of major effect and advances in our understanding of the neural circuitry of sensorimotor gating, habit formation, and procedural memory--together with insights from postmortem brain studies, in vivo brain imaging, and electrophysiologic recordings--we might be on the threshold of a deeper understanding of the phenomenology and natural history of Tourette syndrome.

Scahill L, Erenberg G, Berlin CM, Budman C, Coffey BJ, Jankovic J, Kiessling L, King RA, Kurlan R, Lang A, Mink J, Murphy T, Zinner S, Walkup J, Anonymous00057. · Yale Child Study Center, 230 South Frontage Road, P.O. Box 207900, New Haven, CT 06520, USA. · NeuroRx. · Pubmed #16554257 No free full text.

Abstract: To develop a guide to clinical assessment and pharmacotherapy for children and adults with Tourette syndrome (TS), we reviewed published literature over the past 25 years to identify original articles and reviews on the assessment and pharmacological treatment of Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The literature search also included a survey of reviews published in book chapters. The assessment section was compiled from several reviews. Pharmacological treatments were classified into those with strong empirical support (as evidenced by two positive placebo-controlled studies for tics, OCD, or ADHD in TS samples); modest empirical support (one positive placebo-controlled study), or minimal support (open-label data only). We conclude that accurate diagnosis, including identification of comorbid conditions, is an essential step toward appropriate treatment for patients with TS. In many patients with TS, symptom management requires pharmacotherapy for tics or coexisting conditions. The evidence supporting efficacy and safety for medications used in patients with TS varies. But this evidence offers the best guide to clinical practice.

Carroll DH, Scahill L, Phillips KA. · Yale Child Study Center, Yale University School of Nursing, New Haven, CT 06520-7900, USA. · Arch Psychiatr Nurs. · Pubmed #11925574 No free full text.

Abstract: Body dysmorphic disorder (BDD) is a potentially debilitating psychiatric illness characterized by intense preoccupation with an imagined or slight defect in physical appearance. Until recently, it has gone largely unrecognized and did not appear in the Diagnostic and Statistical Manual of Mental Disorders until 1987. Improved methods of assessment and treatment of BDD have increased interest in this disorder. This article reviews current literature on BDD, including the similarities between BDD and obsessive-compulsive disorder (OCD), current assessment and treatment strategies, and implications for clinical practice and future research.

Grados M, Scahill L, Riddle MA. · Department of Psychiatry and Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. · Child Adolesc Psychiatr Clin N Am. · Pubmed #10442233 No free full text.

Abstract: This article examines the general principles of psychopharmacologic treatment of obsessive-compulsive disorder (OCD) in children and adolescents. It includes a description of the currently approved medications for the treatment of children and adolescents with OCD, their side effect profiles, approaches to refractory OCD, and a discussion of drug interactions. Future directions for research are also considered.

King RA, Scahill L. · Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA. · Child Adolesc Psychiatr Clin N Am. · Pubmed #10442231 No free full text.

Abstract: This article discusses assessment, differential diagnosis, and treatment planning for children and adolescents with obsessions and compulsions. Such children require a detailed assessment of their obsessions and compulsions, comorbid difficulties, and overall developmental and adaptive functioning. Although cognitive behavioral therapy and psychopharmacology are the main forms of treatment for the core symptoms of OCD, comprehensive treatment planning and coordination require attention to the child's overall clinical picture.

Scahill L, Koenig K. · Yale Child Study Center, New Haven, CT, USA. · J Child Adolesc Psychiatr Nurs. · Pubmed #10347430 No free full text.

Abstract: Children with autism and the related PDDs may benefit from serotonin reuptake inhibitors such as clomipramine, fluoxetine, fluvoxamine, and sertraline for targeting repetitive thoughts and behaviors, anxiety, and depressed mood. To date, however, there are few controlled studies of these agents in children with PDD, so definitive evidence is lacking. Despite preliminary results in favor of naltrexone, neuroleptic medication appears to be effective for reducing aggression, self-injurious behavior, agitation, and stereotypies. The primary drawback with traditional neuroleptics is risk of short- and long-term side effects. The newer atypical neuroleptics have the potential for benefit with fewer extrapyramidal side effects, but more study is needed to establish their efficacy and safety. Children on neuroleptic medications should be started at the lowest possible dose, with gradual increases until clinical benefit is observed. The likelihood of untoward side effects is increased if the medication dose is increased rapidly. Baseline measurement of target behaviors can be aided by using standardized scales. The presence of abnormal movements should be assessed before initiating treatment and at regular intervals during the course of treatment--including after medication withdrawal. Weight gain is emerging as a recurrent side effect with the atypical neuroleptics. Thus, weight should be monitored, and the family should be advised about a diet baseline. As with all treatments of children with severe behavioral difficulties, pharmacotherapy should be instituted in the context of an integrated treatment plan.

Blair J, Scahill L, State M, Martin A. · Yale University School of Medicine, New Haven, CT 06520-7900, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #15608546 No free full text.

Abstract: OBJECTIVE: To assess the electrocardiographic safety profile of low-dose ziprasidone (< or =40 mg/day) among pediatric outpatients treated for up to 6 months. METHOD: This was a prospective, open-label trial involving 20 subjects with a mean age of 13.2 +/- 3.0 years. Subjects received a mean ziprasidone dose of 30 +/- 13 mg/day and were followed for 4.6 +/- 2.0 months, receiving a median of nine electrocardiograms each (range 2-11; total, 176). RESULTS: There were statistically significant changes from baseline to peak values in heart rate, PR, and QTc intervals, but not in QRS complex width. The mean QTc prolongation was 28 +/- 26 milliseconds and not related to dose (r = 0.16, p = .07). The peak QTc of three subjects reached or exceeded 450 milliseconds; one subject experienced a 114-millisecond prolongation. There was poor agreement (kappa = 0.25) between automated and manual identification of long QTc intervals (> or =440 milliseconds). CONCLUSIONS: These preliminary findings, occurring at doses low by current treatment standards, suggest that close electrocardiographic monitoring is warranted when prescribing ziprasidone to children, particularly at higher doses or when combined with other QTc-prolonging agents.

Scahill L, Kano Y, King RA, Carlson A, Peller A, LeBrun U, Do Rosario-Campos MC, Leckman JF. · Yale Child Study Center, & Yale School of Nursing, New Haven, Connecticut 06520, USA. · J Child Adolesc Psychopharmacol. · Pubmed #12880496 No free full text.

Abstract: BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous disorder with emerging data suggesting that age of onset and/or the presence of tics may define clinically important subgroups. OBJECTIVE: This study set out to evaluate the impact of age and tic disorders on the symptom profile in a pediatric sample of patients with OCD ascertained from a specialty clinic. METHODS: Eighty children with OCD (50 boys, 30 girls) were assessed for symptom type, severity, age of onset, presence of a tic disorder, and functional status. Each child's most impairing obsessions and compulsions were identified and compared by age category (above and below the age of 11 years) and according to the presence or absence of a tic disorder. RESULTS: The mean age of the sample was 11.1 +/- 3.19 years (range 4-18 years). The most common obsessions reported were contamination and worries about harm. Common compulsions included washing and rituals to prevent harm. The only significant differences across age groups were the percentage of religious worries and slightly higher severity of obsessions in the adolescent age group (p < 0.05). The presence of tics was associated with increased frequency of repetitive behavior unrelated to harm avoidance (p < 0.05). Children without a history of tics were more likely to describe incidents of contamination, washing, and repetitive request for reassurance (p < 0.05 for each). CONCLUSION: In this convenient sample of clinically ascertained children, there were few phenotypic differences in children above or below the age of 11 years. Differences in the distribution of OCD symptoms according to the presence or absence of tics, which has been documented in adult samples, were evident in this sample.

Scahill L, Leckman JF, Schultz RT, Katsovich L, Peterson BS. · Child Study Center, School of Nursing, Yale University, New Haven, CT 06520, USA. · Neurology. · Pubmed #12682319 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and safety of risperidone in children and adults with Tourette syndrome. METHODS: This was an 8-week, randomized, double-blind, placebo-controlled trial. The primary outcome measure was the Total Tic score of the Yale Global Tic Severity Scale (YGTSS). RESULTS: Thirty-four medication-free subjects (26 children and 8 adults) ranging in age from 6 to 62 years (mean = 19.7 +/- 17.0 years) participated. YGTSS Total Tic scores were similar at baseline (26.0 +/- 5.1 for risperidone vs 27.4 +/- 8.5 for placebo). After 8 weeks of treatment (mean daily dose of 2.5 +/- 0.85), the 16 subjects on risperidone showed a 32% reduction in tic severity from baseline, compared to a 7% reduction for placebo patients (n = 18) (F[2,64] = 6.07; p = 0.004). The 12 children randomized to risperidone showed a 36% reduction in tic symptoms compared to an 11% decrease in the 14 children on placebo (F[2,48] = 6.38; p = 0.004). Two children on risperidone showed acute social phobia, which resolved with dose reduction in one subject but resulted in medication discontinuation in the other. A mean increase in body weight of 2.8 kg was observed in the risperidone group compared to no change in placebo (F[2,64] = 10.68; p = 0.0001). No extrapyramidal symptoms and no clinically significant alterations in cardiac conduction times or laboratory measures were observed. CONCLUSION: Risperidone appears to be safe and effective for short-term treatment of tics in children or adults with Tourette syndrome. Longer-term studies are needed to evaluate the durability of efficacy and safety over time.

Nikolov RN, Bearss KE, Lettinga J, Erickson C, Rodowski M, Aman MG, McCracken JT, McDougle CJ, Tierney E, Vitiello B, Arnold LE, Shah B, Posey DJ, Ritz L, Scahill L. · Yale Child Study Center, Yale University, P.O. Box 207900, New Haven, CT, USA. · J Autism Dev Disord. · Pubmed #18791817 No free full text.

Abstract: Objective To evaluate gastrointestinal (GI) problems in a large, well-characterized sample of children with pervasive developmental disorders (PDDs). Methods One hundred seventy two children entering one of two trials conducted by the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network were assessed comprehensively prior to starting treatment and classified with regard to GI symptoms. Results Thirty nine (22.7%) were positive for GI problems, primarily constipation and diarrhea. Those with GI problems were no different from subjects without GI problems in demographic characteristics, measures of adaptive functioning, or autism symptom severity. Compared to children without GI problems, those with GI problems showed greater symptom severity on measures of irritability, anxiety, and social withdrawal. Those with GI problems were also less likely to respond to treatment.

Sukhodolsky DG, Scahill L, Gadow KD, Arnold LE, Aman MG, McDougle CJ, McCracken JT, Tierney E, Williams White S, Lecavalier L, Vitiello B. · The Child Study Center, Yale University, 230 South Frontage Road, New Haven, CT 06520, USA. · J Abnorm Child Psychol. · Pubmed #17674186 No free full text.

Abstract: BACKGROUND: In addition to the core symptoms, children with Pervasive Developmental Disorders (PDD) often exhibit other problem behaviors such as aggression, hyperactivity, and anxiety, which can contribute to overall impairment and, therefore, become the focus of clinical attention. Limited data are available on the prevalence of anxiety in these children. We examined frequency and correlates of parent-rated anxiety symptoms in a large sample of children with PDD. METHODS: The goals of this study were to examine the frequency and correlates of parent-rated anxiety symptoms in a sample of 171 medication-free children with PDD who participated in two NIH-funded medication trials. Twenty items of the Child and Adolescent Symptom Inventory (CASI) were used to measure anxiety. RESULTS: Forty three percent of the total sample met screening cut-off criteria for at least one anxiety disorder. Higher levels of anxiety on the 20-item CASI scale were associated with higher IQ, the presence of functional language use, and with higher levels of stereotyped behaviors. In children with higher IQ, anxiety was also associated with greater impairment in social reciprocity. CONCLUSION: Anxiety is common in PDD and warrants consideration in clinical evaluation and treatment planning. This study suggests that parent ratings could be a useful source of information about anxiety symptoms in this population. Some anxiety symptoms such as phobic and social anxiety may be closer to core symptoms of PDD. Further efforts to validate tools to ascertain anxiety are needed, as are studies to empirically test approaches to treat anxiety in PDD.

Scahill L, McDougle CJ, Williams SK, Dimitropoulos A, Aman MG, McCracken JT, Tierney E, Arnold LE, Cronin P, Grados M, Ghuman J, Koenig K, Lam KS, McGough J, Posey DJ, Ritz L, Swiezy NB, Vitiello B, Anonymous00049. · Yale Child Study Center, Yale University, New Haven, CT 06520, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #16926619 No free full text.

Abstract: OBJECTIVE: To examine the psychometric properties of the Children's Yale-Brown Obsessive Compulsive Scales (CYBOCS) modified for pervasive developmental disorders (PDDs). METHOD: Raters from five Research Units on Pediatric Psychopharmacology (RUPP) Autism Network were trained to reliability. The modified scale (CYBOCS-PDD), which contains only the five Compulsion severity items (range 0-20), was administered to 172 medication-free children (mean 8.2 +/- 2.6 years) with PDD (autistic disorder, n = 152; Asperger's disorder, n = 6; PDD not otherwise specified, n = 14) participating in RUPP clinical trials. Reliability was assessed by intraclass correlation coefficient (ICC) and internal consistency by Cronbach's alpha coefficient. Correlations with ratings of repetitive behavior and disruptive behavior were examined for validity. RESULTS: Eleven raters showed excellent reliability (ICC = 0.97). The mean CYBOCS score was 14.4 (+/- 3.86) with excellent internal consistency (alpha = .85). Correlations with other measures of repetitive behavior ranged from r = 0.11 to r = 0.28 and were similar to correlations with measures of irritability (r = 0.24) and hyperactivity (r = 0.25). Children with higher scores on the CYBOCS-PDD had higher levels of maladaptive behaviors and lower adaptive functioning. CONCLUSIONS: The five-item CYBOCS-PDD is reliable, distinct from other measures of repetitive behavior, and sensitive to change.

Rosario-Campos MC, Miguel EC, Quatrano S, Chacon P, Ferrao Y, Findley D, Katsovich L, Scahill L, King RA, Woody SR, Tolin D, Hollander E, Kano Y, Leckman JF. · Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil. · Mol Psychiatry. · Pubmed #16432526 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) encompasses a broad range of symptoms representing multiple domains. This complex phenotype can be summarized using a few consistent and temporally stable symptom dimensions. The objective of this study was to assess the psychometric properties of the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS). This scale measures the presence and severity of obsessive-compulsive (OC) symptoms within six distinct dimensions that combine thematically related obsessions and compulsions. The DY-BOCS includes portions to be used as a self-report instrument and portions to be used by expert raters, including global ratings of OC symptom severity and overall impairment. We assessed 137 patients with a Diagnostic and Statistical Manual-IV diagnosis of OCD, aged 6-69 years, from sites in the USA, Canada and Brazil. Estimates of the reliability and validity of both the expert and self-report versions of the DY-BOCS were calculated and stratified according to age (pediatric vs. adult subjects). The internal consistency of each of the six symptom dimensions and the global severity score were excellent. The inter-rater agreement was also excellent for all component scores. Self-report and expert ratings were highly intercorrelated. The global DY-BOCS score was highly correlated with the total Yale-Brown Obsessive-Compulsive Scale score (Pearson r = 0.82, P<0.0001). Severity scores for individual symptom dimensions were largely independent of one another, only modestly correlated with the global ratings, and were also differentially related to ratings of depression, anxiety and tic severity. No major differences were observed when the results were stratified by age. These results indicate that the DY-BOCS is a reliable and valid instrument for assessing multiple aspects of OCD symptom severity in natural history, neuroimaging, treatment response and genetic studies when administered by expert clinicians or their highly trained staff.

Bloch MH, Peterson BS, Scahill L, Otka J, Katsovich L, Zhang H, Leckman JF. · Yale Child Study Center, and General Clinical Research Center, Yale University School of Medicine, New Haven, CT 06520-7900, USA. · Arch Pediatr Adolesc Med. · Pubmed #16389213 links to  free full text

Abstract: BACKGROUND: Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is characterized by both motor and phonic tics. One half to two thirds of children with TS experience a reduction or complete resolution of tic symptoms during adolescence. At least one third of adults with TS have comorbid obsessive-compulsive disorder (OCD). OBJECTIVES: To clarify the clinical course of tic and OCD symptoms in children with TS and determine if baseline clinical measurements in childhood are associated with future symptom severity in late adolescence and early adulthood. DESIGN: Prospective cohort study. SETTING: Yale Child Study Center tic and OCD outpatient specialty clinic. PARTICIPANTS: Forty-six children with TS who received a structured clinical evaluation prior to age 14 years. MAIN OUTCOME MEASURES: Expert-rated tic and OCD symptom severity at follow-up interview an average of 7.6 years later (range, 3.8-12.8 years). RESULTS: Eighty-five percent of subjects reported a reduction in tic symptoms during adolescence. Only increased tic severity in childhood was associated with increased tic severity at follow-up. The average age at worst-ever tic severity was 10.6 years. Forty-one percent of patients with TS reported at one time experiencing at least moderate OCD symptoms. Worst-ever OCD symptoms occurred approximately 2 years later than worst-ever tic symptoms. Increased childhood IQ was strongly associated with increased OCD severity at follow-up. CONCLUSION: Obsessive-compulsive disorder symptoms in children with TS became more severe at a later age and were more likely to persist than tic symptoms.

Aman MG, Arnold LE, McDougle CJ, Vitiello B, Scahill L, Davies M, McCracken JT, Tierney E, Nash PL, Posey DJ, Chuang S, Martin A, Shah B, Gonzalez NM, Swiezy NB, Ritz L, Koenig K, McGough J, Ghuman JK, Lindsay RL. · The Nisonger Center, Ohio State University, Columbus, Ohio 43210-1296, USA. · J Child Adolesc Psychopharmacol. · Pubmed #16379507 No free full text.

Abstract: Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as assessed by the SARS, were no more common for drug than placebo, although drooling was reported more often in the risperidone group. There were no differences between groups on the AIMS. Two subjects had seizures (one taking placebo), but these were considered unrelated to active drug. Most AEs were mild to moderate and failed to interfere with therapeutic changes; there were no unanticipated AEs. The side effects of most concern were somnolence and weight gain.

Troost PW, Lahuis BE, Steenhuis MP, Ketelaars CE, Buitelaar JK, van Engeland H, Scahill L, Minderaa RB, Hoekstra PJ. · Department of Psychiatry, University Medical Center Groningen, University of Groningen, The Netherlands. · J Am Acad Child Adolesc Psychiatry. · Pubmed #16239862 No free full text.

Abstract: OBJECTIVE: The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available. METHOD: Thirty-six children with an autism spectrum disorder (5-17 years old) accompanied by severe tantrums, aggression, or self-injurious behavior, started 8-week open-label treatment with risperidone. Responders (n = 26) continued treatment for another 16 weeks, followed by a double-blind discontinuation (n = 24; two patients discontinued treatment because of weight gain) consisting of either 3 weeks of taper and 5 weeks of placebo only or continuing use of risperidone. Relapse was defined as a significant deterioration of symptoms based on clinical judgment and a parent questionnaire. RESULTS: Risperidone was superior to placebo in preventing relapse: this occurred in 3 of 12 patients continuing on risperidone versus 8 of 12 who switched to placebo (p = .049). Weight gain, increased appetite, anxiety, and fatigue were the most frequently reported side effects. CONCLUSIONS: This study indicates the effectiveness of risperidone during a period of several months, reducing disruptive behavior in about half of the children with autism spectrum disorders. The results provide a rationale for the continuing use of risperidone beyond 6 months, although considerable weight gain can limit the use of this agent.

Sukhodolsky DG, do Rosario-Campos MC, Scahill L, Katsovich L, Pauls DL, Peterson BS, King RA, Lombroso PJ, Findley DB, Leckman JF. · Child Study Center, Yale University School of Medicine, New Haven, CT 06520-7900, USA. · Am J Psychiatry. · Pubmed #15930061 links to  free full text

Abstract: OBJECTIVE: The purpose of the study was to examine adaptive, emotional, and family functioning in a well-characterized group of children and adolescents with obsessive-compulsive disorder (OCD) and to evaluate the influence of comorbid attention deficit hyperactivity disorder (ADHD) on the levels of impairment in various functional domains. METHOD: The study group included 287 children and adolescents (191 boys, 96 girls) ages 7-18 years. Fifty-six subjects had a diagnosis of OCD only, 43 had both OCD and ADHD, 95 had ADHD, and 93 were unaffected comparison children. Best estimate DSM-IV diagnoses were assigned on the basis of structured interviews and clinical ratings. The children's functioning was evaluated with a comprehensive battery of well-established, standardized measures, including the Vineland Adaptive Behavior Scales, parents' ratings of social and family functioning, and children's self-reports of emotional adjustment. RESULTS: The children with OCD only were more impaired than were unaffected comparison subjects in most areas of adaptive functioning and emotional adjustment. Children with OCD plus ADHD had additional difficulties in social functioning, school problems, and self-reported depression. Impairment in daily living skills, reduced number of activities, and self-reported anxiety were uniquely associated with the diagnosis of OCD. Family dysfunction was associated with ADHD but not with OCD. CONCLUSIONS: Children and adolescents with OCD are impaired in multiple domains of adaptive and emotional functioning. When comorbid ADHD is present, there is an additional burden on social, school, and family functioning.

Hamrin V, Jonker B, Scahill L. · Yale University, School of Nursing, New Haven, CT, USA. · J Child Adolesc Psychiatr Nurs. · Pubmed #15742797 No free full text.

Abstract: PROBLEM: The prevalence of acute stress disorder symptoms (ASDS) and other psychiatric comorbidities in youth with recent gunshot injuries. METHODS: Children (n=20) admitted to an urban hospital ER for gunshot injuries over a 4-year period were evaluated for ASDS, co-morbid DSM-III-R diagnoses, legal and gang involvement, and psychiatric history; medically hospitalized children (n=36) similar in age, sex, race, and socioeconomic status served as a control group. FINDINGS: Gunshot-injured youth reported a 75% rate of ASDS compared to a 14% rate in medically ill youth (OR 18.6; chi2 = p < .0001). Parent ratings of ASDS closely corresponded with youth ratings. Youth rated reexperiencing the event as the most frequent distressing symptom. Gunshot injury was associated with legal problems, gang involvement, marijuana/alcohol dependence, conduct disorder, social phobia, and agoraphobia compared to youth with medical illness. CONCLUSIONS: Compared to youth with medical illness, gunshot-injured youth were 18.6 times (p = .0001) more likely to show symptoms of ASDS. Further research, developmentally appropriate assessment, prevention, and treatment are needed in this area.

Diler RS, Yolga A, Avci A, Scahill L. · Department of Child and Adolescent Psychiatry, Faculty of Medicine, Cukurova University, Balcali, Adana, Turkey. · J Child Adolesc Psychopharmacol. · Pubmed #12880504 No free full text.

Abstract: OBJECTIVE: To present two cases of rapid-onset obsessive-compulsive symptoms in children treated with risperidone. Cases: "A" was an 8-year-old boy with attention deficit and chronic tic disorder who developed obsessive-compulsive symptoms within 2 weeks of starting risperidone. When the dose of 0.5 mg tid was discontinued, the obsessive-compulsive symptoms resolved with no return over 8 months of follow-up. "B" was an 11-year-old girl with mild mental retardation and aggression who was treated with risperidone 1 mg per day. Obsessive-compulsive symptoms suddenly emerged 10 days after starting risperidone and resolved within 3 days of discontinuation. In both cases, streptococcal pharyngitis was ruled out. CONCLUSION: Although the mechanism is not clear, these cases add to several other reports concerning the sudden emergence of obsessive-compulsive symptoms and anxiety symptoms in children treated with atypical antipsychotics. Clinicians should be alert to the possibility of these adverse effects in children treated with these drugs.

Peterson BS, Thomas P, Kane MJ, Scahill L, Zhang H, Bronen R, King RA, Leckman JF, Staib L. · Division of Child and Adolescent Psychiatry, the Department of Psychiatry, New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons, New York 10032, USA. · Arch Gen Psychiatry. · Pubmed #12695320 links to  free full text

Abstract: BACKGROUND: Despite strong circumstantial evidence that the pathophysiology of Gilles de la Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia, inconsistent findings from relatively small in vivo TS imaging studies have supported contradictory conclusions concerning the role of abnormal anatomical characteristics of the basal ganglia in the pathophysiology of TS. METHODS: Basal ganglia volumes were measured on high-resolution magnetic resonance images acquired for 154 children and adults with TS and 130 healthy control subjects. Repeated-measures analyses tested hypotheses concerning regional specificity, age effects, and abnormal asymmetries in the basal ganglia of subjects with TS. Subjects with prior neuroleptic exposure had larger basal ganglia volumes and were excluded from further statistical analyses. RESULTS: Caudate nucleus volumes were significantly (P =.008) smaller in children and adults with TS. Lenticular nucleus volumes also were smaller in adults with TS and in children with TS who were diagnosed as having comorbid obsessive-compulsive disorder. Regional anatomical asymmetries did not differ across groups. Regional volumes did not correlate significantly with the severity of tic, obsessive-compulsive disorder, or attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS: Reduced caudate nucleus volumes may be a good candidate marker for a trait abnormality in the structure of the basal ganglia in persons with TS. Smaller lenticular nucleus volumes may be an additional marker for the presence of comorbid obsessive-compulsive disorder and for the persistence of tic symptoms into adulthood. Brain regions other than the basal ganglia may have greater clinical relevance in determining the severity of tic symptoms.

Lin H, Yeh CB, Peterson BS, Scahill L, Grantz H, Findley DB, Katsovich L, Otka J, Lombroso PJ, King RA, Leckman JF. · Yale University School of Medicine, New Haven, CT 06520-7900, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #12218428 No free full text.

Abstract: OBJECTIVES: The severity of tic and obsessive-compulsive (OC) symptoms varies over time. Consequently, how do we, as clinicians, know when a change in symptom severity occurs that falls outside of the normal range of fluctuation? The goal of this study was to describe the level of symptom severity fluctuation over time and to establish an objective, prospective, and quantitative method for identifying symptom exacerbations in children with Tourette's syndrome, obsessive-compulsive disorder (OCD), or both. A second major aim was to assess whether fluctuations in tic and OC symptom severity covaried with one another. METHOD: Monthly consecutive Yale Global Tic Severity Scale and Children's Yale-Brown Obsessive Compulsive Scale scores were prospectively obtained in 64 children diagnosed with Tourette's syndrome and/or OCD for periods ranging from 3 to 39 months. Exacerbation thresholds were estimated by using state-of-the-art bootstrap methods. These thresholds were then independently evaluated by asking two expert clinicians to identify, retrospectively, clinically significant exacerbations based on a review of all available clinical and research records. RESULTS: The severity of tic and OC symptoms displayed a high degree of intrasubject variability. Exacerbation thresholds, which incorporated the change score from the previous month and the current symptom score, provided the best agreement with those of expert clinicians. When both tic and OC symptoms were present, they showed a significant degree of covariation. CONCLUSIONS: Evidence-based treatments are coming of age. The use of valid, clinician-rated severity scales will likely become a standard part of clinical practice. Bootstrapping methods may provide a quantitative and convenient way to obtain clinically valid thresholds to assess tic and OC symptom exacerbations. This method has the potential to be applied to other symptom domains where exacerbation thresholds are needed.

Peterson BS, Leckman JF, Tucker D, Scahill L, Staib L, Zhang H, King R, Cohen DJ, Gore JC, Lombroso P. · Yale Child Study Center, New Haven, Conn 06520, USA. · Arch Gen Psychiatry. · Pubmed #10768698 links to  free full text

Abstract: BACKGROUND: Previous studies have provided preliminary serological evidence supporting the theory that symptoms of tic disorders or obsessive-compulsive disorder (OCD) may be sequelae of prior streptococcal infection. It is unclear, however, whether previously reported associations with streptococcal infection were obscured by the presence of diagnostic comorbidities. It is also unknown whether streptococcal infection is associated in vivo with anatomical alterations of the brain structures that have been implicated in the pathophysiology of these disorders. METHODS: Antistreptococcal antibody titers were measured in 105 people diagnosed as having CTD, OCD, or attention-deficit/hyperactivity disorder (ADHD) and in 37 community controls without a disorder. Subjects were unselected with regard to their history of streptococcal exposure. Basal ganglia volumes were measured in 113 of these subjects (79 patients and 34 controls). RESULTS: A DSM-IV diagnosis of ADHD was associated significantly with titers of 2 distinct antistreptococcal antibodies, antistreptolysin O and anti-deoxyribonuclease B. These associations remained significant after controlling for the effects of CTD and OCD comorbidity. No significant association was seen between antibody titers and a diagnosis of either CTD or OCD. When basal ganglia volumes were included in these analyses, the relationships between antibody titers and basal ganglia volumes were significantly different in OCD and ADHD subjects compared with other diagnostic groups. Higher antibody titers in these subjects were associated with larger volumes of the putamen and globus pallidus nuclei. CONCLUSIONS: These findings suggest that the prior reports of an association between antistreptococcal antibodies and either CTD or OCD may have been confounded by the presence of ADHD. They also support the hypothesis that in susceptible persons who have ADHD or OCD, chronic or recurrent streptococcal infections are associated with structural alterations in basal ganglia nuclei.