PubMed Health⌕ Search

Biomedical subjects

L Scahill

Publications and source records attributed to L Scahill.

At least 19 recordsLinked to original sources
PubMed2006

The Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS): an instrument for assessing obsessive-compulsive symptom dimensions.

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.

Adolescent↗
PubMed2003

A placebo-controlled trial of risperidone in Tourette syndrome.

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.

Adolescent↗
PubMed2001

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders.

BACKGROUND: Some cases of Tourette's syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection. METHODS: To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups: TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in normal controls (n = 67). Subjects were ranked after titrations of autoantibodies from 0 to 227 according to their level of immunoreactivity. RESULTS: TS patients had a significantly higher mean rank for total antineural and antinuclear antibodies, as well as antistreptolysin O titers. However, among children and adolescents, only the total antinuclear antibodies were increased in TS patients compared to age matched controls. Compared to SC patients, TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, significantly lower IgG class anticytoskeletal antibodies, and a significantly higher rank for total antinuclear antibodies. Compared to a mixed group of autoimmune disorders, the TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal antibodies, and a significantly higher rank for antistreptococcal antibodies. CONCLUSIONS: TS patients had significantly higher levels of total antineural and antinuclear antibodies than did controls. Their relation to IgG class antineural and antinuclear antibodies, markers for prior streptococcal infection, and other clinical characteristics, especially chronological age, was equivocal.

Adolescent↗
PubMed2001

Regional brain and ventricular volumes in Tourette syndrome.

BACKGROUND: The pathophysiology of Tourette syndrome (TS) is thought to involve disturbances in cortico-striato-thalamo-cortical circuitry. The morphological characteristics of the cortical and associated white matter portions of these circuits have not been previously examined in TS subjects. METHODS: High-resolution anatomical magnetic resonance images were acquired in 155 TS and 131 healthy children and adults. The cerebrums and ventricles were isolated and then parcellated into subregions using standard anatomical landmarks. RESULTS: For analyses that included both children and adults, TS subjects were found to have larger volumes in dorsal prefrontal regions, larger volumes in parieto-occipital regions, and smaller inferior occipital volumes. Significant inverse associations of cerebral volumes with age were seen in TS subjects that were not seen in healthy controls. Sex differences in the parieto-occipital regions of healthy subjects were diminished in the TS group. The age-related findings were most prominent in TS children, whereas the diminished sex differences were most prominent in TS adults. Group differences in regional ventricular volumes were less prominent than in the cerebrum. Regional cerebral volumes were significantly associated with the severity of tic symptoms in orbitofrontal, midtemporal, and parieto-occipital regions. CONCLUSIONS: Broadly distributed cortical systems are involved in the pathophysiology of TS. Developmental processes, sexual dimorphisms, and compensatory responses in these cortical regions may help to modulate the course and severity of tic symptoms.

Adolescent↗
PubMed2001

Methodological issues in designing a multisite trial of risperidone in children and adolescents with autism.

OBJECTIVE: To describe the methodological challenges and decisions made in developing a multisite, controlled study of risperidone in children and adolescents with autism. METHODS: Review the design considerations for clinical trials in children with autistic disorder accompanied by severe tantrums, aggressive and/or self-injurious behaviors. These design considerations include the definition of inclusion criteria that are relevant to clinical practice and matching study design to the goal of evaluating short- and long-term effects. Additional ethical and scientific issues concern the length of trial and sample size. RESULTS: We undertook a short-term, placebo-controlled study to evaluate the efficacy and safety of risperidone in children and adolescents with autistic disorder. This trial design was followed by an extended open-label maintenance on risperidone to confirm durability of treatment effects and to monitor safety. Finally, a placebo-controlled discontinuation study tested the need for continuous treatment. CONCLUSIONS: In the absence of standard pharmacological treatment for children with autistic disorder, a placebo-controlled study remains the most appropriate method of testing efficacy and safety. The clinical relevance of this study is enhanced by the addition of an extended maintenance phase followed by a placebo discontinuation.

Adolescent↗
PubMed2001

A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.

OBJECTIVE: This study evaluated the efficacy and safety of guanfacine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). METHOD: Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. RESULTS: Thirty-four medication-free subjects (31 boys and three girls with a mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, guanfacine was associated with a mean improvement of 37% in the total score on the teacher-rated ADHD Rating Scale, compared to 8% improvement for placebo. Nine of 17 subjects who received guanfacine were blindly rated on the Clinical Global Improvement scale as either much improved or very much improved, compared with none of 17 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 27% in the guanfacine group and 21% in the placebo group, not a significant difference. On the Continuous Performance Test, commission errors decreased by 22% and omission errors by 17% in the guanfacine group, compared with increases of 29% in commission errors and of 31% in omission errors in the placebo group. Tic severity decreased by 31% in the guanfacine group, compared to 0% in the placebo group. One guanfacine subject with sedation withdrew at week 4. Guanfacine was associated with insignificant decreases in blood pressure and pulse. CONCLUSIONS: Guanfacine appears to be a safe and effective treatment for children with tic disorders and ADHD.

Adolescent↗
PubMed2001

Thermal sensitivity in Tourette syndrome: preliminary report.

The effects of heat on tic symptoms were studied in a sample of 78 adults with Tourette syndrome. 62 men and 16 women completed a survey concerning the type, onset, and course of their tics. 10 adult male subjects also participated in a thermal challenge during which ambient temperature was raised from 22 degrees C to 35 degrees C following a control period. Of the 78, 24% or 19 reported increased tics upon exposure to heat. Compared to the remaining 59 subjects, there were no differences in sex distribution, current age, or overall course of illness. In the thermal challenge, there was general increase in tics that was correlated with sweat rate (r = .55, p = .001). This effect was prominent in 5 of 10 subjects (rs = .29 to .63). There were no mean differences in current age, age of onset, or current severity of symptoms between the five subjects of each group. Tic symptoms in a subgroup of patients with Tourette syndrome may be sensitive to heat. Abnormal heat regulation is not a likely explanation for the observed increase in tics. The increase may be due to normal heat-loss mechanisms through dopaminergic pathways.

Adult↗
PubMed2000

Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders.

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.

Adult↗
PubMed2000

Assessment in multisite randomized clinical trials of patients with autistic disorder: the Autism RUPP Network. Research Units on Pediatric Psychopharmacology.

Assessment of autistic disorder (autism) symptoms, primary and secondary, poses more challenging problems than ordinarily found in multisite randomized clinical trial (RCT) assessments. For example, subjects may be uncommunicative and extremely heterogeneous in problem presentation, and current pharmacological treatments are not likely to alter most core features of autism. The Autism Research Units on Pediatric Psychopharmacology (RUPP Autism Network) resolved some of these problems during the design of a risperidone RCT in children/adolescents. The inappropriateness of the usual anchors for a Clinical Global Impression of Severity (CGI-S) was resolved by defining uncomplicated autism without secondary symptoms as a CGI-S of 3, mildly ill. The communication problems, compromising use of the patient as an informant, were addressed by several strategies, including careful questioning of care providers, rating scales, laboratory tests, and physical exams. The broad subject heterogeneity requires outcome measures sensitive to individual change over a wide spectrum of treatment response and side effects. The problems of neuropsychologically testing nonverbal, lower functioning, sometimes noncompliant subjects requires careful instrument selection/adaptation and flexible administration techniques. The problems of assessing low-end IQs, neglected by most standardized test developers, was resolved by an algorithm of test hierarchy. Scarcity of other autism-adapted cognitive and neuropsychological tests and lack of standardization required development of a new, specially adapted battery. Reliability on the Autism Diagnostic Interview (currently the most valid diagnostic instrument) and other clinician instruments required extensive cross-site training (in-person, videotape, and teleconference sessions). Definition of a treatment responder required focus on individually relevant target symptoms, synthesis of possible modest improvements in many domains, and acceptance of attainable though imperfect goals. The assessment strategy developed is implemented in a RCT of risperidone (McDougle et al., 2000) for which the design and other methodological challenges are described elsewhere (Scahill et al., 2000). Some of these problems and solutions are partially shared with RCTs of other treatments and other disorders.

Antipsychotic Agents↗
PubMed2000

Risperidone-associated weight gain in children and adolescents: a retrospective chart review.

OBJECTIVE: Risperidone use has been associated with substantial weight gain in children and adolescents. Reports available to date have consisted of small case series evaluated without standardized indices of developmentally normative weight increase. The purpose of this study was to evaluate age- and gender-adjusted weight changes linked to risperidone use in a juvenile psychiatric inpatient population. METHOD: Thirty-seven child and adolescent inpatients treated with risperidone for 6 consecutive months were compared to a group of 33 psychiatric inpatients with no atypical neuroleptic exposure. Weight, height, and body mass index (BMI) were recorded on at least a monthly basis, and Tanner staging was completed on admission. Percent change from baseline weight, changes in standardized z scores of weight for age and gender, and proportion of subjects experiencing a < or = 7% weight increase from baseline were compared among groups. RESULTS: Subjects in both groups were comparable at baseline except for gender distribution (more males were in the risperidone group, p < 0.05). Risperidone-treated children and adolescents experienced significant weight gain between baseline and endpoint (paired t test, p < 0.001) that was first evident within 2 months of starting treatment, progressed steadily at an average rate of 1.2 kg/month, and did not reach a clear plateau during 6 months of observation. Significant increases in standardized weight were noted at 3 and 6 months for risperidone-treated subjects. Risperidone use conferred a substantial risk of gaining over 7% from baseline weight (odds ratio = 3.5, 95% confidence interval = 1.8-6.6, p < 0.001). CONCLUSIONS: Six-month exposure to risperidone was associated with clinically significant weight gain in 78% of treated children and adolescents (as opposed to 24% of those in the comparison group, p < 0.001). Risperidone dosage, concomitant medication use, and other demographic characteristics such as age, pubertal status, gender, and baseline weight and BMI were not associated with an increased risk of morbid weight gain. Standardized z scores offer advantages for the assessment of weight change among developing children and adolescents.

Adolescent↗
PubMed2000

Ziprasidone treatment of children and adolescents with Tourette's syndrome: a pilot study.

OBJECTIVE: To evaluate the efficacy and tolerability of ziprasidone in children and adolescents with Tourette's syndrome and chronic tic disorders. METHOD: Twenty-eight patients aged 7 to 17 years were randomly assigned to ziprasidone or placebo for 56 days. Ziprasidone was initiated at a dose of 5 mg/day and flexibly titrated to a maximum of 40 mg/day. RESULTS: Ziprasidone was significantly more effective than placebo in reducing the Global Severity (p = .016) and Total Tic (p = .008) scores on the Yale Global Tic Severity Scale. Compared with placebo, ziprasidone significantly reduced tic frequencies as determined by blind videotape tic counts (p = .039). The mean (+/- SD) daily dose of ziprasidone during the last 4 weeks of the trial was 28.2 +/- 9.6 mg. Mild transient somnolence was the most common adverse event. No clinically significant effects were observed on specific ratings of extrapyramidal symptoms, akathisia, or tardive dyskinesia. CONCLUSIONS: In this limited sample, ziprasidone (5-40 mg/day) appears to be effective and well tolerated in the treatment of Tourette's syndrome. Ziprasidone may be associated with a lower risk of extrapyramidal side effects in children. However, additional studies are necessary to evaluate more fully its safety and efficacy in children with tic disorders.

Adolescent↗
PubMed2000

Pharmacologic treatment of tic disorders.

The approach to treating children and adolescents with tic disorders has evolved in recent years such that complete elimination of tics is no longer the primary goal of treatment. Indeed, given the high frequency of psychiatric comorbidity in TS, treatment planning begins with identification of target symptoms. Although traditional neuroleptics still represent standard treatment for tics, many families and clinicians are reluctant to use these agents because of concern about the potential for short- and long-term side effects. Thus, there is great interest in the newer atypical neuroleptics. Interest in the atypical neuroleptics is understandable, but much more study is needed before these agents can become first-line treatments for tics. A small group of non-neuroleptic medications have been used in the treatment of tics. Of these, clonidine, guanfacine, tetrabenazine, pergolide, and botulinum toxin injections have shown some promise for suppressing tics. To date, however, only clonidine has been evaluated in randomized, controlled trials, and the results are not consistent across studies. Although comorbid ADHD is common in children with TS, treatment with stimulant medications was not recommended in children with tics. Recent data suggest that stimulants may be used in some children with TS without adverse effects. Until more is known about which children with ADHD and tic disorders can be safely treated with stimulants, however, the use of stimulants in this population should be undertaken with caution. A handful of nonstimulant medications have been used in the treatment of ADHD with some success, but more study is needed for most of these agents. Evaluation of the stimulants and nonstimulants for the treatment of ADHD in children and adolescents with tic disorders is an area worthy of large controlled trials.

Adolescent↗
PubMed2000

Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. Background and rationale for an initial controlled study of risperidone.

This article has reviewed the background and rationale for the choice of risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on 5-HT and DA neuronal systems, both of which have been implicated in the pathophysiology of autism. Unlike the typical antipsychotics, haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, risperidone's 5-HT2A/DA D2 ratio of receptor blockade appears to produce a lower risk of acute and chronic extrapyramidal side effects, as well as enhanced efficacy for the "negative" symptoms of autism. Indirect clinical and preclinical evidence supports the use of risperidone to treat impaired social behavior, interfering repetitive phenomena, and aggression, targets of pharmacotherapy for many patients with autism. Numerous published open-label trials in children and adolescents with autism and related PDDs and one double-blind, placebo-controlled study in adults suggest that risperidone has promise for the treatment of children and adolescents with autism. Because most of these studies have been short-term, open-label trials in small samples, however, a large-scale controlled study of risperidone in children and adolescents with autism is needed to confirm these results. Finally, because it is likely that children who demonstrate short-term benefit from risperidone will remain on the medication indefinitely, the longer-term effectiveness and safety of risperidone in this population also needs to be determined. The design of this study and the assessments used are described separately.

Adolescent↗