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Biomedical subjects

J Sverd

Publications and source records attributed to J Sverd.

At least 19 recordsLinked to original sources

Long-term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder.

BACKGROUND: This study examined changes in attention-deficit hyperactivity (ADHD) behaviors and motor and vocal tics during long-term treatment with methylphenidate. METHODS: Thirty-four prepubertal children with ADHD and chronic multiple tic disorder (who had participated in an 8-week, double-blind, placebo-controlled methylphenidate evaluation) were evaluated at 6-month intervals for 2 years as part of a prospective, nonblind, follow-up study. Treatment effects were assessed using direct observations of child behavior in a simulated (clinic-based) classroom and behavior rating scales completed by parents and physician. Videotapes of the simulated classroom were scored by coders who were blind to treatment status. RESULTS: There was no evidence (group data) that motor tics or vocal tics changed in frequency or severity during maintenance therapy compared with diagnostic or initial double-blind placebo evaluations. Behavioral improvements demonstrated during the acute drug trial were maintained during follow-up. There was no evidence (group data) of clinically significant adverse drug effects on cardiovascular function or growth at the end of 2 years of treatment. CONCLUSIONS: Long-term treatment with methylphenidate seems to be safe and effective for the management of ADHD behaviors in many (but not necessarily all) children with mild to moderate tic disorder. Nevertheless, careful clinical monitoring is mandatory to rule out the possibility of drug-induced tic exacerbation in individual patients.

Attention Deficit Disorder with Hyperactivity↗

Comparison of internalizing and externalizing symptoms in children with attention-deficit hyperactivity disorder with and without comorbid tic disorder.

This study examined the relation between internalizing and externalizing symptoms in two groups of prepubertal boys (with and without multiple chronic tic disorder) with diagnosed attention-deficit hyperactivity disorder (ADHD). Parents and teachers completed the Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF), respectively. Children were carefully evaluated for the absence of a chronic tic disorder. Boys with ADHD and chronic multiple tic disorder (ADHD/+tics) received significantly higher (p = .0032, Bonferroni correction) scores for the Anxious/Depressed, Thought Problems, and Attention Problem scales of the CBCL and the Delinquent Behavior, Thought Problems, and Somatic Complaints scales of the TRF than did boys without chronic tic disorder (ADHD/-tics). Although many of the individual items that differentiated (p < .05) the two groups of boys pertained to behaviors that characterize motor tics, obsessions, or compulsions, the ADHD/+tics group exhibited higher rates of anxious behavior (CBCL) and obscene language (TRF) than did the ADHD/-tics group. Anxiety/depressive symptoms were associated with aggressive/oppositional behavior in both samples. Children with mild tic disorder were more similar (CBCL) to ADHD/-tics boys than they were to children with more severe tic disorder. The relatively higher rate of comorbidity in the ADHD/+tics group suggests that tics may be a marker for more severe symptomatology in clinic-referred samples of children with ADHD. Furthermore, these data suggest that it is not the presence, per se, but rather the severity of tic disorder that is associated with higher rates of emotional and behavioral disturbances.

Anxiety Disorders↗

Studies of the c-Harvey-Ras gene in psychiatric disorders.

Hérault et al. (1993) previously reported a significant association between autism and the larger fragments of the c-Harvey-Ras (HRAS) Bam H1 polymorphism. We have sought to verify this finding and determine if there was any evidence for an association with other psychiatric disorders. Because of its greater sensitivity, we have examined the HRAS Msp 1 polymorphism. We found a just significant increase in the prevalence of the > 2.1 kb alleles in 48 subjects with autism versus 50 control subjects. There was no increase in the prevalence of the > 2.1 kb alleles in 164 probands with Tourette's syndrome. Examination of 16 preselected symptom clusters, however, showed a significant trend toward higher scores for obsessive-compulsive and phobic symptoms in > 2.1 kb homozygotes. While this locus requires further study, in conjunction with the results of Hérault et al., the present findings suggest that genetic defects in HRAS, and possibly other components of the G protein secondary messenger system, may play a role in some psychiatric disorders.

Adolescent↗

Associated psychopathology in children with both ADHD and chronic tic disorder.

OBJECTIVE: To examine the relation between severity of tic disorder and comorbid psychopathology in 47 prepubertal children with tic disorder who were referred for clinical evaluation of and treatment for attention-deficit hyperactivity disorder (ADHD), oppositional behaviors, and aggressive behaviors. METHOD: Parents and teachers completed the Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF) for each child. RESULTS: Seventy-five percent of the sample was in the clinical range in at least two categories of psychopathology. When the children were divided into two groups on the basis of tic severity, significantly higher scores were obtained for children with more severe tics on the narrow-band Depressed, Uncommunicative, Obsessive-Compulsive, and Aggressive scales, and the broad-band internalizing scale of the CBCL. The severity groups did not differ on TRF scores. Children who were more aggressive also received higher CBCL scores. CONCLUSIONS: The findings from this study suggest that the severity of chronic tics is a clinical indicator of complex psychopathology in children with ADHD who are referred for psychiatric evaluation.

Attention Deficit Disorder with Hyperactivity↗

Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders.

Defects in serotonin metabolism, and abnormalities in both blood serotonin and tryptophan levels, have been reported in many psychiatric disorders. Tryptophan 2,3-dioxygenase (TDO2) is the rate limiting enzyme for the breakdown of tryptophan to N-formyl kenurenine. Functional variants of this gene could account for the observed simultaneous increases or decreases of both serotonin and tryptophan in various disorders. We have identified four different polymorphisms of the human TDO2 gene. Association studies show a significant association of one or more of these polymorphisms and Tourette syndrome (TS), attention deficit hyperactivity disorder (ADHD) and drug dependence. The intron 6G-->T variant was significantly associated with platelet serotonin levels. Only the association with TS was significant with a Bonferroni correction (p = 0.005). Our purpose here is not to claim these associations are proven, but rather to report preliminary results and show that easily testable polymorphisms are available. We hope to encourage additional research into the potential role the TDO2 gene in these and other psychiatric disorders.

Electrophoresis, Polyacrylamide Gel↗

Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder.

BACKGROUND: The findings from case reports and patient questionnaire surveys have been interpreted as indicating that administration of stimulants is ill-advised for the treatment of attention-deficit hyperactivity disorder in children with tic disorder. METHODS: Thirty-four prepubertal children with attention-deficit hyperactivity disorder and tic disorder received placebo and three dosages of methylphenidate hydrochloride (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each, under double-blind conditions. Treatment effects were assessed using direct observations of child behavior in a simulated (clinic-based) classroom and using rating scales completed by the parents, teachers, and physician. RESULTS: Methylphenidate effectively suppressed hyperactive, disruptive, and aggressive behavior. There was no evidence that methylphenidate altered the severity of tic disorder, but it may have a weak effect on the frequency of motor (increase) and vocal (decrease) tics. CONCLUSION: Methylphenidate appears to be a safe and effective treatment for attention-deficit hyperactivity disorder in the majority of children with comorbid tic disorder.

Attention Deficit Disorder with Hyperactivity↗

Prevalence of pervasive developmental disorder in a sample of psychiatrically hospitalized children and adolescents.

Pervasive developmental disorder (PDD) is underrecognized because of lack of awareness of the wide range of severity and differing manifestations of the disorder. A survey of psychiatrically hospitalized children and adolescents was conducted. 3.2% of the sample of boys was found to have PDD. Underappreciation of the presence of PDD characterized the patients. Family members experienced a wide array of psychiatric symptoms and showed evidence for the presence of familial Tourette syndrome.

Adolescent↗

School observations of children with attention-deficit hyperactivity disorder and comorbid tic disorder: effects of methylphenidate treatment.

Although the findings from recent controlled studies suggest that methylphenidate is a safe and effective treatment for many children with attention-deficit hyperactivity disorder (ADHD) and comorbid tic disorder, relatively little is known about drug effects on school behavior. Thirty-four prepubertal children with ADHD and tic disorder received placebo and 3 doses of methylphenidate (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each under double-blind conditions. Treatment effects were assessed using direct observations of child behavior in classroom, lunchroom, and playground settings. Treatment with methylphenidate resulted in marked reductions of hyperactive, disruptive, and aggressive behavior, which was evident even for the 0.1 mg/kg dose. There were no "nonresponders." The only observed changes in tics were a small but statistically significant increase in the frequency of motor tics (classroom, 0.1 mg/kg dose) and a tendency for fewer vocal tics (lunchroom). However, these changes in motor tic frequency were not perceived by care providers as a worsening in the severity of the child's tic disorder. Most dose-response relationships were linear, but the mean (operationally defined) minimal effective dose (MED) was 0.3 mg/kg. In summary, the findings support the conclusions that (1) methylphenidate suppresses ADHD behaviors in the classroom and aggressive behavior in all settings and that (2) a low dose may have a weak exacerbation effect on the frequency of motor tics; but, in general, the majority of youngsters do not experience clinically significant tic worsening with a MED.

Aggression↗

Observations and ratings of tics in school settings.

This paper describes the findings of a school-based tic assessment procedure (direct observations, teacher rating scales) for hyperactive children with comorbid tic disorder. Rates of motor tic frequency were found to be moderately stable across both days and school settings. Correlations between direct observations of tics and clinician rating scales were generally in the low to moderate range as were correlations between teacher and clinician rating scales. Overall rates of hyperactive/disruptive behaviors were not associated with rates of motor tic occurrence, and the behavioral symptoms of both disorders were also independent for specific intervals of time.

Attention Deficit Disorder with Hyperactivity↗

Is Tourette syndrome a cause of sudden infant death syndrome and childhood obstructive sleep apnea?

The cause of sudden infant death syndrome (SIDS) is unknown. Sleep-related impairment of respiratory control and arousal are postulated; hyperdopaminergic and hyposerotonergic dysfunction may contribute to events leading to infant apnea and SIDS. Psychosocial adversity and impulsive and compulsive behaviors characterize some families of SIDS victims. Tourette syndrome (TS) is a common hereditary neurobehavioral disorder characterized by the frequent presence of impulsive and compulsive behaviors. Sleep disorders are common and include sleep apnea and abnormal arousal. Hyperdopaminergic and hyposerotonergic abnormalities are postulated to contribute to the pathophysiology of the disorder. The following is a report of the presence of incidents of infant apnea and SIDS in families in which TS was present. In an additional TS family, a child had obstructive sleep apnea syndrome (OSAS). Results of a preliminary survey suggest that TS gene carriers are at increased risk of life-threatening apneas of infancy and that the prevalence of SIDS in such families may be 2 to 5 times the prevalence in the general population. The presence in some pedigrees of sleep apnea in children and adults suggest that in some instances disorders of sleep-related ventilatory control and arousal occurring throughout the life-span share common pathophysiological mechanisms.

Child↗

Methylphenidate in hyperactive boys with comorbid tic disorder: II. Short-term behavioral effects in school settings.

In this study, 11 prepubertal hyperactive boys with tic disorder received placebo and three doses of methylphenidate (0.1, 0.3, and 0.5 mg/kg) for 2 weeks each, under double-blind conditions. Each boy was observed for approximately 20 hours in the school setting (classroom seatwork activities, lunchroom, and playground). Results showed that methylphenidate effectively suppressed hyperactive/disruptive behaviors in the classroom and physical aggression in the lunchroom and on the playground. Methylphenidate also reduced the occurrence of vocal tics in the classroom and the lunchroom. None of the motor tic measures revealed drug effects, but the lowest mean rate of motor tics occurred on the 0.3 mg/kg dose. On an operationally defined minimal effective dose, only one boy experienced motor tic exacerbation.

Attention Deficit Disorder with Hyperactivity↗

Tourette syndrome and autistic disorder: a significant relationship.

The histories of 10 children with autistic disorder or pervasive developmental disorder (PDD) cooccurring with familial Tourette syndrome (TS) are presented. Evidence from the histories of the patients and their relatives combined with other reports of cases of cooccurrence of TS and autism provides support for the hypothesis that TS may be responsible for cases of coocurrence of the disorders, contributes significantly to the etiological heterogeneity of autistic disorder and that a portion of cases of autism may actually be a result of homozygosity for the TS gene. In addition, the presence of affective disorders and autistic-like syndromes or mild disturbances of social relatedness in some of the pedigrees suggests the hypothesis that TS may be responsible for a subgroup of families with cooccurring affective and autistic disorders and for some cases of familial aggregation of autism-PDD.

Adult↗

Methylphenidate in aggressive-hyperactive boys: I. Effects on peer aggression in public school settings.

One of the least documented "known" effects of methylphenidate in hyperactive children is the suppression of peer aggression. In this study, 11 aggressive-hyperactive children received a low (0.3 mg/kg) and moderate (0.6 mg/kg) dose of methylphenidate and placebo for 2 weeks each under double-blind conditions. Children were observed in public school settings during classroom seatwork activities, lunch, and recess. Results showed that methylphenidate suppressed nonphysical aggression (p = 0.06) in the classroom, and a moderate dose decreased physical aggression (p less than 0.01) and verbal aggression (p = 0.07) on the playground. The effect on the rate of appropriate social interaction was variable. The majority of subjects exhibited either the same or higher levels of appropriate social interaction on the 0.6 mg/kg dose compared with placebo. In the classroom, both doses of methylphenidate also resulted in reduced levels of motor movement, off-task behavior, noncompliance, and disruptiveness. Teacher ratings of hyperactivity and conduct problem symptoms revealed drug effects, whereas parallel parent instruments did not.

Aggression↗