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Biomedical subjects

H L Leonard

Publications and source records attributed to H L Leonard.

At least 37 records · Page 2Linked to original sources
PubMed1996

Obsessive-compulsive disorder in children and adolescents: a review of the past 10 years.

OBJECTIVE: To review the literature on pediatric obsessive-compulsive disorder (OCD) from the perspective of information relevant to American Board of Psychiatry and Neurology recertification in child and adolescent psychiatry. METHOD: The clinical and research literatures were systematically searched or articles that address the diagnosis and treatment of pediatric OCD. RESULTS: Drawing from the literature and their own clinical experience, the authors note that (1) OCD is a common neuropsychiatric disorder; (2) comorbidity is common, especially with tic, attention-deficit, anxiety, and affective disorders; (3) OCD following group A beta-hemolytic streptococcal infection may define an autoimmune sub-grouping calling for immunomodulatory treatments; and (4) OCD-specific cognitive-behavioral psychotherapy and pharmacotherapy with a serotonin reuptake inhibitor define the psychotherapeutic and pharmacotherapeutic treatments of choice, respectively. CONCLUSION: Child psychiatrists should be familiar with the differential diagnosis and treatment of OCD.

Adolescent↗
PubMed1996

Autonomic activity in relation to cerebrospinal fluid neurochemistry in obsessive and disruptive children and adolescents.

Electrodermal activity and heart rate were recorded during rest, simple tones, and a reaction time task in 43 male and female adolescents and children with obsessive compulsive disorder and 30 male adolescents and children with disruptive behavior disorders who had lumbar cerebrospinal fluid drawn during the same week. Partial correlations controlling for age and sex showed that in the obsessive group metabolites of serotonin and dopamine, but not of norepinephrine, were positively correlated with electrodermal responsivity, most consistently in the reaction time task. This result was not replicated in disruptive boys. Adrenocorticotropic hormone was positively related to electrodermal activity and heart rate throughout the session. The results for the obsessive adolescents suggest that nigrostriatal dopamine turnover and central serotonin turnover affect electrodermal activity, generally confirming and extending conclusions from pharmacological studies. Diagnosis may affect these relationships.

Adolescent↗
PubMed1995

Case study: a new infection-triggered, autoimmune subtype of pediatric OCD and Tourette's syndrome.

A review of clinical observations and literature reports leads to the hypothesis that, via a process analogous to Sydenham's chorea, infections with group A beta-hemolytic streptococci, among others, may trigger autoimmune responses that cause or exacerbate some cases of childhood-onset obsessive-compulsive disorder (OCD) or tic disorders (including Tourette's syndrome). If this hypothesis is correct, then immunological treatments should lead to decreased symptoms in some cases. Four cases with abrupt, severe onset or worsening of OCD or tics are presented from an open treatment study. All were boys aged 10 to 14 years. One had OCD, one had Tourette's syndrome, and two had both OCD and Tourette's syndrome. Clinically and on standardized rating scales, their symptoms were in the moderate to very severe range. Two had evidence of recent group A beta-hemolytic streptococci infections, and the others had histories of recent viral illnesses. Two were treated with plasmapheresis, one with intravenous immunoglobulin, and one with immunosuppressive doses of prednisone. All had a clinically significant response immediately after treatment. Diagnostic criteria are provided that describe these cases of pediatric, infection-triggered, autoimmune neuropsychiatric disorders (PITANDs). Suggestions are made regarding the evaluation and management of patients who may have this condition.

Adolescent↗
PubMed1995

Practical guidelines for the assessment and treatment of selective mutism.

OBJECTIVE: To provide practical guidelines for the assessment and treatment of children with selective mutism, in light of the recent hypothesis that selective mutism might be best conceptualized as a childhood anxiety disorder. METHOD: An extensive literature review was completed on the phenomenology, evaluation, and treatment of children with selective mutism. Additional recommendations were based on clinical experience from the authors' selective mutism clinic. RESULTS: No systematic studies of the phenomenology of children with selective mutism were found. Reports described diverse and primarily noncontrolled treatment approaches with minimal follow-up information. Assessment and treatment options for selective mutism are presented, based on new hypotheses that focus on the anxiety component of this disorder. Ongoing research suggests a role for behavior modification and pharmacotherapy similar to the approaches used for adults with social phobia. CONCLUSION: Selectively mute children deserve a comprehensive evaluation to identify primary and comorbid problems that might require treatment. A school-based multidisciplinary individualized treatment plan is recommended, involving the combined effort of teachers, clinicians, and parents with home- and clinic-based interventions (individual and family psychotherapy, pharmacotherapy) as required.

Anxiety Disorders↗
PubMed1995

Electrocardiographic changes during desipramine and clomipramine treatment in children and adolescents.

OBJECTIVE: With the increased use of tricyclic antidepressants in children, and several reports of several sudden deaths associated with desipramine (DMI) treatment, systematic study of their cardiac effects is indicated. In the present study, DMI's and clomipramine's (CMI) short-term effects on the electrocardiogram (ECG) were compared, as well as the long-term effects of CMI. METHOD: The ECGs of 47 children and adolescents in treatment trials were examined at baseline, after 5 weeks of CMI and of DMI treatment, and during CMI maintenance (mean duration 24.6 months). RESULTS: At 5 weeks of CMI and of DMI treatment, the heart rate, PR, QRS, and QT-corrected (QTc) intervals on ECG were significantly increased from baseline (p < .05); DMI increased PR and QRS intervals more than CMI (p < .05), and CMI increased QTc more (p < .05). Tachycardia was the most common change (36%). More patients experienced an incomplete intraventricular conduction delay during DMI treatment (23%, 9/39) than during CMI (2%, 1/47) (p < .05). Four patients (9%) acutely developed a prolonged QTc during either DMI or CMI. Long-term maintenance ECGs during CMI treatment (n = 25) were not significantly different from that at week 5, although some individuals developed or resolved specific ECG changes. CONCLUSION: CMI and DMI both produced ECG changes typically reported for tricyclic antidepressants, and they differed on specific ECG changes. Changes in ECG measures for individuals from short to long term suggest that continued monitoring is required.

Adolescent↗
PubMed1995

Sydenham's chorea: magnetic resonance imaging of the basal ganglia.

Analysis of cerebral magnetic resonance images of 24 subjects with Sydenham's chorea and 48 age-, height-, weight-, gender-, and handedness-matched controls demonstrated increased sizes of the caudate, putamen, and globus pallidus in the Sydenham's chorea group. In contrast, neither total cerebral, prefrontal, or midfrontal volumes or thalamic area were increased. These results indicate the selective involvement of the basal ganglia in Sydenham's chorea.

Adolescent↗
PubMed1995

Neuropsychiatry of obsessive-compulsive disorder in children and adolescents.

Physicians understanding of the pathobiobiology, diagnosis, and treatment of OCD in children and adolescents closely resembles that for OCD in adults. Moreover, it is now clear that OCD is a neurobehavioral disorder involving dysregulation in links between cortical and subcortical circuitry that is substantially influenced by serotonergic neurotransmission. Although current treatments are not generally curative, given a correct diagnosis and the skillful combination of pharmacotherapy with a serotonin reuptake inhibitor and focused cognitive-behavioral psychotherapy, most children can be helped to resume a normal developmental trajectory.

Adolescent↗
PubMed1994

Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine.

BACKGROUND: This study examined the effect of long-term (mean, 19 months) treatment with clomipramine hydrochloride on cerebrospinal fluid (CSF) levels of several neuropeptides and monoamine metabolites in children and adolescents with obsessive-compulsive disorder. METHODS: The CSF levels of corticotropin-releasing hormone, vasopressin, somatostatin, and oxytocin and of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in 17 children and adolescents with obsessive-compulsive disorder before and after long-term treatment with clomipramine. RESULTS: Treatment resulted in significant decreases in CSF levels of corticotropin-releasing hormone (mean +/- SD, 175 +/- 32 vs 152 +/- 25 pmol/L, P < .03) and vasopressin (mean +/- SD, 1.30 +/- 0.57 vs 0.86 +/- 0.54 pmol/L, P < .02) and a trend toward a decrease in somatostatin levels (mean +/- SD, 21.3 +/- 8.5 vs 15.3 +/- 9.8 pmol/L, P < .06). Treatment also significantly increased CSF oxytocin levels (mean +/- SD, 6.05 +/- 1.60 vs 6.70 +/- 1.44 pmol/L, P < .01). Significant changes in CSF monoamine metabolite levels with treatment included significant decreases in CSF levels of 5-hydroxyindoleacetic acid (mean +/- SD, 109 +/- 31 vs 77 +/- 23 pmol/mL, P < .001), CSF homovanillic acid (mean +/- SD, 273 +/- 111 vs 237 +/- 101 pmol/mL, P < .04), and 3-methoxy-4-hydroxyphenylglycol (mean +/- SD, 42.4 +/- 10.2 vs 36.1 +/- 4.8 pmol/L, P < .02) and a significant increase in the homovanillic acid-5-hydroxyindoleacetic acid ratio (mean +/- SD, 2.44 +/- 0.46 vs 3.42 +/- 0.84, P < .0001). CONCLUSIONS: These neuropeptide results coupled with evidence that central administration of corticotropin-releasing hormone, vasopressin, and somatostatin to laboratory animals increases arousal and acquisition of conditioned behaviors whereas central administration of oxytocin has opposite behavioral effects are consistent with a role for these neuropeptides in the pathophysiologic processes and pharmacologic treatment of obsessive-compulsive disorder.

Adolescent↗
PubMed1994

Childhood movement disorders and obsessive compulsive disorder.

Recent investigations of childhood-onset obsessive compulsive disorder (OCD) and pediatric movement disorders such as tics, Tourette's syndrome (TS), and Sydenham's chorea suggest that these disorders may be related. Although comorbid obsessive-compulsive symptoms have long been recognized in individuals with TS, more recent studies have demonstrated that tics and TS are surprisingly common in children with primary OCD, and further, that the two disorders seem to have a common genetic vulnerability. Obsessive-compulsive symptoms are also manifest in Sydenham's chorea, a neurologic variant of rheumatic fever in which antistreptococcal antibodies are thought to cross-react with neuronal tissue, particularly within the basal ganglia, and cause inflammatory changes resulting in neuropsychiatric symptomatology. The frequent comorbidity of OCD and Sydenham's chorea and similar postulates of basal ganglia dysfunction for both disorders suggest that Sydenham's chorea may serve as a medical model for OCD. Of note, however, is that the medications (e.g., neuroleptics) that are effective in treating this and other movement disorders are distinctly different from those that are efficacious for OCD (e.g., serotonin reuptake blockers). Examinations of the similarities and differences among these various neuropsychiatric conditions may lead to greater understanding of the pathophysiology of OCD and offer further insights into the etiology and treatment of this troubling disorder.

Antipsychotic Agents↗
PubMed1993

Individual differences in cerebral metabolic patterns during pharmacotherapy in obsessive-compulsive disorder: a multiple regression/discriminant analysis of positron emission tomographic data.

A multiple regression/discriminant analysis of positron emission tomographic cerebral metabolic (rCMRglc) data in 10 obsessive-compulsive disorder (OCD) patients before and during pharmacotherapy was carried out to see if rCMRglc interdependencies distinguished OCD patients from controls. Before therapy, a discriminant function reflecting parietal, sensorimotor, and midbrain rCMRglc interdependencies correctly classified eight (80%) of the 10 patients as OCD; after therapy, six (70%) were classified as controls, most of whom were responders. Before therapy, rCMRglc interdependencies involving basal ganglia, thalamus, limbic, and sensory and association cortical regions distinguished 67% of patients who clinically responded to drug (RESP, n = 6) and 75% of patients who did not (NRESP, n = 4) from controls. After therapy, all RESP were classified as controls; classification of NRESP remained unchanged. The results suggest the conjunctive utility of this method to assess individual differences in rCMRglc during pharmacotherapy, and to explore the neurobiology of OCD.

Adult↗
PubMed1993

A 2- to 7-year follow-up study of 54 obsessive-compulsive children and adolescents.

OBJECTIVE: Due to the generally poor prognosis previously reported for patients with obsessive-compulsive disorder (OCD), this report systematically assessed the outcome of patients who had had access to new psychopharmacologic treatments to determine whether there had been any long-term gains and if there were any predictors of outcome. DESIGN: Prospective follow-up study of a cohort of consecutive pediatric patients with OCD who had participated in controlled treatment (clomipramine hydrochloride) trials and then received a variety of interim treatments. PATIENTS: Fifty-four children and adolescents were reevaluated 2 to 7 years (mean, 3.4 +/- 1.0 years) after initial clomipramine treatment. Information for 48 (89%) of the patients was from direct interview and for the remaining six (11%) from at least two sources. RESULTS: On follow-up, 23 of the subjects (43%) still met diagnostic criteria for OCD, and only three (6%) could be considered in true remission. Thirty-eight subjects (70%) were taking psychoactive medication at the time of follow-up. Although OCD symptoms continued, the group as a whole was significantly improved at follow-up, with only 10 subjects (19%) rated as unchanged or worse. A worse OCD outcome score at follow-up was predicted in a stepwise multiple regression by (1) more severe OCD symptoms score after 5 weeks of clomipramine therapy, (2) lifetime history of a tic disorder, and (3) presence of parental Axis I psychiatric diagnosis (R2 = .31, P < .01). CONCLUSIONS: With new treatments available, most patients with pediatric OCD can expect significant longterm improvements but not complete remission. This study supports previous reports of the chronicity and intractability of the disorder, as there still remained a significant subgroup of subjects who exhibited continued morbidity despite multiple interventions.

Adolescent↗
PubMed1993

Obsessive compulsive disorder in children and adolescents: issues in management.

Clinical experience with children and adolescents with obsessive compulsive disorder (OCD) suggests the need for long-term care. In addition to maintenance drug treatment, behavior therapy and family counseling are usually indicated. Family counseling can help prevent the avoidant behavior that is a serious complication of OCD. The outcome for OCD in children and adolescents has been improved by the use of these active long-term therapies.

Adolescent↗
PubMed1993

Sydenham's chorea: physical and psychological symptoms of St Vitus dance.

Eleven children with Sydenham's chorea (8 girls and 3 boys, mean age = 8.4 +/- 2.2 [SD] years) underwent comprehensive physical, neuropsychologic, and psychiatric examination. The chorea was manifested as dysarthria, gait disturbances, and frequent adventitious movements of the face, neck, trunk, and extremities. Antineuronal antibodies were present in 10 of 11 children. All children exhibited concomitant psychologic dysfunction, specifically obsessive-compulsive symptomatology, increased emotional lability, motoric hyperactivity, irritability, distractibility, and age-regressed behavior. Obsessive-compulsive symptoms were observed in 9 (82%) children, 4 of whom met diagnostic criteria for obsessive-compulsive disorder. These behavioral symptoms began several days to weeks before the chorea was observed, and they waxed and waned in severity along with the motoric abnormalities. These results suggest that psychologic, particularly obsessive-compulsive, symptoms are accompanying manifestations of Sydenham's chorea which may require medical attention.

Affective Symptoms↗
PubMed1992

Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder.

Cerebrospinal fluid hormones, monoaminergic metabolites, and dynorphin A (1-8 sequence) were examined in 43 children with severe, primary obsessive-compulsive disorder. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid were positively correlated with one of eight obsessive-compulsive disorder severity ratings and three of seven measures of improvement following 5 weeks of treatment with clomipramine hydrochloride. Arginine vasopressin concentration was significantly and negatively correlated with several ratings of obsessive-compulsive disorder symptom severity, while oxytocin concentration was positively correlated with depressive symptoms. The ratio of arginine vasopressin to oxytocin was also negatively correlated with obsessive-compulsive disorder and depressive symptoms. Comorbid affective disorder was associated with decreased arginine vasopressin concentrations, while concomitant anxiety disorder was associated with increased oxytocin. Dynorphin A (1-8 sequence), homovanillic acid, corticotropin, 3-methoxy-4-hydroxyphenylglycol, and corticotropin releasing hormone were not significantly related to obsessive-compulsive disorder symptoms. These results seem to indicate that arginine vasopressin may be related to obsessive-compulsive disorder symptom severity, while 5-hydroxyindoleacetic acid might be associated with drug response.

Adolescent↗
PubMed1992

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy.

To investigate the effects of drug treatment in childhood-onset obsessive-compulsive disorder (OCD), we repeated positron emission tomographic scans in 13 adults with OCD (eight taking clomipramine, two taking fluoxetine, and three taking no drug) after at least 1 year of pharmacotherapy. As a group, the patients had a significant improvement on all OCD and anxiety ratings. Positron emission tomography revealed a significant decrease in normalized orbitofrontal regional cerebral glucose metabolism (relative to global metabolism) bilaterally. Among the treated patients, the decrease in right orbitofrontal metabolism was directly correlated with two measures of OCD improvement. These results extend previous positron emission tomographic findings of regional dysfunction in OCD and suggest involvement of the orbitofrontal regions in the pathophysiology of OCD.

Adult↗