Biomedical subjects

S D Hamburger

Publications and source records attributed to S D Hamburger.

At least 55 records · Page 3Linked to original sources

PubMed1995

A double-blind comparison of clomipramine and desipramine in the treatment of developmental stuttering.

BACKGROUND: Clomipramine, a serotonin reuptake blocker that has been shown to be effective in treating obsessive-compulsive disorder and other unwanted repetitive, ritualized behaviors, was hypothesized to be superior to desipramine, a tricyclic antidepressant with selective noradrenergic effects, for developmental stuttering. METHOD: Seventeen psychiatrically normal subjects, aged 14-61 years, with developmental stuttering completed a 10-week double-blind crossover trial of clomipramine and desipramine after a 2-week single-blind placebo phase. RESULTS: Clomipramine was superior to desipramine (two-tailed, p < .05) for 5 of 10 self-report ratings including stuttering severity on two scales, degree of preoccupation with stuttering and resistance to stuttering on a visual analog scale, and "expectancy" of stuttering on the Perceptions of Stuttering Inventory. CONCLUSION: Clomipramine may be clinically useful for some patients with developmental stuttering. Biological links between developmental stuttering and other repetitive motor patterns that are selectively responsive to serotonergic agents should be explored.

Adolescent↗

PubMed1994

Right frontotemporal activation by tonal memory in dyslexia, an O15 PET Study.

A prior study documented the failure of dyslexic men to activate left temporoparietal cortex during phonologic processing. Because of reports of an anomalous right planum temporale in developmental dyslexia, the functional implications of which are unknown, this study examined the ability of dyslexics to activate right temporal cortex. Regional cerebral blood flow was measured in 15 right-handed dyslexic men during rest and during a tonal memory task expected to activate right-sided cortex in controls. A matched control sample (n = 18) showed significant activation of several right frontotemporal regions as well as of left temporal cortex. In contrast, severely dyslexic men activated fewer right frontotemporal regions, while making many more errors than controls, but showed normal activation of left mid to anterior temporal cortex. These results support hypothesized underlying deficits in rapid temporal processing and possible involvement of right (in addition to left) temporal cortex in severe dyslexia.

Adult↗

PubMed1994

Normal activation of frontotemporal language cortex in dyslexia, as measured with oxygen 15 positron emission tomography.

OBJECTIVE: To assess the ability of dyslexic men to activate left middle to anterior language cortex normally. DESIGN: Positron emission tomography using oxygen 15-labeled water as a tracer during rest and during a syntax task involving sentence comprehension. SETTING: Research hospital. PATIENTS OR OTHER PARTICIPANTS: Fifteen right-handed, severely dyslexic men (mean [+/- SD] age, 27 +/- 5 years) and 20 matched controls. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Cerebral blood flow. RESULTS: During rest, dyslexics showed reduced blood flow (relative to controls) in one left parietal region near the angular/supramarginal gyri, but otherwise normal flow. During syntactic processing, dyslexics and controls showed similar, significant activation of left middle to anterior temporal and inferior frontal cortex. CONCLUSIONS: These results, together with the previously reported failure of dyslexics to activate left temporoparietal cortex during phonologic processing, argue for dysfunction of left cortical language areas restricted to posterior language regions in dyslexia.

Adult↗

PubMed1994

Developmental dyslexia and attention dysfunction in adults: brain potential indices of information processing.

Event-related brain potentials (ERPs) were recorded from a group of 13 men with severe developmental dyslexia and 15 matched normal controls. Auditory and visual stimuli, presented in separate reaction time tasks of graded difficulty, were used to elicit ERPs. No group differences in P300 were seen under relatively undemanding task conditions. However, as task demands increased, visual P300 was reduced in the dyslexic men as compared with the normal readers. An Abbreviated Conners Parent Rating Scale was used to assess retrospectively childhood symptoms of attention-deficit hyperactivity disorder (ADHD). Additional analyses revealed that the dyslexics with a history of many symptoms of ADHD in childhood (high ADHD) accounted for the group differences in P300; the dyslexics with a history of few or no such symptoms (low ADHD) were indistinguishable from the controls at all electrode sites. Furthermore, whereas the low-ADHD dyslexics showed the same hemispheric asymmetry in auditory P300 as did the controls (right > left), auditory P300 was more symmetrically distributed in the high-ADHD dyslexics. The results are interpreted as suggesting that a distinct brain organization may characterize dyslexic men with a history of concomitant deficits in attention.

Adult↗

PubMed1994

Quantitative morphology of the caudate nucleus in attention deficit hyperactivity disorder.

OBJECTIVE: Because the caudate nuclei receive inputs from cortical regions implicated in executive functioning and attentional tasks, caudate and total brain volumes were examined in boys with attention deficit hyperactivity disorder (ADHD) and normal comparison subjects. To gain developmental perspective, a wide age range was sampled for both groups. METHOD: The brains of 50 male ADHD patients (aged 6-19) and 48 matched comparison subjects were scanned by magnetic resonance imaging (MRI). Volumetric measures of the head and body of the caudate nucleus were obtained from T1-weighted coronal images. Interrater reliabilities (intraclass correlations) were 0.89 or greater. RESULTS: The normal pattern of slight but significantly greater right caudate volume across all ages was not seen in ADHD. Mean right caudate volume was slightly but significantly smaller in the ADHD patients than in the comparison subjects, while there was no significant difference for the left. Together these facts accounted for the highly significant lack of normal asymmetry in caudate volume in the ADHD boys. Total brain volume was 5% smaller in the ADHD boys, and this was not accounted for by age, height, weight, or IQ. Smaller brain volume in ADHD did not account for the caudate volume or symmetry differences. For the normal boys, caudate volume decreased substantially (13%) and significantly with age, while in ADHD there was no age-related change. CONCLUSIONS: Along with previous MRI findings of low volumes in corpus callosum regions, these results support developmental abnormalities of frontal-striatal circuits in ADHD.

Adult↗

PubMed1994

Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder.

OBJECTIVE: By means of quantitative neuroanatomic imaging the authors assessed the hypothesis that there are structural brain abnormalities relevant to frontal lobe circuitry in children with attention deficit hyperactivity disorder (ADHD). METHOD: The midsagittal cross-sectional area of the corpus callosum, divided into seven sections, was measured from magnetic resonance images of 18 boys with ADHD and 18 carefully matched normal boys. RESULTS: Two anterior regions, the rostrum and the rostral body, were found to have significantly smaller areas in the ADHD group. These areas correlated in the expected direction with teacher and parent ratings of hyperactivity/impulsivity. CONCLUSIONS: This finding supports theories of abnormal frontal lobe development and function in ADHD.

Adolescent↗

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

A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder.

OBJECTIVE: To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique anti-obsessional properties, is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride. DESIGN: Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10-week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine. SETTING: Outpatient clinic. PATIENTS: A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study. MEASURES: Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale, and the Clinical Global Impressions Scale. RESULTS: Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P < .05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity. CONCLUSION: Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.

Adolescent↗

PubMed1993

Factors affecting expressed emotion in parents of ill and normal children.

In order to examine their relationship to Expressed Emotion, family environment and marital relationships were measured in the parents of disruptive, obsessive-compulsive, and normal children. Satisfactory family and martial environment were found to be related to low Expressed Emotion, while achievement orientation in mothers and greater family conflict were found to be significantly related to high Expressed Emotion.

Adaptation, Psychological↗

PubMed1993

Posterior fossa abnormalities in children with infantile spasms.

In order to explore possible pathophysiologic involvement of the brain stem in infantile spasms, we retrospectively compared clinical and electroencephalographic (EEG) features of 14 children with infantile spasms who had gross posterior fossa abnormalities on neuroimaging studies with 84 children with infantile spasms who had either normal neuroimaging (n = 19) or supratentorial abnormalities (n = 65). Children with posterior fossa abnormalities how lower mean initial and follow-up developmental quotients compared to those with normal imaging or supratentorial abnormalities alone. Age of onset of infantile spasms, latency to treatment, response to steroids, and follow-up EEG pattern were not significantly different among the three groups. Six children (6%) had Dandy-Walker cysts, an association rarely reported with infantile spasms. We conclude that the presence of posterior fossa abnormalities in patients with infantile spasms portends a relatively poor developmental outcome.

Age of Onset↗

PubMed1992

Failure to activate the left temporoparietal cortex in dyslexia. An oxygen 15 positron emission tomographic study.

To test the hypothesis of left temporoparietal dysfunction in dyslexia, suggested by neuropsychological and neuropathologic data, cerebral blood flow was measured with positron emission tomography in 14 right-handed men with severe developmental dyslexia (mean [SD] age, 27 [5] years; median reading level, fifth grade) and 14 matched controls at rest and during an auditory phonologic task (rhyme detection) and an auditory attention task involving the detection of target tones. As expected, normal readers activated left temporoparietal cortex during rhyme detection but not during the nonphonologic attentional task. Dyslexic men failed to activate those left temporoparietal regions activated in controls during rhyme detection but did not differ from controls in these regions during rest or attentional testing. Thus, the expected left temporoparietal dysfunction was demonstrated only when specific probes for these regions were employed.

Adult↗

PubMed1992

A 2-year prospective follow-up study of children and adolescents with disruptive behavior disorders. Prediction by cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and autonomic measures?

A 2-year prospective follow-up study of 100% (N = 29) of a sample of children and adolescents with disruptive behavior disorders found that the baseline lumbar cerebrospinal fluid monoamine metabolite concentration and autonomic nervous system activity predicted some subsequent outcomes. The 5-hydroxyindoleacetic acid concentration significantly predicted severity of physical aggression during follow-up. The skin conductance level significantly predicted institutionalization. Correlations were in predicted directions with lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and autonomic activity correlated with poor outcome. Moreover, in multivariate analyses, which included nonlaboratory measures as predictors, cerebrospinal fluid and autonomic measures still contributed significantly to the prediction. However, hypothesized predictions of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations for suicide attempts and of low autonomic nervous system activity for arrests were not supported thus far. Patients are still at risk; consequently, these results must be considered preliminary. Nonetheless, the results suggest that further investigation of relationships between biological factors and outcome of children with disruptive behavior disorders is warranted.

Adolescent↗

PubMed1992

Differential response of seven subjects with autistic disorder to clomipramine and desipramine.

OBJECTIVE: Clomipramine, a serotonin reuptake blocker that has unique antiobsessional properties, was hypothesized to have a different effect from that of desipramine, a tricyclic antidepressant with selective adrenergic effects, for the stereotyped, repetitive behaviors in autism. METHOD: Seven subjects, ages 6-18 years, with autistic disorder completed a 10-week double-blind, crossover trial of clomipramine and desipramine following a 2-week single-blind, placebo phase. RESULTS: Clomipramine was superior to desipramine and placebo, as indicated by standardized ratings of autism and anger as well as ratings of repetitive and compulsive behaviors. Clomipramine and desipramine were equally superior to placebo for ratings of hyperactivity. Parents of all seven subjects elected to have their children continue to take clomipramine after the study. CONCLUSIONS: Clomipramine and desipramine are differentially effective in treating the obsessive-compulsive and core symptoms in autistic disorder. Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored.

Adolescent↗

PubMed1992

Parental expressed emotion and psychophysiological reactivity in disturbed and normal children.

Increased spontaneous fluctuations in skin conductance (SC) in adult schizophrenics have been associated with high expressed emotion (EE) in their relatives. This is the first study in children where parental EE, parental psychopathology, and autonomic activity, indexed by SC levels and reactivity, have been assessed. The subjects were children and adolescents with disruptive behaviour disorders (DBD, n = 35), a psychiatric contrast group with obsessive-compulsive disorders (OCD, n = 42) and normal controls (NC, n = 45). Children living in homes with two high-EE parents had higher SC activity during rest period and slower adaptation to relaxation. Fathers' EE and maternal psychiatric diagnosis were related to higher SC activity, especially for the OCD group.

Adaptation, Psychological↗

PubMed1991

A double-blind desipramine substitution during long-term clomipramine treatment in children and adolescents with obsessive-compulsive disorder.

Twenty-six children and adolescents with severe primary obsessive-compulsive disorder receiving long-term clomipramine hydrochloride maintenance treatment (mean +/- SD, 17.1 +/- 8.3 months; range, 4 to 32 months) entered an 8-month double-blind desipramine hydrochloride substitution study to assess the necessity of continued drug treatment. All patients received clomipramine for the first 3 months, then half continued with clomipramine therapy (nonsubstituted group) and half had desipramine blindly substituted for the next 2 months; all subjects again received clomipramine for the last 3 study months. Eight (89%) of nine of the substituted and only two (18%) of 11 of the nonsubstituted group subjects relapsed during the 2-month comparison period. Long-term clomipramine treatment seems necessary for this population of children and adolescents with obsessive-compulsive disorder. However, even patients receiving maintenance clomipramine treatment throughout the entire study had continued obsessive-compulsive symptoms, which varied in severity over time.

Adolescent↗

PubMed1991

Determinants of expressed emotion in families of disturbed and normal children.

Both high expressed emotion (EE) and psychiatric disorders were frequent in the parents of children and adolescents with disruptive behavior disorder (DBD, N = 34) and obsessive compulsive disorder (OCD, N = 49) compared to normal controls (NC, N = 41). Parental psychiatric diagnosis was significantly related to high-EE in fathers (p = .0002) and mothers (p = .0001) of all groups combined, and in parents of the ill groups (p = .03). Absence of diagnosis was associated with low-EE in fathers (p = .0006) and mothers (p = .04) of the controls. Psychiatric diagnosis was the only significant predictor for high-EE in fathers, while for mothers child's diagnosis was a stronger predictor.

Adolescent↗

PubMed1990

Neuropsychological divergence of high-level autism and severe dyslexia.

The relationship between cognitive deficits in high-level autism and those in learning disabilities has received little attention. To determine whether high-functioning autistic patients and individuals with severe dyslexia display different cognitive characteristics, 10 nonretarded men (mean age 26 years) with infantile autism, residual state, were compared with 15 severely dyslexic men (mean age 22 years) and 25 matched controls on a neuropsychological test battery. The two clinical groups were dissociated by a reduced digit span seen in the dyslexics and by impaired problem-solving skills (Wisconsin Card Sort and selected subtests from the Binet) seen in the autistic group. These results suggest different localization of brain dysfunction and different educational/habilitative needs.

Adolescent↗

PubMed1989

Treatment of obsessive-compulsive disorder with clomipramine and desipramine in children and adolescents. A double-blind crossover comparison.

Forty-eight children and adolescents with severe primary obsessive-compulsive disorder completed a 10-week double-blind crossover trial of clomipramine hydrochloride (mean dose [+/- SD], 150 +/- 53 mg/d) and desipramine hydrochloride (mean dose [+/- SD], 153 +/- 55 mg/d). Clomipramine was clearly superior to desipramine in significantly reducing obsessive-compulsive symptoms. Age at onset, duration and severity of illness, type of symptom, and plasma drug concentrations did not predict clinical response to clomipramine. Sixty-four percent of patients who received clomipramine as their first active treatment showed at least some sign of relapse during desipramine treatment. We further document the specificity of the antiobsessional effect of clomipramine and the need for maintenance treatment.

Adolescent↗