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J L Rapoport

Publications and source records attributed to J L Rapoport.

At least 19 recordsLinked to original sources
PubMed1997

Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease.

This study examines cerebrospinal fluid from patients with three neuropsychiatric diseases of childhood for the presence and levels of several cytokines relevant to cell-mediated (type 1) and humoral (type 2) immunity. The patient groups include childhood-onset schizophrenia (n = 22), obsessive-compulsive disorder (OCD) (n = 24), and attention deficit hyperactivity disorder (n = 42). The cytokines examined include IL-2, IFN-gamma, TNF-beta/LT, IL-4, IL-5, IL-10, and TNF-alpha. Patients with OCD had a preponderance of type 1 cytokines. IL-4 was detectable only in samples from patients with schizophrenia. IL-10 was rarely detected and never in patients with OCD. Few patients with schizophrenia had detectable amounts of IFN-gamma in CSFL. We conclude that there is a relative skewing of CSFL profiles toward type 1 cytokines in patients with OCD, whereas in schizophrenia the relative preponderance is toward type 2 mediators. Patients with attention deficit hyperactivity disorder exhibited profiles intermediate between OCD and schizophrenia. We infer that cell-mediated immunity may be involved in the etiopathogenesis of OCD, whereas a relative lack of cell-mediated immunity and involvement of humoral immunity may be present in schizophrenia. These data provide a rationale for immune-based strategies of study and therapeutics in childhood neuropsychiatric disease.

Attention Deficit Disorder with Hyperactivity↗
PubMed1997

Pubertal development and onset of psychosis in childhood onset schizophrenia.

In this study, pubertal development was examined for a sample of children and adolescents with childhood onset schizophrenia (COS) defined as psychosis by age 12. Developmental and psychiatric histories were obtained for 28 adolescents (mean age 14.5 +/- 2.3 years) with severe, treatment refractory COS (14 males, 14 females). Age of onset of psychosis was also examined in relation to menarche and development of secondary sex characteristics. Girls had a trend towards developing secondary sex characteristics earlier than boys (P = 0.06), consistent with North American norms. Males (N = 14) and females (N = 14) had similar age of onset of psychosis. The age of development of secondary sex characteristics was associated with onset of psychosis for girls, but this finding was driven by one outlier. There was no significant correlation between development of psychosis and menarche. Neither male nor female probands differed significantly from their well siblings or from North American norms in their age of onset of pubertal development. There was no evidence of early onset of secondary sex characteristics for this sample. Finally, there was an absence of a clear relationship between onset of psychosis and indices of sexual development for these very early onset cases.

Adolescent↗
PubMed1997

Quantitative magnetic resonance imaging of the corpus callosum in childhood onset schizophrenia.

Corpus callosum size has been found to be abnormal in adult schizophrenia, and other studies have implicated abnormal interhemispheric communication in this disorder. To assess continuity with brain abnormalities in the later onset disorder and to further localize brain maldevelopment, this structure was examined in a unique sample of childhood onset schizophrenics. Anatomic brain magnetic resonance imaging scans were acquired for 25 patients (mean age 13.9 +/- 2.1) who had onset of schizophrenia by age 12 (mean age at onset 9.9 +/- 1.9) and 55 normal children. The midsagittal area of the corpus callosum was divided into seven sections. With no adjustment for brain volume, no diagnostic differences were observed. After adjustment for the smaller cerebral volume of the schizophrenics, larger total, anterior and posterior corpus callosum areas emerged for the schizophrenics. These findings provide further evidence for continuity between childhood onset and later onset schizophrenia and support other studies showing white matter sparing in the context of decreased cortical volume.

Adolescent↗
PubMed1997

Tourette syndrome. Medical and surgical treatment of obsessive-compulsive disorder.

Current treatment outcomes for obsessive-compulsive disorder patients are far better than in past decades, but variability in treatment response remains. Most obsessive-compulsive disorder patients, but not all, respond to antidepressant agents with prominent serotonin uptake blocking properties. Because clomipramine's usefulness is limited by side effects which often accompany its use, a considerable degree of attention has shifted to selective serotonin reuptake inhibitors. A number of studies have also provided evidence for the effectiveness of medication other than those mainly involving serotonergic function, either as augmenting agents or for comorbid disorders. Neurosurgery may be useful for highly selected subjects.

Brain↗
PubMed1997

Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine the relation between specific frontostriatal structures (prefrontal cortex and basal ganglia) and response inhibition deficits observed in attention-deficit/hyperactivity disorder (ADHD). METHOD: Children with ADHD and age-matched normal controls were scanned using magnetic resonance imaging (MRI) and tested on three response inhibition tasks. Behavioral performance was correlated with MRI-based anatomical measures of frontostriatal circuitry (prefrontal cortex and basal ganglia) implicated in ADHD. RESULTS: First, significant differences in performance by children with ADHD and normal volunteers were observed on all three response inhibition tasks. Second, performance on these tasks correlated only with those anatomical measures of frontostriatal circuitry observed to be abnormal in children with ADHD (e.g., the region of the prefrontal cortex, caudate, and globus pallidus, but not the putamen) in the authors' previous study. Third, significant correlations between task performance and anatomical measures of the prefrontal cortex and caudate nuclei were predominantly in the right hemisphere, supporting a role of right frontostriatal circuitry in response inhibition and ADHD. CONCLUSION: The data suggest a role of the right prefrontal cortex in suppressing responses to salient, but otherwise irrelevant events while the basal ganglia appear to be involved in executing these behavioral responses.

Adolescent↗
PubMed1997

Controlled stimulant treatment of ADHD and comorbid Tourette's syndrome: effects of stimulant and dose.

OBJECTIVE: To determine the effects of methylphenidate (MPH) and dextroamphetamine (DEX) on tic severity in boys with attention-deficit/hyperactivity disorder (ADHD) comorbid with Tourette's syndrome. METHOD: A 9-week, placebo-controlled, double-blind crossover using a wide range of doses was completed by 20 subjects in three cohorts. RESULTS: Relatively high doses of MPH and DEX in the first cohort produced significant increases in tic severity which were sustained on higher doses of DEX but which attenuated on MPH. Overall, 14 of 20 subjects continued stimulant treatment for 1 to 3 years, generally in combination with other psychotropics. Stimulant-associated adverse effects, including tic exacerbations, were reversible in all cases. CONCLUSION: A substantial minority of comorbid subjects had consistent worsening of tics on stimulants, although the majority experienced improvement in ADHD symptoms with acceptable effects on tics. MPH was better tolerated than DEX.

Analysis of Variance↗
PubMed1997

Statistical approach to segmentation of single-channel cerebral MR images.

A statistical model is presented that represents the distributions of major tissue classes in single-channel magnetic resonance (MR) cerebral images. Using the model, cerebral images are segmented into gray matter, white matter, and cerebrospinal fluid (CSF). The model accounts for random noise, magnetic field inhomogeneities, and biological variations of the tissues. Intensity measurements are modeled by a finite Gaussian mixture. Smoothness and piecewise contiguous nature of the tissue regions are modeled by a three-dimensional (3-D) Markov random field (MRF). A segmentation algorithm, based on the statistical model, approximately finds the maximum a posteriori (MAP) estimation of the segmentation and estimates the model parameters from the image data. The proposed scheme for segmentation is based on the iterative conditional modes (ICM) algorithm in which measurement model parameters are estimated using local information at each site, and the prior model parameters are estimated using the segmentation after each cycle of iterations. Application of the algorithm to a sample of clinical MR brain scans, comparisons of the algorithm with other statistical methods, and a validation study with a phantom are presented. The algorithm constitutes a significant step toward a complete data driven unsupervised approach to segmentation of MR images in the presence of the random noise and intensity inhomogeneities.

Adolescent↗
PubMed1997

Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever.

OBJECTIVE: The authors' goal was to determine whether a trait marker of rheumatic fever susceptibility (labeled D8/17) could identify children with pediatric autoimmune neuropsychiatric disorders (obsessive-compulsive disorder and tic disorders) associated with streptococcal infections (PANDAS). METHOD: Blood samples obtained from 27 children with PANDAS, nine children with Sydenham's chorea, and 24 healthy children were evaluated for D8/17 reactivity. Individuals were defined as D8/17 positive if they had 12% or more D8/17+ cells. RESULTS: The frequency of D8/17-positive individuals was significantly higher in both patient groups than it was among the healthy volunteers: 85% of the children with PANDAS and 89% of the children with Sydenham's chorea, compared with 17% of the healthy children, were D8/17 positive. Further, the mean number of D8/17+ cells was similar in the two patient groups and was significantly higher in these groups than in the group of healthy children. CONCLUSIONS: These results suggest that there may be a subgroup of D8/17-positive children who present with clinical symptoms of obsessive-compulsive disorder and Tourette's syndrome, rather than Sydenham's chorea, but who have similar poststreptococcal autoimmunity.

Adolescent↗
PubMed1997

Childhood-onset schizophrenia: biological markers in relation to clinical characteristics.

OBJECTIVE: The purpose of this study was to examine the relationships between clinical and neurobiological measures of childhood-onset schizophrenia. It was hypothesized that there would be a more striking pattern in the rare cases with very early onset than is seen in subjects with later onset. METHOD: Premorbid, clinical, prenatal, perinatal, and magnetic resonance imaging brain measures were examined in 29 children and adolescents who met the DSM-III-R criteria for schizophrenia with onset before age 12. Specifically, gender, premorbid adjustment, and clinical symptoms were examined in relation to cerebral volume, ventricular volume, and maternal obstetrical complications. RESULTS: Males were more likely to have had an insidious onset than females. There was a significant negative correlation between score on the Scale for the Assessment of Negative Symptoms and total cerebral volume. CONCLUSIONS: These neurobiological associations support the continuity of early-onset schizophrenia with the later-onset disorder; the striking association between smaller cerebral volume and negative symptoms suggests a more homogeneous or more potent neurobiological basis for very early-onset schizophrenia.

Adolescent↗
PubMed1997

Cerebrospinal fluid monoamine metabolites in childhood-onset schizophrenia.

OBJECTIVE: Pediatric studies of cerebrospinal fluid (CSF) monoamine metabolites in childhood-onset schizophrenia may help to elucidate both pathophysiology and treatment response in early-onset psychosis. METHOD: CSF homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) and serum prolactin were measured during drug-free and antipsychotic medication conditions in 18 patients (mean age = 14.2 years, SD = 1.7) who had onset of schizophrenia by age 12 (mean age at onset = 9.9 years, SD = 1.8). Relationships between changes in CSF monoamines and serum prolactin and clinical outcome were examined, and the degree of change in CSF monoamines in response to clozapine treatment was compared with that for 16 patients with later-onset schizophrenia. RESULTS: Despite patients' significant clinical improvement with treatment, CSF monoamine concentrations and ratios of HVA/5-HIAA and HVA/MHPG did not significantly change with 6 weeks of either haloperidol or clozapine treatment. Serum prolactin levels increased during haloperidol treatment. Clozapine had similar effects on CSF monoamines in patients with childhood- and later-onset schizophrenia. CONCLUSIONS: While these data are compatible with continuity between childhood- and later-onset schizophrenia, they also highlight the complexity of the biochemical events mediating clinical changes in schizophrenia.

Adolescent↗
PubMed1997

Three-dimensional cortical morphometry of the planum temporale in childhood-onset schizophrenia.

OBJECTIVE: Anomalous planum temporale asymmetry has been linked to both schizophrenia and dyslexia. The authors examined the planum temporale of adolescents with childhood-onset schizophrenia who had a high rate of prepsychotic language disorders. METHOD: Planum temporale area and asymmetry were measured in 16 right-handed adolescent patients with schizophrenia who had experienced onset of psychosis by age 12. The same measures were made in 16 healthy adolescents matched for age, sex, and handedness. RESULTS: No differences between the healthy adolescents and those with schizophrenia in planum temporale area or asymmetry were observed. Prepsychotic language disorder predicted abnormal planum temporale asymmetry in the adolescents with schizophrenia. CONCLUSIONS: These findings do not support anomalous planum temporale asymmetry as a basis for psychopathology in childhood-onset schizophrenia.

Adolescent↗
PubMed1997

The role of the anterior cingulate in automatic and controlled processes: a developmental neuroanatomical study.

This study examines the role of the anterior cingulate in the development of attention. Task performance relying predominantly on either automatic or controlled processes was correlated with magnetic resonance imaging based measures of the anterior cingulate in 26 normal children ages 5 to 16 years. Attentional measures were assessed with a visual discrimination paradigm. Parasagittal slices from a 3-D, T1-weighted volume data set were used to obtain area measurements of the anterior cingulate. Response latencies decreased with age for both tasks. There were significant correlations between attentional performance and right, but not left, anterior cingulate measures. Performance was faster and more accurate during trials requiring predominantly controlled processes for those children with larger right anterior cingulate measures. The results are consistent with adult neuroimaging findings of activation in the right anterior cingulate during attention tasks and with lesion studies implicating greater right hemisphere involvement in attentional processes.

Adolescent↗
PubMed1996

Blink rate in childhood-onset schizophrenia: comparison with normal and attention-deficit hyperactivity disorder controls.

Several lines of evidence have implicated central dopaminergic pathways in the modulation of blink rate. In the present study, blink rate during smooth pursuit was examined in 17 children with childhood-onset schizophrenia, on and off of clozapine, and compared to that of age-matched normal children and unmedicated children with attention-deficit hyperactivity disorder (ADHD). As has been observed in adolescent and adult schizophrenics, blink rate was significantly higher in schizophrenic children relative to normal and ADHD controls. Within the schizophrenic group, blink rate did not significantly change with the introduction of clozapine and was not related to clinical variables. Blink rate was positively correlated with deterioration in smooth pursuit in normal subjects.

Adolescent↗
PubMed1996

Smooth pursuit eye movements in childhood-onset schizophrenia: comparison with attention-deficit hyperactivity disorder and normal controls.

Abnormalities of the smooth pursuit eye movements of adults with schizophrenia have been well described. We examined smooth pursuit eye movements in schizophrenic children, contrasting them with normal and attention-deficit hyperactivity disorder (ADHD) subjects, to determine whether there is continuity of eye movement dysfunction between childhood- and adult-onset forms of schizophrenia. Seventeen schizophrenic children with onset of illness by age 12, 18 ADHD children, and 22 normal children were studied while engaged in a smooth pursuit eye tracking task. Eye tracking variables were compared across the three groups. Schizophrenic children exhibited significantly greater smooth pursuit impairments than either normal or ADHD subjects. Within the schizophrenic group, there were no significant relationships between eye tracking variables and clinical variables, or ventricular/brain ratio. Childhood-onset schizophrenia is associated with a similar pattern of smooth pursuit abnormalities to that seen in later-onset schizophrenia.

Adolescent↗
PubMed1996

Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: ages 4-18 years.

The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4-18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders.

Adolescent↗
PubMed1996

Autonomic activity in children and adolescents with obsessive-compulsive disorder.

Electrodermal activity and heart rate were recorded from 55 children and adolescents with obsessive-compulsive disorder (OCD) and 58 normal subjects in a protocol that included rest and mild stress periods, and nonsignal and signal stimuli, to determine if autonomic activity might be involved in the pathogenesis of OCD or might be related to important clinical differences. Few differences were observed between OCD and normal subjects despite adequate power to detect small differences due to the large number of subjects. Thus, autonomic activity appears not to be an important etiological factor in childhood OCD. However, electrodermal activity showed consistent positive correlations with ratings of the severity of OCD symptoms (but not with anxiety or depression ratings), suggesting that severely afflicted cases are autonomically sensitive to OCD-related stimuli or, conversely, that low electrodermal activity may be protective of symptom severity. Patients with a coexisting tic disorder (not Tourette's syndrome) had larger electrodermal responses to a novel stimulus and higher heart rate variability than those without tics but did not differ from normal subjects. These few differences seem insufficient to support the hypothesis of a separate etiology of OCD cases with a coexisting tic disorder.

Adolescent↗
PubMed1996

A quantitative MRI study of the corpus callosum in children and adolescents.

Total midsagittal area and seven subdivisions of the corpus callosum were measured on magnetic resonance images of 114 healthy boys and girls, aged 4 to 18. Striking variability of size was noted for all measures. Total midsagittal corpus callosum area increased in a robust and linear fashion from ages 4 to 18 (slope = 13.1 mm2/year, P = 0.0001 and slope = 11.1 mm2/year, P = 0.0001 for females and males, respectively). Posterior and mid regions demonstrated greater age-related changes than anterior regions with the rostrum and genu (anterior regions) having reached adult sizes in the youngest of our subjects. There were no significant effects of sex for any measures. These findings support anatomical studies indicating ongoing myelination of higher association areas throughout adolescence, but raise intriguing questions about anterior-posterior gradients of interhemispheric myelination.

Adolescent↗