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Biomedical subjects

J L Rapoport

Publications and source records attributed to J L Rapoport.

At least 37 records · Page 2Linked to original sources
PubMed2000

Neuropsychological deficits in pediatric patients with childhood-onset schizophrenia and psychotic disorder not otherwise specified.

OBJECTIVE: Children with transient psychotic symptoms and serious emotional disturbances who do not meet current criteria for schizophrenia or other presently recognized diagnostic categories commonly present diagnostic and treatment problems. Clarifying the connections between children with narrowly defined schizophrenia and children with a more broadly defined phenotype (i.e., Psychotic Disorder Not Otherwise Specified, PD-NOS) has implications for understanding the pathophysiology of schizophrenia. In this study, the neuropsychological test performance of a subgroup of children with atypical psychosis was compared with that of patients with childhood-onset schizophrenia (COS). METHOD: Cognitive function was assessed with neuropsychological test battery regimens in 51 neuroleptic-nonresponsive patients within the first 270 at NIMH testing (24 PD-NOS, 27 COS) were included in this analysis. Seventeen (39%) of 44 COS subjects were unavailable for this study as their IQ tested <70. The PD-NOS patients were younger than the COS patients at the time of testing (12.0+/-2.8 vs 14.4+/-1.8years, respectively, p<0.004). The test levels of these groups were compared with each other. RESULTS: The neuropsychological test results for the PD-NOS and COS patients were 1-2standard deviations below normative data across a broad array of cognitive functions. There were no overall differences in the test levels for the six summary scales (F=2.82, df=1, 36, p=0.10) or in the profile shape (F=1.70, df=5, 180, p=0.14) between the PD-NOS and COS groups. For the COS patients, there was a significant difference between their mean full-scale WISC IQ (84.7+/-16.2) and their average standard scores for both the spelling (97.7+/-16.1, n=23, t=4.0, p=0.001) and reading decoding subtests (97.7+/-13.7, n=23, t=3.7, p=0.001) of the Kaufman Test of Educational Achievement. CONCLUSIONS: Treatment-refractory PD-NOS and COS patients share a similar pattern of generalized cognitive deficits, including deficits in attention, learning and abstraction which are commonly observed in adult patients with schizophrenia. These data support a hypothesis that at least some of the PD-NOS cases belong within the schizophrenic spectrum, which is of importance for future genetic studies planned for this cohort.

Adolescent↗
PubMed2000

Update on childhood-onset schizophrenia.

Updated findings from the ongoing National Institute of Mental Health Child Psychiatry Branch longitudinal study of childhood-onset schizophrenia (COS) are presented, along with replications from collaborators at other sites. Clinical and neurobiologic continuities of COS with poor-outcome adult-onset schizophrenia suggests that their underlying pathophysiology is the same. However, these early-onset cases appear to have more striking genetic contributions to their etiology. Updated findings involve risk factors (birth complications, cytogenic abnormalities, early language and motor problems, and familial psychopathology), treatment trials, and brain magnetic resonance imaging studies.

Brain↗
PubMed2000

Lessons from childhood-onset schizophrenia.

Childhood-onset schizophrenia (with an onset of psychosis by age 12) is a rare and severe form of the disorder which is clinically and neurobiologically continuous with the adult-onset disorder. Very early onset diseases provide an opportunity to look for more salient or striking risk or etiologic factors in a possibly more homogenous patient population. For the 47 patients with very early onset schizophrenia studied to date, there were more severe premorbid neurodevelopmental abnormalities, more cytogenetic anomalies, and potentially greater family histories of schizophrenia and associated spectrum disorders than later onset cases. There was no evidence for relatively increased obstetrical complications or environmental stress. These data, while preliminary, suggest a very early age of onset of schizophrenia may be secondary to greater genetic vulnerability. It is anticipated that future genetic studies of these patients may provide important etiologic information.

Age of Onset↗
PubMed2000

An open trial of plasma exchange in childhood-onset obsessive-compulsive disorder without poststreptococcal exacerbations.

Patients with childhood-onset obsessive-compulsive disorder (OCD) with symptom exacerbations following streptococcal infections benefit from treatment with plasma exchange. In this study, 5 patients with treatment-refractory OCD without a history of streptococcus-related exacerbations underwent an open 2-week course of therapeutic plasma exchange. Behavioral ratings, completed at baseline and 4 weeks after the initial treatment, included the Clinical Global Impressions Scale and the Yale-Brown Obsessive Compulsive Scale. All 5 patients completed the trial with few side effects, but none showed significant improvement. Plasma exchange does not benefit children and adolescents with OCD who do not have streptococcus-related exacerbations.

Adolescent↗
PubMed2000

Olanzapine pharmacokinetics in pediatric and adolescent inpatients with childhood-onset schizophrenia.

Well-designed studies investigating how pediatric or adolescent patients with mental disorders respond to and metabolize the newer antipsychotic drugs are practically nonexistent. Without such data, clinicians have difficulty designing appropriate dosage regimens for patients in these age groups. The results from a study of olanzapine pharmacokinetics in children and adolescents are described. Eight inpatients (ages 10-18 years) with treatment-resistant childhood-onset schizophrenia received olanzapine (2.5-20 mg/day) over 8 weeks. Blood samples, collected during dose titration and at a steady state provided pharmacokinetic data. The final evaluation (week 8) included extensive sampling for 36 hours after a 20-mg dose. Olanzapine concentrations in these eight pediatric patients were of the same magnitude as those for nonsmoking adult patients with schizophrenia but may be as much as twice the typical olanzapine concentrations in patients with schizophrenia who smoke. Olanzapine pharmacokinetic evaluation gave an apparent mean oral clearance of 9.6 +/- 2.4 L/hr and a mean elimination half-life of 37.2 +/- 5.1 hours in these young patients. The determination of the initial olanzapine dose for adolescent patients should take into consideration factors such as the patient's size. In general, however, the usual dose recommendation of 5 to 10 mg once daily with a target dose of 10 mg/day is likely a good clinical guideline for most adolescent patients on the basis of our pharmacokinetics results.

Adolescent↗
PubMed2000

MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection.

OBJECTIVE: The authors assessed selective basal ganglia involvement in a subgroup of children with obsessive-compulsive disorder (OCD) and/or tics believed to be associated with streptococcal infection. METHOD: Using computer-assisted morphometric techniques, they analyzed the cerebral magnetic resonance images of 34 children with presumed streptococcus-associated OCD and/or tics and 82 healthy comparison children who were matched for age and sex. RESULTS: The average sizes of the caudate, putamen, and globus pallidus, but not of the thalamus or total cerebrum, were significantly greater in the group of children with streptococcus-associated OCD and/or tics than in the healthy children. The differences were similar to those found previously for subjects with Sydenham's chorea compared with normal subjects. CONCLUSIONS: These results support the hypothesis that there is a distinct subgroup of subjects with OCD and/or tics who have enlarged basal ganglia. These findings are consistent with the hypothesis of an autoimmune response to streptococcal infection.

Autoimmune Diseases↗
PubMed2000

Premorbid speech and language impairments in childhood-onset schizophrenia: association with risk factors.

OBJECTIVE: As both premorbid neurodevelopmental impairments and familial risk factors for schizophrenia are prominent in childhood-onset cases (with onset of psychosis by age 12), their relationship was examined. METHOD: Premorbid language, motor, and social impairments were assessed in a cohort of 49 patients with childhood-onset schizophrenia. Familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications were assessed without knowledge of premorbid abnormalities and were compared in the patients with and without developmental impairments. RESULTS: Over one-half of the patients in this group had developmental dysfunction in each domain assessed. The patients with premorbid speech and language impairments had higher familial loading scores for schizophrenia spectrum disorders and more obstetrical complications, and their relatives had worse smooth-pursuit eye movements. The boys had more premorbid motor abnormalities, but early language and social impairments did not differ significantly between genders. There were no other significant relationships between premorbid social or motor abnormalities and the risk factors assessed here. CONCLUSIONS: Premorbid developmental impairments are common in childhood-onset schizophrenia. The rates of three risk factors for schizophrenia (familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications) were increased for the probands with premorbid speech and language impairments, suggesting that the pathophysiology of schizophrenia involves the abnormal development of language-related brain regions.

Adolescent↗
PubMed2000

Childhood-onset psychotic disorders: magnetic resonance imaging of volumetric differences in brain structure.

OBJECTIVE: Although childhood-onset schizophrenia is rare, children with brief psychotic symptoms and prominent emotional disturbances commonly present diagnostic and treatment problems. Quantitative anatomic brain magnetic resonance images (MRIs) of a subgroup of children with psychotic disorder not otherwise specified were compared with those of children with childhood-onset schizophrenia and healthy comparison subjects. METHOD: Anatomic MRIs were obtained for 71 patients (44 with childhood-onset schizophrenia and 27 with psychotic disorder not otherwise specified) and 106 healthy volunteers. Most patients had been treated with neuroleptics. Volumetric measurements for the cerebrum, anterior frontal region, lateral ventricles, corpus callosum, caudate, putamen, globus pallidus, and midsagittal thalamic area were obtained. RESULTS: Patients had a smaller total cerebral volume than healthy comparison subjects. Analysis of covariance for total cerebral volume and age found that lateral ventricles were larger in both patient groups than in healthy comparison subjects and that schizophrenia patients had a smaller midsagittal thalamic area than both subjects with psychotic disorder not otherwise specified and healthy comparison subjects. CONCLUSIONS: Pediatric patients with psychotic disorder not otherwise specified showed a pattern of brain volumes similar to those found in childhood-onset schizophrenia. Neither group showed a decrease in volumes of temporal lobe structures. Prospective longitudinal magnetic resonance imaging and clinical follow-up studies of both groups are currently underway to further validate the distinction between these two disorders.

Adolescent↗
PubMed2000

Developmental brain anomalies in children with attention-deficit hyperactivity disorder.

The pathoetiology of attention-deficit hyperactivity disorder (ADHD) has been considered to be neurodevelopmental, yet the timing and processes involved are not clearly identified. Neurodevelopmental brain anomalies have been associated with a variety of psychiatric conditions. However, they have never been evaluated in a population of patients with ADHD. This study was designed to determine the frequency of specific developmental brain anomalies in a group of children with ADHD (n = 85; mean age, 10.9 years) and healthy control children (n = 95; mean age, 11.7 years) by visually inspecting brain magnetic resonance imaging scans. Compared to controls, the ADHD group showed an increase in frequency of two developmental anomalies: (1) gray-matter heterotopia, a neuronal migration anomaly, in 2 of 85 patients versus 0 of 95 controls; and (2) posterior fossa abnormality (excess cerebrospinal fluid in the posterior fossa) in 8 of 85 patients versus 2 of 95 controls. There were no differences in frequency of enlarged cavum septi pellucidi between the two groups. These findings support and extend the idea that ADHD is of developmental origin, and further suggest that the timing of aberrant brain development could be in early gestation.

Adolescent↗
PubMed2000

Treatment of obsessive-compulsive disorder in children and adolescents.

This paper reviews the treatment of obsessive-compulsive disorder (OCD) in children and adolescents. Focusing on clinical features of the disorder and its treatment particular to pediatric onset, diagnosis, assessment, and behavioral, pharmacological, as well as new investigative treatments are covered. Adaptation of cognitive-behavioral therapy for children and adolescents, use of augmenting agents in drug treatment, and subtyping of OCD cases are developments relevant for current practice.

Adolescent↗
PubMed1999

Childhood-onset schizophrenia: rare but worth studying.

Childhood-onset schizophrenia (defined by an onset of psychosis by age 12) is a rare and severe form of the disorder that is clinically and neurobiologically continuous with the adult-onset disorder. There is growing evidence for more salient risk or etiologic factors, particularly familial, in this possibly more homogeneous patient population. For the 49 patients with very early onset schizophrenia studied to date at the National Institute of Mental Health, there were more severe premorbid neuro-developmental abnormalities, a higher rate of cytogenetic anomalies, and a seemingly higher rate of familial schizophrenia and spectrum disorders than later onset cases. There was no evidence for increased obstetric complications or environmental stress. These data, while preliminary, suggest that a very early age of onset of schizophrenia may be secondary to greater familial vulnerability. Consequently, genetic studies of these patients may be particularly informative and may provide important etiologic information.

Age Factors↗
PubMed1999

Childhood-onset schizophrenia: progressive brain changes during adolescence.

BACKGROUND: Previous NIMH childhood onset schizophrenia (COS) anatomic brain MRI studies found progression of ventricular volume and other structural brain anomalies at 2-year follow up across mean ages 14 to 16 years. However, studies in adult patients generally do not show progression of ventricular volume or correlation of ventricular volume with duration of illness. To address issues of progression of brain anomalies in schizophrenia, this report extends previous studies to include a third longitudinal scan, uses a larger sample size, and includes measures of the amygdala and hippocampus. METHODS: Volumes of the total cerebrum, lateral ventricles, hippocampus, and amygdala were quantified on 208 brain magnetic resonance imaging scans from 42 adolescents with COS (23 with one or more repeat scan) and 74 age- and gender-matched controls (36 with one or more repeat scan). A statistical technique permitting combined use of cross-sectional and longitudinal data was used to assess age-related changes, linearity, and diagnostic group differences. RESULTS: Differential nonlinear progression of brain anomalies was seen during adolescence with the total cerebrum and hippocampus decreasing and lateral ventricles increasing in the COS group. The developmental curves for these structures reached an asymptote by early adulthood for the COS group and did not significantly change with age in the control group. CONCLUSIONS: These findings reconcile less striking progression of anatomic brain images usually seen for adult schizophrenia and complement other data consistent with time-limited, diagnostic-specific decreases in brain tissue. Adolescence appears to be a unique period of differential brain development in schizophrenia.

Adolescent↗
PubMed1999

Structural maturation of neural pathways in children and adolescents: in vivo study.

Structural maturation of fiber tracts in the human brain, including an increase in the diameter and myelination of axons, may play a role in cognitive development during childhood and adolescence. A computational analysis of structural magnetic resonance images obtained in 111 children and adolescents revealed age-related increases in white matter density in fiber tracts constituting putative corticospinal and frontotemporal pathways. The maturation of the corticospinal tract was bilateral, whereas that of the frontotemporal pathway was found predominantly in the left (speech-dominant) hemisphere. These findings provide evidence for a gradual maturation, during late childhood and adolescence, of fiber pathways presumably supporting motor and speech functions.

Adolescent↗