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Biomedical subjects

Judith L Rapoport

Publications and source records attributed to Judith L Rapoport.

46 records · Page 3Linked to original sources
PubMed2003

Parental schizophrenia spectrum disorders in childhood-onset and adult-onset schizophrenia.

OBJECTIVE: Childhood onset of "adult" psychiatric disorders may be caused, in part, by more salient genetic risk. In this study, the rates of schizophrenia spectrum disorders among parents of patients with childhood-onset and adult-onset schizophrenia and parents of community comparison subjects were compared. METHOD: To assess the presence of axis I and axis II disorders associated with schizophrenia, parents of patients with childhood-onset schizophrenia (95 parents), patients with adult-onset schizophrenia (86 parents), and community comparison subjects (123 parents) were interviewed directly by using semistructured instruments. Information on 19 additional parents (parents of childhood-onset patients, N=2; parents of adult-onset patients, N=11; parents of community comparison subjects, N=6) was obtained by using a family history interview with the same instruments. Transcribed interviews were scored by a rater blind to group membership, and the morbid risks for schizophrenia spectrum disorders in the three groups were compared. RESULTS: Parents of patients with childhood-onset schizophrenia had a significantly higher morbid risk of schizophrenia spectrum disorders (24.74%) than parents of patients with adult-onset schizophrenia (11.35%), and parents of both patient groups had a greater risk of schizophrenia spectrum disorders than did parents of comparison subjects (1.55%). CONCLUSIONS: Parents of patients with childhood-onset schizophrenia have a higher rate of schizophrenia spectrum disorders than parents of patients with adult-onset illness. This is consistent with the hypothesis that a childhood onset of schizophrenia is due, at least in part, to a greater familial diathesis for the disorder.

Adult↗
PubMed2003

Structural brain MRI abnormalities in healthy siblings of patients with childhood-onset schizophrenia.

OBJECTIVE: Childhood-onset schizophrenia shows progressive brain magnetic resonance imaging (MRI) changes during adolescence, which follow a back-to-front "wave." The authors' goal was to examine whether healthy siblings of patients with childhood-onset schizophrenia show structural brain abnormalities and the age-related pattern of abnormalities seen in patients with childhood-onset schizophrenia. METHOD: Anatomic brain MRI scans were obtained from 15 psychiatrically healthy full siblings of 15 patients with childhood-onset schizophrenia and from 32 matched community volunteers. Automated measures were used to compare total and regional brain volumes of the siblings and volunteers. RESULTS: Siblings of patients with childhood-onset schizophrenia had smaller total cerebral volume and total, frontal, and parietal gray matter volumes than volunteers. When divided into younger and older groups, younger siblings had smaller parietal gray matter volumes and older siblings showed trends for smaller total and frontal gray matter volumes. CONCLUSIONS: Healthy siblings of patients with childhood-onset schizophrenia share brain MRI abnormalities with the patients that may follow a similar pattern of progression. Developmental brain abnormalities in childhood-onset schizophrenia may thus be genetic trait markers.

Adolescent↗
PubMed2003

Anatomic brain abnormalities in monozygotic twins discordant for attention deficit hyperactivity disorder.

OBJECTIVE: To examine brain-behavior relationships in attention deficit hyperactivity disorder (ADHD), the authors obtained magnetic resonance imaging (MRI) scans of monozygotic twins discordant for ADHD. METHOD: National recruitment was followed by in-person assessment. MRI scans were measured algorithmically for nine pairs of monozygotic twins discordant for ADHD. RESULTS: The affected twins had significantly smaller caudate volumes (mean difference=-0.56 ml, CI=-0.92 to -0.21) than their unaffected co-twins. CONCLUSIONS: These results provide further support for striatal models of ADHD pathophysiology.

Adolescent↗
PubMed2002

Genetic variation in the 22q11 locus and susceptibility to schizophrenia.

An increased prevalence of microdeletions at the 22q11 locus has been reported in samples of patients with schizophrenia. 22q11 microdeletions represent the highest known genetic risk factor for the development of schizophrenia, second only to that of the monozygotic cotwin of an affected individual or the offspring of two schizophrenic parents. It is therefore clear that a schizophrenia susceptibility locus maps to chromosome 22q11. In light of evidence for suggestive linkage for schizophrenia in this region, we hypothesized that, whereas deletions of chromosome 22q11 may account for only a small proportion of schizophrenia cases in the general population (up to approximately 2%), nondeletion variants of individual genes within the 22q11 region may make a larger contribution to susceptibility to schizophrenia in the wider population. By studying a dense collection of markers (average one single nucleotide polymorphism20 kb over 1.5 Mb) in the vicinity of the 22q11 locus, in both family- and population-based samples, we present here results consistent with this assumption. Moreover, our results are consistent with contribution from more than one gene to the strikingly increased disease risk associated with this locus. Finer-scale haplotype mapping has identified two subregions within the 1.5-Mb locus that are likely to harbor candidate schizophrenia susceptibility genes.

Amino Acid Sequence↗
PubMed2002

Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.

CONTEXT: Various anatomic brain abnormalities have been reported for attention-deficit/hyperactivity disorder (ADHD), with varying methods, small samples, cross-sectional designs, and without accounting for stimulant drug exposure. OBJECTIVE: To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. MAIN OUTCOME MEASURES: Using completely automated methods, initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the brain were compared in patients and controls. RESULTS: On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (-3.2%, adjusted F(1,280) = 8.30, P =.004) and in significantly smaller cerebellar volumes (-3.5%, adjusted F(1,280) = 12.29, P =.001). Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (overall F(2,288) = 6.65; all pairwise comparisons Bonferroni corrected, -5.8%; P =.002) and cerebellar volumes (-6.2%, F( 2,288) = 8.97, P<.001). Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes (F(2,288) = 11.65) compared with controls (-10.7%, P<.001) and with medicated children with ADHD (-8.9%, P<.001). Volumetric abnormalities persisted with age in total and regional cerebral measures (P =.002) and in the cerebellum (P =.003). Caudate nucleus volumes were initially abnormal for patients with ADHD (P =.05), but diagnostic differences disappeared as caudate volumes decreased for patients and controls during adolescence. Results were comparable for male and female patients on all measures. Frontal and temporal gray matter, caudate, and cerebellar volumes correlated significantly with parent- and clinician-rated severity measures within the ADHD sample (Pearson coefficients between -0.16 and -0.26; all P values were <.05). CONCLUSIONS: Developmental trajectories for all structures, except caudate, remain roughly parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.

Adolescent↗
PubMed2002

Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia.

The location of a schizophrenia susceptibility locus at chromosome 22q11 has been suggested by genome-wide linkage studies. Additional support was provided by the observation of a higher-than-expected frequency of 22q11 microdeletions in patients with schizophrenia and the demonstration that approximately 20-30% of individuals with 22q11 microdeletions develop schizophrenia or schizoaffective disorder in adolescence and adulthood. Analysis of the extent of these microdeletions by using polymorphic markers afforded further refinement of this locus to a region of approximately 1.5 Mb. Recently, a high rate of 22q11 microdeletions was also reported for a cohort of 47 patients with Childhood Onset Schizophrenia, a rare and severe form of schizophrenia with onset by age 13. It is therefore likely that this 1.5-Mb region contains one or more genes that predispose to schizophrenia. In three independent samples, we provide evidence for a contribution of the PRODH2/DGCR6 locus in 22q11-associated schizophrenia. We also uncover an unusual pattern of PRODH2 gene variation that mimics the sequence of a linked pseudogene. Several of the pseudogene-like variants we identified result in missense changes at conserved residues and may prevent synthesis of a fully functional enzyme. Our results have implications for understanding the genetic basis of the 22q11-associated psychiatric phenotypes and provide further insights into the genomic instability of this region.

Africa↗
PubMed2002

Correlation of antipsychotic and prolactin concentrations in children and adolescents acutely treated with haloperidol, clozapine, or olanzapine.

Patients with a Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) diagnosis of schizophrenia or psychotic disorder not otherwise specified with onset of psychosis before the age of 13 participated in 6- to 8-week open or double-blind trials of haloperidol (n = 15, mean dose 15.4 +/- 8.1 mg/day [0.27 +/- 0.15 mg/kg/day]), clozapine (n = 30, mean dose 269.9 +/- 173.3 mg/day [4.4 +/- 2.6 mg/kg/day]), or olanzapine (n = 12, mean dose 17.5 +/- 2.8 mg/day [0.30 +/- 0.13 mg/kg/day]). Blood samples were obtained at 6 weeks for evaluation of haloperidol, reduced haloperidol, clozapine, desmethylclozapine, and olanzapine plasma concentrations and serum prolactin concentrations. No gender differences were noted for antipsychotic dose or concentration within each treatment group. Correlations between antipsychotic plasma concentration and serum prolactin concentration were significant only for the olanzapine treatment group (r = 0.80, p = 0.002). Separate correlations for gender were significant only for females receiving olanzapine (r = 0.91, p = 0.03); the patient with the highest serum prolactin experienced galactorrhea. Further studies evaluating the prolactin-elevating properties of antipsychotics are warranted in this population.

Adolescent↗
PubMed2002

Clozapine-induced akathisia in children with schizophrenia.

Akathisia is a relatively rare side effect with the newer atypical antipsychotic agents, particularly clozapine, and is easily misdiagnosed in children. As children are often unable to describe their symptoms verbally, their akathisia can be misdiagnosed as worsening of their psychosis, prompting an unnecessary increase in their neuroleptic dose. Two cases of childhood-onset schizophrenia associated with clozapine-induced akathisia responsive to beta-blocker treatment are described. Akathisia should be considered in all cases of apparent nonresponse to atypical antipsychotics.

Adrenergic beta-Antagonists↗
PubMed2002

Cytogenetic abnormalities in attention-deficit/hyperactivity disorder.

OBJECTIVE: To systematically assess the prevalence of fragile X syndrome, velocardiofacial syndrome, and other cytogenetic abnormalities in a group of children with attention-defict/hyperactivity disorder (ADHD). METHOD: Blood samples were obtained from 100 children (64 boys) with combined type ADHD and normal intelligence and analyzed for the presence of fragile X mutation expansions, the 22q11.2 microdeletion associated with velocardiofacial syndrome, and cytogenetic abnormalities that would be detected with high resolution chromosomal banding. RESULTS: One girl with ADHD had a sex chromosome aneuploidy (47,XXX). One boy had a premutation-sized allele for fragile X; no subjects showed the full mutation. Testing for 22q11.2 microdeletion was negative for all subjects with ADHD screened. None of these differences exceeded those expected by chance. CONCLUSIONS: In the absence of clinical signs or positive family history, these relatively expensive laboratory assessments are not clinically indicated for children with ADHD and normal intelligence, and are not recommended as a component of other genetic investigations of this disorder.

Abnormalities, Multiple↗