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Biomedical subjects

B Geller

Publications and source records attributed to B Geller.

At least 37 records · Page 2Linked to original sources
PubMed1998

Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling.

BACKGROUND: In contrast to differential diagnosis (ddx) of older adolescent and adult bipolarity (BP), which includes schizophrenia and substance use disorders, the main ddx of prepubertal and early adolescent BP is attention-deficit disorder with hyperactivity (ADHD). To address this ddx issue, and to provide prepubertal mania manifestations, interim baseline data are presented from the National Institute of Mental Health (NIMH)-funded study 'Phenomenology and Course of Pediatric Bipolarity'. METHODS: Data are from the first 60 BP and the first 60 ADHD cases from 270 consecutively ascertained subjects (90 BP, 90 ADHD and 90 community controls). Comprehensive assessments included the Washington University at St. Louis Kiddie and Young Adult-Schedule for Affective Disorders and Schizophrenia--Lifetime and Present Episode Version-DSM-IV (WASH-U-KSADS) blindly administered by nurses to mothers about their offspring and to children/adolescents about themselves. Caseness was established by consensus conferences that included diagnostic and impairment data, teacher and school reports, agency records, videotapes and medical charts. RESULTS: Mean baseline age of BP cases was 11.0+/-2.7 years and the mean age at onset of BP was 8.1+/-3.5 years. Elated mood, grandiosity, hypersexuality, decreased need for sleep, racing thoughts and all other mania items except hyperenergetic and distractibility were significantly and substantially more frequent among BP than ADHD cases (e.g., elation: 86.7% BP vs. 5.0% ADHD; grandiosity: 85.0% BP vs. 6.7% ADHD). In the BP group, 55.0% had grandiose delusions, 26.7% had suicidality with plan/intent and 83.3% were rapid, ultra-rapid or ultradian cyclers. LIMITATIONS: Sites for consecutive case ascertainment from the lowest socioeconomic status classes were unavailable due to current health care policies. CLINICAL RELEVANCE: Prepubertal and early adolescent BP cases differentiate from ADHD by mania-specific criteria and commonly present with ultra-rapid or ultradian cycling.

Activity Cycles↗
PubMed1998

Prepubertal and young adolescent bipolarity versus ADHD: assessment and validity using the WASH-U-KSADS, CBCL and TRF.

BACKGROUND: This addendum to 'Prepubertal and early adolescent bipolarity differentiate from ADHD by mania criteria; grandiose delusions; ultra-rapid or ultradian cycling' (in this volume) provides (1) a description of Washington University at St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) with sample sections (hypersexuality, rapid cycling); (2) a comparison of WASH-U-KSADS to KSADS-P/L and KSADS-1986 and (3) a comparison of WASH-U-KSADS to Child Behavior Checklist (CBCL) and Teachers Report Form (TRF) data. METHODS: Data were from the first 60 bipolar (BP) and first 60 ADHD subjects of 270 consecutively ascertained cases (90 BP, 90 ADHD and 90 community controls) in the NIMH funded 'Phenomenology and Course of Pediatric Bipolarity' study. Comprehensive assessments included the WASH-U-KSADS (administered blindly to mothers and separately to children), CBCL and TRF. RESULTS: As reported elsewhere in this volume, WASH-U-KSADS data significantly differentiated BP and ADHD groups. Significant differences were also found with the parent-rated CBCL and the teacher-rated TRF, thereby providing cross-modality and cross-informant validation of the WASH-U-KSADS. Because of the close agreement with published CBCL data from another investigator, cross-site validation also occurred. LIMITATIONS: Venues for consecutive ascertainment from the lowest socioeconomic status classes were unavailable due to current health care policies. CLINICAL RELEVANCE: CBCL and TRF data separated BP from ADHD groups, largely by non-specific externalizing dimensions (e.g., hyperactivity, aggressivity). Clinically relevant differentiation by categorical mania-specific criteria (e.g., elated mood, grandiosity, racing thoughts) occurred with WASH-U-KSADS data. Both types of data are crucial for genetic and neurobiological studies.

Adolescent↗
PubMed1998

Lithium for prepubertal depressed children with family history predictors of future bipolarity: a double-blind, placebo-controlled study.

BACKGROUND: Because of negative studies of TCAs for prepubertal major depressive disorder (PMDD) and because of the potentially high switch rate of PMDD to prepubertal bipolarity (BP), it was hypothesized that lithium would be efficacious treatment for PMDD in children who also had family history (FH) predictors of future BP. METHODS: A double-blind, placebo-controlled, and pharmacokinetically dosed study of lithium for PMDD with FH predictors of future BP was performed. Random assignment was stratified by FH of BP-I or mania versus loaded/multigenerational (L/M) FH of MDD without BP-I or mania. Comprehensive assessments were done during a six week outpatient protocol that included weekly serum lithium levels. RESULTS: Mean age was 10.7+/-1.2 years; 17 subjects were randomized to active and 13 to placebo; 80% had FH of BP-I or mania (40% of parents had BP-I or mania); and 20% had FH of L/M MDD. Using both intent to treat with last observation carried forward (n = 30) and completer (n = 24) analyses, there were no significant differences on continuous or categorical measures between active and placebo groups. Mean serum lithium level was 0.99+/-0.16 mEq/l. There were no significant differences between mean total daily dose or mean serum lithium levels between responders and non-responders. LIMITATIONS: Four subjects on active drug were discontinued because of dose-limiting side effects (three were cognitive impairment). Future studies of treatment for PMDD should consider alternative drugs. CLINICAL RELEVANCE: Lithium was not significantly more efficacious than placebo for PMDD with FH predictors of future BP.

Adolescent↗
PubMed1998

Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency.

OBJECTIVE: To perform a double-blind, placebo-controlled, random assignment, parallel group, pharmacokinetically dosed study of lithium for adolescents with bipolar disorders (BP) and temporally secondary substance dependency disorders (SDD). METHOD: Subjects were 16.3 +/- 1.2 years old and were comprehensively assessed during a 6-week outpatient protocol that included random weekly urine collection for drug assays and random and weekly serum collection for lithium levels. RESULTS: Using both intent-to-treat (N = 25) and completer (n = 21) analyses, there were significant differences on continuous and categorical measures between the active and placebo groups for both psychopathology measures and weekly random urine drug assays. The mean scheduled weekly serum lithium level of active responders was 0.9 mEq/L. Addiction to both alcohol and marijuana was the most frequent category of SDD. Mean age at onset of BP was 9.6 +/- 3.9 years and of SDD was 15.3 +/- 1.3 years. There were multigenerational mood disorders in 96% and multigenerational SDD in 56% of families. CONCLUSIONS: Lithium treatment of BP with secondary SDD in adolescents was an efficacious treatment for both disorders. These results warrant replication with a long-term maintenance phase. The mean 6-year interval between the onset of BP and onset of SDD strongly argues for earliest recognition of BP.

Adolescent↗
PubMed1997

Refractory depression in children and adolescents.

Refractory or treatments resistant depression in child and adolescent populations is a difficult construct to operationalize currently. To date, only one of the small number of completed double-blind placebo-controlled treatment investigations have not demonstrated a significant effect of antidepressants in comparison to placebo. However, it has been established that child and adolescent MDD is a serious disorder that appears to have clinical continuity with adult affective disorders and is generally of long duration with high rates of recurrence and eventual progression to mania, substance abuse, or other serious psychopathology. In addition, families of children with affective disorders evidence substantial genetic loading with high rates of affective disorders contributing both genetic vulnerability and potential environmental risk as well. There have been no empirically identified treatments that alter the long-term course of the illness. Thus treatment resistance is a significant issue for this population. This review will focus on controlled treatment trials and will examine the potential relevance of psychosocial impairment, genetic-familial risk, and neuromorphometric brain differences to treatment resistance in children and adolescents with major depression.

Adolescent↗
PubMed1997

Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis.

We registered 366 families in a study of dominantly inherited amyotrophic lateral sclerosis. Two hundred ninety families were screened for mutations in the gene encoding copper-zinc cytosolic superoxide dismutase (SOD1). Mutations were detected in 68 families. The most common SOD1 mutation is an alanine for valine substitution in codon 4 (50%). We present clinical and genetic data concerning 112 families with 395 affected individuals. The clinical characteristics of patients with familial amyotrophic lateral sclerosis arising from SOD1 mutations are similar to those lacking SOD1 defects. Mean age at onset was earlier (Wilcoxon test, p = 0.004) in the SOD1 group (46.9 years [standard deviation, 12.5] vs 50.5 years [11.5] in the non-SOD1 group). Bulbar onset was associated with a later onset age. The presence of either of two mutations, G37R and L38V, predicted an earlier age at onset. Kaplan-Meier plots demonstrated shorter survival in the SOD1 group compared with the non-SOD1 group at early survival times (Wilcoxon test, p = 0.0007). The presence of one mutation, A4V, correlated with shorter survival. G37R, G41D, and G93C mutations predicted longer survival. This information suggests it will be productive to investigate other genetic determinants in amyotrophic lateral sclerosis and to use epidemiological characteristics of the disease to help discern molecular mechanisms of motor neuron cell death.

Adult↗
PubMed1997

Increased prevalence and earlier onset of mood disorders among relatives of prepubertal versus adult probands.

OBJECTIVE: To compare the familial clustering of affective disorders among first-degree relatives of prepubertal versus adult probands with mood disorders. METHOD: The Family History-Research Diagnostic Criteria (FH-RDC) assessment instrument was used to obtain data on first-degree relatives of all probands. Logistic regression was used to assess the strength of the age of the proband to predict FH-RDC diagnoses in relatives. Survival analysis was used to examine the age-at-onset distribution of first FH-RDC diagnosis while controlling for year of birth. RESULTS: The prevalence of major affective disorders was more than two times higher among first-degree relatives of child probands versus those of adult probands even when controlling for birth cohort. Cumulative risk for lifetime major mood disorders in first-degree relatives of child probands was significantly higher than for those of adult probands. CONCLUSION: These analyses further support that ascertainment of families through affected children identifies pedigrees with a higher proportion of affected relatives than ascertainment through affected adults.

Adult↗
PubMed1997

Child and adolescent bipolar disorder: a review of the past 10 years.

OBJECTIVE: To provide a review of the epidemiology, phenomenology, natural course, comorbidity, neurobiology, and treatment of child and adolescent bipolar disorder (BP) for the past 10 years. This review is provided to prepare applicants for recertification by the American Board of Psychiatry and Neurology. METHOD: Literature from Medline and other searches for the past 10 years, earlier relevant articles, and the authors' experience and ongoing National Institute of Mental Health-funded project "Phenomenology and Course of Pediatric Bipolarity" were used. RESULTS: Age-specific, developmental (child, adolescent, and adult) DSM-IV criteria manifestations; comorbidity and differential diagnoses; and episode and course features are provided. Included are age-specific examples of childhood grandiosity, hypersexuality, and delusions. Differential diagnoses (e.g., specific language disorders, sexual abuse, conduct disorder [CD], schizophrenia, substance abuse), suicidality, and BP-II are discussed. CONCLUSION: Available data strongly suggest that prepubertal-onset BP is a nonepisodic, chronic, rapid-cycling, mixed manic state that may be comorbid with attention-deficit hyperactivity disorder (ADHD) and CD or have features of ADHD and/or CD as initial manifestations. Systematic research on pediatric BP is in its infancy and will require ongoing and future studies to provide developmentally relevant diagnostic methods and treatment.

Adolescent↗
PubMed1996

Treatment-resistant depression in children and adolescents.

Treatment resistance in depressed children and adolescents cannot yet be defined fully because of the paucity of controlled studies that demonstrate efficacy. Therefore, this article addresses several of the age-specific, developmental considerations that may impinge upon treatment response. Areas covered include familial-genetic, psychosocial, and neuroimaging studies in addition to a review of controlled studies to date.

Adolescent↗
PubMed1996

Increased prevalence of alcoholism in relatives of depressed and bipolar children.

OBJECTIVE: Previous publications from the "Nortriptyline in Childhood Depression: Follow-up Study" reported increased prevalence rates of mood disorders and alcoholism in the relatives of prepubertal depressed subjects. This article presents data on the association versus independent transmission of alcohol and mood disorders in the families of these subjects. METHOD: The follow-up study included 6- to 12-year-olds with major depressive disorder (MDD) and matched normal controls. After 2 to 5 years of follow-up, bipolarity developed in 31.7% of the MDD subjects. Family history data for the first- and second-degree relatives and first cousins of the 76 nonadopted MDD subjects and the 31 controls were obtained from the subjects' mothers, using the Family History-Research Diagnostic Criteria. RESULTS: The prevalence of alcoholism among the relatives of the MDD and bipolar probands was two to three times that reported for control relatives and twice that reported for the relatives of adult MDD and bipolar probands. Mood disorders and maternal alcoholism were independently transmitted while paternal alcoholism increased the risk for mood disorder in offspring. CONCLUSIONS: The potential psychosocial and genetic effects of familial alcoholism need to be considered for the clinical management and investigation of childhood-onset mood disorders.

Adolescent↗
PubMed1996

Cardiovascular effects of therapeutic doses of tricyclic antidepressants in children and adolescents.

OBJECTIVE: Tricyclic antidepressants (TCAs) play an important role in the treatment of pediatric psychiatric disorders. Despite widespread clinical use, concerns about their possible cardiovascular risk have arisen following several published reports of sudden death associated with their use in children. Accordingly, available evidence concerning TCA-associated cardiovascular effects in children and adolescents was surveyed. METHOD: A systematic literature search from 1967 to 1996 identified relevant pediatric studies that evaluated cardiovascular effects of TCAs. RESULTS: Twenty-four studies involving 730 children and adolescents given imipramine, amitriptyline, desipramine, or nortriptyline were found. TCA treatment was associated with minor increases in systolic and diastolic blood pressure, in heart rate, and in the electrocardiographic (ECG) conduction parameters, PR, QRS, and QTc. Holter ECG monitoring and exercise testing also revealed minor treatment effects. Some ECG changes related to specific TCAs emerged. Few age-related ECG differences in TCA-treated children, adolescents, or adults were detected. Associations of ECG abnormalities and relatively higher serum TCA levels were found. CONCLUSION: TCA treatment in children and adolescents, like that in adults, is associated with cardiovascular changes of uncertain, but probably minor, clinical significance. More information is needed on the contribution of other physiological conditions on the cardiovascular system during exposure to TCAs. Guidelines for using TCAs in children and adolescents are presented.

Adolescent↗
PubMed1996

Interethnic psychopharmacologic research in children and adolescents.

Interethnic child and adolescent psychopharmacology research is essentially unstudied. Recently there have been reports of interethnic differences in psychopharmacology research on adults. This article addresses the need to focus research on psychopharmacogenetics, pharmacokinetics, pharmacodynamics, and issues of efficacy and effectiveness in child and adolescent populations of different ethnic groups.

Adult↗
PubMed1995

Complex and rapid-cycling in bipolar children and adolescents: a preliminary study.

26 subjects aged 7-18 years were studied. Diagnoses of bipolar disorders were established using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present Episode Version-1986 modified for DSM-III-R criteria and for rating the number and duration of manic and hypomanic episodes. Complex cycling patterns were observed. These included numerous brief episodes suggesting continuous rapid-cycling in 80.8% of cases. Mean age of onset was early (8.5 +/- 4.4 years). Psychotic phenomena, suicidality, hyperactivity and 'mixed mania' were highly prevalent. Data in this report provide support for complex and rapid-cycling patterns in childhood onset bipolar disorder.

Adolescent↗
PubMed1995

Preliminary study of magnetic resonance imaging characteristics in 8- to 16-year-olds with mania.

OBJECTIVE: To examine magnetic resonance imaging (MRI) characteristics in children and adolescents with mania according to DSM-III-R criteria. METHOD: A convenience sample of consecutively referred 8- to 16-year-old manic (n = 10) and normal (n = 5) subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode Version, the Children's Global Assessment Scale, and the Family History-Research Diagnostic Criteria. MRI scans were obtained from unsedated subjects using a 1.5 T MR scanner to acquire T1-weighted coronal and sagittal images and T2-weighted axial images. Images were assessed by blind clinical interpretation, ratings of T2-weighted deep white matter hyperintensities and petalia, and computer-assisted volumetric analysis of ventricular and cerebral volumes. RESULTS: Eight of 10 manic subjects and all 5 controls completed the scans. Scans of 4 manic subjects and 1 control subject showed ventricular or white matter abnormalities by clinical interpretation. Significant findings were positive correlations between increasing age and both right and left ventricular volumes. Two of the 8 manic subjects and no controls had confluent subcortical hyperintensities. CONCLUSIONS: MRI brain scanning was feasible in 8- to 16-year-olds. Preliminary findings from clinical interpretations and structured ratings suggest structural differences between young manic and normal subjects. Investigations of larger samples are needed to better characterize the differences.

Adolescent↗
PubMed1995

Development of a community mammography registry: experience in the breast screening program project.

PURPOSE: To assess the formation, implementation, and operation of a community mammography registry, which is a consolidated database for all mammography and breast biopsy reports within a community. MATERIALS AND METHODS: A registry was created in Lee County, Fla. Mammography interpretation data were provided by 13 facilities and 38 radiologists organized in several private practice groups. RESULTS: The registry contains data on 87,926 mammograms and 3,234 breast biopsies performed between June 1991 and May 1994. The registry calculates individual and group mammography interpretation accuracy measures, such as sensitivity, specificity, positive predictive value, false-positive and false-negative rates, and clinical outcome measures such as sizes and stages of malignant lesions detected. CONCLUSION: The registry allows community radiologists and mammography practices to compare their outcomes with those of their local peers and to published data and encourages focused interventions for quality improvement based on objective experience.

Adult↗
PubMed1994

Rate and predictors of prepubertal bipolarity during follow-up of 6- to 12-year-old depressed children.

OBJECTIVE: To investigate the rate and predictors of onset of DSM-III bipolar I and bipolar II disorders among 6- to 12-year-old prepubertal subjects with DSM-III major depressive disorder (MDD) who were followed for a 2- to 5-year period. METHODS: This was a prospective, blindly rated study of 79 children with MDD and 31 normal control children matched for age, gender, and socioeconomic status. Subjects and a second informant were assessed at 4-month intervals using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present Episode Version-1986 modified to include 4-month interval ratings and to include DSM-III diagnoses. Family history (FH) was assessed using the FH-Research Diagnostic Criteria obtained from the mother about the subject's first- and second-degree relatives. RESULTS: Bipolarity developed in 31.7% (N = 25) of the children with MDD at a mean age of 11.2 +/- 2.0 years and 80% were prepubertal. Loaded FH and multigenerational FH were significantly associated with bipolar I. Neither prior nor current use of tricyclic antidepressants nor atypical depressive features were predictive. CONCLUSIONS: These findings strongly support the need to educate families of children with prepubertal-onset MDD about the possibility of the emergence of manic and hypomanic symptoms to encourage early recognition and appropriate treatment.

Adolescent↗