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Biomedical subjects

W A Weinberg

Publications and source records attributed to W A Weinberg.

At least 19 recordsLinked to original sources

Sleep polysomnography as a predictor of recurrence in children and adolescents with major depressive disorder.

Adults with major depressive disorder (MDD) demonstrate certain sleep polysomnographic abnormalities, including sleep continuity disturbances, reduced slow-wave sleep, shortened rapid eye movement (REM) latency, and increased REM density. Findings of sleep EEG studies in depressed children and adolescents have yielded conflicting results, possibly because of methodological variations across the studies. Generally, however, studies have demonstrated that depressed children and adolescents exhibit less sleep continuity and non-REM sleep differences in comparison with control subjects than do adults. Thus, results from adult sleep polysomnography studies cannot necessarily be generalized to children and adolescents. Depressed adults who have reduced REM latency during the symptomatic episode appear more likely to have a relapse once treatment is discontinued than those with normal REM latency. No studies of the relationship between sleep polysomnographic variables and clinical course have been reported in depressed children and adolescents. Data for baseline clinical variables and 3 nights of sleep polysomnography were examined in 113 depressed children (< or = 12 yr; n = 51) and adolescents (> or = 13 yr; n = 62) (56 in-patients and 57 outpatients) where data was available on at least 1 yr of naturalistic follow-up. Subjects came from 2 studies of sleep polysomnography in children and adolescents with MDD. Clinical course was assessed using the Kiddie-Longitudinal Interval Follow-Up Evaluation (K-LIFE). This interview was used to define recovery from the index episode of MDD and recurrence, a new episode of meeting full criteria for MDD. Clinically, within 1 yr of initial evaluation 102/113 subjects had recovered from their index episode of depression (minimal or no symptoms for 60 d). Of the 102 subjects who recovered, 36 (35.3%) had a recurrence of MDD. The majority of subjects (55%) who had a recurrence were not on medication at the time of recurrence. Subjects who had a recurrence were more likely to report suicidal thoughts or attempts at baseline compared to those without a recurrence (67 vs. 37%; F = 8.77; p = 0.004). On baseline sleep polysomnography, subjects with a later recurrence had decreased sleep efficiency and delayed sleep onset (sleep latency > 10 min). Probability of recurrence at 12 months was 0.39 compared to 0.15 in subjects with non-delayed sleep onset (p = 0.005). Baseline suicidal ideation and sleep dysregulation on sleep polysomnography predicted recurrence in a large sample of depressed children and adolescents. Depression in children and adolescents is frequently a chronic, recurrent illness. Factors that can predict clinical course are important in increasing our understanding of depression in this age group.

Adolescent↗

Affective illness in children and adolescents: patterns of presentation in relation to pubertal maturation and family history.

Affective illness is now recognized as a common problem in all age groups, and the various patterns have been well documented in adults. The objective of this study was to evaluate the patterns of affective illness in children and determine changes with increasing age and family history. One hundred children/adolescents with affective illness (72 boys and 28 girls; age range 2-20 years; mean age 10 years), who were consecutively referred to the Pediatric Behavioral Neurology Program, Children's Medical Center at Dallas, were evaluated for the pattern and course of affective illness symptoms, family history, and pubertal stage. Seven patterns of affective illness were identified. In the 65 prepubertal children (Tanner stage 1), disorders with hypomanic/manic symptomatology were most common (47/65, 72%): mania (2/65, 3%), hypomania (8/65, 12%), cyclothymia (11/65, 17%), juvenile rapid-cycling bipolar disorder/ultradian cycling bipolar disorder (8/65, 12%), and dysthymia with bipolar features (18/65, 28%). In contrast, the 26 fully pubertal adolescents (Tanner stages 3-5) had a predominance of patterns with only depressive symptomatology (16/26, 61%): dysthymia (4/26, 15%) and depression (12/26, 46%), along with juvenile rapid-cycling bipolar disorder/ultradian cycling bipolar disorder (6/26, 23%). Affective illness, alcoholism, and drug abuse were prominent in the family histories, regardless of the child's pattern of symptoms. Family histories of character disorder and Briquet's syndrome were also common, but thought disorder, suicide, and homicide were infrequent. This study supports the clinical observation that the presentation of affective illness changes with age: manic features predominate in younger children, whereas depressive symptomatology is more evident with pubertal maturation.

Adolescent↗

Occipital brain perfusion deficits in children with major depressive disorder.

UNLABELLED: Occipital lobe perfusion defects have been identified on regional cerebral blood flow (rCBF) SPECT scans of adolescent children and young adults with major depressive disorder (MDD). We reinvestigated a series of rCBF SPECT scans obtained several years ago on drug-naive children with a clinical diagnosis of MDD and on healthy children. METHODS: To test whether visually apparent abnormalities in rCBF constitute statistically significant differences between patients, given the relatively small sample sizes, we applied the technique of statistical parametric mapping (SPM). RESULTS: Two groups of patients were identified: 8 with significant posterior flow deficits in the occipital cortex (Brodmann's areas 18 and 19), usually symmetric, and best visualized on paramedian sagittal sections, and 13 without obvious occipital perfusion deficits but with anterior rCBF deficits in a pattern often described in the literature, attaining statistical significance in the right frontal region. Other localizations in the left frontal and bilateral prefrontal regions did not attain significance, but each localization contained statistically significant maxima (z scores). The scan findings of all 18 healthy children were normal. CONCLUSION: With the aid of SPM, 2 groups of children with significantly different rCBF behavior were identified. The reason for this difference is not known but should be investigated to determine its possible significance to patients with MDD.

Adolescent↗

Ultradian rhythms and temporal coherence in sleep EEG in depressed children and adolescents.

BACKGROUND: It has been suggested that a primary ultradian (80-120 minute) rhythm disturbance in EEG underlies sleep abnormalities in adults with depression. The present study evaluated ultradian rhythm disturbances in childhood and adolescent depression. METHODS: Sleep macroarchitecture and temporal coherence in quantitative EEG rhythms were investigated in 50 medication-free outpatients with major depression (25 children and 25 adolescents) and 15 healthy normal controls (5 children and 10 adolescents). RESULTS: Few of the macroarchitectural measures showed significant group effects. In fact, age and sex effects were stronger than disease-dependent components. Temporal coherence of EEG rhythms during sleep did differentiate those with MDD from controls. Both depressed children and adolescents had lower intrahemispheric coherence, whereas interhemispheric was only lower in depressed adolescents in comparison with controls. Gender differences were evident in adolescents, but not children, with MDD with lowest interhemispheric coherence in adolescent girls. CONCLUSIONS: These findings are in keeping with increased risk for depression in females beginning at adolescence and extending throughout adulthood. It was suggested that low temporal coherence in depression reflects a disruption in the fundamental basic rest-activity cycle of arousal and organization in the brain that is strongly influenced by gender.

Activity Cycles↗

Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder.

OBJECTIVE: To develop effect sizes for 3 mood stabilizers--lithium, divalproex sodium, and carbamazepine--for the acute-phase treatment of bipolar I or II disorder, mixed or manic episode, in children and adolescents aged 8 to 18 years. METHOD: Forty-two outpatients with a mean age of 11.4 years (20 with bipolar I disorder and 22 with bipolar II disorder) were randomly assigned to 6 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly Clinical Global Impression Improvement scores and the Young Mania Rating Scale (Y-MRS). RESULTS: Using a > or = 50% change from baseline to exit in the Y-MRS scores to define response, the effect size was 1.63 for divalproex sodium, 1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were as follows: sodium divalproex, 53%; lithium, 38%; and carbamazepine, 38% (chi 2(2) = 0.85, p = .60). All 3 mood stabilizers were well tolerated, and no serious adverse effects were seen. CONCLUSIONS: Divalproex sodium, lithium, and carbamazepine all showed a large effect size in the open treatment of children and adolescents with bipolar I or II disorder in a mixed or manic episode.

Acute Disease↗

A SPECT HMPAO study of regional cerebral blood flow in depressed adolescents and normal controls.

1. The objective of this study was to compare the relative regional cerebral blood flow (rCBF) patterns of a group of adolescents with major depressive disorder (MDD) to a group of normal controls. 2. Seven adolescent patients with symptomatic MDD and 7 age- and gender-matched normal controls, underwent SPECT imaging with 99mTc-HMPAO while unmedicated and in a resting state. These subject's data were normalized to whole brain counts, oriented in Talairach space, and analyzed using a voxel-based, t-image approach. 3. The authors found relative rCBF increases in the depressed group as compared to normals in the right mesial temporal cortex, the right superior-anterior temporal lobe, and the left infero-lateral temporal lobe. We found rCBF decreases in the depressed group as compared to normals in the left parietal lobe, the anterior thalamus and the right caudate. 4. Adolescents with MDD show rCBF abnormalities similar to those found in adult MDD rCBF studies. Further controlled studies with larger numbers of MDD subjects and normal age- and gender-matched controls are necessary before any definitive conclusions can be made from these findings.

Adolescent↗

Fluoxetine in child and adolescent depression: acute and maintenance treatment.

The objective was to present naturalistic 1-year follow-up information of 96 child and adolescent outpatients with major depressive disorder who had been randomized in an 8-week double-blind, placebo-controlled trial of fluoxetine. Subjects were children and adolescents, ages 8-18 years, who were entered in a randomized clinical trial of fluoxetine. Following the acute treatment trial, treatment was not controlled. At 6 months and 1 year, the subjects and parents were interviewed using the Kiddie Longitudinal Interval Follow-up Evaluation (K-LIFE) for course of depression. Eighty-seven of the 96 subjects were followed for 1 year. Of these, 74 (85%) recovered from the depressive episode during that time (47 on fluoxetine, 22 on no medication, and 5 on other antidepressants or lithium). Twenty-nine of the subjects (39%) who recovered had a recurrence of depression during the 1-year follow-up, with 55% of these occurring within 6 months. Results of this study are similar to adult studies, with respect to response and recovery of depressive episodes. Most patients (85%) recover from the episode within 1 year, but approximately 40% have a recurrence within 12 months, which is a higher recurrence rate than in adults. Recovery was associated with younger age, lower severity of depressive symptoms, higher family functioning, and fewer comorbid diagnoses. Recurrence, which occurs both on and off medication, was difficult to predict, as there was little clinical data associated with recurrence in this population.

Acute Disease↗

A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression.

BACKGROUND: Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blind trials of antidepressants (largely tricyclic agents) have yet to reveal that any antidepressant is more effective than placebo. This article is of a randomized, double-blind, placebo-controlled trial of fluoxetine in children and adolescents with depression. METHODS: Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic major depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks. Randomization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks, followed 1 week later by a 1-week, single-blind placebo run-in. Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children's Depression Rating Scale--Revised, a measure of the severity depressive symptoms. RESULTS: Of the 96 patients, 48 were randomized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) receiving placebo were rated "much" or "very much" improved on the Clinical Global Impressions scale at study exit (chi 2 = 5.1, df = 1, P = .02). Significant differences were also noted in weekly ratings of the Children's Depression Rating Scale--Revised after 5 weeks of treatment (using last observation carried forward). Equivalent response rates were found for patients aged 12 years and younger (n = 48) and those aged 13 years and older (n = 48). However, complete symptom remission (Children's Depression Rating Scale--Revised < or = 28) occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients. CONCLUSION: Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression. Complete remission of symptoms was rare.

Adolescent↗

Recurrence of major depressive disorder in hospitalized children and adolescents.

OBJECTIVE: To evaluate the outcome of a sample of children and adolescents hospitalized with major depressive disorder (MDD) and to assess different duration and severity criteria to define recovery and recurrence. METHOD: Fifty-nine of 70 children and adolescents were reevaluated 1 to 5 years later, and the intervening course of depression and other disorders was assessed using the Kiddie-Longitudinal interval Follow-up Evaluation (K-LIFE). RESULTS: Ninety-eight percent of subjects had recovered from their index MDD episode within 1 year of their initial evaluation, but 61% had at least one recurrence during the follow-up period. Of those with recurrences, 47.2% had a recurrence within 1 year and 69.4% by 2 years from the offset of the index episode. Changing the criteria for recovery by increasing the length of time required to define recovery resulted in decreases in the number of episodes of recurrence reported. CONCLUSION: MDD in children and adolescents is often an episodic disorder. Difference in definitions of recovery and recurrence affect the data reported. Consistent definitions of remission, recovery, relapse, and recurrence are needed. These data suggest that recovery may be defined after two consecutive months without symptoms and that episodes of MDD may be briefer, but more frequent, in children and adolescents than in adults.

Adolescent↗

Effective prophylactic therapy for cyclic vomiting syndrome in children using amitriptyline or cyproheptadine.

OBJECTIVE: To evaluate our experience using the antimigraine prophylactic drugs, amitriptyline and cyproheptadine, for the prophylactic management of cyclic vomiting syndrome (CVS) in children. METHODS AND PATIENTS: Twenty-seven patients (16 males) ranging in age from 2 to 16 years at diagnosis, fulfilling the diagnostic criteria for CVS and treated prophylactically with either amitriptyline (22) or/and cyproheptadine (6) were identified through retrospective chart review. Individual patient data were corroborated by the attending physician and/or interviews with patients and families. Minimum follow-up time before entry into the study group was 5 months. Patients were stratified according to three treatment outcomes: 1) complete response-no attacks, 2) partial response-50% or greater reduction in frequency of attacks, and 3) no response-less than 50% decrease in frequency of attacks. RESULTS: Of the 22 patients treated with amitriptyline, 16 (73%) had a complete response while 4 (18%) had a partial response. Of the 6 patients treated with cyproheptadine, 4 (66%) had a complete response and 1 (17%) had a partial response. Thus, 91% of the amitriptyline group and 83% of the cyproheptadine group had at least a partial response to therapy. No patients experienced significant side effects to either medication. CONCLUSION: The antimigraine prophylactic drugs, amitriptyline and cyproheptadine, represent effective prophylactic agents for the management of CVS in the vast majority of patients fulfilling the diagnostic criteria for this syndrome.

Adolescent↗

Use of the Symbol Language and Communication Battery in the physician's office for assessment of higher brain functions.

Higher brain functions are readily observable within the office setting. The Symbol Language and Communication Battery offers a systematic approach to evaluation, with resultant reproducible findings. It should be part of the neurologic evaluation for children who are having difficulty in their environments, with the differences in communication skills categorized into specific syndromes.

Adolescent↗

Sleep EEG features of adolescents with major depression.

A substantial body of research in adults has established that certain sleep polysomnographic abnormalities are commonly found in depressed patients, including sleep continuity disturbances, reduced slow-wave sleep, shortened rapid eye movement (REM) latency and increased REM density. To date the findings in depressed adolescents are equivocal. Three consecutive nights of polysomnographic recordings were obtained in 31 hospitalized depressed adolescents and 17 age-matched normal controls. The depressed adolescents had a shorter REM latency, shorter sleep latency, more REM sleep, and less stage 3 nonREM (NREM) sleep. There was a trend for melancholic and suicidal patients to have a shorter REM latency.

Adolescent↗