Biomedical subjects

B Birmaher

Publications and source records attributed to B Birmaher.

At least 73 records · Page 4Linked to original sources

PubMed1996

The relationship between longitudinal clinical course and sleep and cortisol changes in adolescent depression.

This study examined the relationship between longitudinal clinical course and sleep and cortisol findings in adolescent unipolar major depressive disorder (MDD). Subjects were 28 adolescents (15.4 +/- 1.3 years) systematically diagnosed with unipolar MDD and 35 group-matched normal controls who participated in EEG sleep and neuroendocrine studies. Follow-up clinical assessments were conducted 7.0 +/- 0.5 years later in 94% of the original cohort. Although initial group comparisons failed to show significant differences in biologic measures, analyses incorporating clinical follow-up reveal that changes in sleep and cortisol measures are associated with differential longitudinal course. Normal controls who would develop depression after the biologic studies had shown significantly higher density of rapid eye movements (REM) and a trend for reduced REM latency compared to controls with no psychiatric disorder at follow-up. Depressed subjects with a recurrent unipolar course showed a trend towards elevated plasma cortisol near sleep onset compared to MDD subjects with no further episodes during the follow-up interval.

Adolescent↗

PubMed1996

Sleep onset abnormalities in depressed adolescents.

Sleep measures were obtained in 16 depressed and 21 control adolescents following 1 week of adherence to a uniformly imposed and strictly enforced sleep/wake schedule. Three nights of baseline electroencephalographic (EEG) sleep on the same 10:00 PM to 7:00 AM schedule revealed prolonged sleep latency and reduced rapid eye movement (REM) latency in the depressed adolescents. Following baseline measures, sleep was restricted for 2 nights (10:00 PM-4:00 AM) and measures of recovery sleep were obtained showing further sleep latency differences. There was no evidence for delta sleep changes or sleep continuity differences in depressed adolescents. These results suggest that control over sleep/wake schedules is an important methodological issue in adolescent sleep studies. Furthermore, the findings are consistent with a larger body of evidence indicating that dysregulation near sleep onset represents a primary psychobiological change in early-onset depression.

Adolescent↗

PubMed1996

Corticotropin-releasing hormone challenge in prepubertal major depression.

This study investigates cortisol and ACTH (corticotropin) responses to an infusion of human CRH (corticotropin-releasing hormone) in prepubertal children with major depressive disorder (MDD). Following a period of 24 hours of adaptation to the laboratory environment with an intravenous catheter in place, 34 children with MDD and 22 healthy controls received 1 microgram/kg of human CRH at 5:00 PM. Blood samples for cortisol and ACTH were measured at baseline and post-CRH. Overall, there were no significant differences between the MDD and the normal controls in baseline or post CRH stimulation values of either cortisol or ACTH. Melancholic (n = 4) patients had significantly higher baseline cortisol levels than nonmelancholic (n = 24) patients. Compared with the outpatients and the nonmelancholics, the inpatients (n = 10) and the melancholics showed significantly lower total ACTH secretion (effect size: 0.9 and 1.4, respectively) after CRH infusion. These results are consistent with a broad literature suggesting that the HPA axis abnormalities occur less frequently in early-onset depression than reported in adult studies. The pattern of results in the subgroups of inpatients and in melancholic children, however, raise questions about possible continuities with adult studies.

Adolescent↗

PubMed1996

Nocturnal ACTH, cortisol, growth hormone, and prolactin secretion in prepubertal depression.

OBJECTIVE: To examine nocturnal secretion of adrenocorticotropin, cortisol, growth hormone, and prolactin in 38 medically healthy children with prepubertal major depression compared with 28 medically and psychiatrically healthy control children. METHOD: Prior to sampling, subjects underwent an "adaptation night" with the intravenous catheter in place and electroencephalographic (EEG) electrodes for standard all-night polysomnogram. On the following night, plasma samples were obtained every 20 minutes through an indwelling catheter. Hormonal concentrations were measured by specific radioimmunoassay and aligned by EEG-confirmed sleep onset. Areas under the curve were calculated for total secretion and compared using analysis of variance. RESULTS: Prepubertal depressed children had lower cortisol secretion during the first 4 hours after sleep onset compared with controls. Adrenocorticotropin, prolactin, and growth hormone secretion did not differ between groups. Examination of clinical characteristics in depressed children revealed lower nocturnal adrenocorticotropin concentrations in depressed inpatients versus depressed outpatients and in depressed sexually abused versus depressed nonabused children. A significant sex by diagnosis effect revealed lower growth hormone secretion in depressed females compared with depressed males. CONCLUSIONS: In contrast to neuroendocrine challenge studies in these same subjects, nocturnal neuroendocrine measures did not reveal any of the expected group differences. These results emphasize the contrasts between unstimulated and challenge studies of neuroendocrine secretion and of the importance of considering clinical characteristics and maturation influences in biological studies of prepubertal depression.

Adolescent↗

PubMed1996

A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression.

OBJECTIVE: To determine amitriptyline's (AMI) efficacy in the acute treatment of adolescent major depressive disorder (MDD). METHOD: Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD, diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), participated in a 2-week placebo-washout followed by an 8-week, randomized, double-blind, parallel-design, placebo-controlled trial of AMI, 5 mg/kg per day. The K-SADS nine-item scale, the Hamilton Depression Rating Scale, and the Clinical Global Impressions rating scale were used as outcome measures. RESULTS: Thirty-one subjects were randomized (18 AMI, 13 placebo). Twenty-two subjects were study completers (12 AMI, 10 placebo). AMI's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data. Perhaps the primary limitation of the current study is its small sample size. CONCLUSION: No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD.

Adolescent↗

PubMed1996

Childhood and adolescent depression: a review of the past 10 years. Part I.

OBJECTIVE: To qualitatively review the literature of the past decade covering the epidemiology, clinical characteristics, natural course, biology, and other correlates of early-onset major depressive disorder (MDD) and dysthymic disorder (DD). METHOD: A computerized search for articles published during the past 10 years was made and selected studies are presented. RESULTS: Early-onset MDD and DD are frequent, recurrent, and familial disorders that tend to continue into adulthood, and they are frequently accompanied by other psychiatric disorders. These disorders are usually associated with poor psychosocial and academic outcome and increased risk for substance abuse, bipolar disorder, and suicide. In addition, DD increases the risk for MDD. There is a secular increase in the prevalence of MDD, and it appears that MDD is occurring at an earlier age in successive cohorts. Several genetic, familial, demographic, psychosocial, cognitive, and biological correlates of onset and course of early-onset depression have been identified. Few studies, however, have examined the combined effects of these correlates. CONCLUSIONS: Considerable advances have been made in our knowledge of early-onset depression. Nevertheless, further research is needed in understanding the pathogenesis of childhood mood disorders. Toward this end, studies aimed at elucidating mechanisms and interrelationships among the different domains of risk factors are needed.

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

Childhood and adolescent depression: a review of the past 10 years. Part II.

OBJECTIVE: To review the literature of the past decade covering the assessment, treatment, and prevention of early-onset major depressive disorder (MDD) and dysthymic disorder (DD). METHOD: A computerized search for articles published during the past decade was made, and selected studies are presented. RESULTS: Diagnostic systems and standardized interviews have been developed to reliably assess and diagnose early-onset MDD and DD. To data, few controlled psychotherapeutic trials, in particular cognitive-behavioral therapy (CBT), and one study using fluoxetine have been shown to be efficacious in the acute management of early-onset MDD. While studies of tricyclic antidepressants have shown no difference between medication and placebo, these studies are inconclusive because of the inclusion of small samples and other methodological issues. CBT may also be useful for the prevention of MDD. No studies have been published on maintenance treatment of MDD or the treatment of early-onset DD. CONCLUSIONS: It appears that both pharmacological and psychotherapeutic interventions have a role in the acute treatment of MDD. However, further research on the separate and combined efficacy of these treatments for the acute treatment, maintenance, and prevention of early-onset MDD and DD is needed. The impact of comorbidity and psychosocial consequences of early-onset depression also emphasize the importance of utilizing a multimodal approach to treatment.

Adolescent↗

PubMed1995

Stressful life events and EEG sleep in depressed and normal control adolescents.

EEG sleep measures in 35 depressed and 33 normal control adolescents were examined in relation to stressful life events occurring in the year before sleep studies. There was a significant interaction between stressful life events and diagnostic status for REM latency and total REM time. In the normal controls, the presence of stressful life events was significantly associated with reduced REM latency and increased total REM time. Among the depressed adolescents, there were no significant effects of stressful life events on REM latency or total REM time. The depressed adolescents with no stressful life events (n = 9) had significantly lower REM latency values compared to normal control adolescents with no stressful life events (n = 13)(61.7 +/- 50.0 vs. 132.1 +/- 79.0, p < or = .01). It appears that stressful life events influence at least some measures of adolescent sleep and should be considered in future controlled studies aimed at understanding sleep changes in adolescent depression.

Adolescent↗

PubMed1995

Use of methylphenidate in the treatment of children with autistic disorder.

The use of psychostimulants in autistic disorder has not received extensive evaluation. Furthermore, their use for the symptomatic control of autistic disorder has been felt to be contraindicated. This study investigates the use of methylphenidate (MPH) for the treatment of selected symptoms of autistic disorder. Ten children, ages 7-11, with a DSM-III-R diagnosis of autistic disorder participated in a double-blind crossover study using placebo and two MPH doses (10 mg or 20 mg bid). Subjects showed modest but statistically significant improvement on MPH over placebo. No significant side effects including worsening stereotypic movements occurred on either dose. Improvement in hyperactivity and lack of adverse effects suggest that MPH may be useful in the treatment of hyperactive autistic children.

Autistic Disorder↗

PubMed1995

Unipolar depression in adolescents: clinical outcome in adulthood.

OBJECTIVE: This study examined the longitudinal clinical course and adult sequelae of adolescent unipolar major depressive disorder (MDD) using a controlled longitudinal design. METHOD: Subjects were 28 adolescents (15.4 +/- 1.3 years) with systematically diagnosed unipolar MDD and 35 group-matched control subjects who participated in a cross-sectional electroencephalogram sleep and neuroendocrine study. Using standardized instruments, interviewers who were blind to subjects' initial diagnoses conducted follow-up clinical assessments 7.0 +/- 0.5 years later in 94% of the original cohort. RESULTS: The depressed group showed high rates of recurrence of MDD episodes during the interval period (69%). They also had elevated rates of new-onset bipolar disorder (19%). Twenty-three percent of subjects with an initial diagnosis of MDD had no additional depressive episodes after the index assessment. The rate of new onset of depression in the controls was 21%. Low socioeconomic status predicted recurrence of depressive episodes in the MDD group. MDD subjects with recurrence(s) and controls with new onset of depression during the follow-up period had significant psychosocial morbidity, as evidenced by disruption in interpersonal relationships and dissatisfaction with life and decrease in global functioning, compared with both MDD subjects with no further episodes and control subjects who had never been psychiatrically ill. These psychosocial deficits persisted remission from depressive episode(s). CONCLUSIONS: Adolescent unipolar MDD predicts continued risk for recurrences with persistence of depressive episodes and psychosocial morbidity into adulthood. A sizable minority, however, have sustained periods of remission associated with good social adjustment.

Adolescent↗

PubMed1995

Stressful life events in depressed adolescents: the role of dependent events during the depressive episode.

OBJECTIVE: To examine the relationship between stressful life events and major depressive disorder (MDD) in adolescents. METHOD: Adolescents (aged 12 to 18 years) with a current episode of MDD based on Research Diagnostic Criteria (n = 39) and normal controls free of any Axis I lifetime psychiatric disorder (n = 35) were assessed using the Life Events Record. RESULTS: MDD and normal control adolescents had similar rates of total stressful life events in the year before being interviewed. Stressful life events were dichotomized into those that were most likely either independent of or dependent on the adolescent's influence/behavior. Depressed adolescents had significantly more dependent stressful life events during the previous year than did the normal controls. Further analyses showed that depressed adolescents with dependent stressful life events scored lower on symptom clusters and accordingly were less severely depressed than depressed adolescents without dependent life events. CONCLUSIONS: The results of this study indicate that depressed adolescents have an increased risk for experiencing dependent life events. Furthermore, these data suggest that dependent life events in depressed adolescents are differentially associated with the type and severity of symptom presentation. The temporal occurrence, severity, and type of stressful life events as they relate to the onset, phenotypic expression, and maintenance of depression in adolescents need to be more fully understood.

Adolescent↗

PubMed1995

A case-control family history study of depression in adolescents.

OBJECTIVE: To examine whether depression aggregates in the families of depressed adolescents and to determine whether clinical features and/or comorbid syndromes in the depressed adolescents change the risk of psychopathology in relatives. METHOD: Lifetime prevalence rates of psychopathology in the first-degree (n = 228) and second-degree (n = 736) relatives of 76 adolescents with major depressive disorder (MDD) and the first-degree (n = 107) and second-degree (n = 323) relatives of 34 normal control adolescents were assessed by the Family History-Research Diagnostic Criteria (FH-RDC) method using the parent/guardian as the family informant. RESULTS: Compared with the first-degree relatives of normal controls, the relatives of depressed adolescents had significantly higher lifetime rates of MDD (25% versus 13%) and "any" of the FH-RDC psychiatric disorders (53% versus 36%). The second-degree relatives of adolescents with MDD had significantly higher lifetime rates of FH-RDC "other" psychiatric disorder (12% versus 7%) and "any" of the FH-RDC psychiatric disorders (22% versus 15%) but not MDD (5% versus 6%) compared with the relatives of normal controls. The first-degree relatives of depressed adolescents who were also suicidal had increased lifetime rates of suicidal behavior which significantly cosegregated with MDD. Comorbid conduct disorder in the depressed adolescent was associated with increased rates of antisocial personality disorder in the first-degree relatives and also tended to cosegregate with MDD. CONCLUSIONS: The current study provides further evidence for the familial aggregation of depression in adolescent-onset MDD. This study also suggests that the familial aggregation of nonaffective psychiatric disorders depends on the clinical features and comorbid syndromes present in the depressed adolescent proband.

Adolescent↗

PubMed1994

The 24-hour pattern of prolactin secretion in depressed and normal adolescents.

Plasma prolactin concentrations were measured at 20-min intervals over a 24-hr period in 49 adolescents with major depressive disorder (MDD) and 39 normal control adolescents. Neither the pattern nor the amount of prolactin secretion was significantly different between these two groups. There were significant gender differences, with girls secreting more prolactin than boys, but no significant gender-by-diagnosis interactions were found. With the possible exception of psychosis, dividing the MDD sample based on clinical characteristics failed to reveal differences. These findings are discussed in the context of changes in prolactin in childhood depression using a serotonergic challenge study, as well as in relation to baseline prolactin studies in adult depression.

Adolescent↗

PubMed1994

Cholinergic REM induction test with arecoline in depressed children.

Children with major depressive disorder often fail to exhibit electroencephalographic (EEG) sleep abnormalities similar to those reported in depressed adults. It was hypothesized that a cholinergic rapid eye movement (REM) induction test would contribute to the identification of EEG sleep abnormalities in depressed children. To test this hypothesis, prepubertal children meeting research diagnostic criteria for major depressive disorder (n = 33) and carefully screened healthy control children (n = 15) were enrolled in a 4-day psychobiologic protocol that included 1 night with infusion of arecoline (0.5 mg) during the first non-REM sleep period. Although there had been no significant group differences in baseline sleep measures, results on the arecoline night revealed significantly shorter REM latency in the group of depressed children compared with the control children (mean +/- SD = 105 +/- 51 minutes vs. 140 +/- 46 minutes). The design of the protocol (with an interval break immediately preceding the arecoline night) prevented a direct estimation of arecoline effects within subjects; however, these data provide promising preliminary results regarding cholinergic REM induction tests in childhood depression.

Aging↗

PubMed1994

Cellular immunity in depressed, conduct disorder, and normal adolescents: role of adverse life events.

OBJECTIVE: To determine whether adolescents with major depressive disorder have disturbances in their cellular immunity and to study whether the immunological changes detected are specific to depression or are general responses to stress. METHOD: Twenty subjects with major depressive disorder, 17 nondepressed subjects with conduct disorder, and 17 normal adolescents were recruited. Subjects were assessed with a clinical interview for DSM-III-R and a modified version of the Coddington Life Events Checklist. Blood samples were drawn for total white blood cells, lymphocytes subsets, natural killer cell activity, lymphocyte proliferation response to phytohemagglutinin, and cortisol plasma levels. RESULTS: Overall, there were no significant between-group differences in any of the cellular immune measurements. Natural killer cell activity was significantly negatively correlated with past year and lifetime adverse life events across all effector-target cell ratios. Controlling for diagnoses and socioeconomic status yielded similar results. There were no significant effects of age, sex, race, sleep, nutrition, cigarette use, menstrual cycle, or cortisol on any of the immunological variables. CONCLUSIONS: In this sample of adolescents, we found that independent of the diagnoses and socioeconomic status, increases in adverse life events were associated with low natural killer cell activity.

Adolescent↗

PubMed1994

Fluoxetine for childhood anxiety disorders.

OBJECTIVE: The objective of this open study was to determine the efficacy and safety of fluoxetine for the treatment of children and adolescents with anxiety disorders. METHOD: Twenty-one patients with overanxious disorders, social phobia, or separation anxiety disorder, who were unresponsive to previous psychopharmacological and psychotherapeutic interventions, were treated openly with fluoxetine for up to 10 months. Patients with lifetime histories of obsessive-compulsive disorder (OCD) or panic disorder, or with current major depression, were excluded. Beneficial and adverse effects of fluoxetine were ascertained using the improvement and severity subscales of the Clinical Global Impression Scale (CGIS) in two ways: (1) independent chart reviews by two child psychiatrists and (2) prospective assessments by the treating nurses and the patients' mothers. RESULTS: Eighty-one percent (n = 17) of patients showed moderate to marked improvement in anxiety symptoms. The severity of anxiety as measured by the CGIS was also significantly reduced from marked to mild (effect size: 2.3). There were no significant side effects. CONCLUSIONS: These results suggest that fluoxetine may be an effective and safe treatment for nondepressed children and adolescents with anxiety disorders other than OCD and panic disorder. Future investigations using double-blind, placebo-controlled methodologies are warranted.

Adolescent↗

PubMed1992

The dexamethasone suppression test in children and adolescents: a review and a controlled study.

Dexamethasone Suppression Test (DST) studies conducted in children and adolescents are reviewed, together with factors hypothesized to explain discrepancies in rates of DST nonsuppression across studies. These factors are then examined in a controlled study of 27 adolescents with major depressive disorder (MDD) and 34 normal controls (NC). Subjects were given 1 mg of dexamethasone at 11:00 PM, and the following day serum samples for cortisol were collected each hr from 8 AM to 11 PM through an indwelling catheter. There were no significant differences found between the MDD and NC subjects on any postdexamethasone cortisol measure. Further, cortisol suppressors and nonsuppressors were not distinguished by any of the hypothesized factors identified from the review, including inpatient status, presence of suicidality, endogenous features, psychotic symptoms, or prior history of MDD. Questions about the appropriateness of the 1 mg dose of dexamethasone (currently the standard dose used with adolescents) are raised, together with a discussion of the effects of stress on DST findings.

Adolescent↗