Biomedical subjects

Boris Birmaher

Publications and source records attributed to Boris Birmaher.

At least 19 recordsLinked to original sources

PubMed2025

Psychiatric Polygenic Risk Scores and Week-by-Week Symptomatic Status in Youth with Bipolar Disorder: An Exploratory Study.

Introduction: Prior studies have demonstrated that, in both adults and youth, bipolar disorder (BD) is a polygenic illness. However, no studies have examined polygenic risk scores (PRSs) in relation to the longitudinal course of mood symptoms in youth with BD. Methods: This study included 246 youth of European ancestry with BD (7-20 years old at intake) from the Course and Outcome of Bipolar Youth study and Centre for Youth Bipolar Disorder. Mood symptom severity was assessed at intake and, for 168 participants, prospectively for a median of 8.7 years. PRSs for BD, schizophrenia (SCZ), major depressive disorder (MDD), and attention-deficit/hyperactivity disorder (ADHD) were constructed using genome-wide summary statistics from independent adult cohorts. Results: Higher BD-PRS was significantly associated with lower most severe lifetime depression score at intake (β = -0.14, p = 0.03). Higher SCZ-PRS and MDD-PRS were associated with significantly less time spent in euthymia (SCZ-PRS: β = -0.21, p = 0.02; MDD-PRS: β = -0.22, p = 0.01) and more time with any subsyndromal mood symptoms (i.e., any mania, mixed, or depression symptoms; SCZ-PRS: β = 0.15, p = 0.04; MDD-PRS: β = 0.17, p = 0.01) during follow-up. PRSs for BD and ADHD were not significantly associated with any longitudinal mood variable. Conclusions: This exploratory analysis was the first to examine psychiatric PRSs in relation to the prospective course of mood symptoms among youth with BD. Results from the current study can serve to guide future youth BD studies with larger sample sizes on this topic.

Humans↗

PubMed2007

The Adolescent Depression Rating Scale (ADRS): a validation study.

BACKGROUND: To examine the psychometric properties of the Adolescent Depression Rating Scale (ADRS), a new measure was specifically designed to evaluate adolescent depression. METHODS: The 11-item clinician-report and 44-item self-report versions of the ADRS were developed from a qualitative phase involving interviews of experts and adolescents. These two instruments were then administered to 402 French speaking adolescents with and without depressive disorders. Item distribution, internal consistency, convergent validity, discriminant validity and factorial structure were assessed. RESULTS: After reduction procedures, a 10-item clinician version and a 10-item self-report version were obtained. The ADRS demonstrated good internal consistency (alpha Cronbach coefficient >.70). It also discriminated better between adolescents with and without depression than the Hamilton Depressive Rating Scale and the Beck Depression Inventory (BDI-13). CONCLUSION: The ADRS is a useful, short, clinician-report and self-report scale to evaluate adolescent depression. Further studies to replicate our findings and evaluate ADRS sensitivity to effects of treatment and psychometric properties in populations of adolescents with several psychiatric disorders are warranted.

Adolescent↗

PubMed2006

Psychopharmacologic treatment of pediatric major depressive disorder.

RATIONALE: The role of pharmacotherapy in the treatment of major depressive disorder (MDD) in youth has received much attention in recent years due to concerns of efficacy and safety of the antidepressants for the treatment of MDD in youth. OBJECTIVES: This review describes the existing published and unpublished literature regarding the efficacy and short-term safety of the antidepressants and decision-making process required for the use of these medications for youth with MDD. In addition, current continuation and maintenance treatments are discussed. RESULTS: In general, nine depressed youth must be treated with an antidepressant to obtain one clinical response above that achieved with placebo. To date, fluoxetine has showed the most consistent positive treatment effects. Depressed youth had also acutely responded to other antidepressants, but the response to placebo has also been high. Overall, the antidepressants are well tolerated, but 1-3 children and adolescents of 100 taking antidepressants showed onset or worsening of suicidal ideation and, more rarely, suicide attempts. CONCLUSIONS: There is a positive risk-benefit ratio for the use of antidepressants in the acute treatment of depressed youth. First-line antidepressant treatment with-or without-specific types of psychotherapy is indicated for youth with MDD of at least moderate severity. All youth taking antidepressants must be closely monitored for suicidality and medication side effects. Many youth will likely require psychotherapy or additional medication treatments to address comorbid disorders. Treatments to prevent relapses and recurrences require further study.

Adolescent↗

PubMed2006

Psychotic symptoms in pediatric bipolar disorder and family history of psychiatric illness.

BACKGROUND: Few studies have examined the specificity and non-specificity in patterns of familial loading for presentation of psychotic symptoms in pediatric bipolar disorder (BP). METHODS: Diagnostic assessment of 263 pediatric BP probands included lifetime history of psychotic symptoms as well as longitudinal follow-up; family history of psychiatric illness was determined for 1st degree relatives. RESULTS: Pediatric BP probands with lifetime history of psychosis had a higher percentage of positive family history of anxiety disorders and suicide attempts as compared to probands with no history of psychosis. DISCUSSION: Familial loading for a spectrum of internalizing disorders is associated with presentation of psychotic symptoms in pediatric BP.

Adolescent↗

PubMed2006

Effectiveness of cognitive-behavioral therapy for adolescent depression: a benchmarking investigation.

In this study, we examined the effectiveness of cognitive-behavioral therapy (CBT) for adolescent depression. Outcomes of 80 youth treated with CBT in an outpatient depression specialty clinic, the Services for Teens at Risk Center (STAR), were compared to a "gold standard" CBT research benchmark. On average, youths treated with CBT in STAR experienced significantly slower symptom improvement than youths in the CBT benchmark. However, outcomes for STAR teens were more similar to the research benchmark when accounting for differences in referral source (clinical versus advertisement) between the datasets. Results support further efforts to test the effectiveness of CBT in clinically representative community practice settings and samples.

Adult↗

PubMed2006

Phenomenology of children and adolescents with bipolar spectrum disorders.

CONTEXT: Children and adolescents who present with manic symptoms frequently do not meet the full DSM-IV criteria for bipolar I disorder (BP-I). OBJECTIVE: To assess the clinical presentation and family history of children and adolescents with BP-I, bipolar II disorder (BP-II), and bipolar disorder not otherwise specified (BP-NOS). DESIGN: Subjects and their primary caretaker were assessed by semistructured interview, and family psychiatric history was obtained from interview of the primary caretaker. SETTING: Outpatient and inpatient units at 3 university centers. PARTICIPANTS: A total of 438 children and adolescents (mean +/- SD age, 12.7 +/- 3.2 years) with BP-I (n = 255), BP-II (n = 30), or BP-NOS (n = 153). MAIN OUTCOME MEASURES: Lifetime psychiatric history and family history of psychiatric disorders. RESULTS: Youth with BP-NOS were not diagnosed as having BP-I primarily because they did not meet the DSM-IV duration criteria for a manic or mixed episode. There were no significant differences among the BP-I and BP-NOS groups in age of onset, duration of illness, lifetime rates of comorbid diagnoses, suicidal ideation and major depression, family history, and the types of manic symptoms that were present during the most serious lifetime episode. Compared with youth with BP-NOS, subjects with BP-I had more severe manic symptoms, greater overall functional impairment, and higher rates of hospitalization, psychosis, and suicide attempts. Elevated mood was present in 81.9% of subjects with BP-NOS and 91.8% of subjects with BP-I. Subjects with BP-II had higher rates of comorbid anxiety disorders compared with the other 2 groups and had less functional impairment and lower rates of psychiatric hospitalization than the subjects with BP-I. CONCLUSIONS: Children and adolescents with BP-II and BP-NOS have a phenotype that is on a continuum with that of youth with BP-I. Elevated mood is a common feature of youth with BP-spectrum illness.

Adolescent↗

PubMed2006

Clinical course of children and adolescents with bipolar spectrum disorders.

CONTEXT: Despite the high morbidity associated with bipolar disorder (BP), few studies have prospectively studied the course of this illness in youth. OBJECTIVE: To assess the longitudinal course of BP spectrum disorders (BP-I, BP-II, and not otherwise specified [BP-NOS]) in children and adolescents. DESIGN: Subjects were interviewed, on average, every 9 months for an average of 2 years using the Longitudinal Interval Follow-up Evaluation. SETTING: Outpatient and inpatient units at 3 university centers. PARTICIPANTS: Two hundred sixty-three children and adolescents (mean age, 13 years) with BP-I (n = 152), BP-II (n = 19), and BP-NOS (n = 92). MAIN OUTCOME MEASURES: Rates of recovery and recurrence, weeks with syndromal or subsyndromal mood symptoms, changes in symptoms and polarity, and predictors of outcome. RESULTS: Approximately 70% of subjects with BP recovered from their index episode, and 50% had at least 1 syndromal recurrence, particularly depressive episodes. Analyses of weekly mood symptoms showed that 60% of the follow-up time, subjects had syndromal or subsyndromal symptoms with numerous changes in symptoms and shifts of polarity, and 3% of the time, psychosis. Twenty percent of BP-II subjects converted to BP-I, and 25% of BP-NOS subjects converted to BP-I or BP-II. Early-onset BP, BP-NOS, long duration of mood symptoms, low socioeconomic status, and psychosis were associated with poorer outcomes and rapid mood changes. Secondary analyses comparing BP-I youths with BP-I adults showed that youths significantly more time symptomatic and had more mixed/cycling episodes, mood symptom changes, and polarity switches. CONCLUSIONS: Youths with BP spectrum disorders showed a continuum of BP symptom severity from subsyndromal to full syndromal with frequent mood fluctuations. Results of this study provide preliminary validation for BP-NOS.

Adolescent↗

PubMed2006

MRI study of thalamus volumes in juvenile patients with bipolar disorder.

In vivo imaging studies suggest functional abnormalities of the thalamus in adult patients with bipolar disorder, but the presence of anatomical abnormalities is controversial. Our objective in this study was to compare the thalamus volumes of children and adolescents with bipolar disorder versus healthy controls to determine whether any morphological abnormalities exist early in illness course. We studied 16 patients with bipolar disorder according to DSM-IV criteria (mean age+/-SD=15.5+/-3.4 years) and 21 healthy control subjects (mean age+/-SD=16.9+/-3.8 years). Blinded examiners measured thalamic gray matter volumes with a semiautomated technique. Analysis of covariance, with age, gender, and intracranial brain volume as covariates, revealed no significant differences in left and right thalamic volumes between patients with bipolar disorder and healthy controls. Our findings indicate there are no significant differences in thalamus size between children and adolescents with bipolar disorder and healthy comparison subjects, in contrast to available findings for schizophrenia and first-break psychosis. Any differences in thalamus size that may exist between patients with bipolar disorder and healthy controls must amount to small effect sizes.

Adolescent↗

PubMed2006

Treatment-resistant depression in adolescents: recognition and management.

Approximately 20% of adolescents experience at least one depressive episode by the time they enter their adult years. For most adolescents, depression, although serious, either remits spontaneously or responds to treatment. For a smaller but significant proportion of adolescents, however, depression can be long-lasting and relatively unresponsive to initial treatment. In this article the authors provide an operational definition of treatment-resistant depression, identify factors associated with treatment nonresponse, describe an approach to the management of treatment-resistant depression, and advance suggestions for promising avenues of research.

Adolescent↗

PubMed2006

Course and outcome of bipolar spectrum disorder in children and adolescents: a review of the existing literature.

The longitudinal course of children and adolescents with bipolar disorder (BP) is manifested by frequent changes in symptom polarity with a fluctuating course showing a dimensional continuum of bipolar symptom severity from subsyndromal to mood syndromes meeting full Diagnostic and Statistical Manual of Mental Disorders criteria. These rapid fluctuations in mood appear to be more accentuated than in adults with BP, and combined with the high rate of comorbid disorders and the child's cognitive and emotional developmental stage, may explain the difficulties encountered diagnosing and treating BP youth. Children and adolescents with early-onset, low socioeconomic status, subsyndromal mood symptoms, long duration of illness, rapid mood fluctuation, mixed presentations, psychosis, comorbid disorders, and family psychopathology appear to have worse longitudinal outcome. BP in children and adolescents is associated with high rates of hospitalizations, psychosis, suicidal behaviors, substance abuse, family and legal problems, as well as poor psychosocial functioning. These factors, in addition to the enduring and rapid changeability of symptoms of this illness from very early in life, and at crucial stages in their lives, deprive BP children of the opportunity for normal psychosocial development. Thus, early recognition and treatment of BP in children and adolescents is of utmost importance.

Adolescent↗

PubMed2006

Child mania rating scale: development, reliability, and validity.

OBJECTIVE: To develop a reliable and valid parent-report screening instrument for mania, based on DSM-IVsymptoms. METHOD: A 21-item Child Mania Rating Scale-Parent version (CMRS-P) was completed by parents of 150 children (42.3% female) ages 10.3 +/- 2.9 years (healthy controls = 50; bipolar disorder = 50; attention-deficit/hyperactivity disorder [ADHD] = 50). The Washington University Schedule for Affective Disorders and Schizophrenia was used to determine DSM-IV diagnosis. The Young Mania Rating Scale, Schedule for Affective Disorders and Schizophrenia Mania Rating Scale, Child Behavior Checklist, and Child Depression Inventory were completed to estimate the construct validity of the measure. RESULTS: Exploratory and confirmatory factor analysis of the CMRS-P indicated that the scale was unidimensional. The internal consistency and retest reliability were both 0.96. Convergence of the CMRS-P with the Washington University Schedule for Affective Disorders and Schizophrenia mania module, the Schedule for Affective Disorders and Schizophrenia Mania Rating Scale, and the Young Mania Rating Scale was excellent (.78-.83). The scale did not correlate as strongly with the Conners parent-rated ADHD scale, the Child Behavior Checklist -Attention Problems and Aggressive Behavior subscales, or the child self-report Child Depression Inventory (.29-.51). Criterion validity was demonstrated in analysis of receiver operating characteristics curves, which showed excellent sensitivity and specificity in differentiating children with mania from either healthy controls or children with ADHD (areas under the curve of.91 to.96). CONCLUSION: The CMRS-P is a promising parent-report scale that can be used in screening for pediatric mania.

Adolescent↗

PubMed2006

Child comorbidity, maternal mood disorder, and perceptions of family functioning among bipolar youth.

OBJECTIVE: To examine the association between youth comorbid psychiatric disorders, maternal mood disorder, and perceptions of family cohesion and conflict among youth diagnosed with pediatric bipolar disorder (PBD). METHOD: Three hundred eighty-nine bipolar youths and their parents completed a diagnostic interview and instruments assessing family psychiatric history and functioning. Family functioning was assessed with the Family Adaptability and Cohesion Scales-II and the Conflict Behavior Questionnaire. RESULTS: The presence of a maternal mood disorder was associated with lower family cohesion. The presence of a youth externalizing disorder with or without a co-occurring anxiety disorder was also associated with lower family cohesion as well as higher family conflict. Furthermore, the negative relationship between maternal mood disorder and family functioning was stronger in the presence of a youth externalizing disorder. CONCLUSIONS: Youth comorbidity and maternal mood disorders appear to be associated with worse family functioning among bipolar youths. Family-based treatments with bipolar youths may need to integrate treatment of youth comorbidity and address maternal mood disorder for optimal results.

Adolescent↗

PubMed2006

Steady-state clinical pharmacokinetics of bupropion extended-release in youths.

OBJECTIVE: To examine in children and adolescents the 24-hour, steady-state clinical pharmacokinetics of an extended-release (XL) formulation of bupropion (Wellbutrin XL). METHOD: Subjects were six male and four female patients (ages 11.5-16.2 years) prescribed bupropion XL in morning daily doses of either 150 mg (n = 5) or 300 mg (n = 5) for at least 14 days. During an overnight hospitalization, subjects had serial blood draws every 1.5 to 3 hours from an intravenous port to measure plasma levels of bupropion and its metabolites. Pharmacokinetic variables were determined by noncompartmental analysis for bupropion and exponential analyses for metabolites. RESULTS: Bupropion and metabolites demonstrated linear pharmacokinetics. Bupropion's mean maximum concentration (Cmax) was lower (p = .021) and its mean time to Cmax longer (p = .057) in the current sample on bupropion XL relative to a previously studied sample of youths on bupropion sustained-release (Wellbutrin SR). Mean 24-hour area under the curve ratios of metabolites to bupropion ranged from 1.0 for erythrohydrobupropion to 16.4 for hydroxybupropion. CONCLUSIONS: Once-daily dosing is justified in youths prescribed bupropion XL. The active metabolite hydroxybupropion probably has key pharmacodynamic effects, given its higher and more sustained levels relative to the other metabolites or to bupropion.

Adolescent↗

PubMed2006

Acute antidepressant response and plasma levels of bupropion and metabolites in a pediatric-aged sample: an exploratory study.

Studies examining associations between antidepressant response and plasma levels of bupropion and its metabolites have yielded contradictory findings. There have been no such studies in youth. This study explored such associations in 8 boys and 8 girls, age 11 to 17 years, all prescribed bupropion sustained release (SR) for major depression (n = 6) or depressive disorder not otherwise specified (n = 10) as part of a pharmacokinetic (PK) study. All were started on morning doses of bupropion SR of 100 mg/day, and most eventually had doses increased to 200 mg/day because of inadequate clinical response. After taking prescribed dose of bupropion SR at least 14 days (median = 21 days), subjects had steady-state serial plasma levels of bupropion and its metabolites measured during a 24-hour period after morning doses. A total of 9 subjects underwent these PK assessments on doses of 100 mg/day, and 6 underwent these on doses of 200 mg/day, with 4 studied on both doses. In this 24-hour assessment, the treating psychiatrist rated subjects' antidepressant response using the Clinical Global Impression's Improvement scale (CGI-I), blind to plasma levels, but informed by child and parent rating scales of depressive symptoms and clinical interviews. Relative to 7 nonresponders, 9 responders (CGI-I < or = 2) had significantly higher mean areas under concentration curves for bupropion (P = 0.03), threohydrobupropion (P = 0.02), and erythrohydrobupropion (P = 0.02), and especially hyroxybupropion (P = 0.006). Plasma levels 7.5 hours after morning doses reaching the following cut points discriminated responders from nonresponders: bupropion > or = 37 ng/mL (P = 0.001), hydroxybupropion > or = 575 ng/mL (P = 0.003), threohydrobupropion > or = 240 ng/mL (P = 0.009), or erythrohydrobupropion > or = 45 ng/mL (P = 0.009). These preliminary findings suggest that plasma levels of bupropion and metabolites, particularly hydroxybupropion, may predict acute antidepressant response in depressed youths taking bupropion SR.

Administration, Oral↗

PubMed2006

Pediatric bipolar disease: current and future perspectives for study of its long-term course and treatment.

AIM AND METHODS: Findings from recent long-term, prospective longitudinal studies of the course, outcome and naturalistic treatment of adults with bipolar illness are highlighted as background for long-term developmental study of pediatric bipolar illness. RESULTS: Accumulating knowledge of bipolar illness in adults underscores a high risk for multiple recurrences through the lifespan, significant medical morbidity, high rates of self-harm, economic and social burden and frequent treatment resistance with residual symptoms between major episodes. At present, there is no empirical foundation to support any assumption about the long-term course or outcome of bipolar illness when it arises in childhood or adolescence, or the effects of conventional pharmacotherapies in altering its course and limiting potentially adverse outcomes. The proposed research articulates specific descriptive aims that draw on adult findings and outlines core methodological requirements for such an endeavor. CONCLUSIONS: Innovations in the description and quantitative analysis of prospective longitudinal clinical data must now be extended to large, systematically ascertained pediatric cohorts recruited through multicenter studies if there is to be a meaningful scientific advance in our knowledge of the enduring effects of bipolar illness and the potential value of contemporary approaches to its management.

Age of Onset↗

PubMed2006

Processing emotional facial expressions influences performance on a Go/NoGo task in pediatric anxiety and depression.

BACKGROUND: This study investigated whether processing emotionally salient information such as emotional facial expressions influences the performance on a cognitive control task in pediatric anxiety and depression. METHODS: The sample included 68 participants between 8 and 16 years of age selected into three diagnostic groups: Anxiety Disorder (ANX, n = 23), Major Depressive Disorder (MDD, n = 19), and Low-Risk Normal Control (LRNC, n = 26). Participants completed an Emotional Go/NoGo task in which participants must either respond to (Go trials) or not respond to (NoGo trials) specific facial expressions (angry, fearful, sad, happy, neutral). In order to manipulate the level of cognitive control needed to perform the task, the probability of occurrence of the Go trials was varied across 3 probability conditions (low, moderate, high). RESULTS: Analyses showed that the MDD group had significantly faster reaction times to sad face Go trials embedded in neutral face NoGo trials in the moderate probability condition and that the ANX group had significantly slower reaction times to neutral face Go trials embedded in angry face NoGo trials in the low probability condition. CONCLUSIONS: These data demonstrate that processing emotional facial expressions influences the performance on a cognitive control task in children and adolescents diagnosed with an anxiety disorder and major depression.

Adolescent↗

PubMed2006

Criterion validity of the Mood and Feelings Questionnaire for depressive episodes in clinic and non-clinic subjects.

BACKGROUND: Previous measures of pediatric depression have shown inconsistent validity in groups with differing demographics, comorbid diagnoses, and clinic or non-clinic origins. The current study re-examines the criterion validity of child- and parent-versions of the Mood and Feelings Questionnaire (MFQ-C, MFQ-P) in a heterogeneous sample of children and adolescents from clinic and non-clinic sources. METHODS: Among 470 consecutive youth completing semi-structured interviews at a university-based child psychiatry center, total scores from the 33-item MFQ-C and 34-item MFQ-P were examined across subjects with and without mood disorders using analysis of variance, and receiver operating characteristics analysis. RESULTS: Mean scores of the MFQ-C and MFQ-P, respectively, differed significantly (p < .0005) across youth having major depressive episodes (MDE) (33 and 32, n = 77), mood disorders not meeting criteria for current MDE (24 and 28, n = 75), and no mood disorders (12 and 10, n = 318). In the overall sample, areas under the curve (AUC) for discriminating MDE and any mood disorder, respectively, were .85 and .83 on the MFQ-C, .86 and .90 on the MFQ-P, and .89 and .90 on the MFQ-C and MFQ-P averaged together, suggesting moderate to high criterion validity. Similar findings were noted in subgroups divided by age, sex, race, comorbid psychopathology, and clinic or non-clinic origins. AUCs of these MFQ scores compared favorably with those of the Beck's Depressive Inventory, the Child Behavior Checklist's Anxious/Depressed scale and the Children's Depressive Rating Scale-Revised by the same raters. A score of 29 on the MFQ-C (positive screen rate 21%, sensitivity 68%, specificity 88%) or 27 on the MFQ-P (positive screen rate 23%, sensitivity 61%, specificity 85%) optimally discriminated youth with MDE from the rest of the sample. CONCLUSIONS: The MFQ-C and MFQ-P, especially used in combination, validly identify MDE or other mood disorders in youth diverse in demographic and clinical characteristics.

Adolescent↗

PubMed2006

Increased error-related negativity (ERN) in childhood anxiety disorders: ERP and source localization.

BACKGROUND: In this study we used event-related potentials (ERPs) and source localization analyses to track the time course of neural activity underlying response monitoring in children diagnosed with an anxiety disorder compared to age-matched low-risk normal controls. METHODS: High-density ERPs were examined following errors on a flanker task from 12 children between 8 and 14 years old diagnosed with an anxiety disorder (ANX) and 13 age-matched low-risk normal controls (LRNC). RESULTS: Children diagnosed with an anxiety disorder had increased error-related negativity (ERN) amplitude. The neural generators of the ERN in the ANX group were estimated to be localized in the anterior cingulate cortex (ACC). There were no significant group differences in P(E) amplitude. CONCLUSIONS: These data provide evidence for increased ERN amplitude localized to the ACC in children diagnosed with an anxiety disorder, suggesting altered maturational patterns of the ACC circuitry early in the course of this illness.

Adolescent↗