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Boris Birmaher

Publications and source records attributed to Boris Birmaher.

At least 37 records · Page 2Linked to original sources
PubMed2006

Reward-related decision-making in pediatric major depressive disorder: an fMRI study.

BACKGROUND: Although reward processing is considered an important part of affective functioning, few studies have investigated reward-related decisions or responses in young people with affective disorders. Depression is postulated to involve decreased activity in reward-related affective systems. METHODS: Using functional magnetic resonance imaging (fMRI), we examined behavioral and neural responses to reward in young people with depressive disorders using a reward decision-making task. The task involved choices about possible rewards involving varying magnitude and probability of reward. The study design allowed the separation of decision/anticipation and outcome phases of reward processing. Participants were 9-17 years old and had diagnoses of major depressive disorder (MDD), anxiety disorders, or no history of psychiatric disorder. RESULTS: Participants with MDD exhibited less neural response than control participants in reward-related brain areas during both phases of the task. Group differences did not appear to be a function of anxiety. Depressive and anxiety symptoms were associated with activation in reward-related brain areas. CONCLUSIONS: Results suggest that depression involves altered reward processing and underscore the need for further investigation of relations among development, affective disorders, and reward processing.

Adolescent↗
PubMed2006

[Depression in children and adolescents].

Early onset depression is a widely prevalent, recurrent and familial disorder with a tendency to continue throughout adulthood. It is often accompanied by other comorbidities such as substance abuse, bipolar disorder, suicidal behavior and significant impairment in the child's psychosocial development. The risk factors include genetic, psychological and environmental factors and gene-environment interaction. The evidence-based therapies include cognitive, inter-personal and pharmacological interventions. Recently, the FDA published a warning concerning the use of these pharmacological agents in the pediatric age group. Further research is needed to assess the efficacy and safety of these interventions and to better understand the etiological factors.

Adolescent↗
PubMed2005

MRI study of corpus callosum in children and adolescents with bipolar disorder.

This structural magnetic resonance imaging study examined the length, areas, and circularity of the corpus callosum (CC) in 16 children and adolescents with bipolar disorder and 21 healthy controls. Bipolar disorder patients had lower circularity of the CC splenium compared with healthy controls. No significant differences in CC length or area were observed, suggesting that reported CC abnormalities appear late in the course of bipolar disorder.

Adolescent↗
PubMed2005

Peri-sleep-onset cortisol levels in children and adolescents with affective disorders.

BACKGROUND: Changes in the hypothalamic-pituitary-adrenal (HPA) axis, as evidenced by patterns of cortisol secretion, have been of interest in understanding depression and anxiety disorders across the life span. Previous studies of pediatric depression have pointed to the period around sleep onset as a key time point for observing alterations in cortisol secretion associated with affective disorders. Evidence also indicates that pubertal development may influence the expression of HPA dysregulation. We hypothesized that adolescents with depression and youth with anxiety disorders exhibit elevated peri-sleep-onset cortisol. METHODS: Plasma cortisol was sampled every 20 min around sleep onset from children and adolescents with major depressive disorder (n = 116), anxiety disorders (n = 32), or no history of psychiatric disorder (control; n = 76). Sleep onset was determined by polysomnography. Classification of participants as children or adolescents was based on Tanner staging of pubertal maturation. RESULTS: Children with anxiety disorders had higher peri-sleep-onset cortisol than children with depression or control children. Adolescents with depression had marginally higher peri-sleep-onset cortisol than control adolescents and significantly higher peri-sleep-onset cortisol than children with depression. CONCLUSIONS: Depression and anxiety are associated with altered cortisol secretion around sleep onset, and these changes appear to be influenced by pubertal maturation.

Adolescent↗
PubMed2005

Acute phase and five-year follow-up study of fluoxetine in adolescents with major depression and a comorbid substance use disorder: a review.

This paper reviews the results of an acute phase trial and a five-year follow-up study of fluoxetine in adolescents with major depression and a substance use disorder (SUD). This study included a 12-week open label acute phase study of 13 comorbid adolescents, followed by comprehensive assessments conducted 1, 3, and 5 years after entry into an acute phase fluoxetine trial. The results of the acute phase study and of the 1, 3, and 5-year follow-up assessments have already been published in four papers. The current paper was designed to cover the results of the study across the entire 5-year time spectrum of the study, and to summarize the clinical results across that entire time period. The data from this pilot study suggest that the long-term (5-year) clinical course for the Alcohol Dependence, Cannabis Dependence, and academic functioning of comorbid adolescents following acute phase treatment with SSRIs is generally good. However, the long-term clinical course for the Major Depression of that comorbid adolescent population is surprisingly poor.

Adolescent↗
PubMed2005

Subgenual prefrontal cortex of child and adolescent bipolar patients: a morphometric magnetic resonance imaging study.

The subgenual prefrontal cortex (SGPFC) plays an important role in emotional processing. We carried out a magnetic resonance imaging (MRI) study comparing the volume of the SGPFC in child and adolescent bipolar patients and healthy controls. The sample consisted of 15 children and adolescents who met DSM-IV criteria for bipolar disorder (mean age +/- S.D.=15.5 +/- 3.5 years) and 21 healthy adolescents (mean age +/- S.D.=16.9 +/- 3.8 years). MR images were obtained with a 1.5 T GE Signa Imaging System with Signa 5.4.3 software. SGPFC volumes were measured with the semi-automated software MedX (Sensor Systems, Sterling, VA, USA). ANCOVA was performed to compare SGPFC volumes between groups, using age, gender and intra-cranial volume (ICV) as covariates. The volumes (mean +/- S.D.) of the right and left SGPFC for bipolar patients were 291.27 +/- 88.70 mm(3) and 284.86 +/- 83.98 mm(3), respectively. For healthy controls, the right and left SGPFC volumes were 284.95 +/- 73.33 mm(3) and 307.55 +/- 73.67 mm(3), respectively. There were no statistically significant differences between groups regarding right or left SGPFC volumes. We found no evidence of volumetric abnormalities in the SGPFC of bipolar children and adolescents.

Adolescent↗
PubMed2005

Altered emotional processing in pediatric anxiety, depression, and comorbid anxiety-depression.

The goal of this study was to examine some of the mechanisms underlying emotion regulation in childhood affective disorders by examining the impact of distracting emotional information during performance on a working memory task ("Emotional n-back" or E-n-back). The sample included 75 children (38 girls and 37 boys) between 8 and 16 years of age meeting criteria for: Anxiety disorder (ANX, n = 17), Major depressive disorder (MDD, n = 16), Comorbid anxiety and depression (CAD, n = 24), or Low-risk normal control (LRNC, n = 18). Results showed that the MDD and CAD groups had significantly longer reaction times on negative emotional backgrounds compared to neutral backgrounds, whereas the LRNC group had significantly longer reaction times on positive backgrounds. These results suggest altered processing of emotional information particularly associated with depression. Because the E-n-back task engages higher-order cognitive processes, these results suggest that these alterations in processing emotional information also interfere with the cognitive processes that govern how attentional resources are allocated. Further, research is needed to replicate this study and delineate underlying neural mechanisms.

Adolescent↗
PubMed2005

The risks and benefits of antidepressant treatment for youth depression.

The U.S. Food and Drug Administration (FDA) has mandated that all antidepressants carry a 'black box' warning label indicating that antidepressants increase the risk of suicidality in youth taking these medications. In the U.K., the Medicine and Healthcare Products Regulatory Agency (MHRA) has determined that the balance of risks and benefits favors only the use of fluoxetine in the treatment of depressive illness in children and adolescents. This article reviews the FDA's analysis linking antidepressant medication use and pediatric suicidality in major depressive disorder, discusses the efficacy of antidepressants in treating depression in children and adolescents, and offers suggestions to aid clinicians, patients, and families in making clinical decisions based on an accurate assessment of the benefits and risks of medication and psychosocial treatments for pediatric depression.

Adolescent↗
PubMed2005

Stressful life events in anxious and depressed children.

OBJECTIVE: The aim of this study was to examine the occurrence of stressful life events in anxious and depressed children. METHOD: Children (6-12 years of age) with an anxiety disorder (n = 20), depression (n = 45), and normal controls (n = 11) were assessed using the Life Events Record. Cortisol was assessed from plasma samples collected every 20 minutes from an indwelling catheter in the one and two hour window around sleep onset. RESULTS: Depressed children had significantly more events and events that were most likely independent of the child's behavior, compared to both the anxious and normal control children. Independent loss events were significantly more prevalent among the depressed children in the preceding year, compared to anxious children, with a trend toward more loss events compared to the normal controls. For both overall events and independent events, depressed females were significantly more likely to be exposed to stressful environments compared to anxious and normal control females. There were no effects of stress on cortisol secretion around sleep onset. CONCLUSIONS: The results of this study suggest that stressful life events are significantly more likely to occur in depressed children, particularly females, compared to anxious children, and that these events are predominantly characterized by independent events outside of the child's control. The results also suggest that loss events may be specific for depression in children. Interestingly, stress does not appear to impact the HPA axis in children, which is true for anxious, depressed, and normal control children. The temporal occurrence and severity, as well as the type of stressful life events as they relate to the onset and maintenance of anxiety and depression in children, need to be more fully explored.

Anxiety Disorders↗
PubMed2005

Treatment guidelines for children and adolescents with bipolar disorder.

Clinicians who treat children and adolescents with bipolar disorder desperately need current treatment guidelines. These guidelines were developed by expert consensus and a review of the extant literature about the diagnosis and treatment of pediatric bipolar disorders. The four sections of these guidelines include diagnosis, comorbidity, acute treatment, and maintenance treatment. These guidelines are not intended to serve as an absolute standard of medical or psychological care but rather to serve as clinically useful guidelines for evaluation and treatment that can be used in the care of children and adolescents with bipolar disorder. These guidelines are subject to change as our evidence base increases and practice patterns evolve.

Adolescent↗
PubMed2005

Steady-state pharmacokinetics of bupropion SR in juvenile patients.

OBJECTIVE: To examine the steady-state pharmacokinetic properties of bupropion sustained release (SR) and their potential developmental differences in youths. METHOD: Eleven boys and eight girls aged 11 to 17 years old were prescribed bupropion SR monotherapy for attention-deficit/hyperactivity disorder (n = 16) and/or depressive disorders (n = 16). Bupropion SR was given in morning doses of 100 mg/day (n = 11) or 200 mg/day (n = 8) for 14 days or less, with five subjects studied on both doses. All subjects had blood draws from an intravenous port every 1 to 3 hours for 24 hours after their usual morning doses. Pharmacokinetic variables were determined by noncompartmental and compartmental analyses for bupropion and metabolites, respectively. RESULTS: Bupropion and its metabolites exhibited linear pharmacokinetics. Areas under the concentration curves for the hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were 20, 12, and 2.7 times higher, respectively, than for bupropion. Relative to adults, the mean half-lives of bupropion (12.1 hours) and threohydrobupropion (26.3 hours) were significantly shorter, and areas under the concentration curve ratios of metabolites to bupropion were 19% to 80% higher. CONCLUSIONS: Youths metabolize bupropion SR faster to hydroxybupropion and other active metabolites than adults. Until the clinical importance of bupropion's metabolites is clarified, bupropion SR should be given in divided doses to youths, as the manufacturer recommends for adults taking higher doses.

Adolescent↗
PubMed2005

Pediatric bipolar disorder: a review of the past 10 years.

OBJECTIVE: To review the literature of the past decade covering the epidemiology, clinical characteristics, assessment, longitudinal course, biological and psychosocial correlates, and treatment and prevention of pediatric bipolar disorder (BD). METHOD: A computerized search for articles published during the past 10 years was made and selected studies are presented. RESULTS: Pediatric BD is increasingly recognized, and there are several prevailing views on core features of this disorder. The incidence and prevalence of the disorder and the associated comorbidities vary according to study setting and criteria used. This disorder is highly recurrent and accompanied by substantial psychiatric and psychosocial morbidity. Familial studies, including "top down" (offspring of parents with BD) and "bottom up" (relatives of youths with BD) studies indicate that pediatric BD is aggregated in families with adult or later-onset BD and suggest the existence of genetic predisposition. Greater understanding of the risk factors for early onset BD and recognition of the phenomenology of prodromal symptoms offers hope for early identification and prevention. Neuroimaging studies indicate frontotemporal and frontostriatal pathology, but none of these findings seems to be disorder specific. Combination pharmacotherapies appear promising, and the field awaits further short- and long-term randomized, placebo-controlled trials. Preliminary studies of various psychotherapies, including psychoeducation strategies tailored specifically for BD in youths, look encouraging. CONCLUSIONS: Considerable advances have been made in our knowledge of pediatric BD; however, differing viewpoints on the clinical presentation of BD in children are the rule. Phenomenological and longitudinal studies and biological validation using genetic, neurochemical, neurophysiological, and neuroimaging methods may strengthen our understanding of the phenocopy. Randomized, controlled treatment studies for the acute and maintenance treatment of BD disorder are warranted.

Adolescent↗
PubMed2005

Subjective sleep complaints in pediatric depression: a controlled study and comparison with EEG measures of sleep and waking.

OBJECTIVE: Children with major depressive disorder (MDD) often complain of sleep disturbances; however, polysomnographic studies have failed to find objective evidence of these disturbances. This article examines subjective sleep reports of children with MDD and healthy controls focusing on comparing subjective and objective sleep measures. METHOD: Fifty-one subjects with MDD and 42 healthy subjects, 8-17 years old, participated in a comprehensive psychobiologic study including three nights of EEG sleep recording. Each morning, subjects completed a post-sleep form subjectively rating their sleep, which was then compared with their polysomnographic studies. RESULTS: Depressed subjects reported significantly worse sleep on four scales: subjective sleep quality, perceived number of awakenings, estimated minutes awake, and perceived ease of waking. In contrast to these subjective complaints, objective EEG measures indicated no evidence of disturbed sleep in the depressed sample compared to controls. Furthermore, exploratory analyses focusing on the subset of depressed subjects with the greatest subjective sleep disturbance showed, paradoxically, significantly better sleep in terms of the number of EEG awakenings and objective disturbances. CONCLUSIONS: Despite clinical evidence of subjective sleep complaints in depressed children, our EEG measures showed little evidence to indicate an objective basis for these perceptions. These findings raise provocative questions regarding the nature of sleep complaints associated with early-onset depression.

Adolescent↗
PubMed2005

Fluoxetine for the treatment of childhood anxiety disorders: open-label, long-term extension to a controlled trial.

OBJECTIVE: To assess the efficacy of fluoxetine for the long-term treatment of children and adolescents with anxiety disorders, including generalized anxiety disorder, separation anxiety disorder, and/or social phobia. METHOD: Children and adolescents (7-17 years old) with anxiety disorders were studied in open treatment for 1 year after they completed a randomized, controlled trial (RCT) comparing fluoxetine and placebo. The follow-up phase assessments included clinician, parent, and child ratings with measures of global severity, global improvement, and anxiety symptoms. RESULTS: Subjects taking fluoxetine (n = 42) were compared with those taking no medication (n = 10) during follow-up on anxiety changes from the end of the RCT through the follow-up period. Statistical models included RCT assignment and follow-up psychological treatment. Excluded subjects took other medications (n = 4) or did not complete follow-up (n = 18). Compared with subjects taking no medication, subjects taking fluoxetine showed significantly superior follow-up outcomes on most measures, including clinician, parent, and child ratings. CONCLUSIONS: The results suggest that fluoxetine is clinically effective for the maintenance treatment of anxiety disorders in children and adolescents. A major limitation, however, was the lack of RCT methodology in the follow-up phase. RCTs are needed to determine the long-term risks and benefits of fluoxetine for this group.

Adolescent↗
PubMed2005

Developmental abnormalities in striatum in young bipolar patients: a preliminary study.

OBJECTIVES: Anatomical abnormalities in the basal ganglia of adult mood disorder patients have been reported. To investigate whether these abnormalities are present early in illness course, we compared the volume of striatal structures in young bipolar patients and healthy controls. METHODS: Brain magnetic resonance images of 15 children and adolescents who met DSM-IV criteria for bipolar disorders and 21 healthy controls were obtained. Measurements were performed manually, by trained evaluators, who were blind to subjects' diagnosis. The volumes of caudate and putamen were compared in patients and controls. RESULTS: The volumes of striatal structures were not significantly different in patients and controls (ANCOVA, p > 0.05). However, we found a significant inverse relationship between age and the volumes of left caudate (r = -0.72, p < 0.01), right caudate (r = -0.66, p = 0.02) and left putamen (r = -0.71, p = 0.01) in bipolar patients, not present in healthy controls. CONCLUSIONS: Abnormalities in striatal development may be involved in the pathophysiology of bipolar disorder.

Adolescent↗
PubMed2005

History of suicide attempts in pediatric bipolar disorder: factors associated with increased risk.

BACKGROUND: Despite evidence indicating high morbidity associated with pediatric bipolar disorder (BP), little is known about the prevalence and clinical correlates of suicidal behavior among this population. OBJECTIVE: To investigate the prevalence of suicidal behavior among children and adolescents with BP, and to compare subjects with a history of suicide attempt to those without on demographic, clinical, and familial risk factors. METHODS: Subjects were 405 children and adolescents aged 7-17 years, who fulfilled DSM-IV criteria for BPI (n = 236) or BPII (n = 29), or operationalized criteria for BP not otherwise specified (BP NOS; n = 140) via the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. As part of a multi-site longitudinal study of pediatric BP (Course and Outcome of Bipolar Youth), demographic, clinical, and family history variables were measured at intake via clinical interview with the subject and a parent/guardian. RESULTS: Nearly one-third of BP patients had a lifetime history of suicide attempt. Attempters, compared with non-attempters, were older, and more likely to have a lifetime history of mixed episodes, psychotic features, and BPI. Attempters were more likely to have a lifetime history of comorbid substance use disorder, panic disorder, non-suicidal self-injurious behavior, family history of suicide attempt, history of hospitalization, and history of physical and/or sexual abuse. Multivariate analysis found that the following were the most robust set of predictors for suicide attempt: mixed episodes, psychosis, hospitalization, self-injurious behavior, panic disorder, and substance use disorder. CONCLUSIONS: These findings indicate that children and adolescents with BP exhibit high rates of suicidal behavior, with more severe features of BP illness and comorbidity increasing the risk for suicide attempt. Multiple clinical factors emerged distinguishing suicide attempters from non-attempters. These clinical factors should be considered in both assessment and treatment of pediatric BP.

Adolescent↗
PubMed2005

Reduced NAA levels in the dorsolateral prefrontal cortex of young bipolar patients.

OBJECTIVE: Converging evidence implicates prefrontal circuits in the pathophysiology of bipolar disorder. Proton spectroscopy studies performed in adult bipolar patients assessing prefrontal regions have suggested decreased levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. In order to examine whether such abnormalities would also be found in younger patients, a 1H spectroscopy study was conducted that focused on the dorsolateral prefrontal cortex of children and adolescents with bipolar disorder. METHOD: The authors examined the levels of NAA, creatine plus phosphocreatine, and choline-containing molecules in the left dorsolateral prefrontal cortex of 14 bipolar disorder patients (mean age=15.5 years, SD=3, eight female) and 18 healthy comparison subjects (mean age=17.3, SD=3.7, seven female) using short echo time, single-voxel in vivo 1H spectroscopy. Absolute metabolite levels were determined using the water signal as an internal reference. RESULTS: Bipolar patients presented significantly lower NAA levels and a significant inverse correlation between choline-containing molecules and number of previous affective episodes. No differences were found for other metabolites. CONCLUSIONS: These findings suggest that young bipolar patients have decreased NAA levels in the dorsolateral prefrontal cortex, similar to what was previously reported in adult patients. Such changes may reflect an underdevelopment of dendritic arborizations and synaptic connections. These neuronal abnormalities in the dorsolateral prefrontal cortex of bipolar disorder youth are unlikely to represent long-term degenerative processes, at least in the subgroup of patients where the illness had relatively early onset.

Adolescent↗