Showing papers by "Benjamin I. Goldstein published in 2009"
TL;DR: Inflammation appears relevant to bipolar disorder across several important domains and further research is warranted to parse the reciprocal associations between inflammation and symptoms, comorbidities, and treatments in bipolar disorder.
Abstract: Objective To review extant literature implicating inflammation in the pathophysiology of bipolar disorder. Furthermore, we review evidence regarding the anti-inflammatory actions of mood-stabilizing medication, the putative reciprocal association of inflammation with behavioral parameters and medical burden in bipolar disorder, and the potential role of anti-inflammatory agents in the treatment of bipolar disorder. Data sources MEDLINE and PubMed searches were conducted of English-language articles published from 1950 to April 2008 using the search terms bipolar disorder, manic, or mania, cross-referenced with inflammation, inflammatory, interleukin, cytokine, C-reactive protein, or tumor necrosis factor. The search, which was conducted most recently on August 20, 2008, was supplemented by manually reviewing reference lists from the identified publications. Study selection Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality. Data extraction Studies were reviewed for statistical comparisons of cytokines among persons with and without bipolar disorder, during symptomatic and non-symptomatic intervals and before and after pharmacologic treatment. Significant and nonsignificant findings were tabulated. Data synthesis Available evidence indicates that bipolar disorder and inflammation are linked through shared genetic polymorphisms and gene expression as well as altered cytokine levels during symptomatic (i.e., mania and depression) and asymptomatic intervals. However, results are inconsistent. Several conventional mood stabilizers have anti-inflammatory properties. The cyclooxygenase-2-selective anti-inflammatory celecoxib may offer antidepressant effects. Inflammation is closely linked with behavioral parameters such as exercise, sleep, alcohol abuse, and smoking, as well as with medical comorbidities including coronary artery disease, obesity and insulin resistance, osteoporosis, and pain. Methodological limitations precluding definitive conclusions are heterogeneity in sample composition, cytokine assessment procedures, and treatment regimens. The inclusion of multiple ethnic groups introduces another source of variability but also increases the generalizability of study findings. Conclusion Inflammation appears relevant to bipolar disorder across several important domains. Further research is warranted to parse the reciprocal associations between inflammation and symptoms, comorbidities, and treatments in bipolar disorder. Studies of this topic among youth are needed and may best serve this purpose.
485 citations
TL;DR: Bipolar spectrum disorders in youths are characterized by episodic illness with subsyndromal and, less frequently, syndromal episodes with mainly depressive and mixed symptoms and rapid mood changes.
Abstract: Objective: The authors sought to assess the longitudinal course of youths with bipolar spectrum disorders over a 4-year period. Method: At total of 413 youths (ages 7–17 years) with bipolar I disorder (N=244), bipolar II disorder (N=28), and bipolar disorder not otherwise specified (N=141) were enrolled in the study. Symptoms were ascertained retrospectively on average every 9.4 months for 4 years using the Longitudinal Interval Follow-Up Evaluation. Rates and time to recovery and recurrence and week-by-week symptomatic status were analyzed. Results: Approximately 2.5 years after onset of their index episode, 81.5% of the participants had fully recovered, but 1.5 years later 62.5% had a syndromal recurrence, particularly depression. One-third of the participants had one syndromal recurrence, and 30% had two or more. The polarity of the index episode predicted that of subsequent episodes. Participants were symptomatic during 60% of the follow-up period, particularly with subsyndromal symptoms of depression...
402 citations
TL;DR: Offspring of parents with BP are at high risk for psychiatric disorders and specifically for early-onset BP spectrum disorders and indicate a need for early identification and treatment.
Abstract: Context Whether offspring of parents with bipolar disorder (BP) are at specifically high risk to develop BP and other psychiatric disorders has not been adequately studied. Objective To evaluate lifetime prevalence and specificity of psychiatric disorders in offspring of parents with BP-I and BP-II. Design Offspring aged 6 to 18 years who have parents with BP and community control subjects were interviewed with standardized instruments. All research staff except the statistician were blind to parental diagnoses. Setting Parents with BP were recruited primarily through advertisement and outpatient clinics. Control parents were ascertained by random-digit dialing and were group matched for age, sex, and neighborhood to parents with BP. Participants Three hundred eighty-eight offspring of 233 parents with BP and 251 offspring of 143 demographically matched control parents. Main Outcome Measures Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) Axis I disorders. Results Adjusting for demographic factors, living with 1 vs both biological parents, both biological parents' non-BP psychopathology, and within-family correlations, offspring of parents with BP showed high risk for BP spectrum disorders (odds ratio [OR] = 13.4; 95% confidence interval [CI], 2.9-61.6) and any mood (OR = 5.2; 95% CI, 2.3-11.4), anxiety (OR = 2.3; 95% CI, 1.3-4.0), and Axis I (OR = 2.2; 95% CI, 1.5-3.3) disorders. Offspring of parents with BP with high socioeconomic status showed more disruptive behavior disorders and any Axis I disorders than offspring of control parents with high socioeconomic status. Families in which both parents had BP had more offspring with BP than families with only 1 parent with BP (OR = 3.6; 95% CI, 1.1-12.2). More than 75.0% of offspring who developed BP had their first mood episode before age 12 years, with most of these episodes meeting criteria for BP not otherwise specified and, to a lesser degree, major depression. Conclusions Offspring of parents with BP are at high risk for psychiatric disorders and specifically for early-onset BP spectrum disorders. These findings further support the familiality and validity of BP in youth and indicate a need for early identification and treatment.
329 citations
TL;DR: Adults with BD-I are at increased risk of CVD and HTN, prevalent over a decade earlier than non-BD adults, and strategies are needed to prevent excessive and premature cardiovascular burden in BD- I.
Abstract: Objective
Despite ample evidence of excess cardiovascular mortality in bipolar disorder (BD), few studies have demonstrated increased prevalence of cardiovascular disease (CVD) and/or hypertension (HTN) in BD. We therefore examined this topic in a representative epidemiologic sample.
239 citations
TL;DR: The K-SADS-PL may prove useful for the assessment of psychopathology in preschoolers andInter-rater reliability as well as predictive validity of intake diagnoses at second assessment approximately two years after intake were evaluated.
165 citations
TL;DR: Findings suggest pediatric BP is associated with significant impairment in psychosocial functioning during and between episodes, with greater impairment during mood episodes than during partial remission/recovery.
137 citations
TL;DR: The rate of co-occurrence and the points of pathophysiologic commonality between the metabolic syndrome and major depressive disorder are discussed.
Abstract: The metabolic syndrome and its components are associated with depressive symptomatology. This article discusses the rate of co-occurrence and the points of pathophysiologic commonality between the metabolic syndrome and major depressive disorder.
116 citations
TL;DR: Sexual and/or physical abuse is common in youth with BP particularly in subjects with comorbid PTSD, psychosis, or CD and prompt identification and treatment of these youth is warranted.
97 citations
TL;DR: Supporting evidence is reviewed for the hypothesis that disturbances in inflammatory homeostasis, as marked by elevated TNF-alpha levels, are salient to the pathophysiology of BD and provide a platform for novel drug discovery.
Abstract: Bipolar disorder (BD) is associated with high rates of morbidity, comorbidity, disability, economic and human capital costs as well as premature mortality. Although, the past decade has witnessed substantial progress in the treatment of BD, high rates of non-recovery, inter-episodic symptomatology, and episode recurrence remain an ongoing deficiency. Conventional treatments for BD are capable of alleviating 'surface-based' symptomatology yet no agent is disease-modifying. Translational research initiatives provide evidence that mood disorder symptomatology is subserved by disturbances in interacting immuno-inflammatory, metabolic, and neuroendocrine networks. Numerous studies document elevated pro-inflammatory circulating cytokines [e.g. interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha)], in individuals with BD as compared to healthy volunteers. Elevated peripheral levels of TNF-alpha and its receptors (i.e. TNF-R1 and TNF-R2) are a frequent findings across depressive and manic states and may persist into euthymia. As such, TNF-alpha may constitute a trait marker of BD. Other markers of inflammation including acute phase reactants (e.g. C-reactive protein) and vascular adhesion molecules (e.g. intercellular adhesion molecule-1) are also altered in BD. Herein, we review supporting evidence for the hypothesis that disturbances in inflammatory homeostasis, as marked by elevated TNF-alpha levels, are salient to the pathophysiology of BD and provide a platform for novel drug discovery. In this review, we propose that TNF-alpha modulation is a target for disease-modifying treatment of BD. To support this hypothesis, we review evidence from clinical trials evaluating the efficacy of TNF-alpha antagonists (i.e. adalimumab, etanercept, and infliximab) on depressive symptoms and mental health-associated quality of life measures.
89 citations
TL;DR: There were differences and similarities in type, intensity, and frequency of BP symptoms and comorbid disorders related to age of onset and duration of BP and level of psychosocial development and these factors and the normal difficulties youth have expressing and modulating their emotions may explain existing complexities in diagnosing and treating BP.
Abstract: Objective
To compare the most severe lifetime (current or past) mood symptoms, duration of illness, and rates of lifetime comorbid disorders among youth with Bipolar (BP) spectrum disorders.
70 citations
TL;DR: Clinical findings of childhood-onset major depressive disorder as a more familial form of illness associated with increased comorbidity, suicidality, and treatment use are confirmed and extended.
TL;DR: Substance use is common among adolescents with treatment-resistant MDD and the subjects who had persistently low substance-related impairment or who demonstrated reduced substance- related impairment had better MDD treatment response, although the direction of this association is uncertain.
Abstract: Objective Despite the known association between substance use disorders and major depressive disorder (MDD) among adolescents, little is known regarding substance use among adolescents with MDD. Method Youths with MDD who had not improved after an adequate selective serotonin reuptake inhibitor trial ( N = 334) were enrolled in the Treatment of SSRI-Resistant Depression in Adolescents trial. Analyses examined substance use (via the Drug Use Severity Index) and changes therein in relation to treatment and depressive symptoms. Adolescents meeting substance use disorder criteria via the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version at baseline were excluded. Results Substance use was common: 28.1% reported repeated experimentation at baseline. Substance-related impairment was associated with baseline depression severity, older age, physical/sexual abuse, family conflict, hopelessness, and comorbid oppositional defiant disorder/conduct disorder. There was significant improvement in substance-related impairment among adolescents who responded to MDD treatment. Baseline suicidal ideation was higher among the subjects who progressed to high substance-related impairment (≥75th percentile) versus those whose substance-related impairment remained low ( Conclusions Substance use is common among adolescents with treatment-resistant MDD. The subjects who had persistently low substance-related impairment or who demonstrated reduced substance-related impairment had better MDD treatment response, although the direction of this association is uncertain.
TL;DR: The results of this study support the DSM-IV A criteria for mania in youths, and the irritable-only subgroup has similar clinical characteristics and family histories of BP, as compared with subgroups with predominant elation, which provides support for continuing to consider episodic irritability in the diagnosis of pediatric BP.
Abstract: Objective
To determine whether some children with bipolar disorder (BP) manifest irritability without elation and whether these children differ on socio-demographic, phenotypic, and familial features from those who have elation and no irritability and from those who have both.
TL;DR: Clinicians treating bipolar youth should consider family stress when conducting suicide risk assessment, and treatment goals may include enhancing family communication and addressing issues of loss.
Abstract: The objective of this study was to examine the association between family environment and suicidal ideation among youth with bipolar disorder. Subjects included 446 bipolar (BP) youth (age 7–17) enrolled in the Course and Outcome of Bipolar Youth study. Current suicidal ideation, family functioning and family stress were assessed at intake. BP youth with current suicidal ideation reported more conflict with their mother and less family adaptability. Ideators endorsed more stressful family events over the prior year and higher rates of specific familial stressors. Clinicians treating bipolar youth should consider family stress when conducting suicide risk assessment. Treatment goals may include enhancing family communication and addressing issues of loss.
TL;DR: The prevalence of pain interference is elevated in BD, even compared to MDD or anxiety disorders, and is associated with both medical and psychiatric comorbidities.
TL;DR: Similar to DEP-ANX youth, bipolar youth are exposed to excessive negative independent and dependent life events, which may have implications in the long-term outcome and negative consequences associated with this disorder.
Abstract: Objective To study the relationship between negative life events and demographic and clinical variables in youth with bipolar I disorder, bipolar II disorder, and bipolar disorder not otherwise specified (NOS), as well as to compare the rates of life events in youth with bipolar disorder, depressive and/or anxiety disorders (DEP-ANX), and healthy controls. Method Subjects included 446 youth, aged 7 to 17 years, meeting DSM-IV criteria for bipolar I, bipolar II, or an operationalized definition of bipolar disorder NOS, and were enrolled in the Course and Outcome of Bipolar Illness in Youth study. Subjects completed the Life Events Checklist. Sixty-five DEP-ANX and 65 healthy youth were obtained from previous studies using similar methodology. The study was conducted from October 2000 to July 2006. Results Older age, lower socioeconomic status, living with nonintact family, non-Caucasian race, anxiety, and disruptive disorders were associated with greater number of total negative life events. Specifically, increased independent, dependent, and uncertain negative life events were associated with lower socioeconomic status, nonintact family, and comorbid disruptive disorders. Increased independent negative life events were additionally associated with non-Caucasian race and comorbid anxiety disorders. Increased dependent and uncertain negative life events were also associated with older age. DEP-ANX youth reported a similar rate of negative life events as bipolar youth, and both groups had more negative life events than the healthy controls. Bipolar youth reported fewer total and dependent positive life events compared to DEP-ANX and healthy youths. Conclusions Similar to DEP-ANX youth, bipolar youth are exposed to excessive negative independent and dependent life events, which may have implications in the long-term outcome and negative consequences associated with this disorder.
TL;DR: The specific role of LAR in comparison to other atypical antipsychotics, and the limitations of available studies will be discussed from the perspectives of efficacy, tolerability, and sequential positioning in treatment guidelines.
Abstract: Bipolar disorder is a multidimensional illness typified by fluctuating periods of depression and mania, cognitive dysfunction, abnormal circadian rhythms, and multiple comorbid psychiatric and general medical conditions. Indefinite pharmacological treatment is often required, yet the modest effects of available treatments and frequent difficulties with tolerability and adherence present complex challenges to patients. Long-acting injectable medications offer a therapeutic alternative to oral mood stabilizers and may help facilitate long-term treatment adherence. This article will provide a succinct review of the latest data on the use of long-acting injectable risperidone (LAR) during the maintenance-phase treatment of bipolar disorder. The specific role of LAR in comparison to other atypical antipsychotics, and the limitations of available studies will be discussed from the perspectives of efficacy, tolerability, and sequential positioning in treatment guidelines.
Journal Article•
01 Jan 2009
TL;DR: Findings suggest pediatric BP is associated with significant impairment in psychosocial functioning during and between episodes, with greater impairment during mood episodes than during partial remission/recovery.
Abstract: Background: Evidence indicates that children and adolescents with bipolar disorder (BP) experience significant functional impairment. However, little is known about the association between psychosocial functioning and episodes of illness, demographic, and clinical variables in this population. Methods: Subjects included 446 patients aged 7 to 17 diagnosed with DSM-IV bipolar disorder via the K-SADS for the Course and Outcome of Bipolar Youth (COBY) study. The Psychosocial Functioning Schedule of the Adolescent Longitudinal Interval Follow-Up Assessment (A-LIFE) was administered at study intake. Results: Mild to moderate levels of psychosocial impairment were evident in work (includes academics), interpersonal, and overall domains of functioning among BP youth. Multivariate analyses indicated that the strongest predictors of psychosocial impairment wereadolescence(regardlessofageofonset),currentmoodepisode,currentaffectivesymptomseverity,currentpsychoticsymptoms, and current comorbid conduct disorder. Bipolar youth in-episode were significantly more impaired than those in partial remission/ recovery in every functional domain examined and were less satisfied with their functioning. Yet, BP youth in partial remission/ recovery reported significant psychosocial impairment. Limitations: Limitations include the reliance on patient and parent retrospective report of psychosocial functioning. Additionally, we did not account for the impact of psychosocial and pharmacological interventions on functioning. Conclusions: Findings suggest pediatric BP is associated with significant impairment in psychosocial functioning during and between episodes, with greater impairment during mood episodes than during partial remission/recovery. Additionally, functional impairment in BP appears to increase during adolescence regardless of age of onset. Clinicians should carefully assess and address psychosocial impairment during and between mood episodes, with particular attention to the functioning of BP adolescents. © 2008 Elsevier B.V. All rights reserved.