Comparing diagnostic checklists for pediatric bipolar disorder in academic and community mental health settings

OBJECTIVES: To compare six promising mania measures, the Parent Mood Disorder Questionnaire (P-MDQ), the Adolescent self-report MDQ, the 10-item short form of the Parent General Behavior Inventory (PGBI-SF10), the 28-item Adolescent General Behavior Inventory (AGBI), the Parent Young Mania Rating Scale (P-YMRS), and the adolescent YMRS, in a demographically diverse outpatient sample. METHODS: Participants were 262 outpatients (including 164 males and 131 African-Americans) presenting to either an academic medical center (n = 153) or a community mental health center (n = 109). Diagnoses were based on semi-structured interviews with the parent and then youth sequentially. RESULTS: Ninety youths (34%) met criteria for a bipolar spectrum disorder. Parent measures yielded Areas Under the Receiver Operating Curve (AUROC) values of 0.81 for the PGBI-SF10 to 0.66 for the P-YMRS. Adolescent report measures performed significantly less well, with AUROCs ranging from 0.65 to 0.50. There were no significant differences in the diagnostic performance of the measures across the sites or by racial groups, although the reliability of measures tended to be lower in the urban community mental health site. The PGBI-SF10 made a significant contribution to logistic regression models examining all combinations of the instruments. The P-MDQ added information in the younger age group, and no measure improved classification of bipolar cases after controlling for the PGBI-SF10 in the older age group. DISCUSSION: Results replicate previous findings that, in decreasing order of efficiency, the PGBI-SF10, P-MDQ, and P-YMRS significantly discriminate bipolar from non-bipolar cases in youths aged 5-18; and they appear robust in a demographically diverse community setting. Adolescent self-report measures are significantly less efficient, sometimes performing no better than chance at detecting bipolar cases.     

Pediatric bipolar disorder: phenomenology and course of illness

BACKGROUND: Specific features and diagnostic boundaries of childhood bipolar disorder (BD) remain controversial, and its differentiation from other disorders challenging, owing to high comorbidity with other common childhood disorders, and frequent lack of an episodic course typical of adult BD. METHODS: We repeatedly examined children meeting DSM-IV criteria for BD (excluding episode-duration requirements) and analyzed their clinical records to evaluate age-at-onset, family history, symptoms, course, and comorbidity. RESULTS: Of 82 juveniles (aged 10.6 +/- 3.6 years) diagnosed with BD, 90% had a family history of mood or substance-use disorders, but only 10% of patients had been diagnosed with BD. In 74%, psychopathology was recognized before age 3, usually as mood and sleep disturbances, hyperactivity, aggression, and anxiety. At onset, dysphoric-manic and mixed presentations were most common (48%), euphoric mania less (35%), and depression least (17%). Subtype diagnoses were: BP-I (52%) > BP-II (40%) > cyclothymia (7%). DSM episode-duration criteria were met in 52% of cases, and frequent shifts of mood and energy were common. LIMITATIONS: Partly retrospective study of clinically diagnosed referred outpatients without a comparison group. CONCLUSIONS: Pediatric BD is often mis- or undiagnosed, although it often manifests with mood lability and sleep disturbances early in life. DSM BD criteria inconsistent with clinical findings require revision for pediatric application.     

Community-based care for youths with early and very-early onset bipolar I disorder

OBJECTIVE: Phenomenological and treatment differences between children and adolescents with bipolar I disorder in a public mental health system were examined. METHOD: A systematic medical record review was performed on a sample of 83 patients, focusing on documented DSM IV symptoms of mania or depression, attention deficit hyperactivity disorder, conduct disorder, schizophrenia, and post-traumatic stress disorder. Cross-tabulation and logistic regression analyses were performed comparing the presence/absence of symptoms for each disorder and treatments provided for children and adolescents. RESULTS: Prepubertal patients were significantly more likely to be male, easily distracted, inattentive, detached from others, hyper-vigilant, prescribed stimulant medication, and to meet the diagnostic criteria for attention-deficit/hyperactivity disorder or Conduct Disorder than adolescents. CONCLUSIONS: Consistent with the published literature, phenomenological differences between children and adolescents are present and being recognized for differential diagnosis and treatment by community practitioners. More attention to documenting some cardinal symptoms of mania, the persistence of bipolar symptoms, and the nature of cycling for those with mixed states is needed.     

Juvenile bipolar disorder

OBJECTIVE: Bipolar disorder in children and adolescents is less well studied than bipolar disorder in adults. This review addresses issues related to its underdiagnosis, precursors of bipolarity, comorbidity, natural course and treatment. METHOD: Literature from Medline and other searches, and earlier relevant articles including references from recent review articles on juvenile bipolarity were reviewed. RESULTS: Bipolar disorder in juveniles is underdiagnosed and misdiagnosed on various counts. Few recent studies have reported high rates of comorbid attention deficit and disruptive disorders, prompting some researchers to consider them as probable developmental precursors of juvenile bipolarity. There is also evidence to suggest that some juvenile depression could be pre-bipolar, and that certain temperamental predispositions are probable precursors to bipolarity. Limited data on the natural course and outcome suggest that juvenile bipolar disorder is a highly recurring illness as in adults, and that it is associated with significant functional impairment. The psychopharmacological treatment of juvenile bipolar disorder is remarkably understudied, and treatment is often based on studies of adults. CONCLUSION: There is a need for epidemiological studies of juvenile bipolar disorder. Similarly, there is an urgent need for the methodologically rigorous studies to establish the efficacy of various antimanic drugs. Finally, issues related to comorbidity and temperamental predispositions to juvenile bipolarity need greater clarity, as they may have important treatment and research implications.     

Bipolar disorder in children and adolescents: international perspective on epidemiology and phenomenology

OBJECTIVE: There is considerable skepticism outside the US over the prevalence of pediatric bipolar disorder (BD). We wished to evaluate the epidemiology of BD in children and adolescents in non-US samples. METHOD: We reviewed studies on the prevalence of BD in children and adolescents in international samples. We also describe our sample of 27 children with BD at the University of Navarra. RESULTS: There are important and frequently overlooked differences in the definition of BD between the International Classification of Diseases 10th edition (ICD-10) and DSM-IV and methodological differences in epidemiological studies that may partially explain international differences in prevalence of pediatric BD. The prevalence of bipolar spectrum disorder in young adults in Switzerland is 11%. In Holland the 6-month prevalence of mania in adolescents was 1.9% and of hypomania 0.9%. Only 1.2% of hospitalized youth (<15 years) in Denmark and 1.7% of adolescents in Finland had BD. In our clinic, the prevalence of DSM-IV BD in children 5-18 years old is 4%, and of any mood disorders 27%. There are also data from Brazil, India and Turkey with varying results. CONCLUSION: Relative lack of data, ICD-10 and DSM-IV differences in diagnostic criteria, different levels of recognition of Child and Adolescent Psychiatry as a true specialty in Europe, clinician bias against BD, an overdiagnosis of the disorder in USA and/or a true higher prevalence of pediatric BD in USA may explain these results. US-International differences may be a methodological artifact and research is needed in this field.     

Comparing the effects of sampling designs on the diagnostic accuracy of eight promising screening algorithms for pediatric bipolar disorder.

BACKGROUND: Past studies have used markedly different inclusion and exclusion criteria to form samples used to evaluate diagnostic tests, making it difficult to compare results across studies. The present investigation compared eight screening algorithms in the same sample but under two different design strategies. METHODS: The DSM-IV diagnoses were based on a semi-structured diagnostic interview (KSADS) with the parent and youth sequentially. Raters were blind to index test scores. Participants were 216 youths with bipolar spectrum diagnoses and 284 youths with other Axis I diagnoses or no diagnosis. T-tests evaluated whether areas under the curve (AUC) from receiver operating characteristic analyses differed under the two design conditions. RESULTS: All of the instruments discriminated bipolar cases better when inclusion and exclusion criteria duplicated those used in phenomenological research studies selecting narrow phenotypic cases (AUCs ranging from .90 to .81). The measures performed less well when more heterogeneous clinical presentations were included [AUCs ranging from .86 to .69, t(8) = 4.99, p = 001]. CONCLUSIONS: Results indicate that checklists perform less well discriminating pediatric bipolar disorder under conditions that more closely resemble clinical practice. Test users must consider whether the sampling strategies and participant characteristics used to evaluate tests match the characteristics of their own patients.     

The diagnosis of bipolar disorder in children and adolescents: Past,present and future

Aims

This article examines the ongoing debate concerning the diagnosis of bipolar disorder in children and adolescents. This contentious issue has generated robust discussion over the past two decades without consensus, and as such the true prevalence of so-called paediatric bipolar disorder (PBD) remains unknown. In this article we offer a solution to break this deadlock.

Methods

Recent meta-analyses and additional literature concerning the definition and prevalence of PBD was critically reviewed with a view to understanding the perspectives of those developing the taxonomy of PBD, and those engaged in research and clinical practice.

Results

A key finding is the lack of iteration and meaningful communication between the various groups interested in PBD that stems from deep-seated problems within our classificatory systems. This undermines our research efforts and complicates clinical practice. These problems make the already difficult diagnosis of bipolar disorder in adults even more challenging to transpose to younger populations, and additional complexities arise when parsing clinical phenomenology from normative developmental changes in youth. Therefore, in those manifesting bipolar symptoms post-puberty, we argue for the use of adolescent bipolar disorder to describe bipolar symptoms whereas in pre-pubertal children, we propose a reconceptualisation that allows symptomatic treatment to be advanced whilst requiring critical review of these symptoms over time.

Conclusion

Significant changes in our current taxonomy are necessary and to be clinically meaningful, these revisions to our diagnoses need to be developmentally-informed.     

Review and meta-analysis of the phenomenology and clinical characteristics of mania in children and adolescents

OBJECTIVE: Using predetermined criteria for study quality and methods, a literature review and meta-analysis of seven reports about pediatric bipolar disorder (BPD) was conducted to determine if there is a consistent picture of the phenomenology and clinical characteristics of BPD in children and adolescents. METHODS: Searches were conducted in MedLine and PsycINFO using the terms mania, BPD, children and adolescents, and was limited to published articles in peer-reviewed journals. Seven reports were selected that met the following criteria: a systematic method for the elicitation and reporting of symptoms and clinical characteristics of subjects; subjects were interviewed by a trained researcher or clinician; ages 5-18 years; use of a diagnostic system, either DSM or RDC for categorization; a consensus method for the establishment of the diagnosis of BPD. RESULTS: Most DSM-IV symptoms of mania were common in the children and adolescents with BPD with the most common symptoms being increased energy, distractibility, and pressured speech. On average, four of five bipolar cases also showed threshold levels of irritable mood and grandiosity, and more than 70% of all cases showed elated/euphoric mood, decreased need for sleep, or racing thoughts. Roughly 69% of cases also showed poor judgment, whereas only half of bipolar cases demonstrated flight of ideas, and slightly more than one-third showed hypersexuality or psychotic features. CONCLUSIONS: The clinical picture that emerges is that of children or adolescents with periods of increased energy (mania or hypomania), accompanied by distractibility, pressured speech, irritability, grandiosity, racing thoughts, decreased need for sleep and euphoria/elation.     

Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: a randomized, double-blind, placebo-controlled study

Objectives:  To evaluate the efficacy, safety, and tolerability of risperidone monotherapy for the treatment of an acute mixed or manic episode in children and adolescents with bipolar I disorder.
Methods:  This randomized, placebo-controlled, double-blind, 3-arm study (N = 169) included children and adolescents (ages 10–17 years) with a DSM-IV diagnosis of bipolar I disorder, experiencing a manic or mixed episode. Study participants were randomized to placebo (n = 58), risperidone 0.5–2.5 mg/day (n = 50), or risperidone 3–6 mg/day (n = 61) for 3 weeks. The primary efficacy measure was change in Young Mania Rating Scale (YMRS) total score from baseline to end point. Safety assessments included adverse event (AE) monitoring and scores on extrapyramidal symptom rating scales.
Results:  Improvement in mean YMRS total score was significantly greater in risperidone-treated subjects than in placebo-treated subjects [mean change (SD) −9.1 (11.0) for placebo; −18.5 (9.7) for risperidone 0.5–2.5 mg (p < 0.001); −16.5 (10.3) for risperidone 3–6 mg (p < 0.001)]. The most common risperidone-associated AEs were somnolence, headache, and fatigue. Mean (SD) weight gain was 0.7 (1.9) kg, 1.9 (1.7) kg, and 1.4 (2.4) kg in the placebo, risperidone 0.5–2.5 mg, and risperidone 3–6 mg groups, respectively, during this 3-week study.
Conclusions:  At daily doses of 0.5–2.5 mg and 3–6 mg, risperidone was effective and well tolerated in children and adolescents experiencing acute manic or mixed episodes of bipolar I disorder. Results indicate that risperidone 0.5–2.5 mg has a better benefit–risk profile than risperidone 3–6 mg.     

Attention-deficit hyperactivity disorder -- bipolar comorbidity in children and adolescents

OBJECTIVE: A substantial portion of juvenile bipolar disorder (BD) has a comorbid attention-deficit hyperactivity disorder (ADHD). The aim of our study was to analyze the cross-sectional and longitudinal implications of such comorbidity in children and adolescents with BD. METHODS: Ninety-eight refereed patients (mean age 13.7 +/- 3.0 years) with a diagnosis of BD by the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime version (K-SADS-PL) were followed for 6 months. RESULTS: Thirty-seven BD patients (37.8%) presented a lifetime diagnosis of comorbid ADHD. The mean age of onset of ADHD was 3.7 +/- 1.1 years, and the mean age of onset of BD was 10.0 +/- 3.2 years. Bipolar subjects with comorbid ADHD were predominantly male, younger, and had an earlier onset of BD (8.1 +/- 2.8 versus 11.1 +/- 2.9 years). Bipolar-ADHD patients presented more frequently a chronic rather than an episodic course of BD, with an irritable rather than an elated mood. They showed higher rates of oppositional defiant disorder/conduct disorder, lower rates of panic disorder, and less frequently received antidepressant medications. Finally, ADHD comorbidity was associated with a greater psychosocial impairment. CONCLUSIONS: ADHD comorbidity is frequent in juvenile BD and can influence age of onset, phenomenology, comorbidity, and course of BD. A timely diagnosis should improve our efforts regarding the outcome of these subjects.     

Review of risperidone for the treatment of pediatric and adolescent bipolar disorder and schizophrenia

Risperidone is a commonly used medication for the treatment of bipolar disorder and schizophrenia in children and adolescents. It has been studied as a monotherapy treatment in early onset schizophrenia and as both monotherapy and combination therapy for pediatric bipolar disorder. Studies to date indicate that risperidone is an effective treatment for positive and negative symptoms of schizophrenia and mania symptoms of bipolar disorder. In young patient populations, side effects such as weight gain, extrapyramidal side effects, and prolactin elevation require consideration when evaluating the risk benefit ratio for individual patients. Here we review published studies of risperidone for the treatment of bipolar disorder and schizophrenia in children and adolescents to provide practitioners with an overview of published data on the efficacy and safety of risperidone in these patient populations.     

Differences between prepubertal- versus adolescent- onset bipolar disorder in a Spanish clinical sample

Objective To examine patients attended and diagnosed with bipolar disorder (BD) at a child and adolescent psychiatry service; to record age of diagnosis and age of onset, and to study clinical differences between prepubertal and adolescent onset groups. Methods All patients currently attended for BD type I, type II or non specified BD were reviewed and divided into two age groups: prepubertal onset (beginning before age 13) and adolescent onset (beginning at or above age 13). Results The sample were 43 patients with BD. Fourteen (32.6%) with prepubertal onset and 29 (67.4%) with adolescent onset. Time between onset of symptoms and diagnosis was longer in the prepubertal onset group (1.2 years versus 0.8 years respectively, P = .05). Patients with prepubertal onset BD more frequently presented previous symptoms such as irritability and conduct problems and had a higher rate of comorbidity (more frequently attention-deficit/hyperactivity disorder–ADHD). The adolescent onset group more often presented psychotic symptoms. Conclusion The clinical characteristics of patients with bipolar disorder differ according to whether onset is prepubertal or adolescent.     

A prospective study of bipolar disorder in children and adolescents from India

Bipolar disorder in adults is known to run an episodic course. However, little information exists on the long-term naturalistic course of bipolar disorder in juvenile populations. The present study was undertaken with the objectives of (i) documenting the rates of recovery and relapse, (ii) identifying the predictors of recovery and relapse and (iii) assessing the rates of comorbid conditions. A total of 30 subjects with onset of bipolar illness (according to DSM-III-R criteria) in childhood and adolescence were assessed systematically at baseline and 4 to 5 years later. All 30 subjects (100%) had recovered from their index episodes and none had exhibited chronicity. Twenty of the 30 subjects (67%) had relapsed, with most relapses occurring within 2 years of recovery from index episodes. No predictors of recovery and relapse could be identified. Conduct disorder was the only comorbid diagnosis in two subjects (7%). The main implication of our study, in view of the high rates of relapse in the crucial developmental phase of a young individual, is that long-term maintenance medication should be considered in juvenile bipolar patients, even if it is a first episode.     

Rapid, continuous cycling and psychiatric co-morbidity in pediatric bipolar I disorder

Objectives: The primary purpose of this study was to describe the clinical presentation of bipolar I disorder (BP-I) as it occurs in children and adolescents and to assess whether the manifestations of BP-I were similar in both age groups.

Method: Ninety youths between the ages of 5 and 17 years meeting full diagnostic symptom criteria for BP-I were included in this study. The diagnosis of BP-I was established for these youths based on the results of a semi-structured diagnostic interview and a clinical assessment by a child and adolescent psychiatrist. The course of a subset of these youngsters' illnesses was assessed using the Life Charting Method (LCM). Data regarding the clinical presentation, longitudinal history, psychiatric co-morbidities and parental psychopathology were also obtained.

Results: The clinical presentation of BP-I was similar in children and adolescents. Youths meeting diagnostic criteria for BP-I developed an average of approximately 5.8 of the 7 symptoms of mania during periods of elevated or irritable mood. BP-I was found to be a cyclic disorder characterized by high rates of rapid cycling (50%) with almost no inter-episode recovery. Almost 75% of these subjects also met diagnostic symptom criteria for a disruptive behavior disorder. High rates of mood disorders were found in fathers.

Conclusions: These data suggest that the presentation of juvenile BP-I is a cyclic and valid clinical condition with manifestations on a continuum with the later-onset forms of this illness.     

N-acetylaspartate levels in bipolar offspring with and at high-risk for bipolar disorder

OBJECTIVES: Studies have reported decreased N-acetylaspartate (NAA) in dorsolateral prefrontal cortex (DLPFC) of adults and children with bipolar disorder (BD), suggesting decreased neuronal density in this area. However, it is unclear if this finding represents neurodegeneration after or a trait marker present before BD onset. To address this question, we used proton magnetic resonance spectroscopy ((1)H-MRS) to compare DLPFC levels of NAA among bipolar offspring with early-onset BD, bipolar offspring with subsyndromal symptoms of BD and healthy children. METHODS: Participants were 9-18 years old, and included 60 offspring of parents with bipolar I or II disorder (32 with BD and 28 with subsyndromal symptoms of BD), and 26 healthy controls. (1)H-MRS at 3 T was used to study 8-cm(3) voxels placed in left and right DLPFC. RESULTS: There were no significant group differences in mean right or left DLPFC NAA/Cr ratios. Exploratory analyses of additional metabolites (myoinositol, choline) also yielded no significant group differences. NAA/Cr ratios were not correlated with age, duration of illness, or exposure to lithium or valproate. CONCLUSIONS: Our findings suggest that DLPFC NAA/Cr ratios cannot be used as a trait marker for BD. Although we did not find decreased DLPFC NAA/Cr ratios in children and adolescents with BD, it is still possible that such levels begin to decrease after longer durations of illness into adulthood. Longitudinal neuroimaging studies of patients with BD accounting for developmental and treatment factors are needed to further clarify the neurodegenerative aspects of BD.     

Comorbidity of attention deficit hyperactivity disorder in juvenile bipolar disorder

OBJECTIVE: There is some evidence to suggest that attention deficit hyperactivity disorder (ADHD) and juvenile bipolar disorder could be related. This is based on studies of comorbidity and some preliminary family study data. However, doubts continue to be raised about the relationship between the two disorders. This study examined the comorbidity of disruptive behavior disorders (DBD) that include ADHD, oppositional defiant disorder (ODD) and conduct disorder (CD) in juvenile bipolar disorder. METHOD: Seventy-three subjects with onset of bipolar disorder at age 18 years or younger were evaluated using structured interviews (Missouri Assessment of Genetics Interview for Children, Structured Clinical Interview for DSM-IV Axis I disorders--Clinician Version, and Operational Criteria Checklist for Psychotic Disorders version 3.4). Information was collected from subjects as well as from their parents. Patients with comorbid DBD were compared with patients without DBD. RESULTS: Ten subjects (14%) had one or more comorbid DBD. ADHD, CD, and ODD were present in three (4%), two (3%), and eight (11%) subjects, respectively. Those with DBD had earlier onset of bipolar disorder and spent more time ill compared to those without DBD. CONCLUSIONS: The rates of comorbid DBD in juvenile bipolar disorder are low. The study does not support a definite relationship between ADHD and juvenile bipolar disorder. Higher rates reported previously may be due to differing methods of subject ascertainment. Samples recruited from community and general psychiatric settings may help to clarify the relationship between bipolar disorder and ADHD.     

Initiation of stimulant and antidepressant medication and clinical presentation in juvenile bipolar I disorder

OBJECTIVES: The primary purpose of this study was to examine the extent to which the initiation of stimulant and antidepressant medication was associated with the subsequent onset of juvenile bipolar I disorder (BP I). Another aim was to investigate differences in clinical presentation between youths prescribed stimulant or antidepressant medication before and after the onset of juvenile BP I disorder. METHODS: Youths between the ages of 5 and 17 years meeting full, unmodified DSM-IV diagnostic symptom criteria for BP were included in this study. Data regarding the age of onset of BP I, psychiatric comorbidities, and current symptoms of mania and depression were obtained. Medication history was recorded as part of the assessment interview with parents and youths. RESULTS: Of the 245 youths with BP I, 65% (n = 160) were treated with stimulant medication; 32% (56/173) were treated after the onset of BP I, and 19% (32/173) were treated before the onset of BP I. Forty-six percent (113/245) were treated with antidepressant medication; 33% (67/206) were treated after the onset of BP I, and 3% (7/206) were treated before the onset of BP I. Patients who were treated with stimulants after the onset of BP I were significantly more likely to be younger (p < 0.0001). Patients who were treated with antidepressants before the onset of BP I were significantly more likely to be older and to have lower levels of mania on the Young Mania Rating Scale at assessment (p < 0.01). CONCLUSIONS: Data from this retrospective case series do not support the association between initial stimulant or antidepressant use and the onset of BP I or presenting symptoms of depression or manic symptoms.     

Decreased N-acetylaspartate in children with familial bipolar disorder.

BACKGROUND: Relatively low levels of brain N-acetylaspartate, as measured by magnetic resonance spectroscopy, may indicate decreased neuronal density or viability. Dorsolateral prefrontal levels of N-acetylaspartate have been reported to be decreased in adults with bipolar disorder. We used proton magnetic resonance spectroscopy to investigate dorsolateral prefrontal N-acetylaspartate levels in children with familial bipolar disorder. METHODS: Subjects were 15 children and adolescents with bipolar disorder, who each had at least one parent with bipolar disorder, and 11 healthy controls. Mean age was 12.6 years for subjects and controls. Subjects were allowed to continue current medications. Proton magnetic resonance spectroscopy at 3-Tesla was used to study 8 cm(3) voxels placed in left and right dorsolateral prefrontal cortex. RESULTS: Bipolar subjects had lower N-acetylaspartate/Creatine ratios only in the right dorsolateral prefrontal cortex (p <.02). No differences in myoinositol or choline levels were found. CONCLUSIONS: Children and adolescents with bipolar disorder may have decreased dorsolateral prefrontal N-acetylaspartate, similar to adults with BD, indicating a common neuropathophysiology. Longitudinal studies of at-risk children before the onset and during the early course of bipolar disorder are needed to determine the role of prefrontal N-acetylaspartate as a possible risk marker and/or indication of early bipolar illness progression.