Pharmacological and non-drug treatment of child bipolar I disorder during prospective eight-year follow-up.

OBJECTIVES: The Phenomenology and Course of Pediatric Bipolar Disorders study, a National Institute of Mental Health-funded study of child bipolar I disorder (BP-I) begun in 1995, is a prospective follow-up study that included collecting pharmacological and non-drug treatment data. METHODS: There were 115 first-episode subjects who fit full DSM-IV criteria for BP-I, mixed or manic phase, with severity scores in the clinically impaired range, ascertained by consecutive new case ascertainment. Subjects were assessed with the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS), given separately to parents about their children and to children about themselves. All treatment was provided by the subjects' own community practitioners, exactly as if they had not been in the research study. Thus, families were only seen for research assessments, and research staff were not at all involved in their treatment. Data on type, dose, and duration of pharmacological and non-drug treatment were collected. During follow-up, 93.9% (n = 108) were assessed at each of the nine assessment times. RESULTS: During the eight years, only 62.6% received any antimanic medication (antipsychotic, anticonvulsant, lithium) at any time. Percents who received non-antimanic medication included 77.4% medication for attention-deficit hyperactivity disorder and 64.3% antidepressants. A total of 67.8% of subjects were taking two or more concurrent medication classes. Subjects ascertained from psychiatric versus pediatric sites received antimanics significantly more frequently (p = 0.006). Earlier recovery during eight-year follow-up was predicted by greater percent of weeks on lithium (p = 0.017). CONCLUSIONS: Given these findings, and the poor prognosis from prospective follow-up of this sample reported elsewhere, there is a need for further research that informs the development of effective treatment strategies.

GAD1 single nucleotide polymorphism is in linkage disequilibrium with a child bipolar I disorder phenotype.

BACKGROUND: Pediatric bipolar I disorder (BP-I) and childhood schizophrenia (SZ) share certain symptoms (e.g., psychosis, aggression/irritability [A/I]), and the psychotic and A/I features are treated with neuroleptics in both disorders. Thus, it is of interest to examine the association of GAD1 to child BP-I because of its recently reported association to childhood SZ. METHODS: Child BP-I probands were obtained by consecutive new case ascertainment, and the phenotype was defined as current DSM-IV BP-I (manic or mixed phase) with at least one of the cardinal symptoms of mania (i.e., elation and/or grandiosity) and a Children's Global Assessment Scale score < or =60 (clinical impairment). These child BP-I probands are part of a large, ongoing, longitudinal study in which the phenotype has been validated by unique symptoms, longitudinal stability, and 7-8 times greater family loading than adult BP-I probands. Genotyping was performed using a TaqMan Validated SNP Genotyping Assay, and FBAT was used for analysis. RESULTS: There were 48 families. The rs2241165 A allele was preferentially transmitted (FBAT chi(2) = 5.2, df = 1, p = 0.022). No interaction between this GAD1 SNP and the Val66 BDNF allele was found. CONCLUSIONS: These data are consistent with some shared genetic vulnerability between child BP-I and SZ, which may be related to similar treatments.

Adaptive strategies for treating childhood mania.

The conduct of trials in children is beset with special difficulties associated with the dearth of treatment data, the considerable heterogeneity of pediatric patient populations connected with (for example) developmental stage, and the strong desire of parents to see that children are provided with the best possible care at all times. To address these issues, we propose the adaptive treatment strategy (ATS) study in which medication changes are adaptively determined according to the evolving treatment response of the individual child. To formalize this methodological approach, we parameterize an ATS as a "threshold" decision rule that monitors whether the patient's response trajectory crosses some threshold of failure. In this formulation, the threshold represents a priori judgments about when to give up on response to medication, and the goal is to find the right response thresholds for continuation, augmentation, or switching. Our exposition is developed in the specific clinical context of childhood mania to maximize accessibility of the ideas but applies more generally to other chronic mental and physical health disorders that are difficult to treat.

Controlled, blindly rated, direct-interview family study of a prepubertal and early-adolescent bipolar I disorder phenotype: morbid risk, age at onset, and comorbidity.

CONTEXT: A key question is whether a prepubertal and early-adolescent bipolar I disorder phenotype (PEA-BP-I) is the same illness as adult BP-I. This question arises because of the greater severity, longer current episode duration, preponderance of mania, and high rates of ultradian rapid cycling and comorbid attention-deficit/hyperactivity disorder (ADHD) in PEA-BP-I. OBJECTIVES: To examine morbid risk (MR) of BP-I in first-degree relatives of PEA-BP-I, ADHD, and healthy control probands, as well as imprinting, sibling recurrence risk, and anticipation. DESIGN: Controlled, blind direct interview. There were no family psychopathology exclusions for any proband group. SETTING: University medical school research unit. PARTICIPANTS: First-degree relatives 6 years and older (n = 690) of 219 probands (95 with PEA-BP-I, 47 with ADHD, and 77 healthy controls). The PEA-BP-I and ADHD probands were obtained by consecutive new case ascertainment, and healthy controls were from a random survey; proband diagnoses were validated via 4-year prospective follow-up. The PEA-BP-I probands had a mean +/- SD age of 10.8 +/- 2.6 years. Main Outcome Measure Morbid risk. RESULTS: The MR of BP-I was higher in relatives of PEA-BP-I probands compared with ADHD or healthy controls (P<.001 for both); the MR in relatives of ADHD and healthy controls was similar. The MR of BP-I in relatives with ADHD was higher (P<.001) and age at onset of BP-I was younger in parents with ADHD than in those without (P<.001). The MR of BP-I in relatives with oppositional, conduct, or antisocial disorders was higher than in those without (P<.001). Anticipation was evidenced by a younger age at onset of BP-I in probands than in their parents (P<.001). No imprinting was found. CONCLUSIONS: Findings support that PEA-BP-I and adult BP-I are the same diathesis, 7 to 8x greater familiality in child vs adult BP-I, and family study validation of PEA-BP-I, including its differentiation from ADHD.

Proposed definitions of bipolar I disorder episodes and daily rapid cycling phenomena in preschoolers, school-aged children, adolescents, and adults.

OBJECTIVE: Recent data from several large studies of pediatric bipolar I disorder reported baseline (current) episode duration ranging from less than a month to >or=1 year. These data may reflect actual sample differences, but the absence of uniformly applied definitions of episode duration, number of lifetime episodes and daily rapid cycling patterns during episodes may also account for these differences. METHOD: Proposals for definitions of episode and cycling phenomena were based upon data from the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS). RESULT: Episode would be used for the interval between onset and offset of full DSM-IV criteria for bipolar I disorder. Cycling would be used only to describe daily (ultradian) switching of mood states that occurs during an episode. CONCLUSION: Historically, in the adult bipolar literature the words "episode" and "cycle" were used interchangeably. "Rapid cycling," in this earlier literature, actually referred to multiple episodes per year. To avoid confusing episodes with daily cycling, the proposal is to use "episode" for the duration of DSM-IV criteria, to use "cycling" for daily switching phenomena during an episode, and to replace the historical term "rapid cycling" with "multiple episodes per year." These clarifications will be especially important for phenomenological research on preschool populations.

A brief screening tool for a prepubertal and early adolescent bipolar disorder phenotype.

OBJECTIVE: Although there has recently been increased interest in child mania, there is as yet no brief screening tool that separates a prepubertal and early adolescent bipolar disorder phenotype from attention deficit hyperactivity disorder (ADHD), the most relevant differential diagnosis. METHOD: Parents of 268 consecutively ascertained subjects (93 with a prepubertal and early adolescent bipolar disorder phenotype, 81 with ADHD, 94 in a healthy comparison group) completed the 10-item Conners' Abbreviated Parent Questionnaire, before separate Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia interviews of parents and children. Data from the Conners' Abbreviated Parent Questionnaire were analyzed by using receiver operating characteristic methods. RESULTS: A screening algorithm that yielded a sensitivity of 0.73 and a specificity of 0.86 was developed from the Conners' Abbreviated Parent Questionnaire. CONCLUSIONS: The Conners' Abbreviated Parent Questionnaire is a promising tool as a screen for a prepubertal and early adolescent bipolar disorder phenotype and has similar sensitivity and specificity to screening tools for adult bipolar disorder.

Prepubertal and early adolescent bipolar I disorder: review of diagnostic validation by Robins and Guze criteria.

The phenomenology of pediatric bipolar disorder is a controversial topic in the field of child psychiatry. The first National Institute of Mental Health-funded study in the field, Phenomenology and Course of Pediatric Bipolar Disorders, selected a conservative phenotype for credibility in a contentious field. To address the problems of differentiation of mania from attention-deficit/hyperactivity disorder (ADHD) and of the ubiquitous manifestation of irritability across child psychiatry diagnoses, a prepubertal and early adolescent bipolar I disorder phenotype (PEA-BP) was defined by DSM-IV bipolar I disorder (manic or mixed phase) with elation and/or grandiosity as one criterion. This criterion avoided diagnosing mania by symptoms that overlapped with those of ADHD (e.g., hyperactivity, distractibility) and ensured that subjects had at least 1 of the cardinal symptoms of mania (i.e., elation or grandiosity). This definition was analogous to the requirement that DSM-IV major depressive disorder include at least 1 of the cardinal symptoms of depression (i.e., sad mood or anhedonia). Subjects were 93 children with a mean +/- SD age of 10.9 +/- 2.6 years. Validation of the phenotype was shown according to Robins and Guze criteria: unique symptoms that did not overlap with those of ADHD, stability of the diagnosis (did not become ADHD or other disorders on follow-up) as shown by a 4-year prospective longitudinal study, significantly higher familial aggregation of bipolar disorder in relatives of PEA-BP versus ADHD and healthy control probands, and family-based linkage disequilibrium of the brain-derived neurotrophic factor Val66 allele in PEA-BP probands. Furthermore, PEA-BP resembled the most severe adult bipolar disorder, manifested by a chronic, ultradian-cycling, mixed manic, psychotic course. A conservatively defined child mania phenotype met the Robins and Guze criteria for establishing diagnostic validity in psychiatric illness. Continuities between PEA-BP and adult bipolar disorder and relationships of PEA-BP to other descriptions of child mania are discussed.

Controlled study of encopresis and enuresis in children with a prepubertal and early adolescent bipolar-I disorder phenotype.

OBJECTIVE: To examine the prevalence of encopresis/enuresis, relationship between maternal hostility and encopresis, parent-child concordance of reporting encopresis/enuresis, and familial aggregation of enuresis in subjects with a prepubertal and early adolescent bipolar-I disorder phenotype (PEA-BP), attention-deficit/hyperactivity disorder (ADHD), and healthy controls (HC). METHOD: There were 268 consecutively ascertained subjects (93 PEA-BP, 81 ADHD, and 94 HC). PEA-BP was defined as DSM-IV BP-I (manic or mixed phase) with elation and/or grandiosity. The WASH-U-KSADS and Psychosocial Schedule for School-Age Children-Revised were administered to parents about their children and separately to children about themselves. RESULTS: Encopresis was more prevalent in PEA-BP versus HC subjects (15.1% versus 3.2%, chi2 = 6.4, p = .012). Enuresis was more common in PEA-BP versus HC (21.5% versus 6.4%, chi2 = 7.8, p = .005) and ADHD versus HC (22.2% versus 6.4%, chi2 = 6.1, p = .014) subjects. All enuresis onset in subjects not receiving lithium. Most encopresis (81.8%) and enuresis (75.0%) onset before mania. Familial aggregation of enuresis was more frequent in enuretics than nonenuretics (47.7% versus 5.4%, chi2 = 41.2, p < .0001). Maternal hostility was more prevalent in encopretic versus nonencopretic subjects (91.7% versus 55.6%, chi2 = 8.3, p = .004). Parent-child concordance on reporting encopresis and enuresis was poor to fair. CONCLUSIONS: Children with PEA-BP need to be evaluated for encopresis, enuresis, and mother-child relationships.

Children with a prepubertal and early adolescent bipolar disorder phenotype from pediatric versus psychiatric facilities.

OBJECTIVE: To examine characteristics between subjects with a prepubertal and early adolescent bipolar disorder phenotype from pediatric versus psychiatric venues. METHOD: Subjects (N = 93) with a prepubertal and early adolescent bipolar disorder phenotype were obtained through consecutive new case ascertainment from designated pediatric and psychiatric sites from 1995 to 1998. Children needed DSM-IV bipolar I disorder (manic or mixed phase) with elation and/or grandiosity as one criterion to avoid diagnosing mania only by symptoms that overlapped with those of attention-deficit/hyperactivity disorder. Comprehensive assessment included the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, given separately to parents about their children and to children about themselves by experienced research nurses blinded to subjects' diagnostic status. RESULTS: Rates of mixed mania (chi = 7.1, p = .008) and suicidality (chi = 7.2, p = .007) were significantly higher at psychiatric versus pediatric venues. Subjects from pediatric sites were significantly more likely to be living with their intact biological family (chi = 5.3, p = .022). Significantly more subjects with a prepubertal and early adolescent bipolar disorder phenotype ascertained at psychiatric sites versus pediatric sites were taking an antimanic medication (chi = 9.5, p = .002), while stimulant medication was significantly more common among subjects ascertained at pediatric sites (chi = 19.0, p < .0001). CONCLUSIONS: These pediatric versus psychiatric site differences suggest that pediatricians may under-recognize mania and thus do not prescribe antimanic mood-stabilizing medications. Moreover, pediatricians may be more likely to refer children to psychiatrists when depression or suicidality is evident.

Four-year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar disorder phenotype.

BACKGROUND: Diagnosis of child mania has been contentious. OBJECTIVE: To investigate natural history and prospective validation of the existence and long-episode duration of mania in children. DESIGN: Four-year prospective longitudinal study of 86 subjects with intake episode mania who were all assessed at 6, 12, 18, 24, 36, and 48 months. The phenotype was defined as DSM-IV bipolar I disorder (manic or mixed) with at least 1 cardinal symptom (elation and/or grandiosity) to ensure differentiation from attention-deficit/hyperactivity disorder. Parent and child informants were separately interviewed, by highly experienced research nurses, using the Washington University in St Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS). A Children's Global Assessment Scale score of 60 or less was needed to establish definite impairment. Treatment was by subjects' community practitioners. SETTING: Research unit in a university medical school. PARTICIPANTS: Subjects were obtained from psychiatric and pediatric sites by consecutive new case ascertainment, and their baseline age was 10.8 +/- 2.7 years. Onset of the baseline episode was 7.4 +/- 3.5 years. (Data are given as mean +/- SD.) MAIN OUTCOME MEASURES: Episode duration, weeks ill, recovery/relapse rates, and outcome predictors. RESULTS: Prospective episode duration of manic diagnoses, using onset of mania as baseline date, was 79.2 +/- 66.7 consecutive weeks. Any bipolar disorder diagnosis occurred during 67.1% +/- 28.5% of total weeks, during the 209.4 +/- 3.3 weeks of follow-up. Subjects spent 56.9% +/- 28.8% of total weeks with mania or hypomania (unipolar or mixed), and 38.7% +/- 28.8% of these were with mania. Major or minor depression and dysthymia (unipolar or mixed) occurred during 47.1% +/- 30.4% of total weeks. Polarity switches occurred 1.1 +/- 0.7 times per year. Low maternal warmth predicted faster relapse after recovery from mania (chi(2) = 13.6, P =.0002), and psychosis predicted more weeks ill with mania or hypomania (F(1,80) = 12.2, P =.0008). Pubertal status and sex were not predictive. (Data are given as mean +/- SD.) CONCLUSIONS: These findings validate the existence, long-episode duration, and chronicity of child mania. Differences from the natural history of adult bipolar disorder are discussed.

National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders.

A consensus conference on the use of placebo in mood disorder studies consisted of expert presentations on bioethics, biostatistics, unipolar depression, and bipolar disorder. Work groups considered evidence and presented statements to the group. Although it was not possible to write a document for which there was complete agreement on all issues, the final document incorporated input from all authors. There was consensus that placebo has a definite role in mood disorder studies. Findings of equivalence between a new drug and standard treatment in active control studies is not evidence of efficacy unless the new drug is also significantly more effective than placebo. Add-on studies in which patients are randomized to standard therapy plus the investigational drug or standard therapy plus placebo are especially indicated for high-risk patients. Mood disorders in elderly and pediatric patients are understudied, and properly designed trials are urgently needed. Research is needed on the ethical conduct of studies to limit risks of medication-free intervals and facilitate poststudy treatment. Patients must fully understand the risks and lack of individualized treatment involved in research.

Practical Clues to Early Recognition of Bipolar Disorder: A Primary Care Approach.

Early treatment can favorably impact the course of bipolar disorder, a lifelong illness. Because bipolar disorder can masquerade as various mental and physical illnesses-primarily major depressive disorder-patients with this condition frequently go unrecognized for years. During this recognition lag, such patients may present to their primary care physician on multiple occasions. Accordingly, primary care physicians would benefit from knowing the "clues" to early recognition of the disorder, because early recognition and management can reduce disability, improve social and employment stability, and result in improved functional outcomes. This review describes 3 pathways to the diagnosis of bipolar disorder relevant to the primary care setting: detection of mania or hypomania, differential diagnosis of recurrent depressive episodes, and identification of interepisode disorder and its comorbidities. We summarize these pathways in terms of a practical tool that a primary care physician can use to trigger further evaluation or referral.

Linkage disequilibrium of the brain-derived neurotrophic factor Val66Met polymorphism in children with a prepubertal and early adolescent bipolar disorder phenotype.

OBJECTIVE: Transmission of the brain-derived neurotrophic factor (BDNF) Val66 allele in children with a prepubertal and early adolescent bipolar disorder phenotype was examined. METHOD: The prepubertal and early adolescent bipolar disorder phenotype was defined as current DSM-IV bipolar I disorder (manic or mixed phase) with at least one cardinal mania criterion (i.e., euphoria and/or grandiosity) to ensure differentiation from attention deficit hyperactivity disorder. Probands (mean age=10.7 years, SD=2.7) were obtained by consecutive new case ascertainment from designated pediatric and psychiatric venues. Parents and probands were interviewed separately by research nurses who were blind to the probands' diagnoses. Genotyping was done with TaqMan Assay-on-Demand. Analysis was done with the Family Based Association Test program. RESULTS: There were 53 complete, independent trios. The BDNF Val66 allele was preferentially transmitted (Family Based Association Test: chi(2)=6.0, df=1, p=0.014). CONCLUSIONS: This finding in child bipolar disorder is consistent with data for adults with bipolar disorder that show preferential transmission of the Val66 allele.

Relationship of parent and child informants to prevalence of mania symptoms in children with a prepubertal and early adolescent bipolar disorder phenotype.

OBJECTIVE: A controversy regarding pediatric bipolar disorder is whether to use child in addition to parent informants. To investigate this issue, the authors conducted a study comparing separate child and parent interview data for child bipolar disorder. METHOD: Responses on the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia from 93 child and 93 parent informants were compared by using kappa statistics. Research nurses, blind to subject information, separately interviewed parents about their children and children about themselves. Different nurses were used for the parent and child in each family to avoid bias from the same research nurse interviewing a child after interviewing that child's parent. Mania was defined by DSM-IV criteria, with at least one of the two cardinal symptoms of mania (elated mood and/or grandiosity), to avoid diagnosing mania by symptoms that overlapped with those for attention deficit hyperactivity disorder (ADHD). RESULTS: Parent-child concordance was poor to fair for all cardinal and noncardinal mania symptoms. Kappas were not significantly different by age within the 7-14-year-old age range. CONCLUSIONS: Symptoms endorsed by just the child included substantial proportions of bipolar symptoms that have been shown to best differentiate mania from ADHD (i.e., elation, grandiosity, flight of ideas, racing thoughts, decreased need for sleep). These findings support the need for child informants in research on prepubertal and early adolescent bipolar disorder in children ages 7-14. Differences in mania symptom profiles between investigative groups may be, in part, due to whether child informants were assessed.

Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype.

OBJECTIVE: Longitudinal outcomes of bipolar disorder with onset in the late teenage years or in adulthood have been reported, but little is known about the natural history of childhood-onset mania. This study sought to provide rates and predictors of recovery and relapse in children with a prepubertal and early adolescent bipolar disorder phenotype. METHOD: Eighty-nine consecutively ascertained outpatient subjects (mean age=10.9 years [SD=2.7]) received comprehensive research assessments, including separate interviews of mothers about their children and of children about themselves, at baseline and at 6, 12, 18, and 24 months after baseline. The study phenotype required DSM-IV mania with elation and/or grandiosity as one criterion to distinguish the study phenotype from a diagnosis of mania based on criteria overlapping with those for attention deficit hyperactivity disorder and to ensure that subjects had at least one of the two cardinal features of mania (i.e., elation and/or grandiosity). Subjects were treated by their own community practitioners. RESULTS: The proportions of subjects who recovered from mania and who relapsed after recovery were 65.2% and 55.2%, respectively. The mean time to recovery was 36.0 weeks (SD=25.0). Relapse occurred after a mean of 28.6 weeks (SD=13.2). Living with an intact biological family significantly predicted rate of recovery, and a low level of maternal warmth significantly predicted rate of relapse. CONCLUSIONS: The relatively poor outcomes of these subjects may be related to their phenotypic resemblance to severely ill adults with bipolar disorder who have mixed mania, continuous rapid cycling, psychosis, and treatment-resistant psychopathology. A lower level of effectiveness of mood stabilizers in children cannot be ruled out. Although the significance of maternal warmth as a predictor is consistent with reports in adult mania, the significance of intact family as a predictor may be unique to childhood mania.

Ages of onset and rates of syndromal and subsyndromal comorbid DSM-IV diagnoses in a prepubertal and early adolescent bipolar disorder phenotype.

OBJECTIVE: To study rates and ages of onset of DSM-IV syndromal and subsyndromal comorbidity in a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP) (N = 93) compared to attention-deficit/hyperactivity disorder (ADHD) (N = 81). METHOD: The WASH-U-KSADS was given by raters blinded to subject group separately to mothers about their children and to children about themselves. PEA-BP was defined as DSM-IV mania with at least one cardinal symptom of mania (elation or grandiosity) to avoid diagnosing using only symptoms that overlapped with those for ADHD. Syndromal diagnoses required a CGAS score of 60 or less to ensure severity at a level of definite "caseness." RESULTS: PEA-BP subjects were aged 10.9 (SD = 2.6) at baseline and 6.8 (SD = 3.4) at onset of first mania episode. Rates of oppositional defiant disorder and total number of comorbidities were significantly higher in the PEA-BP group than the ADHD group. In PEA-BP subjects, mean ages of onset of ADHD occurred before the first manic episode, and obsessive compulsive, oppositional defiant, social phobia, generalized anxiety, separation anxiety, and conduct disorders occurred after. CONCLUSIONS: Onsets of ADHD before mania and of oppositional defiant disorder/conduct disorder after mania have clinical and research implications. These include the need to examine for mania symptoms in children with ADHD and/or oppositional defiant disorder/conduct disorder and to develop scales to differentiate preschool mania from ADHD. Comparison with other studies demonstrated the importance of DSM system and severity scales in reporting comorbidity rates.

Definitions of rapid, ultrarapid, and ultradian cycling and of episode duration in pediatric and adult bipolar disorders: a proposal to distinguish episodes from cycles.

OBJECTIVE: To propose terminology to distinguish cycles from episodes in children and adults with bipolar disorder (BP). METHODS: To examine current definitions of rapid cycling and episodes in both child and adult BP, an Internet search of the MEDLINE database was conducted. RESULTS: Investigations of rapid cycling in adults used the terms cycle and episode interchangeably to describe discrete periods of mood disorders. Two studies of children and one study of adults with BP, however, reported cycles occurring daily (ultradian cycling) or every few days (ultrarapid cycling). Without definitions to differentiate cycles from episodes, determining the overall duration of illness in subjects who experience ultrarapid or ultradian cycling is not possible. For example, a child cycled twice a day, every day, for 365 days (1 year). With the terminology currently in use, it is unclear whether this should be described as a single episode that had a duration of 365 days or as approximately 730 episodes (2 cycles per day x 365 days), each less than 24 hours in duration. Moreover, adults with BP may have more intermittent pathology than children (e.g., adults may cycle 4 days per week, versus children may cycle 7 days per week). CONCLUSION: The following definitions are proposed. (1) Episodes will be defined by (a) the duration from onset to offset of a period of at least 2 weeks in length during which only one mood state persists or (b) the duration from onset to offset of a period of ultrarapid or ultradian cycling for at least 2 weeks. (2) Cycles will be defined by mood switches occurring daily or every few days during an episode. Further research will be needed to elucidate potential differences between child and adult cycling patterns.

Phenomenology of prepubertal and early adolescent bipolar disorder: examples of elated mood, grandiose behaviors, decreased need for sleep, racing thoughts and hypersexuality.

OBJECTIVE: Children are developmentally incapable of many manifestations of bipolar symptoms described in adults (e.g., children do not "max" out credit cards or have four marriages). To address this issue, our group investigated prepubertal and early adolescent age equivalents of adult mania behaviors. METHODS: Details of the methods appear in the companion article in this issue (Geller et al. 2002a). Subjects had a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP) that was validated by reliable assessment (Geller et al. 2001b), 6-month stability (Geller et al. 2000c), and 1- and 2-year longitudinal diagnostic outcome (Geller et al. 2001a, 2002b). RESULTS: Examples of elation, grandiosity, decreased need for sleep, racing thoughts, and hypersexuality in PEA-BP subjects were compared to examples in prepubertal normal controls and to examples in late teenage/adult-onset mania. Because it is not intuitive that children can be pathologically happy or expansive, sections on guidelines for differentiating normal versus impairing elation and grandiosity are provided. CONCLUSION: Due to the high comorbidity of PEA-BP and attention deficit hyperactivity disorder (ADHD), recognition of mania symptoms that do not overlap with those for ADHD may aid in avoiding both under- and overdiagnosis of child bipolar disorder. A discussion of how "nonoverlapping with ADHD" Diagnostic and Statistical Manual of Mental Disorders (4th ed.) mania symptoms can be useful in the differential diagnosis of irritability is also provided.

DSM-IV mania symptoms in a prepubertal and early adolescent bipolar disorder phenotype compared to attention-deficit hyperactive and normal controls.

OBJECTIVE: To compare the prevalence of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) mania symptoms in a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP) to those with attention deficit hyperactivity disorder (ADHD) and normal community controls (CC). METHODS: To optimize generalizeability, subjects with PEA-BP and ADHD were consecutively ascertained from outpatient pediatric and psychiatric sites, and CC subjects were obtained from a random survey. All 268 subjects (93 with PEA-BP, 81 with ADHD, and 94 CC) received comprehensive, blind, baseline research assessments of mothers about their children and of children about themselves. PEA-BP was defined by DSM-IV mania with elation and/or grandiosity as one criterion to ensure that subjects had one of the two cardinal symptoms of mania and to avoid diagnosing mania only by criteria that overlapped with those for ADHD. RESULTS: Five symptoms (i.e., elation, grandiosity, flight of ideas/racing thoughts, decreased need for sleep, and hypersexuality) provided the best discrimination of PEA-BP subjects from ADHD and CC controls. These five symptoms are also mania-specific in DSM-IV (i.e., they do not overlap with DSM-IV symptoms for ADHD). Irritability, hyperactivity, accelerated speech, and distractibility were very frequent in both PEA-BP and ADHD groups and therefore were not useful for differential diagnosis. Concurrent elation and irritability occurred in 87.1% of subjects with PEA-BP. Data on suicidality, psychosis, mixed mania, and continuous rapid cycling were also provided. CONCLUSION: Unlike late teenage/adult onset bipolar disorder, even subjects with PEA-BP selected for DSM-IV mania with cardinal symptoms have high rates of comorbid DSM-IV ADHD. High rates of concurrent elation and irritability were similar to those in adult mania.

Temperament and character factors in a prepubertal and early adolescent bipolar disorder phenotype compared to attention deficit hyperactive and normal controls.

OBJECTIVE: To compare temperament and character (T/C) factors in a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP), attention deficit hyperactivity disorder (ADHD), and normal community controls (NC). METHODS: Subjects in PEA-BP (n = 101), ADHD (n = 68), and NC (n = 94) groups were diagnostically assessed with the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia given separately to mothers about their children and to children about themselves. Diagnosis of PEA-BP was defined as Diagnostic and Statistical Manual of Mental Disorders, fourth edition, bipolar disorder (manic or mixed phase) with at least one cardinal symptom of mania (i.e., elation and/or grandiosity) to avoid diagnosing mania by symptoms that overlapped with those for ADHD. The Junior Temperament and Character Inventory (JTCI) was used to measure T/C factors. Separate JTCI data were obtained from mothers about their children and from children about themselves. RESULTS: Parent- and child-reported novelty seeking were significantly higher in PEA-BP than in NC subjects. Novelty seeking was significantly higher in the ADHD group than in the NC group only by parent report. Parent and/or child report showed PEA-BP and ADHD subjects to be significantly less reward-dependent, persistent, self-directed, and cooperative than NC subjects. Parent-reported cooperativeness was significantly lower in PEA-BP than in ADHD subjects. CONCLUSION: These findings are consistent with studies of novelty seeking in adults who had either BP or ADHD and are discussed in relationship to genetic studies of dopamine receptors and novelty seeking.