bipolar disorder in children


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(Updated 1/12/04)

Child & Adolescent Bipolar Foundation

George T. Lynn, M.A., M.P.A., L.M.H.C.
Differentiating AD/HD from Bipolar Disorder In Children [PDF]

National Institute of Mental Health research roundtable on prepubertal bipolar disorder.
J Am Acad Child Adolesc Psychiatry 2001 Aug;40(8):871-8
"OBJECTIVE: A research roundtable meeting was convened at the National Institute of Mental Health on April 27, 2000, to discuss the existing controversial areas in the diagnosis of bipolar disorder in prepubertal children. METHOD: Invited clinicians and researchers with expertise on bipolar disorder in children were asked to share and discuss their perspectives on diagnostic issues for bipolar disorder in prepubertal children. RESULTS: The group reached agreement that diagnosis of bipolar disorder in prepubertal children is possible with currently available psychiatric assessment instruments. In addition to phenotypes that fit DSM-IV criteria for bipolar I and bipolar II, participants agreed on the existence of other phenotypic possibilities that do not meet diagnostic criteria. Bipolar not otherwise specified (NOS) was recommended as a "working diagnosis" for the non-DSM-IV phenotype. CONCLUSIONS: Bipolar disorder exists and can be diagnosed in prepubertal children. In children who present with both the DSM-lV and non-DSM-IV phenotypes (i.e., those given a diagnosis of bipolar-NOS), assessment should include careful evaluation of all behaviors that are impairing. Moreover, these children should be monitored systematically to explore stability and change over time in diagnosis and impairment." [Abstract]

Kim EY, Miklowitz DJ.
Childhood mania, attention deficit hyperactivity disorder and conduct disorder: a critical review of diagnostic dilemmas.
Bipolar Disord. 2002 Aug;4(4):215-25.
"OBJECTIVES: Significant debate exists on whether early onset bipolar disorder is mistakenly attributed to attention deficit hyperactivity disorder (ADHD) or conduct disorder (CD), or whether ADHD and CD are frequently misdiagnosed as mania. We review the literature on the extent to which these disorders can be reliably differentiated, and describe the diagnostic confusion that may be the result of features common to both classes of disorders. METHODS: The review focuses on research studies that have examined whether overlapping symptoms of bipolar disorder, ADHD, and CD contribute to misdiagnosis of the two classes of disorders, the prevalence of early onset bipolar disorder with comorbid ADHD or CD, and theories regarding the origins of this comorbidity. RESULTS: Reliable and accurate diagnoses can be made despite the symptom overlap of bipolar disorder with ADHD and CD. Children with bipolar disorder and ADHD may have a distinct familial subtype of bipolar disorder. Some findings suggest that manic symptoms may represent 'noise' that indicates the general severity of psychopathology in a child or adolescent. CONCLUSIONS: Further prospective studies may confirm whether early onset bipolarity can be successfully differentiated from ADHD or CD, whether all three types of disorders can be recognized in comorbid cases, or whether comorbid cases represent a distinct subtype of bipolar disorder." [Abstract]

Craney JL, Geller B.
A prepubertal and early adolescent bipolar disorder-I phenotype: review of phenomenology and longitudinal course.
Bipolar Disord. 2003 Aug;5(4):243-56.
"OBJECTIVE: Phenomenology, assessment, longitudinal, and psychosocial findings from an ongoing, controlled, prospective study of 93 subjects with a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP) will be reviewed. METHODS: Unlike adult-onset bipolar disorder, for which there were over 50 years of systematic investigations, there were a paucity of rigorous data and much controversy and skepticism about the existence and characteristics of prepubertal-onset mania. With this background, issues to address for investigation of child-onset mania included the following: (i) What to do about the differentiation of mania from attention-deficit hyperactivity disorder (ADHD). (ii) How to deal with the ubiquity of irritability as a presenting symptom in multiple child psychiatry disorders. (iii) Development of a research instrument to assess prepubertal manifestations of adult mania (i.e. children do not 'max out' credit cards or have four marriages). (iv) How to distinguish normal childhood happiness and expansiveness from pathologically impairing elated mood and grandiosity. RESULTS: To address these issues, a PEA-BP phenotype was defined as DSM-IV mania with elated mood and/or grandiosity as one inclusion criterion. This criterion ensured that the diagnosis of mania was not made using only criteria that overlapped with those for ADHD, and that subjects had at least one of the two cardinal symptoms of mania (i.e. elated mood and grandiose behaviors). Subjects were aged 10.9 years (SD = 2.6) and age of onset of the current episode at baseline was 7.3 years (SD = 3.5). Validation of PEA-BP was shown by reliable assessment, 6-month stability, and 1- and 2-year diagnostic longitudinal outcome. PEA-BP resembled the severest form of adult-onset mania by presenting with a chronic, mixed mania, psychotic, continuously (ultradian) cycling picture. CONCLUSION: Counterintuitively, typical 7-year-old children with PEA-BP were more severely ill than typical 27 year olds with adult-onset mania. Moreover, longitudinal data strongly supported differentiation of PEA-BP from ADHD." [Abstract]

Tillman R, Geller B, Bolhofner K, Craney JL, Williams M, Zimerman B.
Ages of onset and rates of syndromal and subsyndromal comorbid DSM-IV diagnoses in a prepubertal and early adolescent bipolar disorder phenotype.
J Am Acad Child Adolesc Psychiatry. 2003 Dec;42(12):1486-93.
"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." [Abstract]

Weckerly J.
Pediatric bipolar mood disorder.
J Dev Behav Pediatr 2002 Feb;23(1):42-56
"The diagnosis of bipolar mood disorder (BP) in preadolescents (pediatric mania) has generated considerable controversy in terms of its estimated prevalence and validity as a diagnostic category. The relative paucity of systematic studies and the current diagnostic confusion related to the disorder are often attributed to the apparent discontinuities in the childhood versus adult presentation of the illness, namely, irritability as the predominant "mood" of mania and a continuous course of symptoms. The goal of this article is to review the current literature and identify sources of confusion relating to pediatric mania by considering results to date within a larger context that include findings from studies on (1) BP illness in adults, (2) mood disorders across the lifespan, (3) the role of development in symptom expression, and (4) patterns of heritability in psychiatric disorders. Whereas much remains to be investigated in the validation of the diagnosis for children, integrating results across studies may provide a framework for understanding the differences in the presentation of severe mood disorders in children and adults." [Abstract]

Biederman J, Mick E, Faraone SV, Spencer T, Wilens TE, Wozniak J.
Current concepts in the validity, diagnosis and treatment of paediatric bipolar disorder.
Int J Neuropsychopharmacol. 2003 Sep;6(3):293-300.
"Despite ongoing controversy, the view that paediatric bipolar disorder is rare or non-existent has been increasingly challenged not only by case reports but also by systematic research. This research strongly suggests that paediatric bipolar disorder may not be rare but that it may be difficult to diagnose. Since children with bipolar disorder are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset bipolar disorder may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. As recommended by Robins and Guze [American Journal of Psychiatry (1970), 126, 983-987], a psychiatric disorder may be considered a valid diagnostic entity if it can be shown to have differentiating features, evidence of familiality, specific treatment responsivity and a unique course. The goal of this article is to review our work and the extant literature within this framework to describe the evidence supporting bipolar disorder in children as a valid clinical diagnosis." [Abstract]

Akin LK.
Pediatric and adolescent bipolar disorder: medical resources.
Med Ref Serv Q 2001 Fall;20(3):31-44
"An increasing body of research suggests the existence of early onset childhood bipolar disorder. The population of pediatric bipolar illness may be small, but current research points to early misdiagnosis of ADD/ADHD, and that attention deficit disorder may masquerade as a harbinger of the mania to come. Since ADD/ADHD estimates range up to 10% of the school population, the notion that ADD/ADHD precedes bipolar disorder leads to a significant increase in diagnosed depressives. This in turn produces an increase in information-seeking behaviors by parents, caregivers, and medical personnel. Variables hindering the information-seeking process include vocabulary, tool failure, co-morbidity, social prejudices, age issues, and environmental factors. This research provides reliable sources, Web sites, databases, key authors, electronic groups, and other accessible medical information in order to better serve the pediatric bipolar community." [Abstract]

Dilsaver SC, Henderson-Fuller S, Akiskal HS.
Occult mood disorders in 104 consecutively presenting children referred for the treatment of attention-deficit/hyperactivity disorder in a community mental health clinic.
J Clin Psychiatry. 2003 Oct;64(10):1170-6; quiz, 1274-6.
"OBJECTIVE: To ascertain the prevalence of mood disorders among consecutively evaluated prepubertal children presenting for the treatment of attention-deficit/hyperactivity disorder (ADHD) in a community mental health clinic. METHOD: 104 children received systematic assessments designed to identify individuals meeting the DSM-IV criteria for major depressive disorder (MDD), mania, and ADHD. "Standard" and "modified" criteria for mania were employed. Modified criteria, in an effort to minimize false-positive diagnoses of mania, required the presence of euphoria and/or flight of ideas. A child meeting the criteria for MDD or either set of criteria for mania was categorized as having a mood disorder. Mood disorders in first-degree relatives were assessed using a systematic interview. Data were gathered from 2000 to 2002. RESULTS: Sixty-two children (59.6%) had a mood disorder. Compared with those who did not have a mood disorder, they were 3.3 times more likely (54.8% vs. 16.7%) to have a family history of any affective disorder (p <.0001) and 18.3 times more likely (43.5% vs. 2.4%) to have a family history of bipolar disorder (p <.0001). Twenty (32.3%) of the children with and none without a mood disorder had psychotic features (p <.0001). Compared with those meeting only the standard criteria for mania, those meeting the modified criteria were 9.1 times more likely (69.8% vs. 7.7%) to have a family history of an affective disorder (p <.0001) and 7.3 times more likely (55.8% vs. 7.7%) to have a family history of bipolar disorder (p =.002). CONCLUSION: Children who presumably have ADHD often have unrecognized affective illness. Our findings support the view that children meeting the modified criteria for mania have veritable bipolar disorder. These findings, which were derived in the course of delivering routine clinical services in a community mental health clinic, are consistent with those obtained in research settings suggesting that children presenting with ADHD often have occult mood disorders, especially unrecognized bipolarity. We suggest that clinicians encountering children with prominent features of ADHD inquire about the presence of euphoria and flight of ideas. We submit that the presence of these "classic" manifestations of mania strongly suggests the presence of occult bipolarity, even if course of illness otherwise markedly deviates from "classic" descriptions." [Abstract]

Luby JL, Mrakotsky C.
Depressed preschoolers with bipolar family history: a group at high risk for later switching to mania?
J Child Adolesc Psychopharmacol. 2003 Summer;13(2):187-97.
"Earlier age of onset of an episode of depression and family history of bipolar disorder (FHBPD) are well known to be associated with increased rates of switching to mania in childhood major depressive disorder (MDD). These findings suggest that the youngest samples of depressed children who have FHBPD might be at very high risk for switching. The finding of a valid depressive syndrome in preschool children has raised the question of whether mania could also manifest at this early stage. We investigated FHBPD among three preschool study groups: a depressed group and two nondepressed comparison groups (attention deficit hyperactivity disorder/oppositional defiant disorder, no disorder). Increased FHBPD was found among the depressed group. Based on this, we explored whether the depressed subgroup with FHBPD (MDD + FHBPD) had a unique constellation of depressive symptoms compared to the depressed subgroup without FHBPD (MDD with no FHBPD). The MDD + FHBPD group was found to have an increased frequency of the MDD symptom of "restlessness and moves around a lot" as compared with the MDD with no FHBPD group. The question of whether this symptom could be an early precursor of later mania was explored. These findings taken together suggest that early risk factors for switching to mania may be present in a subgroup of depressed preschoolers. Longitudinal follow-up of depressed preschool samples to determine rates of switching to mania later in development is critical to determine whether such findings represent early risk factors. Future studies that directly investigate age-appropriate mania manifestations in preschool samples are now warranted." [Abstract]


Dilsaver SC.
Unsuspected depressive mania in pre-pubertal Hispanic children referred for the treatment of 'depression' with history of social 'deviance'.
J Affect Disord 2001 Dec;67(1-3):187-92
"BACKGROUND: Despite an emerging Literature on the mixed nature of pediatric mania, initial presentation with conduct problems continues to mislead mental health clinicians. The present report focuses on Hispanic pre-pubertal children referred for the treatment of depression in the context of conduct problems. METHODS: Eleven boys and two girls received a structured psychiatric assessment in a practice setting to make sense of the presenting clinical complexity. Diagnoses were assigned using the DSM-IV criteria. RESULTS: Ten of the boys and both girls met criteria for depressive mania. Their family histories were replete with affective disorder. Five (50%) of the boys and both of the girls (100%) with depressive mania had family histories of bipolar disorder. Six (60%) of the boys and neither of the girls with depressive mania had psychotic features. Those with depressive mania exhibited clear-cut circadian changes in symptomatology. Euphoria, oscillating with affective states indicative of psychic pain, was characteristically restricted to the evenings or nighttime. However, the drive to seek treatment had stemmed from social 'deviance'. CONCLUSION: Children with depressive mania are often unrecognized in clinical settings. Boys with conduct problems may be disproportionately represented among such children. These data support Akiskal's hypothesis that externalizing (conduct) problems in clinically referred children with depression are indicative of bipolar disorder." [Abstract]

Spencer TJ, Biederman J, Wozniak J, Faraone SV, Wilens TE, Mick E.
Parsing pediatric bipolar disorder from its associated comorbidity with the disruptive behavior disorders.
Biol Psychiatry 2001 Jun 15;49(12):1062-70
"The unique pattern of comorbidity found in pediatric mania greatly complicates accurate diagnosis, the course of the disorder, and its treatment. The pattern of comorbidity is unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder (ADHD), aggression, and conduct disorder. Clinically, symptoms of mania have been discounted as severe ADHD or ignored in the context of aggressive conduct disorder. This atypicality may lead to neglect of the mood component. The addition of high rates of additional disorders contributes to the severe morbidity, dysfunction, and incapacitation frequently observed in these children. A comprehensive approach to diagnostic evaluation is the keystone to establishing an effective treatment program because response to treatment differs with individual disorders. Recognition of the multiplicity of disorders guides therapeutic options in these often refractory conditions. What was previously considered refractory ADHD, oppositionality, aggression, and conduct disorder may respond after mood stabilization. We review these issues in this article." [Abstract]

Masi G, Toni C, Perugi G, Travierso MC, Millepiedi S, Mucci M, Akiskal HS.
Externalizing disorders in consecutively referred children and adolescents with bipolar disorder.
Compr Psychiatry. 2003 May-Jun;44(3):184-9.
"We describe a consecutive clinical sample of children and adolescents with bipolar disorder (BD), in order to define the pattern of comorbid externalizing disorders and to explore the possible influence of such a comorbidity on their cross-sectional and longitudinal clinical characteristics. The sample consisted of 59 bipolar patients: 35 males and 24 females, with a mean age 14.6 +/- 3 years (range, 7 to 18 years), diagnosed as either type I or II according to DSM-IV. All patients were screened for psychiatric disorders using historical information and a clinical interview, the Diagnostic Interview for Children and Adolescents-Revised (DICA-R). Severity and subsequent outcome of the symptomatology were recorded with the Clinical Global Impression (CGI), Severity and Improvement Scales, at the baseline and thereafter monthly for a period up to 48 months. BD disorder type I was present in 37 (62.7%) of the patients; 14 (23.7%) were affected by attention deficit-hyperactivity disorder (ADHD) and 10 (16.9%) by conduct disorder (CD). Comorbid ADHD was associated with an earlier onset of BD, while CD was highly associated with BD type I. Anxiety disorders appeared more represented in patients without CD. At the end of the observation, a lower clinical improvement was recorded in patients with CD. In our children and adolescents with BD, comorbidity with externalizing disorders such as ADHD and CD is common. The clinical implications of comorbid ADHD and CD are rather different. ADHD can be viewed as a precursor of a child-onset subtype of BD, while CD might represent a prodromal or a concomitant behavioral complication that identifies a more malignant and refractory form of BD." [Abstract]

Carlson GA, Youngstrom EA.
Clinical implications of pervasive manic symptoms in children.
Biol Psychiatry. 2003 Jun 1;53(11):1050-8.
"BACKGROUND: Prior investigations of cross-informant agreement among parents, teachers, and clinicians about externalizing and internalizing problems have not directly addressed agreement about manic symptoms. METHODS: We identified three groups from a large cohort of youths, aged 8-12 years, treated on an inpatient unit. All 108 participants met criteria for an externalizing disorder, based on a semi-structured diagnostic interview. Of these, 49 did not have manic symptoms endorsed by either the parent or a teacher; 34 had manic symptoms reported by the parent only, and 25 had pervasive manic symptoms (i.e., corroborated by both sources). RESULTS: The "corroborated mania" group consistently showed the most disruptive behavior on the inpatient unit, the worst behavior problems on multiple scales, and the longest admission durations. The "parent-only" group scored in the midrange on all of these measures, with group differences typically representing small to medium effect sizes. The "externalizing only" group consistently scored lowest on all dependent measures, with the differences representing large to extremely large effects when compared with the corroborated mania group and medium effects as compared with the parent-only group. CONCLUSIONS: Youths for whom multiple informants report manic symptoms appear likely to have more severe symptom presentation and more complicated, refractory courses than do youths without manic symptoms." [Abstract]

Harrington R, Myatt T.
Is preadolescent mania the same condition as adult mania? A British perspective.
Biol Psychiatry. 2003 Jun 1;53(11):961-9.
"Until relatively recently, the prevailing view was that mania was uncommon in preadolescent children. In the past 15 years, however, there has been increasing interest in the idea that mania may be much more common at younger ages than previously recognized. This article is concerned with the issue of whether preadolescent mania represents the same kind of problem as adult mania. It reviews concepts of bipolar disorder and mania in adults and preadolescents, some of the issue that arise in diagnosing mania in children, and the evidence for continuities between preadolescent and adult mania. The diagnosis of mania in preadolescent children often requires that inferences are made about the meaning of some symptoms but it is not always clear that these inferences are valid. It is concluded that the extant evidence does not provide a clear conclusion about the links between preadolescent and adult mania. More work is needed on the phenomenology and diagnosis of mania in children, on its natural history and on its familial correlates." [Abstract]

Mohr WK.
Bipolar disorder in children.
J Psychosoc Nurs Ment Health Serv 2001 Mar;39(3):12-23
"This article presents an overview of bipolar disorder (BPD) in children, a condition that only recently has been recognized as a legitimate diagnosis. Bipolar disorder in children is underrecognized for many reasons including lack of awareness, diagnostic confusion, and the different clinical picture in children. Available data strongly suggest that prepubertal childhood BPD is a non-episodic, chronic, rapid cycling, mixed manic state. It may be comorbid with attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) or it may demonstrate features of ADHD and CD, further complicating recognition and subsequent treatment. Treatment issues are discussed, and some reasons for the urgency of early recognition and treatment are explained." [Abstract]

Weller EB, Danielyan AK, Weller RA.
Somatic treatment of bipolar disorder in children and adolescents.
Child Adolesc Psychiatr Clin N Am. 2002 Jul;11(3):595-617.
"The currently available data from randomized, controlled trials and a considerable amount of open clinical data suggest that adolescent-onset bipolar disorder probably responds to the same agents as adult-onset bipolar disorder. Research examining psychopharmacologic treatment approaches in the early-onset bipolar disorder is limited, however. Methodologic problems include small sample sizes, lack of comparison groups, retrospective designs, and lack of standardized measures. In addition, sometimes no clear differentiation is made between mania and bipolar disorder, the latter term being used broadly in the literature. Often the studies show that symptoms improve because of treatment, but the functioning of the patients does not improve significantly. More research is clearly needed in all aspects of this disorder but especially in examining the efficacy of various types of treatment, its longitudinal course, and diagnostic issues. The indications for, and the overall duration of, long-term maintenance therapy need further study. Many adolescents and children with bipolar disorder do not respond to any of the first-line pharmacologic treatments; therefore, studies with novel agents should be extended to patients in this age range. Furthermore, physicians will probably continue to use combination therapies when confronted by either lack of efficacy or delayed onset of efficacy with a single agent. Thus, such resultant drug-drug interactions also should also be systematically studied [97]." [Abstract]

Bellivier F, Leroux M, Henry C, Rayah F, Rouillon F, Laplanche JL, Leboyer M.
Serotonin transporter gene polymorphism influences age at onset in patients with bipolar affective disorder.
Neurosci Lett 2002 Dec 6;334(1):17-20
"Serotonin transporter (SLC6A4) gene polymorphism is associated with several behavioral and psychiatric traits. In bipolar affective disorder, two polymorphisms of the SLC6A4 gene, a variable number of tandem repeats in the second intron and a 44 bp insertion/deletion in the serotonin transporter gene linked polymorphic region (5-HTTLPR), have been extensively studied. The findings are conflicting possibly because of the heterogeneity of bipolar disorder. Early-onset bipolar disorder appears to be clinically and genetically more homogeneous and was recently suggested to be associated with the 5-HTTLPR polymorphism. We tested the association between two polymorphisms of the SLC6A4 gene and age at onset (AAO) in a sample of bipolar patients. For both SLC6A4 gene polymorphisms, AAO of subjects with different genotypes were compared. SLC6A4 genotype distributions of different AAO groups were also compared. The variable number of tandem repeats (VNTR) polymorphism significantly influences the AAO but the serotonin transporter gene linked polymorphic region (5-HTTLPR) polymorphism did not. Patients carrying at least one VNTR STin2.12 allele began their illness later whereas patients carrying the 'ss' genotype tended to begin their illness earlier. Differential sampling procedures may influence the proportion of AAO subgroups in a given association study, and therefore these results may explain the conflicting results obtained in studies of the association between the SLC6A4 gene polymorphism and bipolar affective disorder (BPAD)." [Abstract]

Geller B, Bolhofner K, Craney JL, Williams M, DelBello MP, Gundersen K.
Psychosocial functioning in a prepubertal and early adolescent bipolar disorder phenotype.
J Am Acad Child Adolesc Psychiatry 2000 Dec;39(12):1543-8
"OBJECTIVE: To compare psychosocial functioning (PF) in a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP) sample to two comparison groups, i.e., attention-deficit/hyperactivity disorder (ADHD) and community controls (CC). METHOD: There were 93 PEA-BP (with or without comorbid ADHD), 81 ADHD, and 94 CC subjects who were participants in an ongoing study, the Phenomenology and Course of Pediatric Bipolar Disorders. Cases in the PEA-BP and ADHD groups were outpatients obtained by consecutive new case ascertainment, and CC subjects were from a survey conducted by the Research Triangle Institute. To fit the study phenotype, PEA-BP subjects needed to have current DSM-IV mania or hypomania with elation and/or grandiosity as one criterion. Assessments for PF were by experienced research nurses who were blind to group status. Mothers and children were separately interviewed with the Psychosocial Schedule for School Age Children-Revised. RESULTS: Compared with both ADHD and CC subjects, PEA-BP cases had significantly greater impairment on items that assessed maternal-child warmth, maternal-child and paternal-child tension, and peer relationships. CONCLUSIONS: Clinicians need to consider PF deficits when planning interventions. In the PEA-BP group, there was a 43% rate of hypersexuality with a <1% rate of sexual abuse, supporting hypersexuality as a manifestation of child mania." [Abstract]

Kent L, Craddock N.
Is there a relationship between attention deficit hyperactivity disorder and bipolar disorder?
J Affect Disord. 2003 Feb;73(3):211-21.
"With the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults and psychotic disorders in children and adolescents, the possibility of a relationship between bipolar disorder (BP) and ADHD has attracted growing interest. This paper critically reviews the scientific literature concerning this postulated relationship by examining evidence from clinico-epidemiological, follow up, family and laboratory studies, including neuroimaging, neuropsychology and genetic studies. The evidence suggests that although the diagnostic categories of BP and ADHD appear to be unrelated, there is support for a possible relationship between some ADHD and manic-like symptoms. However, several fundamental methodological issues require rectification in future research in order to further elucidate the relationship between these disorders." [Abstract]

Geller B, Zimerman B, Williams M, Bolhofner K, Craney JL.
Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder.
Am J Psychiatry 2001 Jan;158(1):125-7
"OBJECTIVE: The authors' goal was to conduct an adult follow-up of subjects who had participated in a study of nortriptyline for childhood depression. METHOD: The study group represented 100 (90. 9%) of the original 110 subjects and included 72 subjects who had a prepubertal diagnosis of major depressive disorder and 28 normal comparison subjects. Subjects were assessed with semistructured research interviews given by research nurses who were blind to the subjects' original diagnoses. RESULTS: In the original study, the mean age of the children with prepubertal major depressive disorder was 10.3 years (SD=1.5); at adult follow-up the mean age of these subjects was 20.7 years (SD=2.0). At follow-up, significantly more of the subjects who had prepubertal diagnoses of major depressive disorder (N=24 [33.3%]) than normal comparison subjects (none) had bipolar I disorder. Subjects who had prepubertal diagnoses of major depressive disorder also had significantly higher rates of any bipolar disorder than normal subjects (48.6% [N=35] versus 7.1% [N=2]), major depressive disorder (36.1% [N=26] versus 14.3% [N=4]), substance use disorders (30.6% [N=22] versus 10.7% [N=3]), and suicidality (22.2% [N=16] versus 3.6% [N=1]). Parental and grandparental mania predicted bipolar I disorder outcomes. CONCLUSIONS: High rates of switching to mania have implications for the treatment of depressed children. The authors discuss the reasons for their finding a higher rate of bipolar disorder in this outcome study than was found in the one other adult outcome study of prepubertal major depressive disorder." [Abstract]

Biederman J, Russell R, Soriano J, Wozniak J, Faraone SV.
Clinical features of children with both ADHD and mania: does ascertainment source make a difference?
J Affect Disord 1998 Nov;51(2):101-12
"OBJECTIVE: We evaluated the structural diagnostic results of children ascertained through an ADHD diagnosis with comorbid mania to determine if they have the same phenotype as children ascertained through a mania diagnosis with comorbid ADHD. METHOD: We compared a sample of children participating in a family genetic study of ADHD to a sample of children ascertained through a study of childhood mania. RESULTS: Similar correlates of ADHD and mania were observed in children satisfying criteria for both disorders irrespective of ascertainment source. CONCLUSIONS: Findings suggest that children with mania and ADHD have two disorders, their features not varying with the primary diagnostic focus. LIMITATIONS: The results may have been limited by small sample size. CLINICAL RELEVANCE: Because the coexistence of ADHD and mania seriously complicates the course and treatment of children, understanding the compatibility of these disorders has important clinical implications in the management of this population." [Abstract]

Geller B, Warner K, Williams M, Zimerman B.
Prepubertal and young adolescent bipolarity versus ADHD: assessment and validity using the WASH-U-KSADS, CBCL and TRF.
J Affect Disord 1998 Nov;51(2):93-100
"BACKGROUND: This addendum to 'Prepubertal and early adolescent bipolarity differentiate from ADHD by mania criteria; grandiose delusions; ultra-rapid or ultradian cycling' (in this volume) provides (1) a description of Washington University at St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) with sample sections (hypersexuality, rapid cycling); (2) a comparison of WASH-U-KSADS to KSADS-P/L and KSADS-1986 and (3) a comparison of WASH-U-KSADS to Child Behavior Checklist (CBCL) and Teachers Report Form (TRF) data. METHODS: Data were from the first 60 bipolar (BP) and first 60 ADHD subjects of 270 consecutively ascertained cases (90 BP, 90 ADHD and 90 community controls) in the NIMH funded 'Phenomenology and Course of Pediatric Bipolarity' study. Comprehensive assessments included the WASH-U-KSADS (administered blindly to mothers and separately to children), CBCL and TRF. RESULTS: As reported elsewhere in this volume, WASH-U-KSADS data significantly differentiated BP and ADHD groups. Significant differences were also found with the parent-rated CBCL and the teacher-rated TRF, thereby providing cross-modality and cross-informant validation of the WASH-U-KSADS. Because of the close agreement with published CBCL data from another investigator, cross-site validation also occurred. LIMITATIONS: Venues for consecutive ascertainment from the lowest socioeconomic status classes were unavailable due to current health care policies. CLINICAL RELEVANCE: CBCL and TRF data separated BP from ADHD groups, largely by non-specific externalizing dimensions (e.g., hyperactivity, aggressivity). Clinically relevant differentiation by categorical mania-specific criteria (e.g., elated mood, grandiosity, racing thoughts) occurred with WASH-U-KSADS data. Both types of data are crucial for genetic and neurobiological studies." [Abstract]

Geller B, Williams M, Zimerman B, Frazier J, Beringer L, Warner KL.
Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling.
J Affect Disord 1998 Nov;51(2):81-91
"BACKGROUND: In contrast to differential diagnosis (ddx) of older adolescent and adult bipolarity (BP), which includes schizophrenia and substance use disorders, the main ddx of prepubertal and early adolescent BP is attention-deficit disorder with hyperactivity (ADHD). To address this ddx issue, and to provide prepubertal mania manifestations, interim baseline data are presented from the National Institute of Mental Health (NIMH)-funded study 'Phenomenology and Course of Pediatric Bipolarity'. METHODS: Data are from the first 60 BP and the first 60 ADHD cases from 270 consecutively ascertained subjects (90 BP, 90 ADHD and 90 community controls). Comprehensive assessments included the Washington University at St. Louis Kiddie and Young Adult-Schedule for Affective Disorders and Schizophrenia--Lifetime and Present Episode Version-DSM-IV (WASH-U-KSADS) blindly administered by nurses to mothers about their offspring and to children/adolescents about themselves. Caseness was established by consensus conferences that included diagnostic and impairment data, teacher and school reports, agency records, videotapes and medical charts. RESULTS: Mean baseline age of BP cases was 11.0+/-2.7 years and the mean age at onset of BP was 8.1+/-3.5 years. Elated mood, grandiosity, hypersexuality, decreased need for sleep, racing thoughts and all other mania items except hyperenergetic and distractibility were significantly and substantially more frequent among BP than ADHD cases (e.g., elation: 86.7% BP vs. 5.0% ADHD; grandiosity: 85.0% BP vs. 6.7% ADHD). In the BP group, 55.0% had grandiose delusions, 26.7% had suicidality with plan/intent and 83.3% were rapid, ultra-rapid or ultradian cyclers. LIMITATIONS: Sites for consecutive case ascertainment from the lowest socioeconomic status classes were unavailable due to current health care policies. CLINICAL RELEVANCE: Prepubertal and early adolescent BP cases differentiate from ADHD by mania-specific criteria and commonly present with ultra-rapid or ultradian cycling." [Abstract]

Leboyer M, Bellivier F, McKeon P, Albus M, Borrman M, Perez-Diaz F, Mynett-Johnson L, Feingold J, Maier W.
Age at onset and gender resemblance in bipolar siblings.
Psychiatry Res 1998 Nov 16;81(2):125-31
"In order to measure the intrafamilial correlation for age at onset and to examine gender resemblance among bipolar siblings, we assessed a sample of 130 bipolar patients belonging to 59 multiple affected sibships. To study the intrafamilial resemblance for age at onset and gender, we used the intraclass correlation and the sibship method, respectively. Within the whole sample, age at onset for affected siblings was correlated (rho = 0.42, P = 0.0001). Gender was randomly distributed among bipolar sibships, demonstrating the absence of gender resemblance among affected siblings. The existence of an intrafamilial correlation for age at onset among bipolar siblings suggests that this variable may assist in the identification of more heritable forms of the illness. No intrafamilial correlation was found for the gender of affected siblings, suggesting that familial vulnerability factors are not gender-specific." [Abstract]

Rao U, Dahl RE, Ryan ND, Birmaher B, Williamson DE, Rao R, Kaufman J.
Heterogeneity in EEG sleep findings in adolescent depression: unipolar versus bipolar clinical course.
J Affect Disord. 2002 Aug;70(3):273-80.
"BACKGROUND: EEG sleep measures in child and adolescent subjects with depression have shown considerable variability regarding group differences between depressed and control subjects. This investigation was designed to assess whether some of the observed variability is related to undifferentiated unipolar and bipolar disorders in a sample that was reported previously. METHODS: Twenty-eight adolescents who met criteria for unipolar major depression and 35 controls with no lifetime psychiatric disorder participated in a cross-sectional sleep polysomnography study. Approximately 7 years later, follow-up clinical evaluations were conducted in 94% of the original cohort. Clinical course during the interval period was assessed without knowledge of subjects' initial diagnostic and psychobiological status. Re-analysis of the original sleep data were performed with the added information of longitudinal clinical course. RESULTS: Depressed subjects who had a unipolar course showed reduced REM latency, higher REM density, and more REM sleep (specifically in the early part of the night) compared with depressed adolescents who converted to bipolar disorder and controls who remained free from psychopathology at follow-up. In contrast to the unipolar group, depressed subjects who would later switch to bipolar disorder had demonstrated more stage 1 sleep and diminished stage 4 sleep. CONCLUSIONS: These preliminary results indicate that some of the observed variability in EEG sleep measures in adolescent depression appear to be confounded by latent bipolar illness. The findings also suggest that sleep regulatory changes associated with unipolar versus bipolar mood disorders may be different." [Abstract]

Faraone SV, Glatt SJ, Tsuang MT.
The genetics of pediatric-onset bipolar disorder.
Biol Psychiatry. 2003 Jun 1;53(11):970-7.
"Although bipolar disorder in adults has been extensively studied, early-onset forms of the disorder have received less attention. We review several lines of evidence indicating that pediatric- and early adolescent-onset bipolar disorder cases may prove the most useful for identifying susceptibility genes. Family studies have consistently found a higher rate of bipolar disorder among the relatives of early-onset bipolar disorder patients than in relatives of later-onset cases, which supports the notion of a larger genetic contribution to the early-onset cases. Comorbid pediatric bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) may also define a familial subtype of ADHD or bipolar disorder that is strongly influenced by genetic factors and may, therefore, be useful in molecular genetic studies. There are no twin and adoption studies of pediatric bipolar disorder, but the heritability of this subtype is expected to be high given the results from family studies. Thus, pediatric- and early adolescent-onset bipolar disorder may represent a genetically loaded and homogeneous subtype of bipolar disorder, which, if used in genetic linkage and association studies, should increase power to detect risk loci and alleles." [Abstract]

Leibenluft E, Charney DS, Towbin KE, Bhangoo RK, Pine DS.
Defining clinical phenotypes of juvenile mania.
Am J Psychiatry. 2003 Mar;160(3):430-7.
"OBJECTIVE: The authors suggest criteria for a range of narrow to broad phenotypes of bipolar disorder in children, differentiated according to the characteristics of the manic or hypomanic episodes, and present methods for validation of the criteria. METHOD: Relevant literature describing bipolar disorder in both children and adults was reviewed critically, and the input of experts was sought. RESULTS: Areas of controversy include whether the diagnosis of bipolar disorder should require clearly demarcated affective episodes and, if so, of what duration, and whether specific hallmark symptoms of mania should be required for the diagnosis. The authors suggest a phenotypic system of juvenile mania consisting of a narrow phenotype, two intermediate phenotypes, and a broad phenotype. The narrow phenotype is exhibited by patients who meet the full DSM-IV diagnostic criteria for hypomania or mania, including the duration criterion, and also have hallmark symptoms of elevated mood or grandiosity. The intermediate phenotypes include 1) hypomania or mania not otherwise specified, in which the patient has clear episodes and hallmark symptoms, but the episodes are between 1 and 3 days in duration, and 2) irritable hypomania or mania, in which the patient has demarcated episodes with irritable, but not elevated, mood. The broad phenotype is exhibited by patients who have a chronic, nonepisodic illness that does not include the hallmark symptoms of mania but shares with the narrower phenotypes the symptoms of severe irritability and hyperarousal. CONCLUSIONS: The presence of distinct episodes and hallmark symptoms can be used to differentiate clinical phenotypes of juvenile mania. The utility and validity of this system can be tested in subsequent research." [Abstract]

Chengappa KN, Kupfer DJ, Frank E, Houck PR, Grochocinski VJ, Cluss PA, Stapf DA.
Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry.
Am J Psychiatry. 2003 Sep;160(9):1636-42.
"OBJECTIVE: Utilizing data from a previously characterized registry of subjects with bipolar illness, the authors examined age at onset of the first illness episode in cohorts of subjects born from 1900 through 1939 and from 1940 through 1959. METHOD: Demographic and clinical characteristics at the first full episode of bipolar disorder of subjects in a diagnostically validated voluntary bipolar disorder registry (N=1,218) were reviewed and subjected to statistical analyses. RESULTS: The median age at onset of the first episode of bipolar illness was lower by 4.5 years in subjects born during or after 1940 (median age=19 years), compared with subjects born before 1940 (median age=23.5 years). The proportion of subjects with bipolar disorder presenting with a prepubertal onset was significantly higher in the later birth-year cohort than in the earlier birth-year cohort. More than 50% of male and female subjects in both cohorts had a depressive episode as the first episode of bipolar illness. Subjects in each cohort who had a parent with major depression, bipolar disorder, or schizophrenia experienced their first episode nearly 4 to 5 years earlier than the other subjects in the cohort. CONCLUSIONS: Prospective epidemiological studies conducted with bipolar disorder subjects are needed to either affirm or refute these data on age at illness onset. If the results are affirmed, the early recognition of prepubertal bipolar disorder will be important, so that the condition can be treated with appropriate medications and medications that could potentially worsen the illness course can be avoided. Similarly, early recognition of bipolar illness is important, especially in women, to minimize use of antidepressant monotherapy for patients with bipolar illness. Among young people presenting with major depression as the first illness episode, a parental history of major depression, bipolar disorder, or psychosis may be a useful pointer to future bipolar disorder. Early recognition and appropriate treatment of bipolar illness may prevent the development of chronicity and serious functional impairment." [Abstract]

Fergus EL, Miller RB, Luckenbaugh DA, Leverich GS, Findling RL, Speer AM, Post RM.
Is there progression from irritability/dyscontrol to major depressive and manic symptoms? A retrospective community survey of parents of bipolar children.
J Affect Disord. 2003 Oct;77(1):71-8.
"BACKGROUND: Although previous studies have discussed age-related changes in the presentation of early onset bipolar illness, the developmental progression of early symptoms remains unclear. The current study sought to trace parents' retrospective report of yearly occurrence of symptoms in a sample of children with and without a diagnosis of bipolar disorder in the community. METHODS: Parents retrospectively rated the occurrence of 37 activated and withdrawn symptoms causing dysfunction for each year of their child's life (mean age 12.6 +/- 6.9). Children were divided into three groups based on parent report of diagnosis by a community clinician: bipolar (n=78); non-bipolar diagnosis (n=38); and well (no psychiatric diagnosis) (n=82). Principal components analysis was performed to understand the relationship among the symptom variables and their potential differences among the three groups as a function of age. RESULTS: Four symptom components were derived and these began to distinguish children with bipolar disorder from the other groups at different ages. Component II (irritability/dyscontrol), which included temper tantrums, poor frustration tolerance, impulsivity, increased aggression, decreased attention span, hyperactivity and irritability, began to distinguish bipolar children from the others the earliest (i.e., from ages 1 to 6). The other components (I, III, and IV) which included symptoms more typical of adult depression (I), mania (III), and psychosis (IV), distinguished the children with a bipolar diagnosis from the others much later (between ages 7 and 12). LIMITATIONS: The data were derived from retrospective reports by parents of their children's symptoms on a yearly symptom check list instrument which has not been previously utilized. Parents' ratings were not validated by an outside rater. Moreover, the children were diagnosed in the community and a formal diagnostic interview was not given. CONCLUSIONS: By parental report, the cluster of symptoms in the irritability/dyscontrol component may characterize the earliest precursors to an illness eventually associated with more classic manic and depressive components that are diagnosed and treated as bipolar disorder in the community. These retrospective survey data suggesting a longitudinal evolution of symptom clusters in childhood bipolar-like illness identify a number of areas for prospective research and validation." [Abstract]

Rajeev J, Srinath S, Reddy YC, Shashikiran MG, Girimaji SC, Seshadri SP, Subbakrishna DK.
The index manic episode in juvenile-onset bipolar disorder: the pattern of recovery.
Can J Psychiatry. 2003 Feb;48(1):52-5.
"OBJECTIVE: Recent studies of patients with juvenile bipolar disorder report low rates of recovery and high rates of chronicity. However, we lack data on the short-term outcome. This study examines the pattern of recovery from the index episode in an aggressively treated juvenile sample. METHOD: We assessed 25 subjects (< 16 years) with a diagnosis of mania, using the Diagnostic Interview for Children and Adolescents-Revised) (DICA-R), Young Mania Rating Scale (YMRS), and Children's Global Assessment Scale (CGAS) at intake and at 3 and 6 months. We studied the time taken to recover from the index episode, the level of functioning, and the factors predicting them. RESULTS: After 6 months, 24 (96%) subjects had recovered from the index manic episode. The median time to recovery was 27 days. Total episode length was significantly longer among those with previous affective episodes. CONCLUSIONS: The findings suggest that juvenile-onset mania has high rates of recovery and low rates of chronicity. These differences from the existing literature need further exploration." [Abstract]

Tillman R, Geller B, Nickelsburg MJ, Bolhofner K, Craney JL, DelBello MP, Wigh W.Tillman R, Geller B, Nickelsburg MJ, Bolhofner K, Craney JL, DelBello MP, Wigh W.
Life events in a prepubertal and early adolescent bipolar disorder phenotype compared to attention-deficit hyperactive and normal controls.
J Child Adolesc Psychopharmacol. 2003 Fall;13(3):243-51.
"OBJECTIVE: To examine life events in subjects with a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP) compared to those in subjects with attention-deficit hyperactivity disorder (ADHD) and normal controls (NC). METHODS: To optimize generalizeability, subjects with PEA-BP (n = 93) and ADHD (n = 81) were consecutively ascertained from pediatric and psychiatric sites. Subjects in the NC group (n = 94) were obtained from a random survey. PEA-BP was defined by Diagnostic and Statistical Manual of Mental Disorders (fourth edition) mania with at least one of the cardinal symptoms of mania (i.e., elation and/or grandiosity) to avoid diagnosing mania only by criteria that overlapped with those for ADHD. All subjects received comprehensive, blind research assessments of mothers about their children and separately of children about themselves. Assessment instruments included the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) and the Life Events Checklist. Data from the Life Events Checklist were examined by total life events and by subcategories of dependent, independent, or uncertain relationships to the child. RESULTS: Total, independent, dependent, and uncertain life events were all significantly more frequent in the PEA-BP subjects compared to both the ADHD and NC groups. CONCLUSIONS: Because there was no a priori reason to expect significantly more independent life events in the PEA-BP compared to the ADHD and NC groups, these results warrant further research into the role of life events in the onset of PEA-BP." [Abstract]

Dienes KA, Chang KD, Blasey CM, Adleman NE, Steiner H.
Characterization of children of bipolar parents by parent report CBCL.
J Psychiatr Res 2002 Sep-Oct;36(5):337-45
"In past research the Child Behavior Checklist (CBCL) has differentiated among various diagnostic categories for children and adolescents. However, research has not been conducted on whether the CBCL differentiates among diagnostic categories for children at high risk for development of psychopathology. This study compares four diagnostic groups [bipolar disorder (BD), attention/deficit-hyperactivity disorder (ADHD), Depressed/Anxious and No Diagnosis] within a cohort of 58 children of bipolar parents to determine whether their CBCL scores will replicate the scores of children not at high risk for bipolar disorder. The cohort of children of bipolar parents received elevated scores on the CBCL scales in comparison with non-clinical populations. In addition, the CBCL distinguished between children of bipolar parents with and without clinical disorders. Finally the BD group differed from the ADHD group only on the Aggressive Behaviors, Withdrawn and Anxious/Depressed subscales of the CBCL. Therefore the CBCL did not discriminate between the BD and ADHD groups as it had in previous studies of children with BD and unspecified family history. It is possible that this discrepancy is due to a group of children of bipolar parents with ADHD who are currently prodromal for bipolar disorder and therefore received higher scores on the CBCL based on prodromal symptomatology. A longitudinal follow-up of this cohort is necessary to ascertain whether this is the case." [Abstract]

Hodgins S, Faucher B, Zarac A, Ellenbogen M.
Children of parents with bipolar disorder. A population at high risk for major affective disorders.
Child Adolesc Psychiatr Clin N Am. 2002 Jul;11(3):533-53, ix.
"Children of parents who suffer from bipolar disorder are largely ignored by psychiatric services despite the fact that they constitute a population at very high risk for major depression and bipolar disorder in adulthood and a wide variety of disorders in childhood and adolescence. Major depression and bipolar disorder are chronic, recurrent disorders that seriously impair psychosocial functioning across the life-span. Evidence suggests that in this population bipolar disorder is preceded by externalizing disorders in childhood in many cases, and by depression in some cases. While heredity provides the vulnerability for the development of these characteristics, being raised by parents who model inappropriate coping skills, create a stressful family environment, and provide inadequate support and structure, contribute to consolidating these characteristics." [Abstract]

Chang KD, Blasey CM, Ketter TA, Steiner H.
Temperament characteristics of child and adolescent bipolar offspring.
J Affect Disord. 2003 Oct;77(1):11-9.
"BACKGROUND: We wished to characterize temperament of children at high risk for bipolar disorder (BD). METHODS: We collected data from the Dimensions of Temperament-Revised (DOTS-R) from 53 biological offspring of at least one parent with BD. RESULTS: Overall, our cohort differed from population means for the DOTS-R, having decreased Activity Level-General scores, and increased Approach, and Rhythmicity-Sleep scores. Offspring with psychiatric disorders differed from those without in having decreased Flexibility, Mood, and Task Orientation scores. Temperament profiles for diagnostic categories of BD and attention-deficit/hyperactivity disorder were performed in a descriptive manner. LIMITATIONS: Self- or parent-report of temperament was used rather than clinical observation. Temperament characterization was cross-sectional and retrospective rather than prospective and may overlap with clinical diagnoses. CONCLUSIONS: Assessment of temperament may be useful in characterizing bipolar offspring. Decreased flexibility and task orientation, and presence of negative moods may be correlated with development of psychopathology." [Abstract]

Lewinsohn PM, Seeley JR, Buckley ME, Klein DN.
Bipolar disorder in adolescence and young adulthood.
Child Adolesc Psychiatr Clin N Am 2002 Jul;11(3):461-75, vii
"The purpose of this article is to present findings from the Oregon Adolescent Depression Project regarding full-syndrome and subthreshold bipolar disorder (BD) in adolescence and young adulthood. BD first incidence peaked around age 14 years. Adolescent BD showed significant continuity across developmental periods and was associated with adverse outcomes during young adulthood. Subthreshold BD results provide partial support for a bipolar spectrum." [Abstract]

Robertson HA, Kutcher SP, Bird D, Grasswick L.
Impact of early onset bipolar disorder on family functioning: adolescents' perceptions of family dynamics, communication, and problems.
J Affect Disord 2001 Sep;66(1):25-37
"OBJECTIVE: This research investigated the impact of adolescent onset bipolar illness on perceived family functioning in stabilized bipolar I (B) and unipolar (U) probands, and normal controls (C). METHOD: Sample N=119: 44 bipolar 1(17 M, 27 F), 30 unipolar (9 M, 21 F), and 45 controls (19 M, 26 F). Mean ages: 19.9, 18.5 and 18.2 years, respectively. INSTRUMENTS: Family Adaptability and Cohesion Scale (FACES II), Parent-Adolescent Communication Scales (PACS), Social Adjustment Inventory for Children and Adolescents (SAICA). RESULTS: There were no significant group or sex differences between controls and mood disordered youth--assessed intermorbidly--in ratings of relationship with either parent. Bipolars acknowledged significantly more minor conflicts with parents than either unipolars or controls. Ratings by mood disordered subjects were significantly less positive in terms of shared activities and communication with siblings. Mood disordered youth and controls were not differentiated on the basis of family adaptability, and all family cohesion scores were within population norms. No significant group differences were observed in communication with parents. LIMITATIONS: This self-report study was conducted intermorbidly, does not include objective measures of family functioning, nor does it assess the effect of psychiatric illness in other family members on family functioning. CONCLUSIONS: Assessed intermorbidly, bipolar adolescents' perceptions of family dynamics do not seem to diverge significantly from controls. Further research is needed to investigate the impact of adolescent bipolar illness on family life during acute phases of the illness, as well as the effect on family functioning of psychiatric disorders in other family members." [Abstract]

Masi G, Toni C, Perugi G, Mucci M, Millepiedi S, Akiskal HS.
Anxiety disorders in children and adolescents with bipolar disorder: a neglected comorbidity.
Can J Psychiatry 2001 Nov;46(9):797-802
"OBJECTIVE: We describe a consecutive clinical sample of children and adolescents with bipolar disorder to define the pattern of comorbid anxiety and externalizing disorders (attention-deficit hyperactivity disorder [ADHD] and conduct disorder [CD]) and to explore the possible influence of such a comorbidity on their cross-sectional and longitudinal clinical characteristics. METHODS: The sample comprised 43 outpatients, 26 boys and 17 girls, (mean age 14.9 years, SD 3.1; range 7 to 18), with bipolar disorder type I or II, according to DSM-IV diagnostic criteria. All patients were screened for psychiatric disorders using historical information and a clinical interview, the Diagnostic Interview for Children and Adolescents-Revised (DICA-R). To shed light on the possible influence of age at onset, we compared clinical features of subjects whose bipolar onset was prepubertal or in childhood (< 12 years) with those having adolescent onset. We also compared different subgroups with and without comorbid externalizing and anxiety disorders. RESULTS: Bipolar disorder type I was slightly more represented than type II (55.8% vs 44.2%). Only 11.6% of patients did not have any other psychiatric disorder; importantly, 10 subjects (23.5%) did not show any comorbid anxiety disorder. Comorbid externalizing disorders were present in 12 (27.9%) patients; such comorbidity was related to the childhood onset of bipolar disorder type II. Compared with other subjects, patients with comorbid anxiety disorders more often reported pharmacologic (hypo)mania." [Abstract]

Wozniak J, Biederman J, Richards JA.
Diagnostic and therapeutic dilemmas in the management of pediatric-onset bipolar disorder.
J Clin Psychiatry 2001;62 Suppl 14:10-5
"Although the diagnosis of pediatric-onset bipolar disorder is controversial, an increasing literature of systematic research has challenged the traditional view that this disorder is a rare condition. This article summarizes research regarding the atypical presentation of pediatric bipolar disorder and its overlap with attention-deficit/hyperactivity disorder and other comorbid conditions, as well as family-genetic and treatment data. When structured interview data were examined, cases of pediatric mania constituted 16% of referrals to our outpatient clinic. Presentation is atypical by adult standards and includes irritability, chronicity, and mixed state. Family-genetic and treatment data help to establish diagnostic validity. Pediatric bipolar disorder is not a rare condition. Treatment requires a combined pharmacotherapy approach to address issues of comorbidity." [Abstract]

DelBello MP, Soutullo CA, Hendricks W, Niemeier RT, McElroy SL, Strakowski SM.
Prior stimulant treatment in adolescents with bipolar disorder: association with age at onset.
Bipolar Disord 2001 Apr;3(2):53-7
"OBJECTIVES: To compare demographic and clinical characteristics between bipolar adolescents with and without a history of stimulant treatment, we hypothesized that adolescents treated with stimulants would have an earlier age at onset of bipolar disorder, independent of co-occurring attention-deficit-hyperactivity disorder (ADHD). METHOD: Thirty-four adolescents hospitalized with mania were assessed using the Washington University at St Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS). We systematically evaluated age at onset of bipolar disorder and pharmacological treatment history. RESULTS: Bipolar adolescents with a history of stimulant exposure prior to the onset of bipolar disorder had an earlier age at onset of bipolar disorder than those without prior stimulant exposure. Additionally, bipolar adolescents treated with at least two stimulant medications had a younger age at onset compared with those who were treated with one stimulant. There was no difference in age at onset of bipolar disorder between bipolar adolescents with and without ADHD. CONCLUSIONS: Our results suggest that stimulant treatment, independent of ADHD, is associated with younger age at onset of bipolar disorder. A behavioral sensitization model is proposed to explain our findings. There are several limitations to our study including the small sample size, the retrospective assessment of stimulant exposure and age at onset of bipolar disorder, and the inclusion of only hospitalized patients, who may be more likely to present with a severe illness. Nonetheless, future prospective longitudinal investigations that systematically assess the effects of stimulant medications in children with or at genetic risk for bipolar disorder are warranted." [Abstract]

Soutullo CA, DelBello MP, Ochsner JE, McElroy SL, Taylor SA, Strakowski SM, Keck PE Jr.
Severity of bipolarity in hospitalized manic adolescents with history of stimulant or antidepressant treatment.
J Affect Disord. 2002 Aug;70(3):323-7.
"BACKGROUND: Childhood bipolarity (BP) and ADHD frequently co-occur, these children often receive stimulants. METHOD: We retrospectively evaluated 80 adolescents hospitalized with BP, manic or mixed, assessed severity of hospital course, and compared groups according to current/past stimulant or antidepressant treatment. RESULTS: Lifetime ADHD rate was 49%; 35% of patients had exposure to stimulants and 44% to antidepressants. Stimulant-exposed patients were younger than non-exposed (mean+/-S.D.=13.7+/-2 vs. 15.1+/-2 years, Z=-3.1, P=0.002). Only stimulant exposure was associated with worse hospitalization course (MANCOVA, Wilks' Lambda=0.87, F=3.4; df=70; P=0.02). CONCLUSION: Stimulant-exposed BP-adolescents may have more severe illness course not fully explained by ADHD comorbidity. LIMITATIONS: Retrospective methodology and lack of structured interviewing make it difficult to quantify exposure to stimulants and antidepressants." [Abstract]

Carlson GA, Jensen PS, Findling RL, Meyer RE, Calabrese J, DelBello MP, Emslie G, Flynn L, Goodwin F, Hellander M, Kowatch R, Kusumakar V, Laughren T, Leibenluft E, McCracken J, Nottelmann E, Pine D, Sachs G, Shaffer D, Simar R, Strober M, Weller EB, Wozniak J, Youngstrom EA.
Methodological issues and controversies in clinical trials with child and adolescent patients with bipolar disorder: report of a consensus conference.
J Child Adolesc Psychopharmacol. 2003 Spring;13(1):13-27.
"OBJECTIVE: To achieve consensus among researchers, pharmaceutical industry representatives, federal regulatory agency staff, and family advocates on a template for clinical trials of acute mania/bipolar disorder in children and adolescents. METHOD: The American Academy of Child and Adolescent Psychiatry, in collaboration with Best Practice, convened a group of experts from the key stakeholder communities (including adult psychiatrists with expertise in bipolar disorder) and assigned them to workgroups to examine core methodological issues surrounding the design of clinical trials and, ultimately, to generate a consensus statement encompassing: (1) inclusion/exclusion criteria, (2) investigator training needs and site selection, (3) assessment and outcome measures, (4) protocol design and ethical issues unique to trials involving children/adolescents, and (5) regulatory agency perspectives on these deliberations. RESULTS: Conference participants reached agreement on 18 broad methodological questions. Key points of consensus were to assign priority to placebo-controlled studies of acute manic episodes in children and adolescents aged 10-17 years, who may or may not be hospitalized, and who may or may not suffer from common comorbid psychiatric disorders; to require that specialist diagnostic "gatekeepers" screen youths' eligibility to participate in trials; to monitor interviewer and rater competency over the course of the trial using agreed upon standards; and to develop new tools for assessment, including scales to measure aggression/rage and cognitive function, while using the best available instruments (e.g., Young Mania Rating Scale) in the interim. CONCLUSIONS: Methodologically rigorous, large-scale clinical trials of treatment of acute mania are urgently needed to provide information regarding the safety and efficacy, in youth, of diverse agents with potential mood-stabilizing properties." [Abstract]

Wozniak J, Monuteaux M, Richards J, E Lail K, Faraone SV, Biederman J.
Convergence between structured diagnostic interviews and clinical assessment on the diagnosis of pediatric-onset mania.
Biol Psychiatry. 2003 Jun 1;53(11):938-44.
"BACKGROUND: Uncertainties remain as to the utility of structured diagnostic methodology to aid in the diagnosis of manic symptomatology in youth. To this end, this study compared structured diagnostic interview based diagnoses of mania in children and adolescents with that of an expert clinician. METHODS: We separately and independently assessed 69 youths recruited for a study of mania in childhood, all but 2 of whom experienced mania, with a structured diagnostic interview administered by trained psychometricians and a clinical assessment by a board-certified child and adolescent psychiatrist (JW) who was blind to the structured interview results. RESULTS: Structured interviews and clinical evaluations converged in all but two cases (67 of 69 or 97% agreement). In one discrepant case, the structured interview diagnosed a full case of mania, but the clinical interview diagnosed cyclothymia/subthreshold mania; in the other discrepant case, the structured interview failed to diagnose mania, but the clinical interview did diagnose mania. CONCLUSIONS: In children referred for evaluation of suspected bipolar disorder, a structured interview diagnosis of mania is very likely to be corroborated by a clinical interview." [Abstract]

Geller B, Zimerman B, Williams M, Bolhofner K, Craney JL, DelBello MP, Soutullo C.
Reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections.
J Am Acad Child Adolesc Psychiatry 2001 Apr;40(4):450-5
"OBJECTIVE: To investigate the reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections. METHOD: The 1986 version of the KSADS was modified and expanded to include onset and offset of each symptom for both current and lifetime episodes, expanded prepubertal mania and rapid cycling sections, and categories for attention-deficit/hyperactivity disorder and other DSM-IV diagnoses. To optimize diagnostic research, skip-outs were minimized. Subjects participated in the ongoing "Phenomenology and Course of Pediatric Bipolar Disorder" study. Mothers and children were interviewed separately by research nurses who were blind to diagnostic group status. In addition, ratings of off-site child psychiatrists, made from the narrative documentation given for each WASH-U-KSADS item, were compared with research nurse ratings. This work was performed between 1995 and 2000. RESULTS: There was 100% interrater reliability, five consecutive times, as both interviewer and observer after 10 to 15 trials. The kappa values of comparisons between research nurse and off-site blind best-estimate ratings of mania and rapid cycling sections were excellent (0.74-1.00). High 6-month stability for mania diagnoses (85.7%) and for individual mania items and validity against parental and teacher reports were previously reported. CONCLUSIONS: The WASH-U-KSADS mania and rapid cycling sections have acceptable reliability." [Abstract]

Dickstein DP, Treland JE, Snow J, McClure EB, Mehta MS, Towbin KE, Pine DS, Leibenluft E.
Neuropsychological performance in pediatric bipolar disorder.
Biol Psychiatry. 2004 Jan 1;55(1):32-9.
"BACKGROUND: Growing awareness of childhood bipolar disorder necessitates further cognitive neuroscience research to determine unique developmental differences between pediatric and adult onset bipolar disorder. We sought to examine whether neuropsychological function in children with bipolar disorder resembles that in adults with the illness and to extend our knowledge about cognitive function in pediatric bipolar disorder. METHODS: We administered a computerized neuropsychological test battery known as the Cambridge Neuropsychological Test Automated Battery to a sample of 21 children and adolescents with bipolar disorder and compared them with 21 age- and gender-matched controls. RESULTS: In comparison to controls, children with bipolar disorder were impaired on measures of attentional set-shifting and visuospatial memory. Post hoc analyses in pediatric bipolar disorder subjects did not show significant associations between neuropsychological performance and manic symptomatology or attention-deficit/hyperactivity disorder comorbidity. CONCLUSIONS: Cambridge Neuropsychological Test Automated Battery data presented here in pediatric bipolar disorder fit well within the broader framework of known neurocognitive deficits in adult bipolar disorder. Our pediatric bipolar disorder subjects demonstrated selective deficiencies in attentional set-shifting and visuospatial memory. Our work suggests altered ventrolateral prefrontal cortex function, especially when linked to other lesion and neuroimaging studies." [Abstract]

Biederman J, Mick E, Wozniak J, Monuteaux MC, Galdo M, Faraone SV.
Can a subtype of conduct disorder linked to bipolar disorder be identified? Integration of findings from the Massachusetts General Hospital Pediatric Psychopharmacology Research Program.
Biol Psychiatry. 2003 Jun 1;53(11):952-60.
"Our intent was to investigate systematically the overlap between conduct disorder (CD) and bipolar disorder (BPD). We hypothesized that neither CD nor manic symptoms were secondary to the other disorder and that children with the two disorders would have correlates of both. Results from a series of programmatic studies examining phenotypic features of bipolar and conduct disorder alone or combined in probands and relatives were evaluated within and without the context of ADHD. Examination of the clinical features, patterns of psychiatric comorbidity, functioning in multiple domains, and familiality showed that children with CD and BPD had similar features of each disorder irrespective of the comorbidity with the other disorder. Our data suggest that when BPD and CD co-occur in children, both are correctly diagnosed. In these comorbid cases, CD symptoms should not be viewed as secondary to BPD, and manic symptoms should not be viewed as secondary to CD." [Abstract]

Biederman J, Faraone SV, Wozniak J, Monuteaux MC.
Parsing the association between bipolar, conduct, and substance use disorders: a familial risk analysis.
Biol Psychiatry 2000 Dec 1;48(11):1037-44
"BACKGROUND: Bipolar disorder has emerged as a risk factor for substance use disorders (alcohol or drug abuse or dependence) in youth; however, the association between bipolar disorder and substance use disorders is complicated by comorbidity with conduct disorder. We used familial risk analysis to disentangle the association between the three disorders. METHODS: We compared relatives of four proband groups: 1) conduct disorder + bipolar disorder, 2) bipolar disorder without conduct disorder, 3) conduct disorder without bipolar disorder, and 4) control subjects without bipolar disorder or conduct disorder. All subjects were evaluated with structured diagnostic interviews. For the analysis of substance use disorders, Cox proportional hazard survival models were utilized to compare age-at-onset distributions. RESULTS: Bipolar disorder in probands was a risk factor for both drug and alcohol addiction in relatives, independent of conduct disorder in probands, which was a risk factor for alcohol dependence in relatives independent of bipolar disorder in probands, but not for drug dependence. The effects of bipolar disorder and conduct disorder in probands combined additively to predict the risk for substance use disorders in relatives. CONCLUSIONS: The combination of conduct disorder + bipolar disorder in youth predicts especially high rates of substance use disorders in relatives. These findings support previous results documenting that when bipolar disorder and conduct disorder occur comorbidly, both are validly diagnosed disorders." [Abstract]

Shrier LA, Harris SK, Kurland M, Knight JR.
Substance use problems and associated psychiatric symptoms among adolescents in primary care.
Pediatrics. 2003 Jun;111(6 Pt 1):e699-705.
"OBJECTIVE: Substance use disorders (SUDs) are associated with other mental disorders in adolescence, but it is unclear whether less severe substance use problems (SUPs) also increase risk. Because youths with SUPs are most likely to present first to their site of primary care, it is important to establish the presence and patterns of psychiatric comorbidity among adolescent primary care patients with subdiagnostic use of alcohol or other drugs. The objective of this study was to determine the association between level of substance use and psychiatric symptoms among adolescents in a primary care setting. METHODS: Patients who were aged 14 to 18 years and receiving routine care at a hospital-based adolescent clinic were eligible. Participants completed the Problem Oriented Screening Instrument for Teenagers Substance Use/Abuse scale, which is designed to detect social and legal problems associated with alcohol and other drugs, and the Adolescent Diagnostic Interview, which evaluates for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnoses of substance abuse/dependence and 8 types of psychiatric symptoms. We examined gender-specific associations of no/nonproblematic substance use (NSU), SUP, and SUD with psychiatric symptom presence (any symptoms within each type), score (symptom scores summed across all types), and number of types (number of different symptom types endorsed). RESULTS: Of 538 adolescents (68% female; mean +/- standard deviation age: 16.6 +/- 1.4 years), 66% were classified with NSU, 18% with SUP, and 16% with SUD, and 80% reported having at least 1 type of psychiatric symptom in the previous 12 months. Symptoms of anxiety were most common (60% of both boys and girls), followed by symptoms of depression among girls (51%) and symptoms of attention-deficit disorder (ADD) among boys (47%). Compared with those with NSU, youths with SUP and those with SUD were more likely to report symptom presence for several types of psychiatric symptoms. Girls with SUP or SUD had increased odds of reporting symptoms of mania, ADD, and conduct disorder; girls with SUD were at increased risk for symptoms of depression, eating disorders, and hallucinations or delusions. Boys with SUP had increased odds of ADD symptoms, whereas boys with SUD had increased odds of reporting hallucinations or delusions. Boys with SUP or SUD had increased odds of reporting symptoms of conduct disorder. Youths with SUP and SUD also had higher psychiatric symptom scores and reported a wider range of psychiatric symptom types (number of types) compared with youths with NSU. CONCLUSIONS: Like those with SUD, adolescents with subdiagnostic SUP were at increased risk for experiencing a greater number of psychiatric symptoms and a wider range of psychiatric symptom types than youths with NSU. Specifically, adolescents with SUP are at increased risk for symptoms of mood (girls) and disruptive behavior disorders (girls and boys). These findings suggest the clinical importance of SUP and support the concept of a continuum between subthreshold and diagnostic substance use among adolescents in primary care. Identification of youths with SUP may allow for intervention before either the substance use or any associated psychiatric problems progress to more severe levels." [Abstract]

Wilens TE, Biederman J, Millstein RB, Wozniak J, Hahesy AL, Spencer TJ.
Risk for substance use disorders in youths with child- and adolescent-onset bipolar disorder.
J Am Acad Child Adolesc Psychiatry 1999 Jun;38(6):680-5
"OBJECTIVE: Previous work in adults has suggested that early-onset bipolar disorder (BPD) is associated with an elevated risk for substance use disorders (SUD). To this end, the authors assessed the risk for SUD in child- versus adolescent-onset BPD with attention to comorbid psychopathology. METHOD: All youths (aged 13-18 years) with available structured psychiatric interviews were studied systematically. From clinic subjects (N = 333), 86 subjects with DSM-III-R BPD were identified. To evaluate the risk for SUD and BPD while attending to developmental issues, the authors stratified the BPD sample into those with child-onset BPD (< or = 12 years of age, n = 50) and those with adolescent-onset BPD (13-18 years of age, n = 36). RESULTS: In mid-adolescence, youths with adolescent-onset BPD were at significantly increased risk for SUD relative to those with child-onset BPD (39% versus 8%; p = .001). Compared with those with child-onset BPD, those with adolescent-onset BPD had 8.8 times the risk for SUD (95% confidence interval = 2.2-34.7; chi 7(2) = 9.7, p = .002). The presence of conduct disorder or other comorbid psychopathology within BPD did not account for the risk for SUD. CONCLUSIONS: Adolescent-onset BPD is associated with a much higher risk for SUD than child-onset BPD, which was not accounted for by conduct disorder or other comorbid psychopathology. Youths with adolescent-onset BPD should be monitored and educated about SUD risk. The identification and treatment of manic symptomatology may offer therapeutic opportunities to decrease the risk for SUD in these high-risk youths." [Abstract]

Chang KD, Steiner H, Ketter TA.
Psychiatric phenomenology of child and adolescent bipolar offspring.
J Am Acad Child Adolesc Psychiatry 2000 Apr;39(4):453-60
"OBJECTIVE: To establish prodromal signs of and risk factors for childhood bipolar disorder (BD) by characterizing youths at high risk for BD. METHOD: Structured diagnostic interviews were performed on 60 biological offspring of at least one parent with BD. Demographics, family histories, and parental history of childhood disruptive behavioral disorders were also assessed. RESULTS: Fifty-one percent of bipolar offspring had a psychiatric disorder, most commonly attention-deficit/hyperactivity disorder (ADHD), major depression or dysthymia, and BD. BD in offspring tended to be associated with earlier parental symptom onset when compared with offspring without a psychiatric diagnosis. Bipolar parents with a history of childhood ADHD were more likely to have children with BD, but not ADHD. Offspring with bilineal risk had increased severity of depressed and irritable mood, lack of mood reactivity, and rejection sensitivity, while severity of grandiosity, euphoric mood, and decreased need for sleep were not preferentially associated with such offspring. CONCLUSIONS: Bipolar offspring have high levels of psychopathology. Parental history of early-onset BD and/or childhood ADHD may increase the risk that their offspring will develop BD. Prodromal symptoms of childhood BD may include more subtle presentations of mood regulation difficulties and less presence of classic manic symptoms." [Abstract]

Carlson GA, Loney J, Salisbury H, Volpe RJ.
Young referred boys with DICA-P manic symptoms vs. two comparison groups.
J Affect Disord 1998 Nov;51(2):113-21
"A total of 23 boys met DICA-P manic symptom and clustering criteria in a diagnostic investigation of 233 outpatient boys between ages 6 and 10. In this manic-symptom group, the most frequently endorsed of an average of five manic symptoms were extreme mood changes, difficulty concentrating, feeling too 'up' to sit still, and racing thoughts. Comparison groups were 23 non-manic boys seen next in the investigation and 23 non-manic boys matched to the manic-symptom boys on symptoms of three comorbid disruptive disorders (ADHD, ODD and CD). Manic-symptom boys differed significantly from next-seen boys, but not from matched comorbid boys, in number of oppositional symptoms and pervasiveness of problems. Manic-symptom boys differed significantly from next-seen boys on six of eight mother-rated RCBCL factors. In contrast, manic-symptom and matched comorbid boys did not differ on any of eight RCBCL factors, which suggests that the RCBCL differences can be attributed to shared ADHD, ODD and/or CD. However, manic-symptom and matched comorbid boys tended to differ on RCBCL Anxiety/Depression. On the teacher-rated TRF, manic-symptom boys were rated higher than next-seen boys on four internalizing factors, and higher than matched comorbid boys on two of those factors, including Anxiety/Depression. Thus, manic symptomatology also predicted substantial emotionality, which was not a controlled comorbidity. The findings of this and other studies suggest that there is a mania dimension or syndrome, which may be an indicator of true bipolar disorder--or simply a marker for disruptive comorbidity, behavioral and emotional multimorbidity, or general severity of psychopathology." [Abstract]

Sanchez L, Hagino O, Weller E, Weller R.
Bipolarity in children.
Psychiatr Clin North Am 1999 Sep;22(3):629-48
"Childhood and adolescent bipolar disorder have been less studied than adult onset bipolar illness. However, case reports of mania in childhood can be found as early as the mid 19th century. Historically, several factors have made the accurate diagnosis of bipolar disorder in childhood difficult: clinical bias against the diagnosis of mania in children; low base rate of disorder; symptom overlap between bipolar disorder and other more prevalent childhood-onset psychiatric disorders; and developmental constraints and variability in clinical presentation. The epidemiology of juvenile-onset bipolar disorder remains an open topic for research. The disorder appears to increase in prevalence with advancing age until young adulthood. Reported phenomenology of bipolar disorder in children and adolescents indicates a highly variable presentation with a developmental trend towards increased resemblance to the adult phenotype with increasing age of onset. Diagnostic accuracy for the disorder is improved by adherence to diagnostic and statistical manual of mental disorders (DSM) criteria and may be aided by structured or semistructured diagnostic interviews. The course of bipolar disorder in children and adolescents has also received limited systematic study. However, research to date supports a clinical picture of a relapsing, recurrent illness with substantial morbidity. Systematic studies of pharmacologic treatments of acute mania in children and adolescents are limited in number and scope. Clinical justification for the use of acute antimanic treatments such as lithium and valproic acid is still based upon studies conducted in adults. There remains an immediate and significant need for additional research into all aspects of juvenile-onset bipolar disorder." [Abstract]

Tramontina S, Schmitz M, Polanczyk G, Rohde LA.
Juvenile bipolar disorder in Brazil: clinical and treatment findings.
Biol Psychiatry. 2003 Jun 1;53(11):1043-9.
"BACKGROUND: Because few studies were conducted to evaluate bipolar disorder in children and adolescents outside North America, this investigation aims to describe clinical features, pattern of comorbidities, and response to pharmacologic treatment in a sample of youths with bipolar disorder (BD) from a pediatric psychopharmacology outpatient clinic in Brazil. METHODS: We performed a retrospective chart review of all patients under age 15 with BD diagnoses who were evaluated and treated in our clinic from 1998-2001. A comparison sample of subjects with attention-deficit/hyperactivity disorder (ADHD) without BD (n = 362) was also evaluated. RESULTS: The prevalence of juvenile BD in our sample was 7.2% (36/500) (95% confidence interval = 5.2-9.9). Irritable mood was detected in 91.7% of the bipolar patients. The main comorbidity found was ADHD (58.3%). Children with BD had significantly higher rates of abnormally elevated CBCL scores in the externalizing dimension, anxiety and depression, delinquent behavior, and aggressive behavior scales than ADHD subjects (p <.05). Most BD patients (78%) needed combination drug therapy to achieve symptomatic control. CONCLUSIONS: Our results replicate clinical and treatment findings from U.S. investigations in a different culture demonstrating that juvenile BD is not a rare disorder in clinical samples." [Abstract]

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Recent Bipolar Disorder in Children Research

1) Landaas ET, Halmy A, Oedegaard KJ, Fasmer OB, Haavik J
The impact of cyclothymic temperament in adult ADHD.
J Affect Disord. 2012 Jul 25;
BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder in children and adults. Many ADHD patients experience affective symptoms that resemble the cyclothymic temperament trait, which is suggested to be a part of the bipolar spectrum. However, the relationship between adult ADHD and cyclothymic temperament has never been systematically studied. METHODS: A sample of 586 clinically diagnosed Norwegian adult ADHD patients and 721 population derived controls responded to the 21-item cyclothymic subscale of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego auto-questionnaire (TEMPS-A). Self-reported data on psychiatric symptoms, comorbidity, educational and occupational level, and known comorbidity in family members, including bipolar disorder, was also obtained. RESULTS: The mean TEMPS-A scores were 13.0 for patients and 4.6 for controls (p<0.001), and 71% of the patients compared to 13% of the controls were classified as having a cyclothymic temperament (TEMPS score ?11 points). Among ADHD patients, cyclothymic temperament was strongly associated with more childhood and adult ADHD symptoms, lower educational and occupational achievements and increased psychiatric comorbidity, including bipolar disorder (10%). In addition, 49% screened positive on the Mood Disorder Questionnaire. LIMITATIONS: Although the cyclothymic TEMPS-A scale has been used in clinical settings in Norway for many years, it has not yet been officially validated. CONCLUSIONS: Cyclothymic temperament is highly prevalent in adults with ADHD, and this characterises a subgroup of more psychiatrically impaired individuals, possibly reflecting an underlying affective instability with a pathophysiology closer to the bipolar spectrum disorders. [PubMed Citation] [Order full text from Infotrieve]


2) Garrett AS, Reiss AL, Howe ME, Kelley RG, Singh MK, Adleman NE, Karchemskiy A, Chang KD
Abnormal amygdala and prefrontal cortex activation to facial expressions in pediatric bipolar disorder.
J Am Acad Child Adolesc Psychiatry. 2012 Aug;51(8):821-31.
[PubMed Citation] [Order full text from Infotrieve]


3) Bohman H, Jonsson U, Pren A, von Knorring L, Olsson G, von Knorring AL
Prognostic significance of functional somatic symptoms in adolescence: a 15-year community-based follow-up study of adolescents with depression compared with healthy peers.
BMC Psychiatry. 2012 Jul 27;12(1):90.
ABSTRACT: BACKGROUND: The lack of population based long-term longitudinal studies of functional physical/somatic symptoms has been stressed in previous research. Little is known about the long-term outcome or whether associated depression is a risk factor or a consequence. This study follows up adolescents with depression and non-depressed controls with or without functional somatic symptoms in a community sample during 15 years. METHODS: The total population of 16-17 year olds, in the city of Uppsala, Sweden, was screened for depression in 1991-1993. Adolescents with positive screening and the same number of healthy controls took part in a semi-structured diagnostic interview. In addition, 21 different self-rated somatic symptoms were assessed. The participants were followed up with a structured interview 15 years later, 64% participated. RESULTS: The number of concurrent somatic symptoms in adolescents with depression predicted adverse adult mental health outcomes in a stepwise manner. The quarter of the depressed adolescents with most somatic symptoms (greater than or equal to 5) subsequently developed recurrent depression (68%), panic disorder (44%), chronic depression (30%), somatoform disorders (26%), bipolar disorder (22%), suicide attempts (16%), and psychotic disorders (8%). Abdominal pain was a strong independent predictor for depression and anxiety.Somatic symptoms predicted adult mental disorders in non-depressed controls. CONCLUSIONS: Somatic symptoms precede depression and predict future mental disorders. The number of somatic symptoms concurrent with adolescent depression is related to subsequent poor mental health in a stepwise manner. Treatment guidelines for individuals with somatic symptoms are needed. [PubMed Citation] [Order full text from Infotrieve]


4) Havel M, Sroka R, Englert E, Stelter K, Leunig A, Betz CS
Intraindividual comparison of 1,470 nm diode laser versus carbon dioxide laser for tonsillotomy: A prospective, randomized, double blind, controlled feasibility trial.
Lasers Surg Med. 2012 Jul 26;
INTRODUCTION: The need for reduction of post-tonsillectomy hemorrhage has led to promotion of tonsillotomy techniques for tonsil tissue reduction in obstructive tonsillar hypertrophy. This trial compares ablative tissue effects using 1,470?nm diode laser and carbon dioxide laser for tonsillotomy in an intraindividual design. METHODS: 21 children aged 3-13 years (mean age 6.3 years) underwent laser tonsillotomy for obstructive tonsillar hypertrophy in this double blind, prospective, randomized, clinical feasibility trial. In each of the blinded patients, tonsillotomy was performed using fiber guided 1,470?nm diode laser (contact mode, 15?W power) on the one side and carbon dioxide laser (12?W power) on the other side. An independent, blinded physician documented clinical presentation and patients' symptoms preoperatively and on Days 1, 3, 7, 14, and 21 post-operatively using standardized questionnaire including VAS for each side separately. RESULTS: The mean duration of operative treatment was 2.7?min using 1,470?nm laser and 4.9?min using carbon dioxide laser respectively. Intraoperative bleeding and the frequency of bipolar forceps use for intraoperative bleeding control was significantly less using 1,470?nm diode laser system. There was no difference in post-operative pain scores between the carbon dioxide laser treated and the 1,470?nm fiber guided diode laser treated side. No infections, hemorrhages or other complications occurred in the course of the 3 weeks post-operative period. CONCLUSIONS: A fiber-guided 1,470?nm diode laser system offers an efficient and safe method for tonsillotomy as treatment of obstructive tonsillar hypertrophy. Compared to our standard practice (carbon dioxide laser), 1,470?nm laser application provides comparable tissue ablation effects with less intraoperative bleeding and shorter operation time. Lasers Surg. Med. 2012 Wiley Periodicals, Inc. [PubMed Citation] [Order full text from Infotrieve]


5) van Dyck LI, Pittman BP, Blumberg HP
Non-right-handedness in adolescents and adults with bipolar disorder.
Bipolar Disord. 2012 Aug;14(5):571-2.
[PubMed Citation] [Order full text from Infotrieve]


6) Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN
Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis.
Bipolar Disord. 2012 Aug;14(5):478-87.
Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis. Bipolar Disord 2012: 14: 478-487. 2012 The Authors. Journal compilation 2012 John Wiley & Sons A/S. Objectives:? Bipolar disorder (BD) is a common and highly disabling disease characterized by substantial cognitive and functional impairment. The exact neurobiological mechanisms underlying the expression of symptoms in this condition remain unknown but there is growing evidence that glutamate might play an important role. Using proton magnetic resonance spectroscopy ((1) H-MRS), a number of studies have examined brain glutamate/glutamine levels in patients with bipolar disorder, but they have produced conflicting results. The objective of this paper was to conduct a systematic review and meta-analysis of the literature on brain glutamate/glutamine in BD as measured by (1) H-MRS. Methods:? A Medline search for the period January 1980-April 2010 was conducted to identify published studies that used (1) H-MRS to measure glutamate?+?glutamine (Glx), the Glx/creatine (Cr) ratio, glutamate (Glu), or the Glu/Cr ratio in any brain region in adult or child/adolescent patients with BD and healthy subjects. A meta-analysis of the pooled data was conducted. Results:? BD patients were found to have increased Glx compared to healthy subjects when all brain areas were combined. This finding remained true in medicated and non-medicated patients, and in frontal brain areas in adults. There was a non-significant trend (p?=?0.09) for an increase in whole-brain Glx/Cr and Glu in patients compared with healthy subjects. No significant difference was found in Glu/Cr. Conclusions:? The results of this meta-analysis suggest that brain Glx levels are elevated in BD patients and support the idea that glutamate might play an important role in the pathophysiology of BD. [PubMed Citation] [Order full text from Infotrieve]


7) Raven M, Parry P
Psychotropic marketing practices and problems: implications for DSM-5.
J Nerv Ment Dis. 2012 Jun;200(6):512-6.
The descriptive diagnostic model since DSM-III has often led to "cookbook" diagnosis and assumptions of "chemical imbalance" for psychiatric disorders. Pharmaceutical companies have exploited this in their marketing. This includes promoting self-diagnosis with online checklists. Significant overprescribing of psychotropics has resulted. DSM-5 will provide new disorders and broader diagnostic criteria that will likely exacerbate this. Most psychotropic prescribing is done by primary care physicians, who are problematically excluded from DSM-5 field trials and are influenced by industry funded key opinion leaders who may promote diagnosis of subthreshold cases. More lax criteria will increase diagnosis of subthreshold cases. Expansion of not otherwise specified (NOS) categories can be used to justify off-label promotion. Pediatric bipolar disorder, constructed within the bipolar disorder NOS category, became an "epidemic" in the United States, fuelled by diagnostic upcoding pressures. Disruptive mood dysregulation disorder may similarly cause overdiagnosis and excessive prescribing, as will other new disorders and lower diagnostic thresholds. [PubMed Citation] [Order full text from Infotrieve]


8) Fayad A, El-Sheikh MG, El-Fayoumy H, El-Sergany R, Bary AA
Effect of Extracorporeal Shock Wave Lithotripsy on Kidney Growth in Children.
J Urol. 2012 Jul 19;
PURPOSE: We investigated whether shock wave lithotripsy affects kidney growth in children. MATERIALS AND METHODS: This prospective controlled study included 150 children with renal stones who presented for shock wave lithotripsy between March 2005 and February 2010 (group A). The control arm included 100 children without any urological problems who were enrolled in the study after obtaining written maternal consent (group B). All children in both groups underwent abdominal ultrasound to assess renal size (bipolar renal length), which was repeated after 6 months for group A and after 1 year for both groups. RESULTS: Bipolar renal size in group A increased significantly at 6 months and 1 year after shock wave lithotripsy. Renal growth did not differ based on patient age at shock wave lithotripsy (p = 0.472), number of shock wave lithotripsy sessions (p = 0.65) or number of stones (p = 0.405). There was no significant difference between the rate of kidney growth in children who underwent shock wave lithotripsy during the year of the study and normal controls. CONCLUSIONS: Shock wave lithotripsy has no deleterious effect on the normal rate of renal growth in children. This outcome is not affected by either the number of stones or the age of the child at shock wave lithotripsy. [PubMed Citation] [Order full text from Infotrieve]


9) Shi XF, Kondo DG, Sung YH, Hellem TL, Fiedler KK, Jeong EK, Huber RS, Renshaw PF
Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus-31 magnetic resonance spectroscopy study.
Bipolar Disord. 2012 Jul 20;
Shi X-F, Kondo DG, Sung Y-H, Hellem TL, Fiedler KK, Jeong E-K, Huber RS, Renshaw PF. Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus-31 magnetic resonance spectroscopy study. Bipolar Disord 2012: 00: 000-000. 2012 The Authors. Journal compilation 2012 John Wiley & Sons A/S. Objectives:? To compare the concentrations of high-energy phosphorus metabolites associated with mitochondrial function in the frontal lobe of depressed adolescents with bipolar disorder (BD) and healthy controls (HC). Methods:? We used in vivo phosphorus-31 magnetic resonance spectroscopy ((31) P-MRS) at 3 Tesla to measure phosphocreatine (PCr), beta-nucleoside triphosphate (?-NTP), inorganic phosphate (Pi), and other neurometabolites in the frontal lobe of eight unmedicated and six medicated adolescents with bipolar depression and 24 adolescent HCs. Results:? Analysis of covariance, including age as a covariate, revealed differences in PCr (p?=?0.037), Pi (p?=?0.017), and PCr/Pi (p?=?0.002) between participant groups. Percentage neurochemical differences were calculated with respect to mean metabolite concentrations in the HC group. Post-hoc Tukey-Kramer analysis showed that unmedicated BD participants had decreased Pi compared with both HC (17%; p?=?0.038) and medicated BD (24%; p?=?0.022). The unmedicated BD group had increased PCr compared with medicated BD (11%; p?=?0.032). The PCr/Pi ratio was increased in unmedicated BD compared with HC (24%; p?=?0.013) and with medicated BD (39%; p?=?0.002). No differences in ?-NTP or pH were observed. Conclusions:? Our results support the view that frontal lobe mitochondrial function is altered in adolescent BD and may have implications for the use of Pi as a biomarker. These findings join volumetric studies of the amygdala, and proton MRS studies of n-acetyl aspartate in pointing to potential differences in neurobiology between pediatric and adult BD. [PubMed Citation] [Order full text from Infotrieve]


10) Sugaya L, Hasin DS, Olfson M, Lin KH, Grant BF, Blanco C
Child physical abuse and adult mental health: A national study.
J Trauma Stress. 2012 Jul 16;
This study characterizes adults who report being physically abused during childhood, and examines associations of reported type and frequency of abuse with adult mental health. Data were derived from the 2000-2001 and 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions, a large cross-sectional survey of a representative sample (N = 43,093) of the U.S. population. Weighted means, frequencies, and odds ratios of sociodemographic correlates and prevalence of psychiatric disorders were computed. Logistic regression models were used to examine the strength of associations between child physical abuse and adult psychiatric disorders adjusted for sociodemographic characteristics, other childhood adversities, and comorbid psychiatric disorders. Child physical abuse was reported by 8% of the sample and was frequently accompanied by other childhood adversities. Child physical abuse was associated with significantly increased adjusted odds ratios (AORs) of a broad range of DSM-IV psychiatric disorders (AOR = 1.16-2.28), especially attention-deficit hyperactivity disorder, posttraumatic stress disorder, and bipolar disorder. A dose-response relationship was observed between frequency of abuse and several adult psychiatric disorder groups; higher frequencies of assault were significantly associated with increasing adjusted odds. The long-lasting deleterious effects of child physical abuse underscore the urgency of developing public health policies aimed at early recognition and prevention. [PubMed Citation] [Order full text from Infotrieve]


11) Siegel M, Milligan B, Robbins D, Prentice G
Electroconvulsive Therapy in an Adolescent With Autism and Bipolar I Disorder.
J ECT. 2012 Jul 13;
OBJECTIVES: We report a positive response to electroconvulsive therapy in a severely functionally impaired adolescent with autistic disorder and classic bipolar I disorder, including an episodic pattern of decreased need for sleep, hypersexuality, expansive and agitated affect, aggression, self-injury, and property destruction. METHODS: After ineffective trials of mood stabilizers and antipsychotics as well as inability to sustain a positive response to lithium due to medication noncompliance, a course of acute and maintenance electroconvulsive therapy was attempted. RESULTS: A marked and sustained improvement across all symptom categories, as measured by directly observed frequency counts of target behaviors in an inpatient setting, was obtained. CONCLUSIONS: Electroconvulsive therapy should be considered a potentially useful intervention in cases of children with autistic disorder and a severe comorbid affective disorder. [PubMed Citation] [Order full text from Infotrieve]


12) Khan A, Faucett J, Emslie GJ, Brown WA
Efficacy and safety of anti-manic agents in children and adults.
Isr J Psychiatry Relat Sci. 2012;49(2):122-7.
Objective: Pediatric trials in depression have led to major concerns about potential suicide inducing properties of antidepressants and doubts about their efficacy. Several trials of anti-manic agents in children were recently conducted and regulatory reviews of the data have become available. Methods: We acquired pediatric and adult anti-mania agent Medical and Statistical Reports from the U.S. FDA. We used these to evaluate efficacy, mortality, severe adverse events and suicidality. Results: The six pediatric studies enrolled 1,228 patients (828 drug/460 placebo). The seven adult drug approval programs enrolled 4,228 patients (2,356 drug/1,932 placebo). Mean mania rating scale baseline (pediatric=30.3/adult=30.3) scores were identical, and drug-placebo difference scores (pediatric=5.8/ adult=5.2) were not significantly different. There were no reported deaths during the pediatric trials. During the 23 adult trials there were 8 deaths (3 in drug group/5 in placebo group), a mortality rate of 3,290/100,000 patient exposure years. The proportion of patients that reported severe adverse events was slightly lower for the pediatric (4.2%) as compared to adult (4.7%) trials. A higher proportion of children (5/460, 1.1%) than adult (7/2,012, 0.3%) patients assigned to placebo reported suicidality, ?2(df=1)=4.2, p=0.04. We did not find evidence of increased suicidality for children assigned to drug (7/828, 0.8%) as compared to the children assigned to placebo (5/460, 1.1%). Conclusions: These data suggest remarkable similarity between the outcomes of pediatric and adult trials for bipolar mania. The therapeutic profile of these anti-manic agents in children is notably better than that for some other psychotropic drugs, for example, antidepressants. [PubMed Citation] [Order full text from Infotrieve]


13) Schneider MR, Adler CM, Whitsel R, Weber W, Mills NP, Bitter SM, Eliassen J, Strakowski SM, Delbello MP
The effects of ziprasidone on prefrontal and amygdalar activation in manic youth with bipolar disorder.
Isr J Psychiatry Relat Sci. 2012;49(2):112-20.
Background: Prior research has found that manic adolescents with bipolar disorder exhibit neurofunctional changes in the amygdala and prefrontal cortex following treatment with some pharmacological agents. We examined the neurofunctional effects of ziprasidone in manic adolescents. Method: Manic adolescents with bipolar disorder (n=23) participated in a placebo-controlled study of ziprasidone and underwent a functional magnetic resonance imaging scanning session while performing a task of sustained attention at baseline, prior to treatment as well as on days 7 and 28 (or early termination) of treatment. A comparison group of healthy adolescents (n=10) participated in a single scanning session. Region of interest analyses were performed to assess activation changes associated with treatment in Brodmann Areas (BA) 10, 11 and 47 and in the amygdala. Results: Compared with placebo, treatment with ziprasidone was associated with greater increases over time in right BA 11 and 47 activation. These effects were not associated with differences in symptom improvement between the treatment groups. Patients who subsequently responded to ziprasidone showed significantly greater deactivation in the right Brodmann area 47 at baseline than those who did not respond to ziprasidone. Similarly, among the bipolar adolescents who were treated with ziprasidone, baseline activation in right BA 47 was negatively correlated with improvement in Young Mania Rating Scale (YMRS) score. Limitations: The small sample size limits the ability to detect significant group differences in other regions of interest. Healthy comparison subjects were scanned only at a single timepoint, which limits the interpretation of the results. Ziprasidone is not currently approved by the United States Food and Drug Administration for the treatment of adolescents with mania, and, therefore, the clinical relevance of these results is limited. Conclusions: The increases in right BA 11 and 47 activation observed during sustained attention tasks following ziprasidone treatment and the association identified between lower baseline BA 47 activation and ziprasidone treatment response suggests that ziprasidone may correct prefrontal dysfunction in manic adolescents with bipolar disorder. [PubMed Citation] [Order full text from Infotrieve]


14) Nadkarni RB, Fristad MA
Stress and support for parents of youth with bipolar disorder.
Isr J Psychiatry Relat Sci. 2012;49(2):104-10.
Background: This article reviews stress related to parenting a youth with bipolar disorder (BD), maladaptive coping, immunologic and physical functioning related to chronic stress; presents preliminary findings about the association between immune parameters and health conditions, mental health indices and interpersonal functioning in parents of children with mood disorders; and provides recommendations for stress management based on clinical trials of family-based psychoeducational psychotherapy (PEP). Data: Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-?), C-reactive protein (CRP), Epstein Barr Virus (EBV), nutritional markers and measures of physical health, mental health and interpersonal functioning were collected from 26 parents of mood disordered children. Higher CRP was associated with more perceived stress, more depression, increased incidence of illness/ physical conditions, and lower albumin levels. Elevated IL-6 was associated with higher nicotine use. Limitations: Sample size and demographics were restricted, limiting generalizability. Conclusion: Pilot data are consistent with literature from adult caregivers, and suggest caregivers who are more stressed also evidence some signs of immune abnormality. Evidence-based strategies to support parents are discussed. [PubMed Citation] [Order full text from Infotrieve]


15) Miklowitz DJ
Family-focused treatment for children and adolescents with bipolar disorder.
Isr J Psychiatry Relat Sci. 2012;49(2):95-101.
The course of bipolar disorder in children and adolescents is highly recurrent and impairing. This article describes the adaptation of family-focused treatment (FFT) for children and adolescents with bipolar disorder. FFT is given in 21 sessions over 9 months, and is usually initiated during the recovery period following an acute episode of depression or (hypo)mania. The treatment consists of an engagement phase followed by psychoeducation, communication enhancement training, and problem-solving skills training. Results of randomized trials in adults and adolescents find that patients with bipolar disorder who receive FFT and pharmacotherapy recover from episodes more quickly and have longer periods of sustained remission than patients who receive briefer forms of therapy and pharmacotherapy. The application of FFT to youth who are genetically at risk for bipolar disorder is described. Problems in disseminating empirically supported family interventions in community settings are discussed. [PubMed Citation] [Order full text from Infotrieve]


16) West AE, Weinstein SM
A family-based psychosocial treatment model.
Isr J Psychiatry Relat Sci. 2012;49(2):86-93.
Background: Pediatric bipolar disorder (PBD) is a chronic and severe disorder that is associated with significant impairments in psychosocial functioning. Psychosocial intervention is an important component of comprehensive treatment for PBD. Method: Child- and family-focused cognitive-behavioral therapy (CFF-CBT), also called RAINBOW therapy, is a manual-based, 12 session psychosocial intervention developed for youth 7-13 with PBD and their families. It combines cognitive-behavioral therapy with psychoeducation and other therapeutic interventions from interpersonal psychotherapy, mindfulness, and positive psychology in an intensive family-based treatment model. Specifically, CFF-CBT therapy aims to improve functioning in seven core areas: routines, affect regulation, self-efficacy, negative thoughts and behaviors, social skills, interpersonal and family problem-solving, and social support. Results and Conclusion: Preliminary open trial results, detailed in this manuscript, have demonstrated promise for CFFCBT's efficacy in reducing symptoms and improving psychosocial functioning and it is now being tested in a randomized clinical trial. [PubMed Citation] [Order full text from Infotrieve]


17) Wegbreit E, Pavuluri M
Mechanistic Comparisons of Functional Domains across Pediatric and Adult Bipolar Disorder Highlight Similarities, As Well As Differences, Influenced by the Developing Brain.
Isr J Psychiatry Relat Sci. 2012;49(2):75-83.
Recent neuroimaging studies have uncovered much about the specific neural deficits in adult bipolar disorder (ABD), but despite promising results, neuroimaging research for pediatric bipolar disorder (PBD) is still developing. The neuroimaging literature is highly heterogeneous, varying in the paradigms used and in participants' mood states and medication status. Despite this variability, several dominant patterns emerge. In response to emotional stimuli, both ABD and PBD show limbic hyperactivity coupled with hypoactivity in ventral prefrontal emotion regulation systems. This pattern occurred most robustly in response to negative incidental stimuli and was especially apparent in manic PBD. ABD showed more variability in ventral prefrontal activity, possibly due to maturational and medication factors. On numerous cognitive paradigms, PBD showed dorsal prefrontal hypoactivity linked to ventral dysfunction, whereas ABD showed compensatory frontal, parietal, and temporal activity with paradigm-specific variations. In emotion-cognition interaction paradigms, patients show dysregulation in regions interfacing between cognitive and emotional brain systems (e.g., ventral prefrontal and cingulate cortices), which expend extra effort to process emotional stimuli effectively and recruit additional posterior attention systems to cope with affective instability. In addition, novel functional connectivity techniques have uncovered connectivity deficits between frontal and limbic regions in ABD and PBD at rest and during active emotional and cognitive tasks. Finally, the neuroimaging literature currently lacks cross-sectional studies comparing PBD with ABD and longitudinal studies following children and adolescents with BD into adulthood. Such studies would provide important insights into patients' prognosis and would determine targets for early interventions in the evolving illness diathesis. [PubMed Citation] [Order full text from Infotrieve]


18) Algorta GP, Youngstrom EA, Phelps J, Jenkins MM, Youngstrom JK, Findling RL
An Inexpensive Family Index of Risk for Mood Issues Improves Identification of Pediatric Bipolar Disorder.
Psychol Assess. 2012 Jul 16;
Family history of mental illness provides important information when evaluating pediatric bipolar disorder (PBD). However, such information is often challenging to gather within clinical settings. This study investigates the feasibility and utility of gathering family history information using an inexpensive method practical for outpatient settings. Families (N = 273) completed family history, rating scales, and the Mini-International Neuropsychiatric Interview (Sheehan et al., 1998) and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kaufman et al., 1997) about youths 5-18 (median = 11) years of age presenting to an outpatient clinic. Primary caregivers completed a half-page Family Index of Risk for Mood issues (FIRM). All families completed the FIRM quickly and easily. Most (78%) reported 1+ relatives having a history of mood or substance issues (M = 3.7, SD = 3.3). A simple sum of familial mood issues discriminated cases with PBD from all other cases (area under receiver operating characteristic [AUROC] = .63, p = .006). FIRM scores were specific to youth mood disorder and not attention-deficit/hyperactivity disorder or disruptive behavior disorder. FIRM scores significantly improved the detection of PBD even controlling for rating scales. No subset of family risk items performed better than the total. Family history information showed clinically meaningful discrimination of PBD. Two different approaches to clinical interpretation showed validity in these clinically realistic data. Inexpensive and clinically practical methods of gathering family history can help to improve the detection of PBD. (PsycINFO Database Record (c) 2012 APA, all rights reserved). [PubMed Citation] [Order full text from Infotrieve]


19) Pouladi MA, Brillaud E, Xie Y, Conforti P, Graham RK, Ehrnhoefer DE, Franciosi S, Zhang W, Poucheret P, Compte E, Maurel JC, Zuccato C, Cattaneo E, Nri C, Hayden MR
NP03, a novel low-dose lithium formulation, is neuroprotective in the YAC128 mouse model of Huntington disease.
Neurobiol Dis. 2012 Jul 10;
Huntington disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene, remains without a treatment to modify the course of the illness. Lithium, a drug widely used for the treatment of bipolar disorder, has been shown to exert neuroprotective effects in a number of models of neurological disease but may have various toxic effects at conventional therapeutic doses. We examined whether NP03, a novel low-dose lithium microemulsion, would improve the disease phenotypes in the YAC128 mouse model of HD. We demonstrate that NP03 improves motor function, ameliorates the neuropathological deficits in striatal volume, neuronal counts, and DARPP-32 expression, and partially rescues testicular atrophy in YAC128 mice. These positive effects were accompanied by improvements in multiple biochemical endpoints associated with the pathogenesis of HD, including normalization of caspase-6 activation and amelioration of deficits in BDNF levels, and with no lithium-related toxicity. Our findings demonstrate that NP03 ameliorates the motor and neuropathological phenotypes in the YAC128 mouse model of HD, and represents a potential therapeutic approach for HD. [PubMed Citation] [Order full text from Infotrieve]


20) Bellani M, Bonivento C, Brambilla P
Interaction between cognition and emotion in developmental psychopathology: the role of linguistic stimuli.
Epidemiol Psychiatr Sci. 2012 May 15;:1-5.
Investigations on emotional words demonstrated that processing emotional information in child patients with anxiety disorders diagnosed for anxiety (generalized anxiety disorder and post-traumatic stress disorder) or depression is biased towards pathology-related stimuli. Also, neuroimaging studies showed a failure of prefrontal areas in inhibiting the emotional reaction in children with bipolar disorder. Finally, despite several studies investigated memory and attention using emotional words, little is known about the development of emotional lexicon in both healthy and psychopathological children. [PubMed Citation] [Order full text from Infotrieve]