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Keywords:

  • bipolar disorder;
  • early diagnosis;
  • child;
  • adolescent;
  • juvenile

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODOLOGY
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. REFERENCES

Aim:  This article reviews research centred around juvenile bipolar disorder with particular reference to diagnostic difficulties. Putative deficits are scrutinized with respect to trait likelihood and the roles of neuropsychology and neuroimaging in enhancing our understanding of juvenile bipolar disorder are discussed.

Methods:  Search terms including childhood, adolescent, youth and juvenile combined with the terms ‘bipolar disorder’, mania, depression and hypomania were used to identify relevant studies in MEDLINE and PsychLit.

Results:  Over recent years research into this relatively new disorder has increased phenomenally. Key issues within the field include diagnostic specificity, the heritability of the disorder, the impact of comorbidity and the implications of neuropsychological and neuroimaging findings.

Conclusion:  Despite concerning controversies in literature the diagnosis of bipolar disorder in children and adolescents as compared with adults, promising future research directions include better neurological characterization of the disorder through the application of findings from clinical populations, neuropsychological and neuroimaging research.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODOLOGY
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. REFERENCES

Bipolar disorder is increasingly being diagnosed in children and adolescents,1 perhaps because of an increasing awareness among clinicians working with paediatric populations that the diagnostic criteria for the disorder as applied to adults (as in Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision),2 do not adequately capture the characteristics of the illness during childhood. Diagnosis is complicated by the overlap of symptoms with other common disorders of childhood and adolescence, such as attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD). Such diagnostic complexities present significant challenges to early intervention initiatives which, as in schizophrenia and other psychotic disorders, are of paramount importance in establishing effective treatments and optimizing prognosis.

Whereas adult bipolar I disorder has a clinical lifetime occurrence of approximately 4% in the US population,3 the figures for childhood and adolescent populations vary considerably due to comorbidity and the variable application of diagnostic criteria. Occurrence of juvenile bipolar disorder (JBD) has been estimated at 1–5%,4 such that approximately 1 million American children and adolescents are affected at any given time (Juvenile Bipolar Research Foundation website). In children, bipolar disorder is characterized by mood and sleep disturbances, aggression, anxiety and hyperactivity.5 Additional symptoms include extreme emotional outbursts, irritability, lack of distinct episodes and poor tolerance and response to medication.6,7 In addition, it can include preoccupation with death, depression and withdrawal.8 Bipolar disorder in youth is an important issue as it is strongly associated with poor psychosocial functioning and higher utilization of mental health services that often persists into early adulthood.4 The aim of this article is to review the key issues pertaining to diagnosis and presentation in child and adolescent populations, and attempt to identify ways in which better detection can be facilitated.

METHODOLOGY

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODOLOGY
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. REFERENCES

Articles were identified by searching MEDLINE and PsycLIT using the keywords ‘juvenile’, ‘child’, ‘adolescent’ combined as necessary with ‘bipolar disorder’. Further, the reference lists of articles retrieved and other literature known to the authors were scrutinized.

Limitations

There are several caveats to consider in reviewing this literature including: (i) diagnostic discrepancies, (ii) age, and (iii) subtype. The issues relating to each one of these are considered and particular emphasis is placed on diagnostic discrepancies, before reviewing the literature in this field.

Diagnostic discrepancies in JBD

Controversy surrounds the diagnosis of JBD with heterogeneity of presentation and discrepancies in diagnostic guidelines between countries. Consistent with adult samples, there is an average delay of 7 years between first onset of symptoms in JBD and subsequent accurate evaluation.5 During childhood and adolescence, however, detection and diagnosis are especially critical as development is rapid, and failure to detect bipolarity may lead to children with JBD being treated inappropriately with stimulants or antidepressants. Most clinicians and researchers indicate that much remains to be done in terms of better characterization of bipolar disorder in younger populations.

Earlier this year the National Institute for Health and Clinical Excellence (NICE9) in the UK produced updated guidelines for the diagnosis and treatment of bipolar disorder in children and adolescents. These guidelines offer some structure to what often seems to be a very fluid diagnosis. Discrepancies can be seen by comparing the NICE guidelines with the recommendations of the National Institute of Mental Health (NIMH) in the USA. The NIMH guidelines are older, having been issued in 2000, but are more permissive in regard to prescription of medication and delineation of the disorder. Examples of the differences include the recommendations that lithium only be prescribed to children over 12 (NICE), with reduced starting doses and greater monitoring than in adults. There are no specified age of medication guidelines in the NIMH recommendations although in another set of US guidelines published last year the Child Psychiatric Workshop on Bipolar Disorder recommended not diagnosing children under 6 years as having bipolar disorder. Further, the NICE guidelines advise not diagnosing bipolar II in children and adolescents as there is insufficient evidence for its validity, whereas NIMH permit its diagnosis and indeed many subsequent studies under the auspices of the NIMH have used ‘bipolar II’ and ‘bipolar NOS’ (not otherwise specified) as if they were well validated constructs in the childhood literature. The NIMH guidelines indicate that irritability is more likely in childhood mania than in adulthood whereas irritability is not a core diagnostic criterion in the NICE guidelines. However, according to NICE euphoria must be present most days and most of the time to meet criteria for bipolar disorder in children or adults. Such variation has shaped research and investigation of the disorder as children that may be considered bipolar II in the USA may be considered ‘at risk’ of developing bipolar disorder in the UK and treated quite differently as a result.

In order to bridge these differences it may be possible to categorize some children and adolescents based on low versus high risk, according to subgroups of symptoms, as has been done with good effect in schizophrenia (e.g. Cornblatt et al.10, Niendam et al.11). An approach such as this may provide important information about a potential bipolar prodrome. The latter of these studies found that adolescents in a schizophrenic prodrome exhibited significant cognitive deficits that were not associated with severity of clinical symptomatology.11 The application of a similar rationale to bipolar disorder is likely to extend our understanding of the link between symptomatology and functional impairment and may highlight potential early markers. Althoff et al. (2006)12 have had some success using latent class analysis with the Child Behaviour Checklist to identify symptoms that appear to cluster together but this is still far from capturing a bipolar prodrome12 and other attempts have identified prodromal characteristics that are not unique to bipolar.13

Individual differences in affective development may further complicate the diagnosis of JBD, such that some researchers have cautioned against overuse of the diagnosis in children.14 In addition, whereas symptoms may reflect individual differences from children’s normal developmental trajectory, Leibenluft et al.15 highlight changes in the salience of symptoms at different points along the course of development (e.g. grandiosity, elation). As discussed above, this presents problems for clinicians in differentiating bipolar II in particular, but also more generally highlights the risk of pathologizing ‘normal’ childhood behaviours.

Age

The majority of research studies in JBD fail to differentiate between childhood and adolescent populations and this is a major hindrance in describing the phenotype accurately. Most research in prepubertal bipolar disorder has emerged from a small set of dedicated clinics, and these studies have broadly defined the target population as those under 18 years of age (e.g. Pavuluri et al.16, Wozniak et al.17, Birmaher et al.18). This approach has been informative in preliminary investigations of the disorder, however, there are clearly limits to the deductions that can be made from similarities between a 4-year-old and a 16-year-old child. In addition, changes that occur during adolescence, such as menarche in girls and reaching sexual maturity in boys, are known to be associated with alteration in mood stability alongside physiological changes. Further, there is evidence to suggest that adolescents may have better recovery rates than children.19,20 In this review, it has not always been possible to separate studies according to whether the primary population being investigated involved children or adolescents. What is more, there are only a few studies that report data about index episode or early onset and those that do are often reporting retrospectively (e.g. Geller et al.8, Strober et al.20, Jairam et al.21

Subtype

Another problem that is apparent in the body of literature on JBD is the lack of subtype differentiation and use of the NOS criterion as described in DSM-IV. In adult studies, bipolar I and II are frequently grouped together and diagnostic subtype is simply not specified. In recent years it has become apparent that these subtypes are best treated differently in terms of both psychosocial interventions and pharmacotherapy. Failing to extend this same distinction into childhood has the potential to muddy findings and produce suboptimal recommendations for diagnosis and treatment.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODOLOGY
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. REFERENCES

In an attempt to clarify the occurrence of the disorder in a defined population, Hunt et al.22 assessed the frequency of manic symptoms and bipolar spectrum disorders in 391 consecutive adolescent psychiatric inpatients using the K-SADS (Schedule for Affective Disorders and Schizophrenia for School-age Children-present and Lifetime Version, K-SADS-PL)23 and Mania Rating Scale.24 They predicted rates would be higher in inpatients than in outpatient and community samples. As expected, they found high rates of bipolar symptomatology in inpatients with a high rate of adolescents satisfying criteria for bipolar disorder (19.6%), significantly more so than in community and outpatient samples.25,26

Faedda et al.5 further characterized the disorder by examining a sample of 82 juveniles diagnosed with bipolar disorder attending a mood disorders unit and found moodiness and irritability to be more associated with girls, whereas aggression and anxiety were more characteristic of boys. Sixty per cent of the participants had a previous diagnosis of ADHD, yet only 11% had current diagnoses, highlighting the prevalence of this comorbidity and its diagnostic complexity. In this sample 73% of the bipolar patients were prepubertal at entry to the clinic with an even higher proportion being reported as prepubertal at the onset of the illness (82%).5 This disparity raises the possibility of subgroups, in which the initial presentation is such that identification is difficult or symptoms may not manifest until much later. The sample in the study had an average age of 10.6 years, however, the average age for the onset of symptoms was 2.8 years. In contrast to most adult samples a 2:1 male : female ratio was reported in this study and the authors speculated that this may have resulted from the earlier referral of boys for disruptive behaviour problems.5 Further distinctions included boys reporting more dysphoric mania and girls reporting more mixed states. Suicidality also appears to be higher in children with bipolar disorder as compared with other childhood disorders.27 Earlier studies support the hypothesis that mixed symptoms in particular are a characteristic of bipolar disorder in children and adolescents26,28 and it is well documented in the adult literature that mixed states obfuscate diagnosis.29

Lish et al.,30 Chengappa et al.31 and Biederman et al.32 have found irritability and high comorbidity with ADHD and ODD to be common in child and adolescent bipolar samples (all USA-based studies), but there is variability in the co-occurrence of mixed episodes, psychosis, anxiety comorbidity and CD. As discussed by Carlson many of these symptoms overlap with other disorders such as CD7 and many children and adolescents displaying symptoms do not meet full DSM-IV criteria for the disorder.33 Of this group with subthreshold symptoms some may develop bipolar disorder in adulthood, others may not have bipolar disorder, others may recover or remit. Another approach to consider is that they may fit into Akiskal and Pinto’s ‘soft’ bipolar spectrum,34 and indeed it seems that many of these children reflect their adult counterparts by failing to meet duration criteria for a full episode.33 However, whether widespread acceptance of the soft spectrum in adult psychiatry will occur remains to be seen, as does the applicability of its subdiagnoses in younger samples.

Attempts to identify ‘at risk’ populations have indicated that the prodrome for bipolar disorder could prove difficult to detect due to the low specificity of symptoms of depression and anxiety13 and other studies have indicated the prodrome may overlap with that of schizophrenia.35 Studies of the children of bipolar parents have shown they present with higher levels of mood symptoms, show more negative affect and more unstable self-esteem than controls.36

Family history

In order to gain a better understanding of the aetiology of JBD, recent studies have attempted to investigate genetic and family risk factors.37–41 There is good evidence to support the familial nature of adult bipolar disorder, and preliminary studies indicate that the prevalence of bipolar disorder in families of juvenile onset bipolar patients may be even higher.37 Family members of patients with bipolar disorder that develop the disorder themselves seem to have a severe form of the disorder, which is possibly due to greater environmental influence in the juvenile form than in the adult disorder.38 Hypothesized brain metabolic markers of bipolar disorder have been investigated by examining the bipolar and non-bipolar offspring of bipolar parents40 but these do not adequately differentiate the groups. The offspring of parents with bipolar disorder have, however, been shown to manifest more manic and hypomanic symptoms39 and more mood symptoms generally.42 Further to this, children of bipolar parents have been found to engage in more risk taking, use more ruminative coping styles, have higher levels of negative affect and more instability in self-esteem when compared with children of control group parents.42

Genetic studies examining the basis of bipolar disorder have discovered a genetic component that possibly influences age of onset,43 however, identification of specific endophenotypes is difficult within such an aetiologically heterogeneous disorder.

Assessment issues

Most clinical assessments of JBD rely on broad assessments of childhood disorders or use adapted adult criteria and instruments. Notably, some measures labelled as specific to bipolar disorder include a number of symptoms that overlap with other disorders, for example, obsessive compulsive disorder, ODD and others (e.g. The Child Bipolar Questionnaire44). Whereas clinical evaluation of comorbid disorders is essential, it becomes difficult to assess the severity of the disorder in adolescents and children without a specific measure. Indeed, in order to evaluate severity it is likely that two distinct measures for use with child and adolescent populations would more accurately describe symptomatology. The assessment of mania in paediatric bipolar disorder is particularly problematic, in that there are very few measures designed for use with this population. There has been specific criticism levelled at the Young Mania Rating Scale, which gives considerable weight to irritability as a symptom and is also more often used as a measure of severity rather than as a diagnostic tool.22 Furthermore, this scale also includes a hypersexuality item that may not be relevant to many of the adolescent/child population.45

Interestingly, Hudziak et al.46 have shown that elevated levels as rated on the ‘attention problems’, ‘aggressive behaviour’, and ‘anxious-depressed’ subscales from the Child Behaviour Checklist47 reliably predict bipolarity in a young sample to the point where it may be considered a diagnostic tool. The distinction between attentional and affective disorders among childhood samples thus requires further investigation. It is important to note that the Child Behaviour Checklist is a parent report measure and further evidence in the literature suggests parental report may be more accurate than teacher report or self-report by adolescents.48

Reliability of report is an important consideration when assessing severity of symptoms in childhood affective disorders given that adolescents have been found to under-represent their symptoms.49 The inclusion of both parent and child ratings for diagnosis has thus been recommended,50 as many child-endorsed symptoms have proven to be those that distinguish bipolar disorder from ADHD. Recommended instruments include the Washington Kiddie Schedule for Affective Disorders and Schizophrenia and the Parent Version of the Young Mania Rating Scale.9 The Conner’s Abbreviated Parent Questionnaire has also been recommended as a screen for bipolar disorder distinguishing it from ADHD in prepubertal and early adolescent samples,51 however, there is still difficulty in separating childhood symptoms from adolescent symptoms. A recent interview format (the Jeannie and Jeffrey interview; Juvenile Bipolar Research Foundation) contains illustrations of many children’s symptoms of bipolar and appears to be user friendly. However, this instrument is not equally applicable to adolescents, and therefore does not assist in differentiating childhood and adolescent bipolar disorder.

Age of onset

The main differences between prepubertal onset and postpubertal or peripubertal onset of bipolar disorder have been recently described.14 Mania is most commonly representative of prepubertal onset, with rapid cycling or mixed states occurring frequently, along with a greater incidence of boys with high ADHD comorbidity.14 This type of presentation may also be indicative of poorer outcome.17 In contrast, adolescent onset bipolar more closely resembles the adult form of the disorder with first-episode onset most commonly being depression, less rapid cycling,52 more equal gender ratio53 and less comorbid ADHD.54 In addition, some evidence from an older sample of adolescents suggests that early onset is specifically associated with switching.55

Another focus of investigations in the juvenile form of the disorder has lead researchers to classify a proportion of at-risk adolescents as ‘cyclotaxic’. These individuals have parents with diagnosed bipolar disorder or with subclinical symptoms of the disorder,56 such that inherited personality factors and/or temperament render them liable for the development of affective disorder. These adolescents, displaying subsyndromal bipolar symptoms, have been shown to have significant mood problems and debilitating symptoms requiring treatment, in comparison to a clinically syndromal group and a non-bipolar group.39

It has been further suggested that an early onset form of the disorder may be a distinct subtype of bipolar disorder, and some studies suggest that this subtype may be more treatment resistant than adult variations of the disorder.7 This may be because some adult predictors of poor outcome (such as substance abuse, comorbidity) are common in youth with bipolar disorder. Indeed, with its high comorbidity with ADHD, CD and anxiety disorders, the distinction of further subtypes may be imminent despite the current lack of strong data to support this.45

Further controversy exists in relation to age of onset which also plagues research in the adult form of the disorder whereby previous depressive episodes may be re-interpreted as onset of bipolar disorder in light of a later manic episode. However, clinically it is important to note that a judgement needs to be made weighing up the competing benefits of diagnosis (conferring clarity with respect to management) and delay (allowing greater confidence of diagnostic label). Again the necessity of improving diagnosis through better and early detection is highlighted by this confounder and as in adult samples there may be symptoms of bipolar depression that help distinguish it from unipolar illness.57

Response to treatment

Further evidence of familial influences upon the development of bipolar disorder may be derived by comparing children of parents with bipolar disorder who respond to lithium with children of non-responders.58 The children of non-responders demonstrate a wider range of psychopathology, higher rates of comorbidity, and more affective episodes than children of responders.58 In addition, premorbid functioning, IQ of less than eighty, and bipolar family history have been shown to be predictive of poor outcome.59

With regard to efficacy of treatment Strober et al.60 found lithium less effective in adolescents with bipolar disorder and comorbid ADHD. However, in contrast Kafantaris et al.61 indicated psychotic symptoms were the most important predictor of poor response to lithium in young people but have found it to be an effective treatment.62 Adherence to treatment was found to be predictive of relapse in a group of young people with bipolar disorder with 53% of those compliant with treatment relapsing compared with 100% of the non-compliant group.21 Strober et al.,63 reported similar results.

In a treatment outcome trial, Masi et al.45 evaluated 40 children and adolescents through clinical interviews, ratings and observations over a 3-year period. Clinical global impressions were rated at baseline and on a monthly basis thereafter. All patients were placed on lithium and/or an anticonvulsant. Twenty of the participants showed a response to the pharmacological intervention, confirming findings by Kowatch et al.64 who found 50% of children and adolescents with bipolar disorder are treatment refractory. The non-responders showed higher rates of CD, ADHD and externalizing disorders. Several studies suggest an earlier age of onset of BD is associated with higher levels of comorbid ADHD,26,45,54 but there is evidence that this is not the case for CD.65

The efficacy of medication warrants further investigation. Some evidence is emerging to suggest lithium has a neurotropic and neuroprotective effect in treating bipolar in adolescents.66

Comorbidity with anxiety disorders

Estimates of comorbidity of affective and anxiety disorders vary from 22.6%67 in prepubertal and early onset bipolar, to 33% lifetime prevalence in a sample aged 14–18 years,25 reaching as high as 70% or more in clinically referred samples aged 4–6 and 7–9 years.68 Data from the Systematic Treatment Enhancement Programme for Bipolar Disorders (STEP-BD69) suggest risk of developing a comorbid anxiety disorder increases with earlier age of onset. STEP-BD data also suggest lifetime rates for anxiety disorders in adults with bipolar disorder are 51.2% and 30.5% for a current anxiety disorder diagnosis, therefore suggesting the co-occurrence of comorbid anxiety disorders is more prevalent in juvenile forms of bipolar disorder. Specific anxiety comorbidities range from 12% to 13% in generalized anxiety disorder and social phobia67 reaching as high as 49% in obsessive compulsive disorder.45,49 There is also variation in comorbidity across age groups with 57% of preschoolers with bipolar disorder also meeting criteria for separation anxiety disorder, in later years this drops off to 17.2%.67

Collectively, these studies suggest that anxiety disorders have an earlier age of onset in youth with bipolar disorder but it is not clear whether or not the occurrence of anxiety as a symptom is a ‘marker’ for bipolar disorder although there is evidence to suggest it is salient in some paediatric samples.5 The lack of clarity surrounding the role of anxiety in JBD, as well as other comorbidities, highlights the need for comprehensive assessment of symptoms upon initial presentation of behavioural problems in childhood, as well as further detail of symptoms that present initially.

Neuropsychological studies

Neuropsychological investigation of juveniles with bipolar disorder suggests that the same abnormalities present in adult bipolar sufferers may also be present in children. Table 1 summarizes traditional neuropsychological investigations of bipolar disorder. Evidence from these studies indicates the existence of impairments in various cognitive processes in JBD.

Table 1.  Neuropsychological investigations of child and adolescent populations
StudySubjectsAge rangeNeuropsychological testsPrincipal findings
  1. AD, anxiety disorder; ADHD, attention deficit hyperactivity disorder; BD, bipolar disorder; C, Control group; CANTAB, Cambridge Automated Neuropsychological Test Battery; CCPT, Conners’s Continuous Performance Test;83 CD, conduct disorder; CELF-3, Clinical Evaluation of Language Fundamentals-3;84 CVLT, California Verbal Learning Test;85 FSIQ, Full Scale Intelligence Quotient; MD, Major Depression; NOS, not otherwise specified; ODD, oppositional defiant disorder; PIAT, Peabody Individual Achievement Test;86 PIQ, Performance Intelligence Quotient; RCFT, Rey Complex Figure Test;87 SCWT, Stroop Colour Word Test;88 TMT, Trail Making Test;89 TOMAL, Test of Memory and Learning;90 TONI, Test of Non-verbal Intelligence;91 VIQ, Verbal Intelligence Quotient; WASI, Wechsler Abbreviated Scale of Intelligence;92 WCST, Wisconsin Card Sort Test;93 WISC-III, Wechsler Intelligence Scales for Children Version 3;94 WMS, Wechsler Memory Scale;95 WRAT, Wide Range Achievement Test version 2.96

Castillo et al.7010 BD 10 C6–12 yearsWoodcock-Johnson Psychoeducational Battery-Revised NEPSYLower scores on attention, executive function, sensorimotor tasks, memory, problem solving, visual attention, visual motor speed, facial recognition
Shiratsuchi et al.7112 BD (euthymic)10–15 yearsWISC-IIILower general intellectual functioning than population norms
Lagace et al.7244 BD (remitted) 30 MD 45 CNot specified. Mean age = 18.7 yearsWRAT-R2 PIATMathematical deficits
Robertson et al.7344 BD (remitted) 30 MD 45 CNot specified. Mean age = 18.7 yearsWISC-III WCST CCPTNo differences except in self report of attentional problems
McClure et al.7411 BD 10 AD 25 CNot specified Mean age = 13.7 yearsStandardized photos of happiness, sadness, anger and fearDeficits in facial-emotional recognition
Dickstein et al.7521 BD (18 BD, 3 BD-NOS) 21 C6–17 yearsCANTABImpaired reversal learning/cognitive flexibility in BD Greater response latency in pattern recognition, Poorer spatial memory span
McCarthy et al.7622 BD 90 other8–17 yearsWISC-IIINo significant difference in sustained attention, lower PIQ than ADHD, CD, ODD
DelBello et al.7720 BD (10 euthymic, 10 manic/mixed) 10 C12–18 yearsCPT-IPNo difference in sustained attention
Doyle et al.7857 BD 46 C10–18 yearsWISC-III subtests WRAT-III SCWT WCST RCFT CVLT-II and CVLT-C CPTImpaired sustained attention, working memory and processing speed Increased academic difficulties Lower FSIQ and VIQ
McClure et al.7940 BD (32 BD I, 8 BD II) 22 CNot specified. Mean age = 12.9 yearsSubtests from: Comprehensive Assessment of Spoken Language, Diagnostic Analysis of Non-verbal Accuracy Scale, Test of Language CompetenceDeficits in pragmatic language, facial recognition, response flexibility
McClure et al.8035 BD (21 euthymic, 14 depressed/manic/mixed) 20 CNot specified Mean age = 12.9 yearsCVLT-C RCFT Subtest s from TOMALDeficits in verbal learning and memory
Caetano et al.818 BD + CD 10 CD only Stroop WCST TOMAL CELF-3 Judgement of line orientationImpairments in cognitive ability Set-shifting Verbal memory Visuospatial memory
Glahn et al.8241 BD (21 BD I, 10 BD II, 10 BD NOS) 17 C8–16 yearsCVLT-C TONIPoor verbal learning and memory.
Pavuluri et al.1656 BD 28 C8–17 yearsWASI TMT WMS-III CVLT-C Subtests from Upenn Computerized BatteryDeficits in working memory, verbal memory, sustained attention and executive function

For example, in a mass spectroscopy study comparing bipolar children with controls, Castillo et al.70 found bipolar children to demonstrate lower scores across a wide range of domains. This may be due in part to the severity of illness in the participants, as 88% demonstrated comorbid diagnoses and all were withdrawn from medication 1 week prior to the study. Similarly, Shiratsuchi et al.71 used prospective data gathered prior to diagnosis to assess the characteristics of bipolar disorder in a sample of adolescents and found a high incidence of psychosis and low general intellectual functioning in this group. However, these results should be interpreted with caution because sample size was small and a control group was not used.

There is inconsistent evidence to suggest that deficits in sustained attention are present in adolescent or childhood samples with DelBello et al.77 and McCarthy et al.,76 suggesting performance comparative to controls. On the other hand some studies suggest attention is impaired in children and adolescents with bipolar disorder.16,77 Ability to attend is also affected by ADHD comorbidity and negatively impacts on a wide range of everyday functions. Bipolar adolescents have been shown to rate the subjective impact of success and failure on a win/lose gambling task more extremely than controls97 suggesting greater sensitivity to personal reward and loss, possibility relating to selective attention processes.

Using a more extensive battery to assess a wider range of neuropsychological and academic abilities in a sample of young people with bipolar disorder, Doyle et al.78 found the disorder to impact negatively on overall cognitive functioning as well as attention, memory and executive functioning. Verbal learning and memory deficits have been found in this population79,82 as well as reduced cognitive flexibility, difficulties with pattern recognition and lower Performance IQ on the Wechsler Intelligence Scales for Children, a scale which is considered to be a reliable index of non-verbal intelligence.75,76 Details of the populations studied in these investigations are also summarized in Table 1.

The findings reported here replicate those in adults (e.g. Murphy and Sahakian,98 Sax et al.99). Adults with bipolar disorder have not been found to have lower Verbal IQ scores or Full Scale IQ scores which may be due to the direct impact of disease processes or due to disrupted academic functioning in the younger population.78 Finally, studies focused on social-cognitive skills have reported facial recognition problems in JBD100 consistent with findings in adult bipolar samples.74,79

There are a few studies not included in Table 1 that have not explicitly assessed neuropsychological functioning, but nonetheless provide further evidence that cognitive deficits exist in children and adolescents with bipolar disorder. For example, caregiver reports suggest the existence of executive functioning deficits in adolescents with bipolar disorder101 and a longitudinal study of young adults with bipolar disorder has reported attentional deficits throughout adolescence.7 A recent study by Goldstein et al.102 reported deficits in social behaviour and interpersonal functioning in adolescents with bipolar disorder, even when relatively well.

Recent neuropsychological evidence from Pavuluri et al.16 may represent trait deficits in bipolar disorder, based on comparisons between groups of medicated adolescents with bipolar disorder, unmedicated adolescents with bipolar disorder, and healthy individuals. Patients with bipolar disorder performed more poorly than healthy controls on tests of verbal fluency, executive functioning, attention and working memory, regardless of medication status. These authors argue that as this study demonstrates the presence of neuropsychological deficits regardless of medication status and mood state, these may represent trait markers of illness. This study also revealed that patients with comorbid ADHD demonstrated more severe deficits in the domains of attention and executive function, although there has been some evidence that continuous performance tasks do not demonstrate this difference.72,103

Specific patterns of neuropsychological performance have been associated with ADHD and other disorders104 and medication effects have been noted in adults with bipolar disorder (see Savitz et al.105 for an overview). However, there is a need for further investigation of the neuropsychological characteristics of JBD while taking into account the effects of comorbidity, age of onset, medication status and other potentially confounding variables. In addition, more studies of normal affective development are needed for comparison.

Neuroimaging studies

The lack of clarity surrounding the clinical picture of childhood bipolar disorder places high premium on the examination of neurophysiology and in vivo investigations of brain function in this population. However, given that the brain undergoes major developmental changes throughout childhood and adolescence, continuing until the mid-twenties, the interpretation of neurophysiological data in comparison with adult samples will undoubtedly be fraught with confounds related to normal brain development. For example, amygdala and hippocampal volumes have been shown to increase during adolescence alongside a reduction in caudate volume.106 There are also whole-brain changes associated with arborization and pruning of cells during maturation. The process of myelination is generally agreed to occur from back to front and from the bottom to top of the brain. This results in subcortical structures reaching maturation before the prefrontal and frontal areas. It is therefore conceivable that subcortical abnormalities in childhood could be picked up by imaging several years in advance of abnormalities being detected with confidence in the frontal area.107 Despite these developmental neurophysiological considerations, there is clear evidence of cognitive dysfunction and mood symptoms reflecting abnormalities compared with normal developmental patterns in the child and adolescent bipolar population.

Treatment outcome

The outcome of JBD in terms of prophylaxis and relapse prevention needs further investigation. In a 5-year follow up of 54 consecutive inpatients with lithium as the primary treatment 96% of the adolescents investigated were found to recover from their index episode, however, 65% had at least one relapse with mixed state being predictive of relapse.20 A pattern of incremental improvement in response to treatment (psychotropics) was noted by Biederman et al.108 with a third of the 59 child participants improved after 1 year, rising to two-thirds in the second year of investigation.109 Jairam et al.21 found all their participants (inpatients and outpatients) recovered from their index episode, but relapse rates were 64% and were predicted by longer index episode. Further, 87% of the 86 community-based participants investigated by Geller et al.8 were found to recover from index episode at 4-year follow up but 70% had relapsed during this time. Less than half this sample were on any medication at 2-year follow up.8 It is clear from these studies that although treatment of the index episode is effective there is a very high level of relapse in the disorder. More research into the efficacy of psychotropics, the implications of comorbidity and prophylaxis is needed to clarify optimum treatments for children and adolescents with bipolar disorder.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODOLOGY
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. REFERENCES

A problem regarding the diagnosis of JBD is that children presenting with hyperactivity, aggression and difficulty in affect regulation are difficult to distinguish as suffering from ADHD or affective disorder. It has been noted that the use of certain standardized assessment tools may inflate comorbid diagnoses.109 The key features of ADHD which overlap with bipolar disorder are attentional difficulties, distractibility, hyperactivity and impulsivity; however, opinions vary as to whether children and adolescents with comorbid ADHD represent a particular subgroup of JBD or are misdiagnosed due to symptomatic overlap.53

Based on the US NIMH criteria, the narrow phenotype of JBD is generally used to refer to children and adolescents that meet the adult criteria for Bipolar I or II symptomatically, but not in terms of duration.110 In contrast the broad phenotype has much overlap and comorbidity with key features being chronicity, affective instability and mood dysregulation.1 There are also differences in the presentation of mania in children and adolescents as compared with adults. It is important for clinicians and researchers to retain awareness that the boundaries of the disorder are not yet clearly defined and hence the criteria used in different studies can be subject to wide variation.

The discrepancies between the recommendations of the NIMH and NICE highlight the international controversies about diagnosis of bipolar disorder in children and adolescents but as yet there are no definitive guidelines specific to Australia. It would seem to be of vital importance that Australian researchers define their position in regard to these issues as not only have they significance for the understanding of these disorders but they shape the direction of longitudinal research which is going to be critical and definitive in this disorder. Studies now being set up to follow up differing presentations of bipolar disorder indicate the likelihood of continuing disparity between medical bodies in the USA and UK, with bipolar II remaining a diagnostic category included in these studies in the USA.

It has been suggested that as many as 20% of bipolar II children and adolescents convert to bipolar I and there is high conversion from bipolar NOS to bipolar disorder.18 Exploration of differences between the juvenile and adult forms of the disorder indicates that adolescents display more changes in polarity, mood swings and symptom changes.18 In a study screening 247 adolescents during a major depressive episode 82% of the study population that had bipolar I or II were likely to have mixed states,111 suggesting that a lack of awareness of mixed states may lead to under-diagnosis in adolescent populations. Further to this, given the overlap of hypomanic symptoms with ‘normal’ mood swings and inconsistencies in adolescent behaviour, it appears that bipolar II may be difficult to differentiate and symptomatically distinguish during adolescence such that a more useful method of approaching the disorder may be to consider severity of presentation and whether criteria are met according to ‘narrow’ or ‘broad’ definitions of the disorder.

CONCLUSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODOLOGY
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. REFERENCES

In summary, JBD is a complex, multifaceted disorder that is increasingly being investigated by researchers in adult and child populations alike. It appears to be marked by a high comorbidity overlapping with other disorders such as ADHD, CD and anxiety disorders. Additionally, it may show preponderance in boys and frequently presents with mixed states and rapid mood cycling. Further investigation into the course and outcome of the disorder is clearly needed.

Accurate and reliable diagnosis of the disorder is constrained by the lack of specific instruments tailored for use with this population, as well as the difficulty in clinically teasing out symptoms that overlap with other common disorders during childhood and adolescence. Further difficulties describing psychiatric disorders in these populations are inherent in the reliance on child and adolescent self-report, such that frequently the disorder may remain undiagnosed for many years.

Neuropsychological testing in adult populations has shed light on deficits in cognitive functioning that may assist in developing a signature presentation of bipolar disorder. In the same way neuropsychological investigation of child and adolescent populations has begun to reveal common impairments, and is likely to develop a clearer picture of deficits that may emerge earlier in the trajectory of the illness. This will assist not only in refining diagnostic tools for use with juvenile samples, but will also aid in the development of effective treatments and improved understanding of this profoundly debilitating disorder.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODOLOGY
  5. RESULTS
  6. DISCUSSION
  7. CONCLUSION
  8. REFERENCES
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