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Child and Adolescent Clinical Psychology 762 Carr, A. (2009). Bipolar disorder in young people. description, assessment and evidence-based treatment. Developmental Neurorehabilitation, 12, 427-441. Child and Adolescent Clinical Psychology 763 Bipolar Disorder in Young People: Description, Assessment and Evidence-Based Treatment Alan Carr Running head or short title: bipolar disorder Keyword: paediatric bipolar disorder, bipolar disorder Correspondence to Professor Alan Carr, School of Psychology, College of Human Sciences, John Henry Newman Building, University College Dublin, Belfield, Dublin 4, Ireland. Tel: +353-1-716-8740 (Direct) 716-8120 (Secretary) Fax: + 353-1-716-1181. email: [email protected] Submitted in May 2009 to: Jeff Sigafoos [email protected] Child and Adolescent Clinical Psychology 764 ABSTRACT Objective. The literature on bipolar in children and adolescents was reviewed to provide an update for clinicians. Review process. Literature of particular relevance to evidence-based practice was selected for critical review. Outcomes. An up-to-date overview of clinical features, epidemiology, prognosis, aetiology, assessment and intervention was provided. Conclusions. Bipolar disorder in children and adolescence is a relatively common, multifactorially determined, and recurring problem which persists into adulthood. Psychometrically robust screening questionnaires and structured interviews facilitate reliable assessment. Multimodal chronic care programmes involving medication (notably lithium) and family oriented psychotherapy are currently the treatment of choice. Child and Adolescent Clinical Psychology 765 INTRODUCTION Bipolar disorder in children has been described as far back as 1884 when Greves [1] gave an account of an episode of mania in a 5 year old in Liverpool infirmary. Kraepelin [2] reported that about a fifth of adult cases of bipolar disorder had their onset in late adolescence. Early case studies and cases series of bipolar disorder in children and adolescents [3-6], and reviews of this literature [7] emphasized the rarity of the condition and the possibility that it may be confused with other disorders, including schizophrenia, depression, anxiety and disruptive behaviour disorders because symptomatology typical of these conditions is often present in paediatric bipolar cases. In recent years the rate of diagnosis of bipolar disorder in children and adolescents has increased dramatically [8]. This increase is due to a shift in practice from confining diagnosis to cases that conform to the classical prototypical description of manic depression (as given in ICD 10, in Table 1) to extending diagnosis to cases with key symptoms of mania and cases that show a broad phenotype [9]. This broad phenotype includes subsyndromal and atypical cases that fall on the bipolar spectrum and are referred to in DSM IV TR as bipolar disorder not otherwise specified (BDNOS). Increasingly children and young adolescents, who have brief, frequent cycles of mood lability, irritability, aggression and recklessness are diagnosed with bipolar disorder, a practice that has led to significant controversy within the field [10, 11]. There is also evidence of a secular trend in the incidence of mood disorders including bipolar disorder in successive cohorts, with age of onset decreasing in more recent cohorts [12, 13]. CLINICAL FEATURES Bipolar disorder is a recurrent episodic mood disorder characterized by episodes of mania or hypomania, depression, and mixed mood states [14, 15]. The DSM IV TR and ICD 10 diagnostic criteria for bipolar disorder are given in Table 1. For a DSM IV TR diagnosis, a Child and Adolescent Clinical Psychology 766 7 day manic episode or 4-day hypomanic episode is required, and for an ICD 10 diagnosis, two episodes of mood disorder are required involving either elevated or depressed mood. In DSM IV TR a distinction is made between cases characterized by at least one manic or mixed episode (bipolar I) and cases characterized by both depressive and hypomanic episodes, but without manic or mixed episodes (bipolar II). Bipolar I disorder is the classic prototype of the condition historically known as manic-depression. In DSM IV TR cyclothymia and BDNOS are also listed as bipolar conditions. In children and adolescents, cyclothymia is diagnosed when, over a period of at least a year, there are many hypomanic episodes alternating with periods characterized by depressive symptoms that do not meet the full criteria for a major depressive episode. BDNOS refers to cases with bipolar features that do not meet criteria for bipolar I or II, or cyclothymia. These include those that show too few symptoms or episodes that are too brief to meet other bipolar diagnostic criteria; cases which show rapid cycling manic and depressive symptoms over days rather than weeks; and cases that show irritable hypomania [16]. An important question is the degree to which empirical studies provide evidence for bipolar disorder in young people under 18 years, and the patterning of symptoms in such cases. In a meta-analysis of seven diagnostic studies of bipolar disorder in youngsters aged 5-18 years, Kowatch et al. [17] found that the most common symptoms were increased energy, distractibility, and pressured speech. About 80% of cases also showed irritable mood and grandiosity, and more than 70% showed elated mood, decreased need for sleep, or racing thoughts. Sixty nine percent of cases also showed poor judgment. Only half demonstrated flight of ideas, and slightly more than onethird showed hypersexuality or psychotic features. High levels of motor activity and aggression, while common in paediatric bipolar disorder, and important to consider in case management, are not diagnostically specific since they occur in disruptive behaviour disorders such as ADHD and oppositional defiant disorder. Child and Adolescent Clinical Psychology 767 COURSE AND OUTCOME Birmaher and Axelson [18] reviewed 7 prospective studies of paediatric bipolar disorder and 10 retrospective studies which documented the childhood adjustment of adult bipolar cases. They drew the following conclusions about the course of bipolar disorder in children and adolescents. In preadolescence bipolar disorder does not always present with the classic adult pattern of discrete episodes of mania and depression. Rather, children present with episodes of mood disturbance, but within these episodes there are multiple cycles involving changes in symptom polarity. Episodes characterized by mixed symptomatology are also more common in children and adolescents. Over time, symptoms follow a fluctuating course varying from subthreshold levels to levels that meet full diagnostic criteria. They also show more frequent episodes, more episodes in which irritability and aggression may be salient features, and more incomplete recovery between episodes. Seventy to 100% of children and adolescents with bipolar disorder recover from their initial index episode, but 80% eventually relapse. Even when treated pharmacologically, episodes may last from about 6 to 12 months. In the long term, bipolar disorder places young people at risk for social, academic and occupational difficulties including school failure, relationship problems with family and peers, legal problems and difficulties with career development. In addition, young people with bipolar disorder are at increased risk of frequent hospitalization, substance abuse and suicide. In the multicentre Course and Outcome for Bipolar Youth (CORBY) study, 263 cases were followed up at 6 month intervals for two years [19]. The worst outcome occurred in cases where there was an early onset of bipolar symptoms; where symptoms persisted for a long time; where there were mixed episodes with psychotic features and comorbid disorders such as ADHD, conduct disorder, substance abuse and anxiety; and where youngsters came from families of low socio-economic status, characterized by family discord and a history of psychopathology. In the CORBY study Birmaher et al. [19] Child and Adolescent Clinical Psychology 768 found that 25% of 92 cases initially diagnosed with BDNOS deteriorated sufficiently to meet the diagnostic criteria for bipolar I or II after two years. Geller et al. [20] conducted a longitudinal study of 115 children diagnosed as bipolar disorder in childhood or early adolescence. At eight year follow up about half of the participants were over 18. The cohort spent 60% of the eight-year study period in episodes of abnormal mood and 39% of the time in episodes of mania. During the study, 87% recovered from mania, but 73% relapsed to mania. First, second and third episodes of mania were almost a year in duration, and were characterized by psychosis, and daily (ultradian) cycling. Bipolar disorder may occur at any point across the lifespan from the preschool years to adulthood. Studies of pre-school children with bipolar disorder show that children as young as 3 may meet the DSM IV TR diagnostic criteria for BDNOS and bipolar I disorder [21-23]. The most common symptoms are irritability and aggression, and mixed mood states. Up to 90% of cases have co-morbid ADHD. In adults with bipolar disorder, there is evidence for three distinct subgroups with different ages of onset, and each is probably associated with a distinct aetiology [24, 25]. These ages of onsets are in the late teens, the midtwenties and between 30 and 40. Studies of adults with bipolar disorder have shown that the interval between episodes decreases as the condition progresses, a phenomenon explained by the kindling model [26]. It is not yet know if the same pattern occurs in paediatric bipolar disorder. In an attempt to investigate the boundaries of paediatric bipolar disorder in longitudinal studies Leibenluft et al. [9] have operationalized the broad phenotype of severe mood and behavioural dysregulation (SMD), the diagnosis of which is currently controversial. In childhood and adolescence these cases show severe unremitting and socially impairing irritability, and developmentally inappropriate reactivity to negative stimuli. They also show ADHD-like hyperarousal involving three of the following: insomnia, Child and Adolescent Clinical Psychology 769 intrusiveness, pressured speech, racing thoughts, distractibility and psychomotor agitation. For SMD symptoms must begin before the age of 12 years and occur at least 3 days per week. Carlson and Meyer [27] have concluded that only some, but not all cases that show the broad phonotype of SMD develop bipolar disorder in adulthood. Others develop unipolar depression [28], antisocial personality disorder with affective symptoms [29], and borderline personality disorder [30]. Thus, children who meet the criteria for SMD and who are often referred because they have ’rages’ are not necessarily children with bipolar disorder. COMORBIDITY Comormbid ADHD, oppositional defiant disorder and anxiety are relatively common among young people with bipolar disorder. In a quantitative review of 4 studies of comorbidity among child and adolescent cases of bipolar disorder, Carlson and Meyer [27] found that 61-93% of cases had comorbid ADHD; 43 - 91% had comorbid oppositional defiant disorder; 13 - 56% had comorbid anxiety disorder; and 0-18% had comorbid substance abuse. Goldstein et al. [31] found that the lifetime prevalence of substance use disorder among 249 adolescents with bipolar disorder was 16%, but Geller et al. [20] found that by 18 years the rate of substance abuse in their cohort of 115 cases had increased to 35%. Carlson and Meyer [27] noted that in studies of adults with bipolar disorder only 10-20% had ADHD, but 40-78% had anxiety disorders and 21-72% had substance use disorders. Thus, compared with children and adolescents, co-morbid ADHD is less common among adults with bipolar disorder, but co-morbid anxiety disorders and substance abuse are more common. EPIDEMIOLOGY Child and Adolescent Clinical Psychology 770 In a US community school survey of 1507 adolescents aged 14-18 years, Lewinsohn et al. [32] found the lifetime prevalence rate of bipolar disorder to be about 1%. In an epidemiological survey of 14-16 year olds Carlson and Kashani [33] found a lifetime prevalence rate for mania of 0.6%. These rates are lower than those found in studies of adults. For example, in the US National Comorbidity Survey Replication study, Kessler et al. [34] found a 12 month prevalence rate for bipolar I and II of 2.6%. Similar rates of bipolar disorder have been found for boys and girls, although males may present with more mania and comorbid ADHD, while females may present with more depressive symptomatology [35, 36]. GENETIC FACTORS Currently no studies of the role of genetic factors in the aetiology of paediatric bipolar disorder have been published [37]. Results of twin and family studies confirm the important role of genetic factors in the aetiology of bipolar disorder in adults [38]. Recent well controlled twin studies have found that the heritability of bipolar disorder ranges from 59 to 87%, and family studies show that children with a first degree relative with bipolar disorder have a 10 fold increased risk for developing the condition [39]. In a recent metaanalysis of 18 genome scan data sets, no region achieved genomewide statistical significance, although the most significant occurred on chromosomes 9p22.3-21.1, 10q11.21-22.1, and 14q24.1-32.12 [40]. This failure to identify genomewide risk loci is not surprising. It is probable that the bipolar disorder phenotype (broadly or narrowly defined) subsumes a heterogeneous group of conditions, and vulnerability of homogeneous subtypes within this heterogeneous group may be associated with different sets of risk loci and alleles. There is some evidence from family aggregation studies of bipolar adults that genetically homogeneous subgroups may be delineated based on the presence of psychotic features [41], co-morbid panic attacks [42], puerperal status [43], age of onset [44], and responsivity to lithium [45]. Child and Adolescent Clinical Psychology 771 With regard to paediatric bipolar disorder, studies of the familiality of age of onset and response to lithium are of particular interest. Children whose parents had early onset bipolar disorder have been found to be at increased risk of bipolar disorder and to be less responsive to treatment with mood stabilizing medication [39]. In a study of 438 children and adolescents, Rende et al. [46] found that compared with first degree relatives of young people whose bipolar disorder began in adolescence, those of youngsters with childhood-onset bipolar disorder had higher rates of depression, anxiety, ADHD, conduct, and substance dependence disorders and suicidal behaviours. The results of these studies suggest that early onset bipolar disorder may be a more heritable and more severe subtype of the condition [37]. Linkage studies are required to identify the risk loci and alleles associated with this phenotype. PSYCHOLOGICAL CHARACTERISTICS Research on psychological characteristics of children of adults with bipolar disorder who may be genetically at risk of developing bipolar disorder, and research on psychological and neurobiological functioning of children diagnosed with bipolar disorder suggest that certain vulnerabilities characterize these young people. Children of adults with bipolar disorder Reviews by DelBello and Geller [47] of 17 studies and by Jones and Bentall [48] of an additional 10 recent studies concluded that children of parents with bipolar disorder showed higher rates of psychopathology, mood disorders and bipolar disorder. Rates of mood disorder in children of bipolar adults ranged from 5-67% compared with 0-38% of normal controls. Rates of non-mood disorders such as anxiety or disruptive behaviour disorders ranged from 5-52% in children of bipolar parents compared with 0-25% of normal controls. Child and Adolescent Clinical Psychology 772 Children of parents with bipolar disorder have distinct neuropsychological characteristics, cognitive styles, and personality traits. Klimes-Dougan et al. [49] found that asymptomatic adolescent children of bipolar mothers showed deficits in executive functioning and selective deficits in spatial memory and attention in comparison with children of mothers with unipolar depression and without any disorder. Gotlib et al. [50] found that, compared with normal controls, children of bipolar parents showed biases in attention and memory towards negative stimuli, similar to those found for bipolar and unipolar depressed adults, suggesting that children at increased risk for affective disorder are characterized by a negative cognitive style that can be activated by low mood. In a wide ranging review Jones and Bentall [48] found that compared with normal controls, children of bipolar parents had higher levels of sensation seeking [51] and disinhibition [52], but also higher levels of creativity [53]. Thus, a genetic predisposition to mood disorders may also confer some benefits. Characteristics of children with bipolar disorder Distinctive temperamental and neuropsychological and neurobiological characteristics have been found to characterize children and adolescents with bipolar disorder. Temperamental characteristics and personality traits Compared with normal controls, children and adolescents with bipolar disorder have been found to show more difficult temperaments [54], greater irritability when frustrated [55], higher levels of novelty seeking, and less reward-dependence, persistence, selfdirectiveness, and cooperativeness [56, 57]. These temperamental characteristics and personality traits are not unique to bipolar disorder and some, such as novelty seeking, reward-dependence, persistence, selfdirectiveness are found among children with ADHD [56, 57]. These temperamental characteristics and personality traits may be an indicator of a bipolar diathesis, or may Child and Adolescent Clinical Psychology 773 reflect an underlying dysfunction in affective processes that increases risk of bipolar disorder. Neuropsychological characteristics Adults with bipolar disorder in remission show deficits in attention, visuospatial and verbal memory and executive functioning [58]. Similar deficits have been found in studies of paediatric bipolar disorder. In a meta-analysis of neuropsychological studies in which cases of paediatric bipolar disorder were compared with normal controls, Joseph et al. [59] found effect sizes of .77 for verbal memory, .62 for attention and executive functioning, and .6 for working memory. Effect sizes for other functions were smaller, specifically: .51 for visual memory, .48 for visual perceptual skills, .45 for verbal fluency, .4 for reading, .33 for motor speed and .32 for intelligence quotient. Young people with bipolar disorder have been found, in a series of studies, to show impaired cognitive flexibility as assessed by neuropsychological tests such as the intradimensional/extradimensional shift task of the Cambridge Neuropsychological Testing Automated Battery [60-63]. There is also evidence that these difficulties are specific to bipolar disorder and are not shown by young people with SMD [61]. Cognitive flexibility deficits may underpin aberrant reward processing which in turn may partially explain manic and depressive symptoms. Neurobiological characteristics Structural magnetic resonance imaging (MRI) studies have been used to investigate volumetric differences in brain structures of young people with bipolar disorder and normal controls. The most consistent finding from structural MRI studies has been the small volume of the amygdala in paediatric bipolar disorder. The amygdala, which is part of the limbic system, has a central role in processing emotional stimuli and regulating emotional responses [64]. In a meta-analysis of 11 studies, Pfeifer et al. [65] concluded that, Child and Adolescent Clinical Psychology 774 compared with normal controls, children and adolescents with bipolar disorder had smaller amygdala volumes (standardized mean difference = .74). In contrast, the amygdala volumes in bipolar adults did not differ significantly from normal control adults. However, in structural MRI studies of bipolar adults, increased volumes in the striatum and reduced volumes in the prefrontal cortex (especially the anterior cingulate cortex and dorsolateral prefrontal cortex) have consistently been found [66]. Inconsistent results have been obtained from paediatric bipolar disorder studies of these brain regions which regulate attention and responses to emotionally salient stimuli and which mediate stimulus-reward relationships [67]. The difference is relative size of the amydala in young people and adults with bipolar disorder, and inconsistencies in results from studies of bipolar children and adults concerning the striatum and prefrontal cortex may be due to differences in medication exposure and degree of substance abuse in children and adults, or these differences may arise because the disorder is subserved by different neurophysiological factors at different developmental stages or in different subgroups of bipolar cases with differing ages of onset. Functional MRI studies have shown that patterns of activation in the amydala, striatum and prefrontal cortex, and temporal cortex in response to tasks that involve facial emotion processing, attention, memory, motor inhibition and empathy in young people with bipolar disorder differ from those of normal controls. Young people with bipolar disorder show deficits in facial emotion processing, including incorrectly identifying facial emotional expressions [68, 63], negatively misinterpreting emotionally neutral facial expressions [69], and misjudging extreme emotional facial expressions as being of moderate to mild intensity [70-72]. Functional MRI studies have shown that deficits in facial emotion processing are associated with aberrant patterns of activation in the amydala, striatum and prefrontal cortex [69, 73-75]. For young people with bipolar disorder, increased activation of the striatum has been found in functional MRI studies of cognitive interference [76] and working memory [77], Child and Adolescent Clinical Psychology 775 while reduced activation of the striatum was found in a study of unsuccessful motor inhibition [78]. Schenkel et al. [79] found that young people with bipolar disorder showed Theory of Mind deficits, i.e., a reduced capacity to infer what others are thinking. In a functional MRI study, Mahli et al [80] found that Theory of Mind deficits in euthymic young people with bipolar disorder were associated with reduced activation in regions recognized for mental state reasoning, in particular the insula, inferior frontal, supramarginal and angular gyri, and temporal cortex. Theory of Mind deficits may compromise the ability of young people with bipolar disorder to understand the emotions and intentions of others, and also may limit appreciation of the impact of their own symptoms on others. This deficit may adversely affect interpersonal relationships and social functioning. STRESFUL LIFE EVENTS Evidence form studies of adults and children suggest that stressful life events may affect the course of bipolar disorder. In adults with bipolar disorder, severe negative life events trigger some episodes of bipolar depression but not mania, and life events that disrupt circadian rhythms or those associated with goal attainment trigger some episodes of manic symptoms [81]. Studies of children of bipolar parents and adolescents with bipolar disorder have shown that life events affect the course of bipolar disorder [82]. Hillegeres et al. [83] and Wals et al. [84] found that an accumulation of stressful life events over a five-year period in the children of bipolar parents precipitated the onset of paediatric bipolar disorder. Kim et al. [85] found that stressful life events, as well as stressful family, peer and romantic relationships were associated with less improvement in mood regulation over the course of a year in a group of 38 adolescents with bipolar disorder being treated with mood stabilizing medication and psychosocial interventions. FAMILY CHARACTERISITCS Child and Adolescent Clinical Psychology 776 Evidence form studies of adults and children suggest that stressful family environments may affect the course of bipolar disorder. High levels of expressed emotion (as evidence by critical comments, hostility and emotional overinvolvement) in patients’ families have been shown to contribute to relapse in adults with bipolar disorder and many other conditions [86]. In a study of 20 adolescents with bipolar disorder, who participated in a two-year multimodal programme involving family therapy and pharmacotherapy, Milkowitz et al. [87] found that 74% of families received high expressed emotion scores prior to therapy. During treatment young people from families characterized by high expressed emotion were more symptomatic than those from families in which there was low expressed emotion. However, over the course of the study, the association between expressed emotion and symptomatology weakened, indicating that family therapy reduced the impact of parental expressed emotion on the symptoms of bipolar adolescents. Schenkel et al. [88] found that, compared to controls, relationships between parents and children with bipolar disorder were characterized by significantly less warmth, affection, and intimacy, and more quarrelling and forceful punishment. Greater parentchild conflict was associated with more pronounced mania symptoms, comorbid ADHD, an earlier age of onset, living in a single parent home, and the presence of a parental mood disorder. In a study of 115 children with bipolar disorder who were followed up annually over 8 years until they reached adulthood, Geller et al. [20, 89] found that low ratings of maternal warmth by children and parents predicted relapses into manic episodes and longer manic episodes. The family also had a protective influence in that children who lived with both of their parents had briefer manic episodes than children living in one-parent families. However, these are correlational findings. It may be that parental warmth dropped in response to subsyndromal symptoms, and that single parent families have higher genetic loadings for affective disorders. Child and Adolescent Clinical Psychology 777 In adults there is an association between bipolar disorder and a history of childhood physical and sexual abuse [90]. In a study of 446 bipolar children and adolescents Romero et al. [91] found that 20% had experienced physical and/or sexual abuse. Compared with non-abused cases, those who reported both types of abuse were more likely to come from non-intact families; to be older with a longer duration of bipolar disorder; and to have comorbid PTSD, conduct disorder and psychosis. ASSESSMENT Guidelines for the assessment and management of bipolar disorder in adults and children have been produced by a variety of authoritative groups [92-99]. Clinicians should expect a base rate of bipolar disorder of about 1% in school settings; 5% in non-specialist clinical settings; and a rate that is five times higher where the referred child has a parent with a diagnosis of bipolar disorder [99]. In routine clinical assessment where there is evidence of parental bipolar disorder, mania or hypomania occurring in response to antidepressant treatment, delusions and / or hallucinations associated with mood disturbance, rapid cycling depressive and manic symptoms, episodic, unplanned highly aggressive behaviour, then a thorough evaluation for paediatric bipolar disorder should be conducted [99]. The diagnosis of mood disorder is based on the lifetime history of episodes of mood disorders, and not simply on the clinical presentation. In assessing young people who may have bipolar disorder, data should be gathered from multiple informants over a series of appointments. Extending assessment over time is important for tracking the course of mood fluctuations. Self-report data from young people is particularly useful is documenting depressive symptoms and internalizing behaviour problems, while parent reports are useful in documenting symptoms of mania and externalizing behaviour problems. Teacher reports provide information on academic and social functioning in a school and peer group context. Child and Adolescent Clinical Psychology 778 The process of assessment is a critical opportunity for forming a strong working alliance with the young person and their parents, since a strong working alliance has been shown to predict treatment response in adults with bipolar disorder [100]. A preliminary screening should be conducted, followed by a thorough psychiatric and psychological assessment. This should cover all of the symptoms listed in Table 1 and also include a detailed personal and family history. The following brief screening instruments may be useful in detecting cases of paediatric bipolar disorder [99]: the externalizing subscale of the Achenbach Empirically Based Assessment instruments (ASEBA) [101] including the Child Behaviour Checklist, Teacher Report Form and Youth Self-report form; the self-report [102] and parent [103] versions of the Young Mania Rating Scale (YMRS); and the hypomanic/biphaic scale of the self-report [104] and parent [105] versions of the General Behaviour Inventory (GBI). Detailed probabilistic data for all of these instruments useful in screening for paediatric bipolar disorder are available [99,106]. The Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) [107, 108] has been used extensively in research on paediatric bipolar disorder, but may be impractical to use in routine clinical settings, because of it takes a number or hours to administer. The Children’s Interview for Psychiatric Syndromes [109] is a much briefer structured interview that covers a range of DSM IV diagnoses including bipolar disorder, and is useful in clinical practice. In making a diagnosis, while rages, irritability, distractibility and hyperactivity may be the symptoms of greatest concern to parents and teachers, and greatest familiarity to most clinicians, the presence of elevated mood (happiness that is inappropriate in intensity, duration and context), grandiosity, pressured speech and racing thoughts are symptoms that alert clinician’s to the possibility of bipolar disorder [110]. It is important to retrospectively reconstruct from history, or prospectively chart over time, constellations of symptoms present in each episode of mood disturbance [111]. Child and Adolescent Clinical Psychology 779 The main alternatives to include in the differential diagnosis of bipolar disorder, are ADHD, conduct disorder, schizophrenia, drug abuse, endocrinopathies such as hypertyroidism, and neurological conditions such as temporal lobe epilepsy [92, 112, 113]. Youngsters with bipolar disorder, like those with ADHD, may show distractibility, impulsivity and overactivity. However, ADHD has an earlier onset than bipolar disorder; the symptoms of distractibility, impulsivity and overactivity are persistent, not episodic; and elated mood rarely occurs in ADHD. Children with bipolar disorder, like those with conduct disorder, may show oppositional behaviour, tantrums, defiance, sexual promiscuity and a pattern of rule-breaking and socially deviant behaviour. However, in bipolar disorder, this overall pattern of behaviour is episodic rather than persistent and usually there is a family history of mood disorder. With bipolar disorder, guilt or remorse may be expressed for rule-breaking, which is rare in conduct disorder. Neither flight of ideas nor pressured speech are present in conduct disorder or ADHD, but both occur in bipolar disorder. Delusions and hallucinations may occur during manic episodes, making children with this type of presentation difficult to distinguish from youngsters with schizophrenia. In such cases extended periods of observation may be required. A family history of schizophrenia rather than mood disorder and an insidious onset of current difficulties suggest a diagnosis of schizophrenia rather than bipolar disorder. Youngsters who abuse amphetamines or hallucinogenic drugs may present with hypomanic-like behaviour. However, this typically abates over time. A thorough medical and neurological assessment (including an EEG if seizure disorder is suspected) is essential to outrule endocrinopathies such as hypertyroidism, and neurological conditions such as temporal lobe epilepsy which can contribute to a hypomanic-like presentation. Differential diagnosis of bipolar disorder is complicated by the fact that in young people this condition rarely occurs alone. The most common comorbid disorders are ADHD, oppositional defiant disorder, conduct disorder, and learning disorders, all of which are more common and more familiar to most practicing clinicians, and all of which have Child and Adolescent Clinical Psychology 780 symptoms that overlap with bipolar disorder [110]. In adolescents, co-morbid substance abuse may occur and so deserves assessment. While data on suicide risks associated with paediatric bipolar disorder are unavailable, in adults bipolar disorder is associated with suicide risk. Consequently suicide risk assessment should be routinely conducted. Guidelines for such interviews are given in Carr [114, 115] and elsewhere 116, 117] The level of critical and hostile emotions expressed by parents (a central aspect of expressed emotion) affects the course of paediatric bipolar disorder and so is a focus for psychosocial intervention [87]. In view of this, the periodic assessment of parental attitudes towards young people with bipolar disorder is important. In routine clinical settings it is not practical to administer the Camberwell Family Interview [118] to asses the construct of expressed emotion. However, brief alternatives that may be useful in assessing relevant parental attitudes in routine practice are the Family Attitudes Scale [119] and the Level of Expressed Emotion scale [120]. The YMRS [102], the Children’s Depression rating Scale [121] and the KSADS Mania and Depression rating scales [122] are brief sensitive rating scales which may be used to periodically monitor symptomatic improvement in young people with bipolar disorder. TREATMENT Guidelines for the treatment of paediatric bipolar disorder have been developed [92, 95] based on results of many well controlled trials of adults with the condition [123, 124], and a small number of predominantly open trials of young people with bipolar disorder [125, 126]. Available evidence supports the multimodal treatment of bipolar disorder with antimanic medication in the first instance, and then maintenance medication and adjunctive psychotherapy to prevent relapse [124, 126]. Pharmacological treatment Child and Adolescent Clinical Psychology 781 In a comprehensive review of trials of pharmacological treatment of paediatric bipolar disorder from 1995 to 2006, Smarty and Findling [125] concluded that there was limited evidence from double-blind, placebo-controlled trials regarding the treatment of paediatric bipolar disorder. The principal medication for treating paediatric bipolar disorder in both the acute phase and the long-term maintenance phase is lithium, but there is also evidence for the effectiveness of valproate, carbamezepine, risperidone, olanzapine, and quetiapine. About 50% of bipolar cases with mania do not respond to lithium monotherapy, and in these cases it is recommended that lithium be augmented with one of the other effective medications; where no response occurs, another medication from those listed above should be tried; and for both monotherapy and treatment with two or more medications, side-effects should be carefully monitored [92, 95]. Where young people present with mania characterized by psychotic features, lithium may be combined with an antipsychotic agent such as risperidone or olanzapine [95]. In clinical practice 6-8 weeks is reasonable period within which to evaluate the responsiveness of a case to a particular medication regime, and young people and their parents should be given information about the effects and side-effects of regimes so that they can make informed choices about treatment [92, 95]. A number of clinical issues deserve consideration it the treatment of young people with bipolar disorder [95, 127, 128]. It is worth noting that atypical antipsychotics may lead to severe weight gain, a side-effect that may interfere with later compliance of adolescents with prophylaxis. Benzodiazepines such as clonazepine or lorazepam may also be used where severe agitation is present. For acute depression, antidepressants in conjunction with lithium are usually prescribed. An anti-depressant taken alone is associated with the risk of rapidly switching from a depressive to a manic episode. Tricyclic antidepressants carry a greater risk of precipitating this switch to mania compared to other antidepressants such as selective serotonin reuptake inhibitors (SSRI), so SSRIs are preferred. For long-term prophylaxis lithium, valproate, or carbamezapine Child and Adolescent Clinical Psychology 782 are usually prescribed and some combination of these medications may prevent rapid relapse in about 70% of cases. Non-adherence to prophylactic medication regimes leads to rapid relapse in over 90% of cases. Youngsters may show non-adherence problems because prophylaxis, especially with lithium, may have unpleasant side-effects including weight gain, skin rashes and cognitive dulling. Lithium levels require careful 3 monthly monitoring, because excessive levels can have adverse effects on renal functioning. Lithium should be discontinued during pregnancy because of potentially negative effects on foetal development. Rapid withdrawal of lithium can precipitate an episode of mania. Sodium valproate may be preferred for prophylaxis in adolescents because it has less toxic side effects and because it may be more effective alone and in combination with carbamezapine for mixed manic-depressive episodes and rapid cycling bipolar disorder. Psychological treatment Evidence for the value of psychotherapy in the treatment of paediatric bipolar disorder comes from a handful of trials of multimodal programmes in which young people were treated with medication and family oriented psychotherapy [126]. In clinical practice, after acute management of manic episodes, prophylactic treatment should include both medication and family focused intervention as described below. Family focused treatment for adolescents Family focused treatment (FFT) was developed by Miklowitz [129] as an adjunctive psychosocial intervention for families of bipolar adolescents taking mood-stabilizing medication such as lithium. FFT aims to reduce adolescents’ psychosocial impairment and delay relapse by increasing medication adherence, reducing family stress and enhancing family support. The programme is premised on the finding that high levels of intrafamilial expressed emotion (involving criticism, hostility and overinvolvement) are associated with relapse in bipolar disorder and other conditions [86]. FFT is offered to Child and Adolescent Clinical Psychology 783 families of young people with bipolar disorder over 21 sessions and includes modules on psychoeducation, communication, and problem-solving. In the psychoeducation module, families learn how family stress and support can affect the course of bipolar disorder. They also practice mood monitoring and develop a relapse prevention plan. In the communication module, families practice active listening, and in the problem-solving module they practice skills for developing solutions to resolve family conflicts. In a single group outcome study of 20 bipolar adolescents and their families, Milkowitz et al. [130] found that FFT led to improvements in depressive and manic symptoms and behaviour problems. In a randomized controlled trial involving 58 bipolar adolescents and their families, Miklowitz et al. [131] found that compared with 3 family session of relapse prevention and pharmacotherapy, adolescents who participated in 21 sessions of FFT over 9 months and received concurrent pharmacotherapy recovered more quickly from depressive symptoms, and showed fewer depressive symptoms during 2 years following treatment. Child and family focused cognitive behaviour therapy The RAINBOW programme is a child and family focused cognitive behavioural intervention developed by Pavuluri et al. [132] for pre-adolescent children aged 8-12 years. RAINBOW is an acronym derived from the first letters of seven key elements of the programme: Routine, Affect regulation, I can do it!, No negative thoughts and live in the now, Be a good friend and lifestyle for parents, Oh, how can we solve the problem, and Ways to get support. This 12 session programme includes conjoint family sessions as well as sessions with the bipolar child alone, the parents alone, the parents and siblings, and the bipolar child’s school teacher. The programme provides children, families and teachers with psychoeducation about bipolar disorder, strategies for reducing familybased expressed emotion and stressful events, and training in coping skills, communication and problem-solving. In a single group outcome study of 34 young people Child and Adolescent Clinical Psychology 784 ages 5-17 years with bipolar disorder who were on mood stabilizing medication, Pavuluri et al. [132] found that the RAINBOW programme led to improvements in depressive and manic symptoms, aggression, ADHD symptoms and global functioning. Multi-family psychoeducational groups Multi-family psychoeducational group (MFPG) therapy involves eight 90-minute sessions for parents from a number of families with concurrent sessions for children [133]. The curriculum for MFPG is similar to that of the RAINBOW programme, but the group format creates a context within which parents and children gain social support from other families with similar difficulties. In the child-focused sessions children learn to externalize their mood disorder and construe it as separate form themselves so they can join forces with their parents in combating their mood disorder. They also learn a variety of CBT strategies for combating to help them with this process. In a trial of MFPG involving 16 bipolar cases and 19 cases with unipolar depression Fristad et al. [133] found that after treatment and at four months follow-up families of both groups showed significant gains in knowledge, skills, support, and positive attitudes towards treatment. CONCLUSION Paediatric bipolar disorder is a relatively common, multifactorially determined, and recurring problem which persists into adulthood. The condition probably arises when genetically at-risk young people with psychological and neurobiological vulnerabilities which compromise their capacity for mood regulation are exposed to stressful life events and participate in ongoing stressful interactions with their families. Clinical management involves assessment of young people and their families with psychometrically robust screening questionnaires and structured interviews, followed by multimodal treatment with medication (notably lithium) and family oriented psychotherapy. Treatment should be Child and Adolescent Clinical Psychology 785 offered within the context of a chronic care model of service delivery, since bipolar disorder is a chronic condition requiring life-long prophylaxis. FURTHER READING For clients Fristad M, Goldberg J. Raising a moody child: How to cope with depression and bipolar disorder. New York: Guilford; 2004. Miklowitz DJ, George EL. (2007). The Bipolar Teen: What you can do to help your child and your family. New York; Guilford Press; 2007. Pavuluri M. What works for bipolar kids: help and hope. New York: Guilford; 2008. For professionals Miklowitz DJ. Bipolar disorder: A family-focused treatment approach. 2nd ed. New York: Guilford Press; 2008. 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Child- and Child and Adolescent Clinical Psychology 800 family-focused cognitive behavioural therapy for paediatric bipolar disorder: Development and preliminary results. Journal of the American Academy of Child and Adolescent Psychiatry 2004; 43: 528-537. 133. Fristad MA, Goldberg-Arnold JS, Gavazzi SM. Multifamily psychoeducation groups MFPG for families of children with bipolar disorder Bipolar Disorders 2002; 4: 254–262 Child and Adolescent Clinical Psychology 801 Table 1. Definitions of bipolar disorders in DSM IV TR and ICD 10 DSM IV TR Bipolar I Disorder. At least one manic, hypomanic or mixed episode. Bipolar II Disorder. One or more episodes of both major depression and hypomania, but no manic or mixed episodes. A seasonal pattern or rapid cycling should be specified for both bipolar I and II. A seasonal pattern represents a course of illness where the major depressive episodes occur consistently at a particular time of year. Rapid cycling involves at least four episodes of a mood disturbance (major depression, mania, mixed, or hypomania) over a 12-month period. Cyclothymia. Numerous hypomanic episodes and episodes characterized by depressive symptoms that do not meet criteria for a major depressive episode lasting at least 2 years in adults and 1 year in children and adolescents. Bipolar disorder not otherwise specified. Disorders with bipolar features that do not meet criteria for bipolar I or II or cyclothymia. Manic Episode A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood lasting at least 1 week (or any duration if hospitalization is necessary). B. During the period of mood disturbance, three (or more) of the following symptoms have persisted: 1. inflated self-esteem or grandiosity 2. decreased need for sleep 3. more talkative than usual or pressured speech 4. flight of ideas or racing thoughts 5. distractibility 6. increased goal-directed activity or psychomotor agitation 7. excessive involvement in pleasurable reckless activities (e.g. buying sprees or sexual indiscretion) C. The mood disturbance is not part of a mixed manic-depressive episode. D. The mood disturbance causes marked impairment in educational, occupational or social functioning. This may include the need for hospitalization, or the presence of psychotic symptoms. E. The symptoms are not due to the direct effects of a substance (e.g., drug abuse, antidepressant medications), or to a general medical condition. Hypomanic Episode. A hypomanic episode has similar symptoms as a manic episode, but differs in the severity and duration criteria. The symptoms must be present for at least 4 days, and must produce an unequivocal change in the patient’s functioning that is observable by others. However, by definition, there is no marked deterioration in functioning, need for hospitalization, or psychotic symptoms; otherwise, a manic episode is diagnosed. Mixed Episode. A mixed episode is diagnosed when the criteria are met for both a manic episode and a major depressive episode over at least a 1-week period. The requirement for significant impairment, and the exclusion of organic causes are the same as for a manic episode. Major depressive episode A. Five or more of the following symptoms have been present during the same two week period nearly every day and represents a change from pervious functioning; at least one of the symptoms is ether (1) depressed mood or (2) Loss of interest or pleasure. Symptoms may be reported or observed. 1. Depressed mood. In children and adolescents can be irritable mood. 2. Markedly diminished interest or pleasure in almost all daily activities. 3. Significant weight loss or gain (of 5% per month) or decrease or increase in appetite. In children consider failure to make expected weight gains. 4. Insomnia or hypersomnia. 5. Psychomotor agitation or retardation. ICD 10 Bipolar disorder is characterized by repeated (i.e. at least two) episodes in which the patient's mood and activity levels are significantly disturbed, this disturbance consisting on some occasions of an elevation of mood and increased energy and activity (mania or hypomania), and on others of a lowering of mood and decreased energy and activity (depression). Characteristically, recovery is usually complete between episodes. Manic episodes usually begin abruptly and last for between 2 weeks and 4-5 months (median duration about 4 months). Depressions tend to last longer (median length about 6 months), though rarely for more than a year, except in the elderly. Episodes of both kinds often follow stressful life events but the presence of such stress is not essential for the diagnosis. The frequency of episodes and the pattern of remissions and relapses are both very variable, though remissions tend to get shorter as time goes on and depressions to become commoner and longer lasting after middle age. Manic episode Distinctions are made between hypomania, mania, mania with psychotic symptoms, mixed episodes, and depressive episodes. Mania. Mood is elevated out of keeping with the individual's circumstances and may vary from carefree joviality to almost uncontrollable excitement. Elation is accompanied by increased energy, resulting in overactivity, pressure of speech, and a decreased need for sleep. Normal social inhibitions are lost, attention cannot be sustained, and there is often marked distractibility. Self-esteem is inflated, and grandiose or over-optimistic ideas are freely expressed. Perceptual disorders may occur, such as the appreciation of colours as especially vivid and usually beautiful, a preoccupation with fine details of surfaces or textures, and subjective hyperacusis. The individual may embark on extravagant and impractical schemes, spend money recklessly, or become aggressive, amorous, or facetious in inappropriate circumstances. In some manic episodes the mood is irritable and suspicious rather than elated. The episode should last for at least 1 week and should be severe enough to disrupt ordinary work and social activities more or less completely. The mood change should be accompanied by increased energy and several of the symptoms referred to above (particularly pressure of speech, decreased need for sleep, grandiosity, and excessive optimism). Hypomania. Hypomania is a lesser degree of mania, in which abnormalities of mood and behaviour are too persistent and marked to be included under cyclothymia but are not accompanied by hallucinations or delusions. There is a persistent mild elevation of mood for at least several days on end, increased energy and activity, and usually marked feelings of well-being and both physical and mental efficiency. Increased sociability, talkativeness, overfamiliarity, increased sexual energy, and a decreased need for sleep are often present but not to the extent that they lead to severe disruption of work or result in social rejection. Irritability, conceit, and boorish behaviour may take the place of the more usual euphoric sociability. Concentration and attention may be impaired, thus diminishing the ability to settle down to work or to relaxation and leisure, but this may not prevent the appearance of interests in quite new ventures and activities, or mild over-spending. Mania with psychotic symptoms. The clinical picture is that of a more severe form of mania as described above. Inflated self-esteem and grandiose ideas may develop into delusions, and irritability and suspiciousness into delusions of persecution. In severe cases, grandiose or religious delusions of identity or role may be prominent, and flight of ideas and pressure of speech may result in the individual becoming incomprehensible. Severe and sustained physical activity and excitement may result in aggression or violence, and neglect of eating, drinking, and personal hygiene may result in dangerous states of dehydration and self-neglect. One of the commonest problems is differentiation of this disorder from schizophrenia, particularly if the stages of development through hypomania have been missed and the patient is seen only at the height of the illness when widespread delusions, incomprehensible speech, and violent excitement may obscure the basic disturbance of affect. Patients with mania that is responding to neuroleptic medication may present a similar diagnostic problem at the stage when they have returned to normal levels of physical and mental activity but still have delusions or hallucinations. Mixed episode. Although the most typical form of bipolar disorder consists of alternating manic and depressive episodes separated by periods of normal mood, it is not uncommon for depressive mood to be accompanied for days or weeks on end by overactivity and pressure of speech, or for a manic mood and grandiosity to be accompanied by agitation and loss of energy and libido. Depressive symptoms and symptoms of hypomania or mania may also alternate rapidly, from day to day or even from hour to hour. Depressive episode In a typical depressive episode the individual usually suffers from depressed mood, loss of interest and enjoyment and reduced energy leading to increased fatigueability and diminished activity. Marked tiredness after only slight effort is common. Other common symptoms are: a. reduced concentration and attention b. reduced self-esteem and confidence c. ideas of guilt and unworthiness d. bleak and pessimistic views of the future e. ideas or acts of self harm or suicide f. disturbed sleep g. diminished appetite. Child and Adolescent Clinical Psychology 6. Fatigue or loss of energy. 802 The lowered mood varies little from day to day and is often unresponsive to circumstances and may show a characteristic diurnal variation as the day goes on. 7. Feelings of worthlessness, excessive guilt. 8. Poor concentration and indecisiveness 9. Recurrent thoughts of death, suicidal ideation or suicide attempt. B. Symptoms do not meet criteria for mixed episode of mania and depression. C. Symptoms cause clinically significant distress or impairment in social occupational, educational or other important areas of functioning D. Symptoms not due to the direct effects of a drug or a general medical conditions such as hypothyroidism. Some of the above symptoms may be marked and develop characteristic features that are widely regarded as having special significance for example the somatic symptoms which are: loss of interest or pleasure in activities that are normally enjoyable; lack of emotional reactivity to normally pleasurable surroundings; waking in the morning 2 hours or more before the usual time; depression worse in the mornings; psychomotor retardation or agitation; marked loss of appetite or weight; marked loss of libido. Usually the somatic syndrome is not regarded as present unless at least four of these symptoms are present. Atypical presentations are particularly common in adolescence. In some cases anxiety, distress, and motor agitation may be more prominent at times than depression and mood changes may be masked by such features as irritability, excessive consumption of alcohol, histrionic behaviour and exacerbation of preexisting phobic or obsessional symptoms or by Hypochondriacal preoccupations. A duration of two weeks is required for a diagnosis. E. The symptoms are not better accounted for by uncomplicated bereavement. Note: Adapted from DSM IV TR (APA, 2000), ICD 10 (WH0, 1992).