Bipolar Disorder in Children: Misdiagnosis,Underdiagnosis, and Future Directions

ELIZABETH B. WELLER, M.D., RONALD A. WELLER, M.D., AND MARY A. FRISTAD, PH.D.

ABSTRACT

Bipolar disorder has not been well studied in prepubertal children, despite its potentially debilitating effects on growth

and development. However, there have been case reports of mania in this age group dating back to Esquirol in the

mid-19th century. Despite anecdotal case reports, explicit criteria to diagnose mania in children were not used until

1960. Since 1980 the DSM-IIIIDSM-III-R criteria have indicated adult criteria can be used to diagnose childhood mania,

with some modifications to adjust for age differences. Bipolar disorder has not been frequently considered in the

psychiatric differential diagnosis of children. However, if a diagnosis of mania is made, clinical rating scales can be

used to rate the severity of manic symptoms and to monitor treatment. A manic child should be treated using a

biopsychosocial approach. To date, lithium carbonate has been the most commonly used psychopharmacological

treatment, but results have been variable. Additional research is needed, including double-blind, placebo-controlled

studies to document the beneficial effects of mood-stabilizing medications. Also, diagnostic instruments should be

refined to improve their utility. Finally, children at high risk for developing mania should be studied to identify predictors

of bipolar disorder in children. J. Am. Acad. Child Ado/esc. Psychiatry, 1995, 34, 6:709-714. Key Words: mania, bipolar

mood disorder, children, preschool children, diagnosis, treatment.

The study of bipolar disorder in prepubertal childrenhas received little attention, despite its potentially debil­itating effects on growth and development. This, atleast in part, stems from the general neglect of mooddisorders in children that occurred for many years inthis country. For example, childhood depression wasnot officially recognized in the United States until the1975 National Institute of Mental Health (NIMH)Conference on Depression in Childhood (Schulter­brandt and Raskin, 1977). At that conference, it wasconcluded that adult criteria could be used to diagnosedepression in children as long as appropriate modific­ations to accommodate for age and stage of develop­ment were made. Now, almost 20 years later, maniain children and adolescents is receiving similar attentionfrom the NIMH.

There have been case reports of mania in preschoolchildren and prepubertal school-age children datingback to Esquirol in the mid-19th century (1845).Kraepelin (1921), Kasanin (1931), Barrett (1931),

Accepted October 7, 1994.From the DepartmentofPsychiatry, The Ohio State University, Columbus.0890-8567/95/3406-0709$03.0010©1995 by the American Academy

of Child and Adolescent Psychiatry.

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Bleuler (1934), Olsen (1961), and Campbell (1952)have also reported cases of mania in this age group.

Kraepelin (1921) believed that mania existed inprepubertal children and that the occurrence of maniaincreased with the onset of puberty. Of 900 patientswith mania he studied, 0.4% had the onset of maniabefore the age of 10 years. Kraepelin also presentedthe case of a 5-year-old boy with mania.

Kasanin (1931) stated that there was a tendency toclassify mood disturbances that occurred in childrenas childhood schizophrenia. He repeated the explana­tion of another psychiatrist, Homburger (1926), as towhy mania was infrequently recognized. According tothis theory, children lack the capacity to analyze theiremotions verbally. They merely state that they do notfeel well, and this is taken as evidence of physicalillness. Thus, many cases are seen by pediatricians whousually do not suspect the affective nature of the illness.In discussing the difficulty of diagnosing mania inchildren, Kasanin quoted Ziehen (1917), who stated,"the behavior of a normal child resembles closelyhypomanic activity and any slight variations are notapt to the noticed." Other prominent child psychiatristshave also doubted the existence of mania in children(Kanner, 1937).

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Despite anecdotal case reports, explicit criteria todiagnose mania in children were not used until 1960.At that time Anthony and Scott reviewed 60 cases ofreported mania in children and applied diagnosticcriteria that they had developed. They concluded thatonly 3 (5%) of 60 cases satisfied their criteria formania. They also included a case report of a patientwho met their criteria for mania at age 12 yearsand when followed up as an adult (Anthony andScott, 1960).

A closer examination of Anthony and Scott's diag­nostic criteria might explain why they assigned thediagnosis of mania to only 5% of the sample theyreviewed. Their criteria included (1) an abnormal psy­chiatric state approximating the descriptions of maniaprovided by Kraepelin (1921), Bleuler (1934), Meyer(1952), and others; (2) a positive family history ofmania; (3) a history of either cyclothymia or sporadicmanic or depressive outbursts; (4) two or more similarepisodes; (5) a diphasic pattern; (6) an endogenousorigin; (7) treatment in an inpatient setting with heavysedation or electroconvulsive therapy (ECT); (8) anabnormal underlying personality; (9) the absence ofschizophrenia or organic states; and (10) current, notretrospective, assessments to establish the diagnosis. Allof these criteria had to be fulfilled to make a diagnosisof mania.

Most of Anthony and Scott's criteria do not appearin DSM-III-R For example, a positive family history,two episodes of mania, and diphasic illness are notnecessary to diagnose mania in DSM-III-R, but areessential for the diagnosis, by Anthony and Scott'scriteria. Anthony and Scott also required that theassessment of symptoms be current and not based onhistory. In psychiatry, it is often necessary to rely onhistory to clarify presenting problems. Also, very fewchildren ever receive heavy sedation or ECT; hencethis criterion cannot be satisfied in children. Finally,as personality disorders are rarely diagnosed in childpsychiatry, this criterion also would not be met inmost cases. Thus, Anthony and Scott's criteria makeit very difficult to diagnose mania in children, even ifthey clearly meet DSM-III-R criteria.

Fifteen years after Anthony and Scott's paper, asecond set of criteria to diagnose mania in childrenwas presented by Weinberg and Brumback (1976).Weinberg and Brumback were pediatric neurologistsworking at Washington University at the same time

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the Feighner criteria (Feighner et al., 1972), whichlater served as the basis of the DSM-III diagnosticsystem, were developed. These neurologists modifiedthe Feighner criteria to be suitable for use with children.Their criteria to diagnose mania included (a) euphoricor irritable mood, and (b) three or more of the follow­ing, which should reflect a change from the child'snormal behavior: (1) hyperactive, intrusive behavior;(2) push of speech; (3) flight of ideas; (4) grandiosity;(5) decreased amount of sleep or unusual pattern ofsleep; and (6) distractibility. Symptom duration of 1month was required to diagnose mania in children.

In 1979, Davis presented primary and secondarycriteria for mania. Primary criteria (all of which mustbe present) were (1) affective storms; (2) family historyof mania; (3) hyperactivity; (4) chronically disturbedpersonal relations; and (5) absence ofpsychotic thoughtdisorders. Secondary criteria (one or more of whichmust be present) were (1) soft neurological signs; (2)sleep disturbance; (3) abnormal EEG; (4) evidence ofminimal brain dysfunction; and (5) enuresis. Davis'criteria were somewhat "softer" than the previous crite­ria and would probably result in more diagnoses ofmania in children than with earlier criteria (Davis,1979).

Since 1980 the DSM-III and DSM-III-R criteriahave specified that adult criteria can be used to diagnosemania in children, with some modifications to takeinto account differences in age and developmental stage.

As bipolar disorders had been historically underdiag­nosed in adults in the United States compared toEurope (Taylor and Abrams, 1973), Weller et al. (1986)did a study to determine whether this might also betrue in children. They reviewed the English-languagepsychiatric literature from 1809 to 1984 and selectedfor review the case reports of 157 children whosediagnoses were manic depression, psychosis, schizo­phrenia, or "severely disturbed," because they believedthat potentially manic cases were most likely to havebeen assigned these diagnoses. Patients with mentalretardation, organic mood disorder, attention deficitdisorder, and pervasive developmental disorders wereexcluded from review. DSM-III-R criteria were usedto rediagnose these casesto determine whether they metcriteria for mania. However, the DSM-III-R criterion of"Involvement in activities with a high potential forpainful consequences" was deleted, as it was thoughtthat this criterion might be very common in children

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with attention deficit and conduct disorder and wouldthus be difficult to assess in a case reviewstudy. Thirty­three children of the 157 children were identified asmanic. Ofthese, 17 (52%) had been previouslyassignedsome other diagnosis, including obsessive-compulsivedisorder, loss reaction, "psychopathic" personality, bor­derline personality, immature personality, or schizo­phrenia. Thus it appeared mania may have beenunderdiagnosed in these children.

Prevalence and Epidemiology

To date, no epidemiological study has been under­taken to determine the prevalence of bipolar disorderin prepubertal children. However, when adult patientswith a well-established diagnosis of bipolar disorderwere asked the age of onset of their illness, 0.5%reported their age of onset was between the ages of 5and 9 years, and 7.5% reported onset between ages10 and 14 years (Loranger and Levine, 1978).

Clinical Description

Becauseof apparently low base rates, variable clinicalpresentation, symptomatic overlap with more commondisorders, and developmental constraints on symptomexpression, bipolar disorder has not been frequentlyconsidered in the differential diagnosisof psychiatricallyill children (Bowring and Kovacs, 1992). Regardingdevelopmental differences in clinical presentation,Lowe and Cohen (1983) proposed three possible mod­els for mania in children and adolescents: (1) both thegenotype and phenotype are similar to adult mania;(2) the genotype is similar, but the phenotype differssomewhat from adult mania; and (3) the phenotypeis similar to adult mania, while the genotype differs.The limited literature on mania in children describesmostly boys, usually around age 11 years, who havehigh rates of affectivespectrum disorders in their familyhistories, have few personal resources, and have experi­enced repeated losses.

A literature review by Carlson (1983) reported irrita­bility and emotional lability were more common inmanic children who were younger than 9 years ofage, while euphoria, elation, paranoia, and grandiosedelusions were more common in children older than9 years.

In young children, it is difficult to identify discreteepisodes. The clinical presentation usually includes aworsening of disruptive behavior, moodiness, difficulty

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BIPOLAR DISORDER IN CHILDREN

sleeping at night, impulsivity, hyperactivity, and aninability to concentrate. Episodic short attention span,low frustration tolerance, and explosiveanger followedby guilt, sulkiness, depression, and poor school per­formance are also described. There are reports of"model" children who dramatically change and become"wild" (Carlson, 1990).

In preschool children, pathologically prolonged statesof emotional arousal in response to minimal stimuliand episodic frenzied activity with minor symptomsof depression have been described by Carlson (1983).Explosive and unmanageable temper tantrums, sexualjoking, and nightmares with violent imagery have beendescribed by Popper (1984). Poznanski et al. (1984)described a 4-year-old with hypomania who on follow­up as an adolescent manifested full-blown manic epi­sodes. In our children's unit, a review of all casesadmitted from April 1988 to October 1992 indicatedthat of 36 preschool children, 6 (17%) met DSM­III-R diagnostic criteria for mania or hypomania (Tu­muluru et al., personal communication). The clinicalpresentation of these children was not substantiallydifferent from that of older children.

In a study of 6- to 12-year-old prepubertal children,our group reported on 10 children who were diagnosedto have mania by DSM-III-R criteria (Varanka et al.,1988). All of these children reported mood distur­bances. However, 50% reported a primarily elatedmood and 50% reported a primarily irritable mood.All were restless; 90% reported decreased sleep; 70%reported visual hallucinations and persecutory delu­sions; 60% reported increased sexual activity, pressuredspeech, and racing thoughts; 50% reported increasedtalkativeness, increased distractibility, flight of ideas,and auditory hallucinations. Grandiose delusions werereported by 20%. A positive family history of maniawas present in 20%, 50% had a family history ofdepression, and 60% had a family history of alcoholism.Other psychiatric diagnoses observed in the familiesof these manic children included substance abuse,antisocial personality, and paranoid disorder.

Comorbidity

In child psychiatry, it is the exception rather thanthe rule for children to present with a single diagnosis,especiallyif they require hospital admission. No studiesthat systematicallyassess comorbidity in manic childrenhave been conducted. Anecdotal reports of mania being

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comorbid with hyperactivity (Koehler-T roy, 1986) ,Tourette's disorder (Bleich et aI., 1985), and alcoholdependence (Famularo et aI., 1985) have beenpublished.

Differential Diagnosis

The differential diagnosis of mania includes bothmedical and psychiatric conditions. Medically, iatro­genic conditions such as steroid use, endocrine disorderssuch as hyperthyroidism, and neurological conditionssuch as head trauma and multiple sclerosis should beconsidered and ruled out.

The psychiatric differential diagnoses for manic chil­dren include three major categories: attention-deficithyperactivity disorder (ADHD), conduct disorder(CD) , and schizophrenia.

Attention-Deficit Hyperactivity Disorder. Althoughchildren with this disorder are distractible and haveincreased motor activity, which are symptoms alsofound in manic children, the onset of attention deficitdisorder is in the preschool years and the course ismore chronic. Children with ADHD often have lowself-esteem due to demoralization but should not haveany psychotic symptoms. While children with ADHDoften require less sleep than peers of the same age andhave difficulty falling asleep at night, these sleep pat­terns are typical and do not reflect a changefrom usualbehavior, as is observed in children with mania.

Conduct Disorder. Children with CD often becomeinvolved in dangerous acts with painful consequences.However, the manic child's behavior is usually moremischievous whereas the child with CD is more hurtfuland vindictive, with a motive to get others in trouble,and does not usually show any guilt or remorse. Chil­dren with CD, unlike those with mania, do not havepsychotic symptoms, push of speech, or flight of ideas.Suspiciousness observed in these children with CDmight be mistaken for paranoia. However, this suspi­ciousness is frequently caused by their fear of gettingcaught, which is often legitimate, as they truly haveaggravated others and thus may actually be "caught"and punished.

Schizophrenia. Although children with schizophreniaare psychotic by definition, schizophrenia can be differ­entiated from mania. Children with schizophrenia usu­ally have a more insidious onset of illness and have afamily history of schizophrenia instead of affectiveillness. They do not have push of speech or flight of

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ideas and usually do not have the engaging quality ofa child with mania.

Assessment

There is no substitute for a well-trained clinicianwho does a comprehensive assessment. This includesinterviewing the child with the family, the child alone,and the family alone; obtaining teacher observations;and then integrating all the information to arrive at aclinical diagnosis. A complicating factor in diagnosingmania in children is that parents of these childrenoften have ongoing psychopathology. Thus, it is criticalto ensure that the parents are reporting their child'ssymptoms and not their own symptoms. It is essentialto get information from the school as the child spends6 to 8 hours a day there. Most teachers can providean objective assessment, comparing the identified childwith age-matched children in the classroom, and reporton the child's behavior in a setting with different taskdemands than are present at home (e.g., to sit stilland focus attention in a group setting).

Diagnostic instruments used to assess mania includeboth structured and semistructured interviews. Struc­tured interviews include the Diagnostic Interview forChildren and Adolescents-Revised (D ICA-R) (W.Reich and Z. Welner, unpublished) and the DiagnosticInterview Schedule for Children (Costello er aI., 1982).Semistructured interviews include the Interview Sched­ule for Children (Kovacs, 1978) and the Schedulefor Affective Disorders and Schizophrenia for School­Age Children (Chambers et aI., 1985). Advantagesof these interviews are their thorough coverage ofDSM-III/DSM-III-R disorders. Structured interviewscan be completed by trained lay interviewers , whereassemistructured interviews usually require completionby a clinician. Both, unfortunately, are lengthy andcumbersome. Also, our unpublished data suggest theDICA-R tends to overdiagnose mania in children withCD and ADHD.

Once a diagnosis of mania is made, clinical ratingscales can be used to document the severity of maniaand to track changes in target symptoms as treatmentprogresses. The Mania Rating Scale developed byYoung et aI. (1978) has been studied by our group inchildren (Fristad et al., 1992). It has acceptable validityand reliability and can distinguish between manic andhyperactive children. Other instruments widely usedby child psychiatrists are the Conners Teacher and

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Parent Scales (Conners, 1985). These instruments donot appear to differentiate between manic and hyperac­tive children (Fristad et aI., 1992).

Treatment

A biopsychosocial approach is recommended in treat­ing a manic child. Both the child and his or her parentsneed to be considered in developing the treatmentplan. Pharmacologically, mania in children has beentreated with lithium carbonate in open trials withvariable results. Other medications such as carbamaze­pine and valproic acid have also been used, and severalpsychosocial approaches been employed.

Indications for the use oflithium in children (Camp­bell et aI., 1984) include (1) disabling episodes ofmania and depression; (2) severe depression with apossible history of hypomania; (3) depression withpsychomotor retardation and psychotic features; (4)acute psychotic disorder with mood symptoms; and/or (5) aggressive behavior with mood symptoms witha family history of mood disorder responsive to lith­ium treatment.

Lithium is well tolerated by preschool and school­age children. Weller et al. (1986) reported a protocolto safely start children on lithium carbonate accordingto their weight. In lithium treatment, lithium levelsas high as 1.4 mEq/L have been reported with minimalside effects. Lithium can be monitored safely in theblood or the saliva (Weller et aI., 1987). As the currenttendency is not to discontinue lithium in a child witha well-established diagnosis of bipolar disorder who isresponding well to treatment, the possibility of salivamonitoring for long-term treatment should beconsidered.

Parents need to know about all the potential effectsof lithium. There are anecdotal reports of proteinuria(Lena, 1979). There is also a concern about lithiumdepositing in the bones, and the clinical significanceof this in a growing child is unknown. Informed consentand assent should be obtained before starting treatment.

Psychosocial treatment should include psychoeduca­tion, school intervention, and treatment for the parentsas needed. While the adult literature suggests patientsdo best in families with low levelsof expressed emotion(Miklowitz et al., 1988), no similar srudies have iden­tified family variables associated with lowered relapserates in children.

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BIPOLAR DISORDER IN CHILDREN

Outcome and Follow-up Data

There are no systematic follow-up data on preschoolchildren or prepubertal school-age children with well­diagnosed bipolar disorder. Anecdotal' data support theobservation that manic children "don't grow out ofit" (Poznanski, 1993).

Research Directions

Bipolar disorder in preschool and school-age childrenhas been understudied. Despite this, clinicians are usinglithium, carbamazepine, and valproic acid in an effortto treat manic children with uncontrollable behavior.Double-blind, placebo-controlled studies should beconducted to document the beneficial effects of mood­stabilizing medications in preschool and prepubertalschool-age children. Diagnostic instruments need tobe refined so mania can be more precisely diagnosedand monitored. Children at high risk for developingmania should be carefully studied. These are childrenwith prepubertal depression or dysthymia, children ofparents with mood disorders, and children with afamily history of mania. Predictors of bipolar disorderin children should be identified. Such predictors mightinclude family history, family environment and sup­ports, and stressful life events (particularly repeatedlosses). Biological markers of bipolar disorder shouldalso be investigated. There is still much that needsto be learned so that bipolar disorder can be betterrecognized and treated in preschool and prepubertalschool-age children.

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