Psychiatric Phenomenology of Child and Adolescent Bipolar Offspring

Psychiatric Phenomenology of Child and Adolescent Bipolar Offspring KIKI D. CHANG, M.D., HANS STEINER, M.D., AND TERENCE A. KEITER, M.D.

ABSTRACT

obfeahre:To establish prodromalsigns of and risk factors for childhood bipolar disorder (BD) by characterizingyouths at high risk for BD. Method: Structured diagnostic interviews were perfwmedon 60

offspring of at least one parent with BD.

Demographics, family histories, and parental history of childhood disruptive behavioral disorders were also assessed. Rewb: Fiftyme percent of bipolar offspring had a psychiatric disorder, most commonly attention-defcithypelhvperactnntydis-

order (ADHD), major depression or dysthymia,and BD. BD in offspringtended to be assoCiated with earliec parental symptom onset when compared Hnth offspring without a psychiatric diagnosis. Bipolar parents with a history of childhood ADHD were

more likely to have children with ED, but not ADHD. Offspring with bilineal risk had increased seventy of depressed and irritable mood, lack of mood reactivii, and rejectii sensitiwty, while seventy of grandiosity,euphoric mood, and decreased need for sleep were not preferentially associated with such offspnng. Conduelons: Bipolar offspring have high levels of psychopa-

thology. Parental history of early-onset ED and/or childhood ADHD may increase the risk that their offspring will develop BD.

Prodromal symptoms of childhood BD may include more SUM presentations of mood regulation diffiiculties and less presence of classic manic symptoms.J. Am. Acad. ChiM Addesc. Psychiafry 2000,39(4):453-460.K q Words: bipolar disorder, offspring, prodromal symptoms, risk factors.

Bipolar disorder (BD) has historically been underdiagnosed in children and adolescents. While the incidence appears to be about 1% in adults (Weissman et al., 1988) and adolescents (Carlson and Kashani, 1988; Lewinsohn et al., 1995), the incidence in prepubertal children is unknown. Epidemiological studies have suggested that the onset of psychiatric symptoms meeting criteria for BD is rare before age 14 years (Goodwin and Jamison, 1990). However, surveys of adults with BD reveal up to one third having an onset of significant psychiatric symptoms, not necessarily meeting criteria for BD, before age Accepted Scprnnbcr 29,1999. Fmm the Department of &hiany and Behavioral sn'nrrr. Stanfini Univm i 9 School of Medicine#S t a n j i d CA. Dr Cbang was an NIMH Postdoctoral Fellow and Dr Steinrr u R.f;sor and Dinrtor of Training in the Division of Chiki Pychiaq and Child Deuelopmmt. Dr. Kencr is Associate Rofrrror of +biaq and Behavioral Scimces and C b q f o f the Bipolar Disorah Clinic. Thu work was supported in pan N I M H p n t 5 T32 MH19908-03 (OK. %w and Chand and by a gnrntfrom the Stanlcy Foundation (Dr. I(rtur). The authors thank Claudia Santosa* M.A.. Dr. Barbara Glhc and Dr. Gabritlh CIlrlron fir their inualuablr mutanre. Rrprint nqucm to Dr. Chang, Stanfinl Univrni9 School of Medicine, Divuwn of Child Pychiaq and Child Drvrlopmcnt, 401 Q u a y Road, S t a n f i d CA 943055540; kchang88@scany%rdedu. 0830-8567/00/3904~53Q2000by the American Academy of Child and Adolescent Psychiatry.

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14 (Lish et al., 1994), most commonly depressed mood. In this sample there was an average of 5 years' delay from symptom onset until receiving treatment. Recognition of BD in younger chiidren may be difficult because of phenomenological differences with later adolescent and adult-onset BD. Adolescent mania ofien appears very different from adult mania, presenting with more mixed states and psychoses (Bdlenger et al., 1982; Geller et al., 1995). Prepubertal BD may present even more atypically, with briefer manic episodes or sustained conduct and impulse-control problems (Womiak et al., 1995).Early disruptive behavior in some children may in fict be a p& mal sign of bipolar or other mood disorder (Carlson, 1995; Carlson and Weinuaub, 1993; Wozniak et al., 1995). Thus, childhood-onset BD is commonly associated with or preceded by conduct disorder (CD), attentiondeficit/hyperactivity disorder (ADHD), and/or oppositional defiant disorder (ODD). Researchers have reported that as many as 57% to 86% of bipolar children and adolescents have comorbid ADHD and 69% have comorbid C D (Borchardt and Bernstein, 1995; Faraone et al., 1997a; Kovacs and Pollock, 1995; Milberger et al., 1995; West et al., 1995a). The question remains whether these are truly comorbid conditions, prodromal or concurrent rep453

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resentations of BD itself, or a byproduct of taxonomid overlap. Other researchers have described adolescent-onset BD to have less comorbidity with ADHD, CD, or O D D and to have more classic features (Faraone et al., 1997b; Geller and Luby, 1997).This raises the possibility of a further distinction of prepubertal-onset and adolescentonset BD as 2 distinct entities, or as the manifestations of the same disorder at different developmental stages. It remains to be determined whether the current diagnostic criteria for BD are usefd for children and adolescents. A new set of criteria may especially need to be established to diagnose BD in prepubertal children. That is, antecedent symptoms of BD may need to be recognized, and these symptoms may differ from those of classic BD, reflecting an earlier nonisomorphic presentation. To recognize these antecedent symptoms, it would be llsefLl to study psychiatric symptoms in children at high risk fbr developing BD. Offspring of bipolar parents have been identified as such a high-risk group. One study found the risk of developing an affective disorder for first-degree relatives of BD probands to be 24%. This risk may increase to 27% if one parent and to 74% if both parents have BD (Gershon et al., 1982). A recent meta-analysis estimated a 4.0 times greater risk in bipolar offspring for developing a mood disorder compared with offspring of healthy parents (Lapalme et al., 1997). Previous studies have reported high rates of psychiatric disorders in offspring of BD patients, most frequently major depression and dysthymia (Hammen et al., 1990; Laroche et al., 1987). Bipolar disorders, especially cyclothymia, were also found to be more common in these children than in controls (Akiskal et al., 1985; Klein et al., 1986; Todd et al., 1996). Longitudinal studies are important to support or refute the assumption that many of these oflipring will also eventually develop BD. There have been only a few longitudinal studies of bipolar offspring (Hammen et al., 1990; Nurnberger et al., 1988;Zahn-Waxler et al., 1988), following fewer than 20 oflipring over 1 to 3 years. Furthermore, these studies were geared toward identifying DSM-III diagnoses only, not toward identifying early prodromal symptoms. These studies also did not consider bipolar I1 or not otherwise specified subtypes, as they were based on DSM-IIIcriteria for BD (i.e., DSMbipolar I disorder) and therefore may have underreported bipolar outcomes in offspring. A more recent study addressed prodromal symptoms, finding attentional and behavioral problems in children of bipolar parents to be predictive of the development of mood disorders as young adults (Carlson and 454

Weintraub, 1993). Furthermore, in depressed children and adolescents, mood-congruent psychosis, psychomotor retardation, and a Emily history of BD may put them at increased risk for developing subsequent manic episodes (Geller et al., 1994; Strober and Carlson, 1982). Geller et al. (1994) have reported that up to 30% of prepubertal depressed children may go on to develop BD. These studies support the concept that prodromal symptoms of BD may occur in children and adolescents. The specific prodromal symptoms of BD in children remain to be firmly established. In adults with BD, the most common retrospectively described initial symptoms (mostly occurring in childhood and adolescence) were depressed mood/hopelessness (33%), manidhyperactivity (32%), lack of sleep (24%), mood swings (13%), and angerhitability (9%) (Lish et d., 1994).The most important risk factors for children developing BD are also yet to be determined. Of crucial importance, it is not yet known whether prepubertal BD is a distinct subtype of later-onset BD or simply an earlier manifestation of the same disease. We sought to explore these issues by investigating psychiatric symptoms in children who are ofipring of bipolar parents, a high-risk group for the development of BD, which may be later followed prospectively and longitudinally to determine their outcome in later adolescence and adulthood. At this point our study is a cross-sectional description of the range of impairments that children may suffer with a well-diagnosed parent; we generally expect that at least 27% of these children will indeed develop DSM-IVBD. We hypothesized the following: 1. There will be a cluster of attentional, behavioral, and mood symptoms in certain subjects, representing a prodrome of BD. 2. Subjects already meeting full DSM-Ncriteria for bipolar I disorder will be less common than those described in hypothesis 1. 3. There will be a positive correlation between increased family history of mood disorder and an increased incidence of these prodromal symptoms in the bipolar offspring. 4. Bipolar parents who have had a childhood history of behavioral disorders will have children with a similar presentation. METHOD Design Sky subjms were mruited from p a n t s who wcrc patients at the Stanford University Bipolar Disorders Chic, from 1 o d support groups

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for bipolar adults, and h m the surrounding community. Subjects were enrolled consecutively from 38 different families, between June 1997 and August 1998;were between 6 and 18 years old; and had at least one biological parent with bipolar I or I1 disorder. Attempts were made to include all ofkpring from each bipolar parent. One child was unable to participate in the evaluation because of mental retardation and was excluded from the study. Assessment and Diagnosis After written informed consent was obtained, parents were intcrviewed and diagnosed according to DSM-N(AmericanRyduamc A.uociation, 1994) criteria. Parents were further assessed retrospectively for childhood ADHD, ODD, and C D by supplements from the Schedule for Affective Disorders and Schizophrenia for School-Age ChildrenPresent and Lifetime version (K-SADS-PL) (Puig-Antich and Ryan, 1986) and asked at what age they first experienced significant psychiatric symptoms, including mood and behavioral problems. Psychiatric family history for all first- and second-degree relatives was obtained by the Family History-Research Diagnostic Criteria (FH-RDC) (Andrcasen et al., 1977). Offspring of bipolar parents were evaluated by the Mective Disorders module of the Washington University Schedule for Mective Disorders and Schizophrenia for School-Age Children (WASH-UKSADS) (Geller et al., 1998) and the K-SADS-PL (Puig-Antich and Ryan, 1986). The WASH-U-KSADS is a semistructured diagnostic interview based on the K-SADS which concentrates heavily on &ective symptoms, recording severity on a Liken-type 8-point d e and frequency of symptoms. Thus, generally a score of 0 to 3 indicates no symptoms to mild, subthreshold symptom presence. A score of 4 to 6 indicates significant presence of the symptom in order to count for the DSM-Ndiagnosis. Subjectswere evaluated either by a trained child and adolescent psychiatrist or research assistant (master‘s-level, with 2 years experience in psychiatric interviewingof children and adults), who were both nonblinded to parental stam. Interrater reliability was established at the outset by rating videotaped interviews, observing trained rater interviews, and performing interviews with observation by a trained rater, as described by Geller ct al. (1992). Diagnostic decisions were ultimately made by a child and adolescent psychiatrist based on personal interview, discussion with the rcsearch assistant, and written notes of parental and subject responses to individual WASH-U-KSADS quesrions. Each patient was assigned a Global Assessment of Functioning (GAF) xore by the interviewer. The parents were as0 interviewed for psychiatric history of first- and seconddegree relatives following the FH-RDC. Subjects were assessed for manic symptoms by the Young Mania Raring Scale (Young et al., 1978),which has been reported effective in assessing children with mania (Fristad et al., 1992, 1995).Attentional and behavioral symptoms were assessed by parental report using the Child Behavior Checklist (Achenbach, 1991) and the Conners 10Question Parent-Teacher Quationnaire (Conners, 1994).

Cohort Demographic information collected included age, gender, parental occupation and level of education, household income, ethnic status, birth order and number of siblings, and parental age of illness onset. Socioeconomic status (SES) was assessed using Hollingsheads Two Factor Index of Social Position (Hollingshead and Redlich, 1958). Statistical Methods Descriptive statistics and nonparametric statistics, such as MannWhitney analysis of variance (ANOVA), were used as appropriate.

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RESULTS Demographic Information

Sixty oflipring of 37 families with at least one bipolar parent participated in this study; mean age of oflipring was 11.1 i 3.5 years. Forty-eight percent were boys.The sample was 82% white, 8% Asian American, 3% Hispanic, 2% African American, and 5% other. Thirty of the families (93% of the subjects) had a mother as the only bipolar parent. SES was divided as 0% category I, 9% category 11, 42% category 111,27% category N, and 21% category V. Mean parental age at onset of bipolar symptoms was 14.8 * 8.3 years. Parental Characteristics

The parents were representative of the catchment area in race and SES (Table 1). Ninety-eight percent of h i lies had a parent currently employed or with a successful employment history in the previous 5 years. The identified bipolar parents had an average of 2 prior hospidizations. All parents were considered euthymic and able to cooperate at the time of the interviews. Families, and thus offspring, were divided into 2 categories: (1) a bilineal category, with both parents having mood disorders (one with bipolar I or I1 disorder, the other with BD or major depression); and (2) a unilineal category, with one parent with bipolar I or I1 disorder and the other without a mood disorder (Table 1). Psychiatric Diagnoses

Fifty-five percent of the sample had an Axis I disorder as determined by DSM-IV. Twenty-eight percent had ADHD, 15% had major depressive disorder or dysthymia, 15% had BD or cyclothymia, 10% had ODD, 3% had obsessive-compulsive disorder, 3% had tic disorder, and 5% had other anxiety disorders (separation anxiety disorder, generalized anxiety disorder, and social phobia) (Table 2). These were lifetime diagnoses, with the majority of diagnoses being current at the time of evaluation. Mean GAF score was 76.0 * 12.0. Eighty-eight percent of children with BD had comorbid ADHD. Both BD and ADHD were more likely to be diagnosed in males (Fisher exact test; BD: x2, = 5.67, p = .02; ADHD: x21= 9.47, p = .003). Diagnosis of BD or ADHD was not associated with age - or SES. There was a trend of BD and ODD being associated with earlier parental psychiatric symptom Onset when ‘Ompared with no Axis I Fable 2, (ANOVA with Bonferroni/Dunn correction, p = .07). 455

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TABLE 1 Characteristics of Bipolar Parents and Bipolar Offspring Grouped by Risk Group

No. of families Mean age of parental symptom onset, yr (SD) Parents with ADHD (%) Gender of bipolar parent Mothers Fathers Both SES (Yo) Category I, I1 Category I11 Category IV,V Relatives with mood disorder, Yo (SD) Offspring

Bilineal Group

Unilincal Group

18 13.6 (10.1) 11 (58)

19 15.7 (6.1) 4 (21)

13 4 1

P NS

NS .02 NS

17 2 0

NS

n

Mean age, yr (SD) GAF (SD) Conners (SD) YMRS (SD) Diagnoses of offspring Bipolar disorder ADHD Major depressionldysthymia Anxiety disorder

9.5 38.1 52.4 62 (18)

3.4 55.2 41.4 40 (15)

30 11.6 (4.0) 74.4 (12.6) 11.3 (6.8) 5.1 (6.1)

30 10.8 (3.0) 78.5 (10.4) 11.2 (8.4) 3.0 (3.9)

6 10 7 2

<.0001

NS NS NS NS NS NS NS NS NS

3 7 2

5

Note: Some subjects have more than one diagnosis. ADHD = attention-deficidhyperactivity disorder; SES = socioeconomic status; GAF = Global Assessment of Functioning; YMRS = Young Mania Rating M e ; NS = not significant.

grandiosity, and decreased need for sleep. Mood reactivity asks to what degree and how quickly the mood state (depression or irritability) is able to resolve with external consoling. A rating of 1 refers to being able to snap out of low or irritable moods to euthymic mood quickly (i.e., within minutes). A rating of 6 indicates that the subject is not usually able to be consoled and that the mood state persists for days. This should not be confused with “mood lability,” which generally refers to the tendency to experience differing moods rapidly. Symptom severity was not associated with increasing ncrmded b i l y history of mood disorder. However, severity of depressed mood,

However, this was not significant when compared with other psychiatric diagnoses. BD was not associated with increasing family history of mood disorder in first- and second-degree relatives. BD was also not significantly associated with any parental risk category (unilineal or bilineal). PhenomenologicalFindings

Six symptoms from the WASH-U-KSADS were hypothesized to be increased in severity as family history and parental genetic risk increased: depressed mood, euphoric mood, irritable/angry mood, mood reactivity,

TABLE 2 Characteristics of Bipolar Offspring Grouped by Psychiatric Diagnosis Bipolar

ADHD ~~

n (Yo)

Males Females Mean age, yr (SD) 1 and 2 relatives with mood disorders (%) Bilineal risk group (%) Mean age of parental onset, yr (SD)

Depression

Other Axis I

No Axis I

~

~

Total ~

9 (15) 17 (28) 9 (15) 8 (13) 27 (45) 60 (100) 8 14 4 3 9 30 1 3 5 18 30 5 10.9 (3.2) 11.3 (3.3) 12.3 (3.5) 12.4 (2.6) 10.4 (3.9) 11.1 (3.5) 53 46 49 49 55 50 48 78 63 56 38 36 10.7 (5.3) 11.9 (5.5) 13.9 (11.0) 14.5 (4.2) 16.7 (9.2) 14.7 (8.2)

No&: Some subjects have more than one diagnosis. A D H D = attention-deficitlhyperactivitydisorder.

456

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irritable/angry mood, and mood reactivity was associated with the bilineal category of increased parental genetic risk (Mann-Whitney ANOVA, p = .03, p = .04, p = .02) (Fig. 1). Severity of grandiosity, euphoric mood, or decreased need for sleep was not associated with either the unilineal or bilineal category. Symptom severity was not associated with age, parental age at onset of psychiatric symptoms, or SES. Post hoc analysis revealed the symptom severity of “rejection sensitivity,” “social withdrawal,” and “crying” to be associated with the bilineal group as well (MannWhitney ANOVA, p c.05 in all cases) (Fig. 1). No other K-SADS mood symptoms were preferentially associated with either familial group. Comparing child and parental presentations, 29% of offspring with and 20% of offspring without ADHD had a bipolar parent with a childhood history of ADHD, a nonsignificant difference. However, significantly more offspring with (56%) than without BD (17%) had a bipolar parent with a childhood history of ADHD. Thus, bipolar parents with childhood ADHD were more likely to have children with BD, but not ADHD (Fisher exact test, xZ1= 4.37, p = .OZ). Finally, Conners, Young Mania Rating Scale, and GAF scores did not differ significantly between the unilineal and bilineal groups (Table 1). DISCUSSION

Our study of 60 children of bipolar parents demonstrated high levels of diverse psychopathology, encompassing affective disorders as well as behavioral and anxiety

4 4 3.5

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8

2 1.5 1 0.5

n mp”lmmlmy bad

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Symptom Fig. 1 Severity of mood symptoms in the bilineal and unilincal risk groups. &verity is on a 1 (least) to 6 (most) scale. ‘p c.01; *’p <.02.

I.

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disorders, notably a 28% prevalence of ADHD and a 15% prevalence of BD. There was a male gender preference for these disorders (81% of offspring with ADHD and 88% of offspring with BD). Phenomenologically, the children at the highest risk for BD were distinguishable from the unilineal group by the severity of distinct mood symptoms (irritability and depression) and mood regulation problems (rejection sensitivity and lack of mood reactivity). Transgenerational analysis revealed bipolar parents of offspring with BD to be more likely to have had ADHD themselves, as well as tending to have an earlier age at onset of psychiatric symptoms than parents of offspring without any Axis I disorders. Despite the increased risk for psychopathology in this cohort, 45% of the offspring did not have any diagnosable Axis I disorder by DSM-Ncriteria, similar to the percentage of offspring without psychopathology found in other offspring studies involving depressed or schizophrenic parents (Marcus et al., 1993).There was also no association of extended h i l y history of mood disorder with BD in the offspring. Finally, there was no preferential association of the more classic manic symptoms-such as euphoria, grandiosity, and decreased need for s l e e p w i t h the bilineal group of offspring. Some of these findings may be due to the cross-sectional nature of this study As the mean age of the cohort was 11.1 years, many of these “unaffected” children may yet develop diagnosable Axis I disorders. Conversely, diagnosable children may become asymptomatic as development proceeds. Many offspring had significant psychiatric symptoms but did not meet diagnostic criteria. Regardless, our intention was not to produce an epidemiological study but to collect phenomenological data on children at high risk for developing BD. Ours is the largest cohort of bipolar offspring to date, with an even gender distribution, diagnosed using a structured interview sensitive for mood disturbance. Our data corroborate past findings of high levels of psychopathology among offspring of parents with BD. The 55% of our cohort having a mental disorder is close to the 52% reported in a recent meta-analysis of bipolar offspring studies (Lapalme et al., 1997).The 15% with major depression or dysthymia is similar to the 18% reported by Laroche et al. (1987) and the 12% reported by Todd et al. (1996), but somewhat less than the 28% reported by Hammen et al. (1990). However, the high percentage with ADHD has not previously been noted in previous bipolar offspring studies. The 15% with BD or cyclothymia in our cohort is similar to the 12% reported by Todd et al. (1996), 457

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but much higher than the average of 5.4% found in earlier reports (Lapalme et al., 1997). This discrepancy may be partially due to the differences in diagnostic criteria between DSM-III, DSM-III-R, and DSM-IK Recruiting bias, as noted below, also may have increased the prevalence of BD in this cohort. Finally, as we used the WASH-U-KSADS, which was designed specifically to elicit affective symptoms, we may have been more successful in detecting mood symptoms in our subjects and thus diagnosing BD in children who in the past studies may have had only ADHD diagnosed. As 88% of our bipolar children also met criteria for ADHD, they might represent a subset of children previously receiving only the ADHD diagnosis. Prevalence of this comorbidity has not previously been reported in studies of bipolar ofipring but is congruent with previous studies of children in general with BD (Faraone et al., 1997b; West et al., 1995b). The association of parental ADHD+BDwith BD ofipring has not been previously reported. This finding reinforces the possibility of genetic transmission of a distinct type of BD, or a more ‘‘virulent‘‘form of BD which presents at an earlier age and which indudes the features of ADHD (Faraone et al., 1997a). Indeed, bipolar parents with childhood ADHD tended to have an earlier age at onset of their bipolar symptoms (11.3 years) than those without ADHD (15.6 years). The association between A D H D and male gender agrees with previous findings in clinical samples, reporting A D H D 6 to 9 times more common in boys than girls (American Psychiatric Association, 1994). Our findings of BD being much higher in males have not previously been reported, although BD has been proposed to be as high as 4 times more likely in boys (Faedda et al., 1995). This presentation of A D H D in boys may represent a gender-specific pathway to BD, with ADHD being a precursor or representing a distinct subtype of early-onset BD (Faraone et al., 1997a) in males. Depressive disorders, however, were evenly distributed between genders. Carlson and Weintraub (1993) grouped bipolar offspring by presence or absence of behavioral or attentional problems and noted an association of these with onset of mood disorders in young adults. We have furthered this concept by studying individual mood symptoms as possible prodromal symptoms of BD. Our findings of increased severity of irritability, depression, lack of mood reactivity, and rejection sensitivity in the bilineal group suggest an innate difficulty with mood regulation in this group at highest risk for BD. In addition, these symptoms 458

may be part of a prodromal state of BD. More classic symptoms of mania, such as grandiosity, euphoric mood, and decreased need for sleep, were not found to be significantly different among the groups. These symptoms may not be important early symptoms but rather later symptoms of a more advanced, crystallized presentation of BD. This difference may explain why BD is often not diagnosed until many years after the appearance of psychiatric symptoms (Lish et al., 1994)-clinicians may not recognize subtle mood difficulties as harbingers of BD. Decreased mood reactivity and increased rejection sensitivity are dynamic characteristics indicating a problem with mood regulation. Children with a lack of mood reactivity persist in an angry or depressed mood despite efforts to console. These characteristics may provide more insight into the likelihood of hture mood disorders, as they may mediate how children respond to external stressors. This idea is similar to a temperamental characteristic of the “difficult” child, which has been found to be associated with conduct and behavioral problems in adolescence (Windle, 1991). Experimental studies of mood regulation in response to stress are needed to elucidate further this proposed characteristic of bipolar offspring. In summary, and addressing our hypotheses, we found that bipolar offspring have many difficulties with attention, behavior, and mood. Many of these children have BD, but others have what may be prodromal BD, which will only be known by longitudinal monitoring. Second, there were more children with these various symptoms than there were children with DSM-NBD. Third, family history was not correlated with increased psychopathology, possibly representing a ceiling effect. However, bilineal pamtaf history of mood disorder was correlated with increased mood regulation difficulties. Finally, parental childhood behavioral disorders were at least partially correlated with their offsprings psychopathology, in that parents with childhood ADHD tended to have children with BD (who mostly had ADHD as well). Other parental childhood disruptive behavioral disorders, ODD and CD, were not correlated with such diagnoses in their children. Other parental childhood symptoms, such as mood difficulties, were not assessed systematically enough to compare with their offspring’s symptoms. While we have shown high rates of psychopathology in bipolar offspring and described distinct mood regulation difficulties in this cohort, it remains for longitudinal study to determine whether these are indeed prodromal states of BD or false-positives.

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Limitations

Our findings must be considered with several limitations in mind. We did not include a control group of families without psychiatric disorders or families with parents with other psychiatric disorders. Thus, interviews were not conducted in a blind fashion, possibly adding interviewer bias to the diagnostic findings. Subjects were predominantly white (82%) and of a middle to high SES level, reflecting the general catchment area of our clinic. In addition, the bipolar parents in this study were largely female (84%). It is not known what effect this gender preference may have had on our findings. A previous study has reported higher transmission of BD to offspring from bipolar mothers compared with bipolar fathers (McMahon et al., 1995). The reason for this gender discrepancy of bipolar parents in our study is also unclear. We received multiple inquiries about our study from mothers with children whose fathers had a diagnosis of BD; in almost all of these cases,the father was not available or interested in participating in the study. There may also have been selection bias, in that parents whose children were exhibiting psychiatric symptoms were more likely to participate. Some families had multiple children in the study, which could skew prevalence data if these families had some type of increased predisposition for psychopathology; however, we did attempt to evaluate every child in each family that met our inclusion criteria (age, ability to be interviewed). Furthermore, parents received a clinical interview, not a standardized research diagnostic interview. We do not know the validity of retrospective childhood diagnoses of these parents. We also did not interview each family member to obtain family history data; FH-RDC data were obtained by interviewing available parents and grandparents. Offspring ADHD diagnoses were made without data from teachers. Offspring diagnoses of mood disorders were obtained by using the WASH-U-KSADS, a nonstandard form of the K-SADS. The WASH-U-KSADS allowed us to assess subtle mood-related symptoms that may not necessarily be included in the DSM-Was symptoms of a specific mood disorder. While this practice would not appear to affect our prevalence of psychiatric disorders data, our results should be considered with this in mind. Clinical Implications

It is important for clinicians to recognize these putative symptoms of prodromal BD in children of bipolar par-

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ents, especially those from families with a bilineal history of mood disorder. The concept of “kindling” as described by Post (1992) would indicate that if left untreated, these children may go on to develop manic and depressive episodes. This offers a unique window for prevention of major psychopathology. By recognizing early symptoms and risk factors, the clinician may be able to intervene to prevent the progression to the full-blown BD. As well, the clinician should be aware of manifestations of attentional and behavioral symptoms of bipolar offspring. The implications of using stimulants or antidepressants with the potential of triggering or worsening manic states should be considered. Perhaps it may be argued that such ofhpring would be better served by prophylactic treatment with mood stabilizers. Our study also has implications for psychiatrists caring for adults. As one half of bipolar offspring will have psychiatric conditions, general psychiatrists need to ask their adult patients about their children. Finally, it is important for mental health practitioners to realize that the first signs of BD may appear earlier in life than previously thought. The mean parental age at onset of bipolar symptoms in our cohort was 14.8 years, and 44% had an onset before age 15 years. The mean age of their offspring who already had a diagnosis of BD was 10.9 years. Prepubertal mood and behavioral difficulties in bipolar offspring need to be considered as potential prodromal manifestations of BD. REFERENCES Achenbach TM (1991), Manualfir the Child Behavior Chtcklist/&lB and 1771 hJi&. Burlington: University of Vermont Department of Psychiatry AkisM HS. Downs J. Jordan C Watson S, Daughcrty D. Pruin DB (1985), Affective disorders in referred children and younger siblings of manicdepressives: mode of onset and prospective course. Arch Gen Bychiany 42996-1003 American Psychiatric Association (1994), Diagnortic and SratirricalManual of Mental Dirordm, 4th edition (DSM-/I?. Washington, DC: American Psychiatric Association Andrcaxn NC, Endicott J, Spimr RL, Winokur G (1977). The family history method using diagnostic criteria: reliability and validity.Arch Grn A+any 34:122%1235 Ballenger JC, Reus VI,Post RM (1982). The “atypical”clinical picture of adolcscent mania. Am/Plychiahy 139:602-606 Borchardt CM. krnstein GA (1995). Comorbid disorders in hospitalized bipolar adolescents compared with unipolar deprerscd adolcsccnts. Child Bychiany Hum DN 26: 11-18 Carlson GA (1995), Identifytng prepubertal mania. / Am Acad Child AdoLrc Bychiany 34:75&753 Carlson GA. Kashani J H (1988). Manic symptoms in a non-referredadolescent population. ]A& Disord 15:219-226 Carlson GA, Weintraub S (1993), Childhood behavior problems and bipolar disorder: relationship or coincidcncc?]Aff;.o Disord 28: 143-153 Conncrs K (1994), Connrrs Abbreviated Symptom Questionnaire. North Tonawanda, NY: Multi-Hdth Systems

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J. AM. ACAD. C H I L D ADOLESC. PSYCHIATRY, 39:4. APRIL 2000