Article. This article is featured in this month s AJP Audio and is the subject of a CME course (p. 483).

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1 Article Adult Psychitric Outcomes of Girls With Attention D efi cit H yp erctiv ity D isorder: 1 1 -Yer Follow -U p in Long itudinl Cse-Control Study Joseph Biedermn, M.D. Crter R. Petty, M.A. Michel C. Monuteux, Sc.D. Ronn Fried, Ed.D. Deirdre Byrne, B.S. Tr Mirto, B.A. Thoms Spencer, M.D. Timothy E. Wilens, M.D. Stephen V. Frone, Ph.D. Objective: Few follow-up studies hve been conducted of girls with, nd none hve followed girls into dulthood. The uthors sought to estimte the prevlence of psychopthology in girls with nd without followed into young dulthood. Method: The uthors conducted longitudinl cse-control study of 6- to 18-yer-old girls with (N=140) nd without (N=122) scertined from psychitric nd peditric sources. At the 11-yer follow-up, 96 (69%) of the girls with nd 91 (75%) of the comprison girls were ressessed (men ge=22 yers). Prticipnts were blindly ssessed by structured dignostic interviews. Results: Lifetime nd 1-yer risks for ll composite ctegories of psychopthology were significntly greter in girls with grown up reltive to comprison girls; lifetime hzrd rtios were 7.2 (95% CI= ) for ntisocil disorders, 6.8 (95% CI= ) for mood disorders, 2.1 (95% CI= ) for nxiety disorders, 3.2 (95% CI= ) for developmentl disorders, 2.7 (95% CI= ) for ddictive disorders, nd 3.5 (95% CI= ) for eting disorders. For lifetime psychopthology, ll six composite ctegories remined sttisticlly significnt fter controlling for other bseline psychopthology. Except for ddictive disorders, significnt 1-yer findings remined significnt fter controlling for bseline psychopthology. The 1-yer prevlences of composite disorders were not ssocited with lifetime or 1-yer use of mediction. Conclusions: By young dulthood, girls with were t high risk for ntisocil, ddictive, mood, nxiety, nd eting disorders. These prospective findings, previously documented in boys with, provide further evidence for the high morbidity ssocited with cross the life cycle. (Am J Psychitry 10; 167: ) Although ttention deficit hyperctivity disorder () is more prevlent in boys thn in girls, there is little doubt tht it is lso n importnt cuse of psychitric disbility in girls (1, 2). Yet, the scientific literture on girls with is scrce nd mostly cross-sectionl. Mikmi nd Hinshw (3) showed tht girls with hve more disruptive behviors compred with girls who do not hve. In previous study, we compred 140 girls with nd 122 comprison girls without nd found tht those with were more likely to hve conduct, mood, nd nxiety disorders (4). Similr findings were reported in study of 140 girls with nd 88 comprison girls by Hinshw (5), who found ssocitions between nd mood nd nxiety problems, disruptive behviors, nd lnguge problems in girls with. Becuse lmost ll the vilble literture on follow-up studies of is limited to studies of boys, there is scrcity of follow-up studies of girls with. The first follow-up study of girls compred 12 girls nd 24 boys with DSM-II dignosis of hyperctivity nd 24 mle compri- son subjects (6). In community survey (7), girls identified t bseline s hyperctive were more likely to report cdemic nd interpersonl reltionship problems t the dolescent follow-up. We reported results of 5-yer followup study into the mid-dolescent yers from smple of girls with DSM-III-R-defined nd comprison subjects (8). Girls with were t significntly higher risk for disruptive behvior nd mood, nxiety, nd ddictive disorders in dolescence. Hinshw et l. (9) nd Owens et l. (10) reported similr findings in girls followed into dolescence; the mjority of girls with continued to struggle with functionl impirments cross multiple domins. Although these follow-up studies documented the high morbidity nd disbility ssocited with in girls, no informtion is vilble on whether these findings extend to dulthood. Understnding of outcomes of girls with in dulthood hs clinicl nd public helth implictions. Cliniclly, such informtion would help in prognosis nd would lert clinicins to the importnce of recognizing This rticle is fetured in this month s AJP Audio nd is the subject of CME course (p. 483). Am J Psychitry 167:4, April 10 jp.psychitryonline.org 409

2 AD U LT PSYCH IATR IC OU TCOMES OF GIR LS WITH AD H D TAB LE 1. B seline Chrcteristics of Girls With AD H D nd Comp rison Girls, Strtifi ed b y Attrition Sttus Chrcteristic Lost to Follow-Up Assessed t Follow-Up Girls with (N=44) Girls with (N=96) Men SD Men SD Hollingshed socioeconomic scle score Age (yers) Lifetime Globl Assessment of Functioning Scle score N % N % Cucsin Intct fmily Ascertined in mjor cdemic medicl center Conduct disorder Mjor depressive disorder Any nxiety disorder Comprison girls (N=31) Comprison girls (N=91) Men SD Men SD Hollingshed socioeconomic scle score Age (yers) Lifetime Globl Assessment of Functioning Scle score N % N % Cucsin Intct fmily Ascertined in mjor cdemic medicl center Conduct disorder Mjor depressive disorder Any nxiety disorder Study prticipnts were scertined either in mjor cdemic medicl center (peditric psychophrmcology clinic for ptients with nd peditric outptient medicl clinic for comprison subjects) or in the peditric clinics of mjor helth mintennce orgniztion. nd ssocited comorbid disorders in girls for tretment plnning nd erly intervention strtegies. From public helth perspective, the bility to predict the outcome of in girls would help focus limited resources on those individuls who re t higher risk for persistent illness with complicted outcomes. Here we report results from n 11-yer longitudinl study of psychitriclly nd peditriclly referred girls with nd without followed into young dulthood. Our min im ws to estimte the burden of psychopthology ssocited with in young dulthood. We hypothesized tht girls with would show greter rtes of disruptive behvior nd mood nd nxiety disorders thn girls without. To our knowledge, this is the first prospective study of girls with followed into young dulthood. Method Prticipnts Detils of the study methods hve been reported elsewhere (4, 8). Prticipnts were from longitudinl cse-control fmily study of girls with nd without. At bseline, we scertined girls 6 17 yers of ge with (N=140) nd without (N=122) DSM- III-R-defined from peditric nd psychitric clinics. We excluded ptients who hd been dopted, those whose nucler fmily ws not vilble for study, nd those who hd mjor sensorimotor disbilities (prlysis, defness, blindness), psychosis, utism, indequte commnd of the English lnguge, or fullscle IQ below 80. All girls in the group met DSM-III-R criteri for t the time of the clinicl referrl, nd ll hd ctive symptoms of the disorder t the time of recruitment. Prticipnts were recruited irrespective of comorbid disorders. In this study, we nlyzed dt on 96 girls with nd 91 comprison girls from the originl smple who completed full follow-up ssessment men of 11 yers (rnge=8 to 14 yers) fter enrollment. Prticipnts rnged from 15 to yers of ge (men=22.1 yers, SD=3.3) t follow-up. Eighty-three (86%) of the girls in the group nd 90 (99%) of those in the comprison group hd reched ge 18 by the 11-yer follow-up. Prticipnts provided written informed consent, nd prents lso provided consent for offspring under the ge of 18 nd for their report on their offspring. Adolescents provided written ssent to prticipte. The humn reserch committee t Msschusetts Generl Hospitl pproved this study. Follow-Up Assessment Procedures We used the Structured Clinicl Interview for DSM-IV (SCID) (11) supplemented with modules from the DSM-IV modified Schedule for Affective Disorders nd Schizophreni for School- Age Children Epidemiologic Version (K-SADS-E) (12) to ssess childhood dignoses. The K-SADS-E ws used for prticipnts under ge 18. We interviewed ll prticipnts nd interviewed their mothers bout their offspring. Of the 187 girls for whom full dignostic interview ws conducted, the proportion for whom we hd direct only, mother only, nd both types of reports were 89%, 3%, nd 8%, respectively (47%, 3%, nd 50%, respectively, for the module). We combined dt from direct nd indirect interviews by considering dignostic criterion positive if it ws endorsed in either interview. Interviewers were blind to bseline scertinment group, scertinment site, nd prior ssessments. They hd undergrdute degrees in psychology nd were extensively trined. The principl investigtor (J.B.) supervised them throughout the study. Kpp coefficients between interviewers nd bord-certified child nd 410 jp.psychitryonline.org Am J Psychitry 167:4, April 10

3 B IED ER MAN, PET TY, MON U TEAU X, ET AL. TAB LE 2. D emog rp hic Chrcteristics of Girls With AD H D nd Comp rison Girls t 1 1 -Yer Follow -U p Chrcteristic Comprison Girls (N=91) Girls With (N=96) Men SD Men SD Age (yers) Follow-up time (yers) Hollingshed socioeconomic scle score N % N % Ethnicity/rce Africn Americn Cucsin Asin Americn More thn one Ascertined in mjor cdemic medicl center b Significnt difference between groups, p<0.05. b Study prticipnts were scertined either in mjor cdemic medicl center (peditric psychophrmcology clinic for ptients with nd peditric outptient medicl clinic for comprison subjects) or in the peditric clinics of mjor helth mintennce orgniztion. Of the 140 girls with nd 122 comprison girls recruited t bseline, 96 (69%) nd 91 (75%), respectively, were ressessed t the 11-yer follow-up. The follow-up rte did not differ between the groups. There were no significnt differences between girls successfully followed up nd those lost to follow-up on socioeconomic sttus, ge, rce, GAF score, fmilil intctness, scertinment source, or psychitric outcomes (Tble 1). At the 11-yer followup, girls in the group were on verge 1 yer youngdult psychitrists nd licensed clinicl psychologists hve been reported elsewhere (8); the medin kpp coefficient for individul disorders ws We considered disorder present if DSM-IV dignostic criteri were unequivoclly met. Dignostic uncertinties were resolved by committee of bord-certified child nd dult psychitrists nd child psychologists blind to the prticipnt s sttus, referrl source, nd ll other dt. Dignoses presented for review were considered positive only if dignostic criteri were met to cliniclly meningful degree. We estimted the relibility of the dignostic review process by computing kpp coefficients of greement for clinicin reviewers. Kpp coefficients between individul clinicins nd the review committee hve been reported elsewhere (8); the medin kpp coefficient for individul disorders ws Prticipnts were sked to describe the degree of impirment in dily functioning ssocited with ech positive disorder on three-level ordinl scle: miniml (little to no impirment), moderte (difficulties in dily life tsks), or severe (unble to perform essentil dily tsks). To void flse positive dignoses, we dignosed mjor depression only if it ws ssocited with severe impirment. This is consistent with prior reserch (13) nd comprble to wht we did t prior ssessments. Becuse there is not similr precedent for bipolr disorder, we dopted less stringent pproch nd mde the dignosis only when symptoms were ssocited with t lest moderte impirment. Persistent ws defined s meeting full or subthreshold criteri for DSM-IV during the intervl between the 5-yer nd 11-yer ssessments. Prticipnts were defined s hving subthreshold if they endorsed more thn hlf of, but less thn full, dignostic criteri (i.e., four or five symptoms) but met ll other dignostic requirements (e.g., ge t onset). Socioeconomic sttus ws mesured with the 5-point Hollingshed scle (14). To mesure overll lifetime functioning, we used the DSM-IV Globl Assessment of Functioning Scle (GAF) (12). Sttisticl Anlysis Anlyses of demogrphic fctors relied on Person chi-squre tests nd t tests for binry nd dimensionl vribles, respectively. We exmined psychopthology throughout the lifespn nd within the pst yer (1-yer prevlence), using three-pronged strtegy to void the inflted type I error rte tht could result from multiple sttisticl testing. First, to decrese the initil number of tests, we ggregted dignostic outcomes into composite ctegories: mood disorders comprised mjor depression nd bipolr disorder; nxiety disorders comprised seprtion nxiety, pnic disorder, gorphobi, specific phobi, socil phobi, generlized nxiety disorder, nd obsessive-compulsive disorder (seprtion nxiety ws not included in the nlysis of 1-yer out- comes); ntisocil disorders comprised conduct disorder, oppositionl defint disorder, nd ntisocil personlity disorder; developmentl disorders comprised enuresis, encopresis, lnguge disorder, nd Tourette s/tic disorders (developmentl disorders were not included in the nlysis of 1-yer prevlences); substnce dependence comprised lcohol dependence, drug dependence, nd nicotine dependence; nd eting disorders comprised full or subthreshold norexi nervos nd bulimi nervos. These summry disorders were coded positive if ny of the constituent dignoses were endorsed, nd negtive otherwise. Second, we conducted set of six tests (the six composite dignostic ctegories) tht ech compred the nd comprison groups using Holm s sequentil Bonferroni method (15) to correct for multiple testing nd mintin fmily-wise error rte of Third, for ny composite ctegory tht ws significnt, we tested ech of the constituent dignoses using Holm s method. To estimte the lifetime prevlence of psychopthology, we used Cox proportionl hzrds survivl models. For ech disorder, lifetime history of ny disorder ws defined s positive if positive response ws given t ny ssessment (bseline, 5-yer follow-up, or 11-yer follow-up). These models used ll vilble dt for ech prticipnt, including those not ssessed t the 11- yer follow-up; thus, ll 262 girls re included. We used the erliest ge t onset in computing the survivl time for cse subjects nd the ge t the most recent interview s the time of censoring for noncse subjects. To estimte cumultive prevlence, we clculted Kpln-Meier morbidity risks in the nd comprison groups up to ge 22 (the men ge of the smple). For the 1-yer prevlence nlysis, we used logistic regression to compre the nd comprison groups. One-yer prevlence ws defined s positive if the prticipnt met criteri for given disorder in the yer prior to the 11-yer follow-up. R esults Prticipnt Chrcteristics Am J Psychitry 167:4, April 10 jp.psychitryonline.org 411

4 AD U LT PSYCH IATR IC OU TCOMES OF GIR LS WITH AD H D FIGU R E 1. Cumultive R isks for D isorders in Girls With AD H D R eltive to Comp rison Girls for Six Comp osite D ig nostic Ctegories Mood Disorders Anxiety Disorders b Antisocil Disorders c Developmentl Disorders d Substnce Dependence Disorders e Eting Disorders f Hzrd rtio=6.8, 95% CI= , p<1. b Hzrd rtio=2.1, 95% CI= , p<1. c Hzrd rtio=7.2, 95% CI= , p<1. d Hzrd rtio=3.2, 95% CI= , p<1. e Hzrd rtio=2.7, 95% CI= , p<1. f Hzrd rtio=3.5, 95% CI= , p=1. er thn comprison girls (Tble 2). Survivl models for lifetime disorders ccounted for this difference in ge, nd ge ws used s covrite in logistic regression models of 1-yer prevlence. At the 11-yer follow-up, 93% of the girls in the group hd received some form of tret- ment for during their lives; 1% received counseling lone (N=1), 21% received mediction lone (N=), nd 71% (N=68) received both counseling nd mediction. During the 1-yer period before the 11-yer follow-up ssessment, 42% were receiving some form of tretment 412 jp.psychitryonline.org Am J Psychitry 167:4, April 10

5 B IED ER MAN, PET TY, MON U TEAU X, ET AL. TAB LE 3. Cumultive Morb idity R isks nd H zrd R tios for Psychitric D isorders in Girls With AD H D nd Comp rison Girls Disorder Comprison Girls (N=122) Girls With (N=140) Anlysis Morbidity Risk 95% CI Morbidity Risk 95% CI Hzrd Rtio 95% CI Test Sttistic Mood disorders Mjor depressive disorder (with z=5.32 <1 severe impirment) Bipolr disorder (with moderte or z=3.92 <1 severe impirment) Anxiety disorders Seprtion nxiety disorder z=3.80 <1 Agorphobi z=4.85 <1 Socil phobi z=4.10 <1 Obsessive-compulsive disorder z= Specific phobi z=4.05 <1 Pnic disorder z= Generlized nxiety disorder z=3.93 <1 Antisocil disorders Oppositionl-defint disorder z=6.68 <1 Conduct disorder z=4.13 <1 Antisocil personlity disorder b z= Developmentl disorders Tourette s/tic disorders z= Lnguge disorder z= Enuresis z= Encopresis NA c NA c χ 2 = Substnce dependence disorders Nicotine dependence z=3.53 <1 Alcohol dependence z= Drug dependence z= Eting disorders Anorexi nervos z= Bulimi nervos z= Cumultive morbidity risk of disorder by ge 22 s estimted by Kpln-Meier filure function. b Estimtes bsed only on prticipnts who were interviewed with the Structured Clinicl Interview for DSM-IV t lest once. c Not vilble becuse there were no comprison subjects with encopresis; Person s chi-squred test ws used insted. p for the disorder; 17% (N=16) were receiving mediction lone nd 25% (N=24) were receiving both counseling nd mediction. Among the 96 girls in the group rescertined t the 11-yer follow-up, the rte of full or subthreshold during the intervl between the yer 5 nd yer 11 ssessments ws 69% (N=66), nd the rte of current (i.e., in the pst month) full or subthreshold DSM- IV ws 62% (N=60). Risk for Lifetime Psychitric Disorders The risks for ll six composite lifetime dignostic ctegories were higher in the group thn in the comprison group; hzrd rtios were 6.8 (95% CI= ) for mood disorders, 2.1 (95% CI= ) for nxiety disorders, 7.2 (95% CI= ) for ntisocil disorders, 3.2 (95% CI= ) for developmentl disorders, 2.7 (95% CI= ) for substnce dependence disorders, nd 3.5 (95% CI= ) for eting disorders (Figure 1). All six composite ctegories remined sttisticlly significnt fter controlling for bseline psychopthology for ech of the other four ctegories. girls hd significntly higher lifetime prevlences of mjor depression, bipolr disorder, seprtion nxiety disorder, gorphobi, socil phobi, specific phobi, pnic disorder, generlized nxiety disorder, oppositionl defint disorder, conduct disorder, ntisocil personlity disorder, Tourette s/tic disorders, lnguge disorder, enuresis, encopresis, nicotine dependence, lcohol dependence, drug dependence, nd bulimi nervos (Tble 3). However, when we corrected for other bseline psychopthology, the lifetime risks for encopresis, nicotine dependence, lcohol dependence, nd drug dependence lost sttisticl significnce. Risks for 1-Yer Psychitric Disorders The group hd significntly higher 1-yer prevlences of composite mood, nxiety, ntisocil, nd substnce dependence disorders reltive to the comprison group (Tble 4). The 1-yer prevlence of eting disorders ws not significntly different between the nd comprison groups (7% versus 3%, z=1.07, p=0.29). Except for substnce dependence disorders (p=0.07), Am J Psychitry 167:4, April 10 jp.psychitryonline.org 413

6 AD U LT PSYCH IATR IC OU TCOMES OF GIR LS WITH AD H D TAB LE 4. Adjusted 1 -Yer Prev lence Estimtes for Psychitric D isorders in AD H D nd Comp rison Sub jects t the 1 1 -Yer Follow -U p Disorder Comprison Group (N=91) Group (N=96) Prevlence 95% CI Prevlence 95% CI Controlling for Age Test Sttistic b p Anlysis Controlling for Age nd Bseline Psychopthology Test Sttistic b Mood disorders z= z= Mjor depressive disorder (with z= z= severe impirment) Bipolr disorder (with moderte z= z= or severe impirment) Anxiety disorders z=3.49 <1 z= Agorphobi z=3.60 <1 z= Socil phobi z= z= Obsessive-compulsive disorder z= z= Specific phobi z= z= Pnic disorder z= z= Generlized nxiety disorder z= z= Antisocil disorders z= z= Oppositionl-defint disorder z= z= Conduct disorder Exct 0.48 Exct Antisocil personlity disorder d Exct 0.04 Exct 0.10 Substnce dependence disorders z=3.73 <1 z= Nicotine dependence z= z= Alcohol dependence z= z= Drug dependence z= z= Eting disorders z= z= Anorexi nervos Exct Exct Bulimi nervos z= z= Bseline sttus of the disorder predicted t follow-up nd bseline vlues of the other composite ctegories (except substnce dependence nd eting disorders). b Exct=exct logistic regression, used in lieu of logistic regression. c Estimtes bsed only on prticipnts who were interviewed with the Structured Clinicl Interview for DSM-IV t lest once. p significnt findings remined significnt fter controlling for ll bseline psychopthology (i.e., bseline mood, nxiety, nd ntisocil disorders), including the bseline sttus of the disorder predicted t follow-up. Corrections for bseline psychopthology in this ltter nlysis did not include eting disorders or substnce dependence t bseline becuse they were rre t bseline (N=5 nd N=9, respectively). Similr findings were observed for 1-yer rtes of individul disorders. The rtes of mjor depression, gorphobi, socil phobi, oppositionl defint disorder, nd nicotine dependence were higher in the group reltive to the comprison group (Tble 4). However, when findings were djusted for bseline psychopthology (including the bseline sttus of the disorder predicted t followup), only gorphobi remined sttisticlly significnt (p<1). The 1-yer prevlences of composite psychitric disorders were not ssocited with lifetime or 1-yer mediction use for. D iscussion This is the first follow-up study of girls with into young dulthood nd the longest follow-up study of girls with (11 yers). By men ge of 22 yers, 62% of girls with continued to hve impiring symptoms, which is consistent with met-nlysis of follow-up studies (16). They lso hd significntly greter lifetime nd 1-yer risks for ntisocil, mood, nd nxiety disorders reltive to comprison subjects, even fter correcting for bseline psychopthology. These results extend to girls findings tht were previously documented in boys (17), stressing the significnt psychitric morbidity ssocited with in both sexes cross the lifespn. They lso stress the criticl importnce of erly recognition of this disorder for prevention nd erly intervention strtegies. Strengths of this study include the lrge smple of wellchrcterized girls with nd without nd the long follow-up into young dulthood. This is especilly importnt since few studies hve followed youths with into dulthood, nd none hs exmined girls with. The lifetime prevlences of psychitric disorders in the comprison girls re consistent with the prevlences of psychitric disorders reported in epidemiologicl studies (18), supporting the vlidity of the ssessment methodology. Comprisons of 1-yer prevlence estimtes between this study nd our study of boys with (17) revel similr pttern of risk for comorbid disorders, which could 414 jp.psychitryonline.org Am J Psychitry 167:4, April 10

7 B IED ER MAN, PET TY, MON U TEAU X, ET AL. not be ccounted for by either lifetime or 1-yer mediction use for. Notble differences include higher rte of ntisocil personlity disorder in boys with grown up compred with girls with grown up (13% nd 6%, respectively) nd higher rtes of mjor depressive disorder nd nxiety disorders in girls with grown up compred with boys with grown up (mjor depressive disorder, % nd 8%, respectively; gorphobi, 25% nd 3%, respectively; socil phobi, % nd 4%, respectively). Although boys nd girls with shre significnt risks for vriety of comorbid disorders, these rtes identify different profiles of comorbidity between the sexes in young dulthood. Our finding tht girls with hd significntly greter risks for ntisocil disorders, mjor depression, nd nxiety disorders in young dulthood is consistent with the results we obtined t the dolescent follow-up ssessment (8). They re lso consistent with Hinshw nd collegues report (9) of elevted rtes of externlizing nd internlizing disorders in girls with followed into dolescence. Our results t the dolescent follow-up showed lifetime prevlence rtes up to ge 25 (8), while the present nlysis shows rtes up to ge. Although lifetime rtes of ntisocil nd nxiety disorders were shown to fltten by ge 25, rtes of mood disorders continued to climb between ges 25 nd (Figure 1). Therefore, some comorbidities ssocited with in girls do not develop until fter ge 25, which highlights the importnce of following this popultion into dulthood. The incresing risk for mjor depression into young dulthood confirms epidemiologicl surveys (19), fmily study dt ( 23), studies of dults with (24), nd met-nlytic studies (25) showing tht is significnt risk fctor for mjor depression. Our findings lso confirm studies of referred femle dults with (24, 26), s well s report from the Ntionl Comorbidity Survey Repliction study s representtive smple of the U.S. popultion, which documented elevted rtes of mjor depression nd ntisocil, ddictive, nd nxiety disorders in dults with reltive to comprison subjects (27). Our findings bout bipolr disorder re prticulrly interesting given controversies bout dignosing the disorder in children, especilly those with, nd bout discriminting mnic symptoms from severe chronic irritbility, hyperrousl, nd hyperrectivity (28, 29). Reports of comorbidity between nd bipolr disorder hve been questioned becuse some dignostic criteri re shred by both disorders. Thus, it is possible tht the comorbidity of bipolr disorder nd is due to overlpping dignostic criteri. However, when Milberger et l. () ccounted for overlpping dignostic criteri, they continued to find significnt comorbidity between the two disorders. Despite ongoing controversy bout the dignosis of peditric bipolr disorder, these concerns should be interpreted in the context of lrge emerging literture supporting the vlidity of dignosing bipolr disorder in youths nd the fct tht two medictions, risperidone nd ripiprzole, hve lredy gined pprovl from the U.S. Food nd Drug Administrtion for the tretment of peditric bipolr disorder s monotherpy. Notbly, prctice prmeter from the Americn Acdemy of Child nd Adolescent Psychitry (31) nd two independent reviews of phenomenologicl, longitudinl, tretment-response, neuroimging, neuropsychologicl, nd genetic studies (32, 33) concluded tht bipolr disorder cn be vlidly dignosed in youths. This literture lso shows tht peditric bipolr disorder is frequently persistent, is highly morbid, is commonly ssocited with significnt functionl impirment in multiple domins, nd is ssocited with elevted risks for psychitric hospitliztion, ntisocil behviors, ddictions, nd suicidl idetion. The review by Geller nd Tillmn (33) is of prticulr interest becuse it showed tht peditric bipolr disorder meets the Robins nd Guze criteri for vlid psychitric disorder. Our work dds to this literture by reporting tht girls with grown up continue to hve n incresed risk for bipolr disorder. This finding confirms results from our dolescent follow-up (8, 34) nd is consistent with our studies of femle dults with (24, 26). It is lso consistent with results from the Ntionl Comorbidity Survey Repliction study (27) documenting significnt nd bidirectionl ssocition between nd bipolr disorder in dults of both sexes. Moreover, this overrepresenttion of bipolr disorder in girls with grown up is consistent with studies of peditric (35) nd dult smples (24) s well s studies of bipolr children (36) nd dults (37) documenting bidirectionl ssocition between nd bipolr disorder in both sexes cross the lifespn. The finding tht girls with hd n elevted risk for eting disorders in dulthood confirms our report from the 5-yer follow-up (8) nd Hinshw nd collegues (9) finding of elevted eting disorder symptoms in their dolescent follow-up study of girls with. Studies of dult femles hve lso found n elevted prevlence of bulimi in femles with (24). These results should lert clinicins to need to monitor young femle ptients with for eting disorder pthology. Our results must be interpreted in the context of methodologicl limittions. Our lifetime psychopthology outcomes re potentilly subject to recll bis, especilly in the context of comorbidity. However, in our own work, lifetime dignoses hve shown excellent interrter relibility, s noted in the Method section, nd good to excellent test-retest relibility over 1 yer (38). Becuse our dignoses of in some prticipnts relied on self-report, our estimtes of prevlence my be lower thn they would hve been if reports from prents or spouses hd been incorported. Becuse our smple ws referred nd mostly Cucsin, our results my not be generlizble to the generl popultion or to other rcil or ethnic groups. However, our results Am J Psychitry 167:4, April 10 jp.psychitryonline.org 415

8 AD U LT PSYCH IATR IC OU TCOMES OF GIR LS WITH AD H D should generlize to girls seen in peditric nd psychitric settings. Becuse we did not mnipulte tretment s n independent vrible, we cnnot use our study to determine tretment effectiveness (39) or to describe the untreted course of. While our min im ws to ssess the outcome of girls in young dulthood, smll portion of our smple hd not yet reched dulthood. Our smple ws originlly scertined ccording to DSM-III-R criteri, nd it is possible tht our results my not generlize to smples scertined by DSM-IV criteri. However, considering the very high overlp between the two definitions (93% of DSM-III-R cses received DSM-IV dignosis [40]), ny effect should be miniml. Despite these limittions, in lrge smple of girls with nd without followed into young dulthood originlly scertined from peditric nd psychitric sources, our 11-yer follow-up confirms nd extends results from the bseline nd mid-dolescent ssessments. We observed strong ssocition between nd lifetime risks for ntisocil, mood, nxiety, developmentl, nd substnce dependence disorders t the 11-yer followup. These dt provide further evidence for the morbidity nd disbility ssocited with from childhood into young dulthood in individuls of both sexes with. Received My 16, 09; revisions received July 24 nd Oct. 5, 09; ccepted Oct. 8, 09 (doi: /ppi.jp ). From the Clinicl nd Reserch Progrms in Peditric Psychophrmcology, Deprtment of Psychitry, Msschusetts Generl Hospitl; nd the Deprtment of Psychitry nd Behviorl Sciences, SUNY Upstte Medicl University, Syrcuse, N.Y. Address correspondence nd reprint requests to Dr. Biedermn, Msschusetts Generl Hospitl, Peditric Psychophrmcology Progrm, Ywkey Center for Outptient Cre, YAW-6A-6900, 32 Fruit St., Boston, MA 02114; jbiedermn@ prtners.org (e-mil). Dr. Biedermn hs received reserch support, consulttion fees, or speker s fees from Abbott, Alz, AstrZenec, Bristol-Myers Squibb, Celltech, Cephlon, Eli Lilly, Esi, Forest, GlxoSmithKline, Glitech, Jnssen Phrmceuticls, McNeil, Merck, NARSAD, Ntionl Institute on Drug Abuse, Ntionl Institute of Child Helth nd Humn Development, NIMH, New River, Novrtis, Noven, Neuroserch, Orgnon, Otsuk, Pfizer, Phrmci, Prechter Foundtion, Shire, Stnley Foundtion, UCB Phrm, nd Wyeth. Dr. Fried hs received honorri from Shire. Dr. Spencer hs received reserch support from or hs served s speker or on dvisory bords for Cephlon, Eli Lilly, Glxo- SmithKline, Jnssen, McNeil, NIMH, New River, Novrtis, Pfizer, nd Shire. Dr. Wilens hs received reserch support from or hs served s speker or on dvisory bords for Abbott, AstrZenec, Eli Lilly, GlxoSmithKline, Merck, Ntionl Institute on Drug Abuse, NIH, Neuroserch, Novrtis, Ortho-McNeil, Pfizer, nd Shire nd received roylties from Guilford Press. Dr. Frone hs received reserch support or consulting or speking fees from or hs served on dvisory bords for Eli Lilly, McNeil, Pfizer, NIH, nd Shire. The others uthors report no finncil reltionships with commercil interests. Supported in prt by grnt from the Eli Lilly nd Compny Foundtion nd the Peditric Psychophrmcology Philnthropy Fund. R eferences 1. Monuteux MC, Frone SV, Gross LM, Biedermn J: Predictors, clinicl chrcteristics, nd outcome of conduct disorder in girls with ttention-deficit/hyperctivity disorder: longitudinl study. Psychol Med 07; 37: Seidmn LJ, Biedermn J, Vler EM, Monuteux MC, Doyle AE, Frone SV: Neuropsychologicl functioning in girls with ttention-deficit/hyperctivity disorder with nd without lerning disbilities. Neuropsychology 06; : Mikmi AY, Hinshw SP: Buffers of peer rejection mong girls with nd without : the role of populrity with dults nd goldirected solitry ply. 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