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ssociation of Bipolar and Substance Use Disordersn Parents of Adolescents With Bipolar Disorderimothy E. Wilens, Joseph Biederman, Joel Adamson, Michael Monuteaux, Aude Henin,tephanie Sgambati, Alison Santry, and Stephen V. Faraone

ackground: We have previously shown that juvenile bipolar disorder (BPD) is a risk for substance use disorders (SUD). Here we examinehe expression of both disorders in families of youth with BPD to evaluate the familial risk mechanism.

ethods: We studied 108 adolescent BPD probands with 187 parents (34 with SUD and 58 parents) and 96 control probands with 177arents with structured interviews. We compared the prevalence of BPD and SUD with Cox proportional hazards models with time to onsetf BPD or SUD as the dependent variable and proband diagnosis (Control, BPD, or BPD�SUD) as the independent variable.

esults: The parents of the proband youth with BPD (without SUD) and BPD�SUD were more likely to develop BPD than the parents ofontrol subjects [omnibus test �2 � 10.18, p � .006]; we found no differences between the two bipolar groups. Parents of proband youthith BPD and with BPD�SUD were more likely than relatives of control subjects to develop SUD [omnibus test �2 � 14.69, p � .001];owever, we found no differences between the parents of the two proband bipolar groups. Within the parents of proband youth withPD�SUD, we found higher risk of SUD in parents with BPD than in those without BPD [�2 � 8.39, p � .004], although the frequency of BPDas low in this group of parents.

onclusions: Bipolar disorder and SUD are prevalent in the first-degree relatives of adolescents with BPD. Adults with BPD were more likely

o manifest SUD with preliminary evidence of BPD and SUD cosegregation.

ey Words: Adolescents, bipolar disorder, cosegregation, familial,arents, substance abuse

ecent studies of adolescents and adults indicate an impor-tant relationship between bipolar disorder (BPD) andsubstance use disorders (SUD; including drug and alcohol

buse or dependence) (Dunner and Feinman 1995; Dunner et al.979; McElroy et al. 2001; Strakowski et al. 1992, 1995, 1998,000; Winokur et al. 1993, 1995). These data signal that child-ood or early onset BPD is particularly related to a high risk forUD (Dunner and Feinman 1995; Dunner et al. 1979; Lin et al.006). For example, Lin et al. (2006) described that the onset ofPD disorder before 21 years of age was associated with a higherisk for SUD. A growing body of literature also shows a strongssociation between SUD and BPD in adolescents (West et al.996; Wilens et al. 1999, 2004). We have previously shown thatPD in adolescence is a major risk factor for SUD independent ofonduct disorder (Wilens et al. 1999, 2004). Although high SUDates are reported in samples of adolescents with BPD, theechanism of association remains unclear.Although environmental and intrapsychic issues play a role

Faraone et al. 1997; Wilens et al. 1999), the familial relationshipetween these two disorders in adolescent samples remainsnstudied. Evaluating familial risks will allow us to better under-tand the youth’s intrinsic and extrinsic vulnerabilities to SUD.

rom the Pediatric Psychopharmacology Unit (TEW, JB, JA, MM, AH, SS, AS),Massachusetts General Hospital; Department of Psychiatry (TEW, JB,MM), Harvard Medical School, Boston, Massachusetts; and Neuroscience& Physiology (SVF), Department of Psychiatry, State University of NewYork Upstate Medical University, Syracuse, New York.

ddress reprint requests to Timothy Wilens, M.D., Massachusetts GeneralHospital, Pediatric Psychopharmacology Unit, 32 Fruit St, Yawkey Centerof Outpatient Care-YAW-6A-6900, Boston, MA 02114, Tel: 617-726-1731,FAX: 617-724-3742; E-mail: twilens@partners.org.

eceived August 25, 2006; revised November 21, 2006; accepted November

22, 2006.

006-3223/07/$32.00oi:10.1016/j.biopsych.2006.11.022

Likewise, understanding the relationship between SUD and BPDin parents will provide additional data on ultimate risks in thosewho have passed through the age of SUD risk.

Studies indicate that genes and environment have etiologicroles in the development of alcohol and drug use disorders(Bierut et al. 1998; Cadoret 1980, 1991; Cloninger et al. 1981;Merikangas et al. 1998, 1991; Mirin et al. 1986; Pickens et al.1991; Schuckit 1986; Tsuang et al. 1996, 1998). Similarly, BPD hasa substantial genetic component (Faraone and Santangelo 1992;Strober 1992; Todd et al. 1996a, 1996b) with twin studiesindicating a heritability of .6–.8, as well as 30%–40% of BPDyouth having a first degree relative with BPD (Goodwin andJamison 1990; Strober et al. 1988; Todd et al. 1996b). Thefamily-study literature linking BPD and SUD has produced conflict-ing findings (Winokur et al. 1993). Several studies have shown afamilial association between BPD and SUD (Dunner et al. 1979;Maier and Merikangas 1996; Morrison 1975; Penick et al. 1978;Raskin and Miller 1993), raising the question that the two mightshare genetic or other etiologic factors. Conversely, Winokur et al.(1993, 1995) found a higher than expected rate of alcoholism inBPD but noted that BPD � alcoholism was not accounted for byfamilial alcoholism. They also observed dissimilarities in alcohol usepatterns between BPD and nonBPD groups, leading them toconclude that alcoholism in BPD is secondary to BPD (Winokur etal. 1993, 1995).

Given the potential differences in the familial patterns ofBPD transmission in juveniles compared with adults (Geller etal. 1994; Goldstein et al. 1997; Goodwin and Erickson 1979;Strober 1992; Wozniak et al. 1995), the familial relationshipbetween BPD and SUD in youth warrants systematic study. Aspart of a controlled, family-based evaluation of the risk of SUDin adolescents with BPD, we now present data on SUD andBPD in parents of adolescent probands. We hypothesized:1) higher rates of BPD and of SUD would be observed in theparents of probands with BPD; 2) evidence of cosegregationof BPD and SUD would be observed in the parents of

probands with BPD; and 3) parents with early onset BPD

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ould be at higher risk for SUD compared with parents withater onset BPD.

ethods and Materials

ubjectsThe current analysis is based on our baseline assessments of

ur ongoing, controlled, family-based study of BPD adolescents.he detailed methods of the study are described in detaillsewhere (Wilens et al. 2004). We ascertained 108 bipolardolescent probands and 102 non–mood-disordered controlrobands and their first-degree relatives. Potential subjects werexcluded if they had been adopted; if their nuclear family wasot available; or if they had major sensorimotor handicapsparalysis, deafness, blindness), autism, inadequate command ofhe English language, or a Full Scale IQ � 70. Parents providedritten informed consent for their children, and children pro-ided written assent to participate. The study was approved byhe institutional review board at Massachusetts General Hospital.

As described previously (Wilens et al. 2004), a two-stagescertainment procedure selected subjects. For BPD probandsnd control subjects, the first stage was a systematic phonecreening. The second stage was the structured psychiatricnterview (described in the following section). Only subjects whoeceived a positive (or negative for control subjects) diagnosis atoth stages were included in the sample. We eliminated anyood disorder from our ascertainment of control subjects sec-ndary to concerns of “manic switching” from dysthymia ornipolar depression to BPD (Geller et al. 1994, 2001; Strober andarlson 1982).

ssessmentsAll diagnostic assessments were made with DSM-IV–based

tructured interviews, by raters with bachelor’s degrees in psy-hology who had been trained and supervised by senior inves-igators (JB, TW). Raters were blind to the ascertainment status ofhe probands. Psychiatric assessments relied on the Kiddiechedule for Affective Disorders and Schizophrenia for School-ged Children Epidemiologic Version (K-SADS-E) (Ambrosini000) and were based on independent interviews with mothersnd direct interviews of probands and siblings. Subjects (pro-ands, parents, or siblings) ages 18 and older received psychi-tric diagnoses in the Structured Clinical Interview for DSM-IVSCID; Spitzer et al. 1990) with supplemental sections from the-SADS-E for childhood diagnoses. For every diagnosis, weathered data regarding the ages at onset and offset of fullyndromatic criteria. The SUD was diagnosed on the basis ofSM-IV criteria with K-SADS-E. Rates of disorders reported are

ifetime prevalence. All cases were presented to a committeeomposed of board certified child psychiatrists and psycholo-ists. Diagnoses presented for review were considered positivenly if the diagnosis would be considered clinically meaningful.ll cases of suspected SUD were reviewed with a child and adultsychiatrist with addiction credentials.

We computed � coefficients of agreement by having threexperienced, board-certified child and adult psychiatrists diag-ose subjects from audiotaped interviews made by the assess-ent staff. On the basis of 500 assessments from interviews of

hildren and adults, the median � coefficient was .98. The �oefficients for individual diagnoses included: attention-deficit/yperactivity disorder (ADHD) (.88), conduct disorder (CD)

1.0), oppositional defiant disorder (ODD) (.90), antisocial per-

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sonality disorder (ASPD) (.80), major depression (1.0), mania(.95), and SUD (1.0).

Statistical AnalysesWe characterized family environment with intactness (di-

vorced/separated or intact) and the five-point Hollingshead-Redlich Socioeconomic Status (SES) scale, in which highernumbers indicate lower SES. We used logistic regression forbinary outcomes, Fisher’s Exact Test for hypotheses of assortativemating, linear regression for age, and ordinal logistic regressionfor SES.

We divided probands and relatives into three groups on thebasis of proband BPD and proband SUD: Control, BPD�SUD(no lifetime history of substance use), and BPD�SUD (lifetimehistory of substance use). We ascertained 6 control probandswho endorsed SUD; we eliminated this group of probands andtheir 12 relatives from this analysis due to low statistical powercaused by small sample size. For a second set of analyses, wegrouped relatives according to proband BPD and parent BPDdiagnosis into Control, BPD Parents without BPD, and BPDParents with BPD.

We calculated Kaplan-Meier failure curves to describe thetime to onset of BPD or SUD; we used Cox Proportional Hazardsmodels to compare failure curves between groups. We usedHuber-White robust variance estimators to account for repeatedmeasures within families. We considered a p value significant fordemographic variables at the .1 level and significant at the .05level elsewhere; all statistical tests are two-tailed. If an omnibustest reached significance, we tested for pairwise differencesbetween groups with linear Wald tests. All statistical tests wereperformed with Stata (2005) 9.2.

Results

DemographicsOverall, our BPD and control probands were of similar age

(Control 13.8 � 2.1 years vs. BPD 13.6 � 2.5, p � .5). Table 1compares the demographics of parents of three groups ofprobands: Control, BPD�SUD, and BPD�SUD. Parents ofBPD�SUD probands were significantly younger than parentsof control subjects. We found a significant difference across thethree groups in the gender of parents. All analyses comparingparents of control probands with parents of BPD probandscorrected for gender. We found no differences in intactnessbetween BPD�SUD, BPD�SUD, and control families. Familiesof BPD probands had significantly lower SES, and in our samplelower SES predicted SUD (logistic regression: odds ratio 1.64,

Table 1. Demographics of Parents, Siblings, and Families

Control BPD � SUD BPD � SUD OmnibusStatistic pn � 96 n � 74 n � 34

Parents n � 177 n � 129 n � 58Age, mean � SD 46.2 � 6.9 43.1 � 6.1a 44.8 � 5.7 F � 5.9 .003Gender (male),

n (%) 83 (47) 55 (42)c 25 (43) �2 � 5.43 .07Families n � 96 n � 74 n � 34SES, mean � SD 1.9 � 0.9 2.2 � .9b 2.0 � .9c �2 � 12.26 .002Intactness, n (%) 54 (56) 42 (57) 18 (53) �2 � .2 .93

Pairwise tests versus Control. BPD, bipolar disorder; SUD, substance usedisorder; SES, socioeconomic status.

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5% confidence interval 1.31–2.08, p � .001); all further analysesontrolled for SES.

Table 2 shows the age and gender of parents stratified byroband BPD status and parental BPD status. Both groups ofPD parents were significantly younger than control parents; weid not find differences in age between the two BPD parentroups. The BPD parents without BPD were significantly moreikely to be male. All analyses of these groups corrected forender.

isk of BPD and SUD in RelativesFigure 1 shows the cumulative lifetime prevalence of BPD by

ge of parents of adolescent probands. Parents of BPD�SUD andPD�SUD probands were more likely to develop BPD thanarents of control probands [BPD�SUD compared with controlubjects: �2 � 10.2, p � .001; BPD�SUD compared with controlubjects: �2 � 6.5, p � .01]. Parents of BPD�SUD and BPD�SUDrobands did not differ in their risk for BPD [�2 � .41, p � .5].igure 2 shows the cumulative lifetime prevalence of SUD by agef the parents of control and bipolar probands. Parents ofPD�SUD and BPD�SUD probands were more likely to de-elop SUD than parents of control probands [BPD�SUD com-ared with control subjects: �2 � 10.6, p � .001; BPD�SUDompared with control subjects: �2 � 10.4, p � .001]. We foundo differences in SUD between the parents of probands withPD�SUD compared with BPD�SUD [�2 � .07, p � .8]. Table 3hows rates of alcohol abuse and dependence and drug abuse

able 2. Age and Gender in Parents Stratified by Proband and Parent BPDiagnosis

ControlParents

BPD ParentsWithout BPD

BPD ParentsWith BPD Omnibus

Statistic pn � 177 n � 159 n � 27

ge, mean � SD 46.2 � 6.9 44.0 � 5.6a 41.8 � 8.0a F � 5.5 .005ender (male),n (%) 83 (47) 64 (40)a 16 (57) �2 � 8.42 .01

Pairwise tests versus Control. Abbreviations as in Table 1.ap � .01.

igure 1. Age-adjusted lifetime prevalence of bipolar disorder (BPD) inarents of adolescent probands stratified by proband status and probandubstance use disorder (SUD) diagnosis; omnibus test [�2 � 10.18, p � .006].ontrol, parents of Control probands (n � 177); BPD�SUD, parents of pro-ands with BPD and no SUD (n � 129); BPD�SUD, parents of probands with

PD and SUD (n � 58).

and dependence. We found significantly higher lifetime age-adjusted risk of alcohol abuse and drug abuse in BPD�SUD andBPD�SUD parents compared with control parents; again, wefound no differences between BPD�SUD and BPD�SUD.

We then evaluated the development of SUD in the parentsof control probands and parents of BPD probands (Figure 3).The BPD probands’ parents without BPD were more likely toendorse SUD than parents of control subjects [�2 � 9.4, p � .002].The BPD probands’ parents with BPD were more likely toendorse SUD than control parents [�2 � 33.6, p � .001] or BPDprobands’ parents without BPD [�2 � 13.5, p � .001]. Table 4shows rates of alcohol abuse and dependence and drug abuseand dependence in Control, BPD parents without BPD, and BPDparents with BPD. We found significant variance across thesegroups in lifetime age-adjusted risk of all four disorders; wefound significantly higher lifetime age-adjusted risk of alcoholdependence, drug abuse, and drug dependence in BPD parentswith BPD compared with BPD parents without BPD.

We then evaluated the onset of SUD in relation to BPD onsetwith SUD failure curves between parents with childhood-onsetBPD (� 18 years; n � 13) and those with adult-onset (n � 15).Although 74% of parents with BPD developed SUD, we found nosignificant differences between juvenile onset BPD and adultonset BPD in the development of SUD in the parents. Similarly,although limited by small sample sizes, within 22 parents with

Figure 2. Age-adjusted lifetime prevalence of substance use disorder (SUD)in parents of adolescent probands stratified by proband status and probandSUD diagnosis; sample sizes given in Figure 1; omnibus test [�2 � 14.69, p �.001]. Other abbreviations as in Figure 1.

Table 3. Prevalence of Parental SUDs Stratified by Proband BPD and SUDDiagnoses

Control BPD � SUD BPD � SUD�2 pn � 177 n � 129 n � 58

Alcohol Abuse 46 (27) 57 (45)a,b 30 (53)a,b 8.34 .015Alcohol Dependence 17 (10) 28 (22) 9 (16) 4.96 .084Drug Abuse 35 (20) 41 (33)a,d 22 (38)a,d 9.17 .010Drug Dependence 18 (10) 21 (17) 10 (18) 1.28 .528

All numbers shown are n (%); Cox proportional hazards models; pairwisecomparisons. Abbreviations as in Table 1.

aVersus Control.bp � .05.cVersus BPD � SUD.

dp � .01.

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PD plus SUD, we found no differences in the onset precedencef BPD to SUD with respect to juvenile onset BPD (Fisher’s Exactest: p � .6).

vidence of CosegregationWe then evaluated whether the increased rate of BPD and

UD in parents of BPD�SUD probands is accounted for byosegregation of the two disorders. Cosegregation refers to theo-transmission of two disorders in families more often thanxpected by chance. We found that among the parents ofrobands with BPD�SUD, parents with BPD (n � 7) were moreikely to endorse SUD than those parents without BPD [n � 44;2 � 8.39, p � .004; Figure 4]. However, the strength of thisosegregation finding is limited by the low frequency of BPDarents in the BPD�SUD group. To further evaluate the hypoth-sis of cosegregation, we conducted a secondary analysis includ-ng cases of subthreshold BPD, thereby increasing group size byhree subjects. Without controlling for SES, which further limitsample size, we found that parents with subthreshold or full BPDn � 10) experienced significantly greater lifetime age-adjustedisk of SUD than BPD�SUD parents without BPD [n � 48; �2 �3.9, p � .001]. Furthermore, our conclusions were identicalhen we included the effects of SES [BPD n(%SUD) � 9(100%),o BPD n � 25(58%); �2 � 11.7, p � .001]. All results except the

igure 3. Age-adjusted lifetime prevalence of SUD in parents of adolescentrobands stratified by proband status and parent BPD diagnosis; Control� 177, BPD Parents without BPD n � 159, BPD Parents with BPD n � 27;

mnibus test [�2 � 34.38, p � .001]. Other abbreviations as in Figure 1.

able 4. Prevalence of Parental SUDs Stratified by Proband BPD andarent SUD Diagnoses

ControlParents

BPD ParentsWithout BPD

BPD ParentsWith BPD

�2 pn � 177 n � 159 n � 27

lcohol Abuse 46 (27) 70 (45)a,b 17 (61)a,b 9.24 .01lcohol Dependence 17 (10) 23 (15) 14 (56)a,c,d 29.62 �.001rug Abuse 35 (20) 47 (30)a,b 16 (59)a,c,d,e 20.31 �.001rug Dependence 18 (10) 18 (12) 13 (50)a,c,d 15.56 �.001

All numbers shown are n (%); Cox proportional hazards models; pairwiseomparisons. Abbreviations as in Table 1.

aVersus Control Parents.bp � .05.cVersus BPD Parents without BPD.dp � .001.

ep � .01.

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cosegregation of BPD and SUD maintained significance when wecontrolled for conduct and antisocial personality disorder. Wealso tested whether assortative mating accounts for the increasedrate of BPD and SUD in parents of BPD�SUD probands. Wefound positive preference of mothers with SUD for mating withfathers with BPD in our entire sample of parents of BPDprobands (Fisher’s Exact Test p � .01); however, when werestricted the sample to parents in the BPD�SUD group, wefound no difference in the rate of SUD in the mates of motherswith BPD (100%) compared with the mates of mothers withoutBPD (87%; Fisher Exact Test p � 1.0; n � 25 complete pairs ofparents of BPD�SUD probands). Likewise, the rates of SUD inmates of fathers who did have BPD (42%) did not differ from therate of SUD in mates of fathers who did not have BPD (60%;Fisher’s Exact Test p � .5). Assortative mating cannot explain thecomorbidity of BPD and SUD in parents of BPD�SUD probands.

Discussion

Our findings from a controlled family-study of adolescentswith BPD support our hypothesis of higher rates of BPD and ofSUD in the parents of youth with BPD—maintained whencontrolling for conduct and antisocial disorders. We also foundsome evidence of cosegregation of BPD and SUD in the parentsof youth with BPD. We failed to demonstrate that parents withchildhood-onset BPD were at higher risk for SUD compared withthose with later onset BPD. The aggregate data derived from theparents of our probands highlight that BPD and SUD are familialand probably cosegregate.

Our findings of elevated rates of BPD and of SUD in familymembers of BPD individuals are similar to those of other reportsin adults (Dunner et al. 1979; Maier and Merikangas 1996;Morrison 1975; Penick et al. 1978; Raskin and Miller 1993).Morrison (1975) found significantly more alcoholism in therelatives of the adult patients with BPD and alcoholism, specu-lating that BPD and alcoholism were independently transmitted.Our finding of a significant increase in SUD in parents ofadolescents with BPD is similar to that of Todd et al. (1996a),who also reported a significantly higher prevalence of alcoholismamong relatives of probands with BPD (Todd et al. 1996a). In thecurrent study, our findings were maintained even controlling for

Figure 4. Age-adjusted lifetime prevalence of SUD in parents of BPD�SUDadolescent probands stratified by parent BPD diagnosis; BPD n � 7, no BPDn � 44; [�2 � 8.39, p � .004]. Other abbreviations as in Figure 1.

conduct and antisocial disorders—independent risk factors for

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UD—further underscoring the link between BPD and SUD inoth pediatric and adult samples.

We found some evidence in parents of cosegregation of BPDlus SUD: SUD was predicted by the presence or absence of BPD

n the parents of our BPD�SUD probands—and was not ac-ounted for by assortative mating. Our finding of a link betweenPD and SUD is similar to the findings of Dunner et al. (1979),ho showed that the morbid risk for any affective disorder wasigher in the relatives of BPD�SUD compared with BPD only.ur findings of cosegregation are somewhat dissimilar to thosef Winokur et al. (1993, 1995), who found a higher thanxpected rate of alcoholism in BPD but noted that BPD �lcoholism was not accounted for by familial alcoholism. Differ-nces might be in the potential confound of disruptive comor-idity in Winokur et al’s sample or the age groups of the sample.

Adults with BPD had higher risk for SUD compared withdults without BPD, confirming again the increased risk acrosshe lifespan of SUD in BPD (Lin et al. 2006; McElroy et al. 2001).urthermore, parents with BPD manifest more abuse or depen-ence with both alcohol and drugs relative to adults without BPDith either a drug or alcohol use disorder. Our findings of aigher risk of SUD and more pernicious SUD in adults with BPDre consistent with a growing literature (Lin et al. 2006; McElroyt al. 2001; Strakowski et al. 1995; Winokur et al. 1993). Fornstance, Strakowski et al. (2000) reported that the duration oflcohol and marijuana use was related to the duration ofepression and mania, respectively, in a study of new onset adultPD. These data highlight the complex relationship betweenPD and SUD that onsets in adolescence (Wilens et al. 1999,004) and extends into adulthood (Strakowski et al. 2000).linicians need to be mindful that BPD at any age increasesreatly the risk for SUD.

Our results provide some insights into the mechanisms thatight account for the comorbidity between BPD and SUDs. Our

inding of cosegregation shows that comorbidity cannot beimply accounted for by referral bias or any other sourcef statistical artifacts. Our analyses of age at onset found thateither SUD nor BPD systematically onset before the otherisorder. This suggests that neither disorder is routinely second-ry to the other disorder.

We found a high rate of SUD among parents of probands withPD, regardless of proband SUD diagnosis; this finding might

ndicate that the two disorders share transmissible familial riskactors. For example, this transmission pattern would occur ifenes that increase risk for BPD also increase risk for SUD; itould also occur if the environment created by a substance-busing parent increased the risk for BPD in their child or if theifficulties of raising a BPD child trigger parental SUD.

Our finding of a lack of consistent SUD relative to BPDartially supports the notion of secondary SUD in BPD in somedults (Strakowski et al. 1998; Winokur et al. 1995) and/or of theemporal onset of shared risk factors for both SUD and BPD. Fornstance, Strakowski et al. (1998) have noted a pattern by whichhe course of BPD is related to the course of SUD. Winokur et al.1993, 1995) observed differences in alcohol use patterns be-ween BPD and nonBPD suggestive of alcohol use as a result ofhe individual’s BPD. In the current sample, BPD was associatedith increases in SUD, suggesting an effect or familial associationf the BPD on the SUD.

Our findings must be interpreted with some methodologicalimitations. The sample was primarily Caucasian and might noteneralize to other ethnicities. Similarly, because our sample was

rawn largely from advertisements, it might not generalize to the

population. The results reported are from adults and thereforeare retrospective. The SUD was determined by structured inter-view and not by objective urine toxicologies, although recentlyreported data highlights the usefulness of structured psychiatricinterviews for capturing current and lifetime SUD (Gignac et al.2005). Probands in our study were not through the full risk ofSUD, probably producing an under-representation of the fullSUD risk. The lack of significant differences between our twogroupings of parents of BPD probands might indicate censoringof SUD diagnoses in the BPD�SUD probands. Despite oursignificant finding of cosegregation, the frequency of parents ofBPD�SUD probands showing BPD was small.

Despite these limitations, our findings indicate that higherrates of both BPD and of SUD are found in the parents ofprobands with BPD. Likewise, parents with BPD were morelikely to develop SUD than parents without BPD. The relation-ship of BPD and SUD in the adult parents, similar to findings inadolescents with BPD, is not accounted for by conduct orantisocial disorders. These data, derived from parents of ourprobands, highlight that BPD and SUD are familial and satisfycriteria for cosegregation.

This study was supported by NIH RO1 DA12945 (TW), U10DA15831 (TW) and K24 DA016264 (TW).

Dr. Timothy Wilens receives grant support from the followingsources: Abbott Laboratories, Ortho-McNeil, Eli Lilly and Com-pany, National Institute on Drug Abuse (NIDA), Neurosearch,and Shire Laboratories Inc. Dr. Timothy Wilens is a speaker forthe following speaker’s bureaus: Ortho-McNeil, Novartis Pharma-ceuticals, and Shire Laboratories Inc. Dr. Timothy Wilens is aconsultant for: Abbott Laboratories, Ortho-McNeil, Glaxo-Smith-Kline, Eli Lilly and Company, National Institute on Drug Abuse(NIDA), Novartis, Pfizer, Shire Laboratories Inc.

Dr. Joseph Biederman receives/d research support from, is/hasbeen a speaker for, or is/has been on the advisory board for thefollowing pharmaceutical companies: Shire, Eli Lilly, Pfizer,McNeil, Abbott, Bristol-Myers-Squibb, New River Pharmaceuti-cals, Cephalon, Janssen, Novartis, UCB Pharma, Astra-Zeneca,Forest Laboratories, Glaxo-SmithKline, Neurosearch, StanleyMedical Institute, Inc, Lilly Foundation, Prechter Foundation,National Institute of Health (NIH), National Institute of MentalHealth (NIMH), National Institute of Child Health and Develop-ment (NICHD), and National Institute on Drug Abuse (NIDA).

Dr. Stephen Faraone receives/d research support from, is/hasbeen a speaker for, or is/has been on the advisory board for thefollowing companies: Eli Lilly & Company. McNeil Consumer &Specialty Pharmaceuticals, Shire US Inc., Noven Pharmaceuti-cals, Cephalon, National Institute of Mental Health (NIMH),National Institute of Child Health and Human Development(NICHHD), and National Institute of Neurological Disorders andStroke (NINDS). Joel Adamson, Michael Monuteaux, Aude He-nin, Stephanie Sgambati, and Alison Santry do not have anyfinancial interests to disclose.

Ambrosini PJ (2000): Historical development and present status of theschedule for affective disorders and schizophrenia for school-age chil-dren (K-SADS). J Am Acad Child Adolesc Psychiatry 39:49 –58.

Bierut L, Dinwiddie S, Begleiter H, Crowe R, Hesselbrock V, Numberger J, et al.(1998): Familial transmission of substance dependence: Alcohol, mari-juana, cocaine, and habitual smoking. Arch Gen Psychiatry 55:982–988.

Cadoret RJ (1991): Genetic and environmental factors in initiation of druguse and the transition to abuse. In: Glantz M, Pickens R, editors. Vulnera-bility to Drug Abuse. Washington, DC: American Psychological Press, 99 –

114.

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