Drug and Alcohol Dependence 55 (1999) 165–176

Hormonal and behavioral homeostasis in boys at risk for substanceabuse

Michael A. Dawes a,*, Lorah D. Dorn b, Howard B. Moss a, Jeffrey K. Yao a, Levent Kirisci a,Robert T. Ammerman a,c, Ralph E. Tarter a

a Center for Education and Drug Abuse Research (CEDAR), Department of Psychiatry, Uni6ersity of Pittsburgh School of Medicine,3811 O’Hara Street, Pittsburgh, PA 15213, USA

b Uni6ersity of Pittsburgh, School of Nursing, and Department of Psychiatry, Pittsburgh, PA 15213, USAc Department of Psychiatry, Allegheny Uni6ersity of the Health Sciences, Pittsburgh Campus, Allegheny General Hospital, Pittsburgh,

PA 15212, USA

Received 5 June 1998; accepted 16 December 1998

Abstract

This study modeled the influences of cortisol reactivity, androgens, age-corrected pubertal status, parental personality, familyand peer dysfunction on behavioral self-regulation (BSR), in boys at high (HAR) and low average risk (LAR) for substance abuse.Differences between risk groups in cortisol and androgen concentrations, and cortisol reactivity were also examined. Subjects were10- through 12-year-old sons of substance abusing fathers (HAR; n=150) and normal controls (LAR; n=147). A multidimen-sional construct of BSR was developed which utilized multiple measures and multiple informants. Boys reported on familydysfunction and deviant behavior among their peers. Parents reported on their propensity to physically abuse their sons, and theirown number of DSM-III-R Antisocial Personality Disorder symptoms. Endocrine measures included plasma testosterone,dihydrotestosterone, and salivary cortisol. HAR boys, compared to LAR boys, had lower mean concentrations for testosterone,dihydrotestosterone, salivary cortisol prior to evoked related potential testing, and lower cortisol reactivity. The number ofmaternal Antisocial Personality Disorder symptoms, parental potential for physical abuse, degree of family dysfunction, and peerdelinquency were significantly associated with BSR. Parental aggression antisocial personality symptoms and parental physicalabuse potential are likely to influence sons’ behavioral dysregulation and homeostatic stress reactivity. These key components ofliability are posited to increase the likelihood of developing suprathreshold Psychoactive Substance Use Disorder (PSUD). © 1999Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Substance abuse liability; Hormonal and behavioral homeostasis; Personality; Family and peer dysfunction

1. Introduction

Empirical findings (Reich et al., 1993; Martin et al.,1994; Dawes et al., 1997; Mezzich et al., 1997a,b), aswell as theoretical literature (Gorrenstein and Newman,1980; Tarter et al., 1989; Newman and Wallace, 1993)indicate that specific behavioral characteristics increasethe likelihood of developing a Psychoactive SubstanceUse Disorder (PSUD; DSM-III-R, American Psychi-

atric Association, 1987). Disorders of inattention, im-pulsivity, and hyperactivity (Barkley et al., 1990;Biederman et al., 1996), childhood aggressivity (Kellamand Brown, 1982; Brook et al., 1996), and conductdisorder (Kandel et al., 1986; Robins and McEvoy,1990), have been shown to increase the risk for PSUD.Converging evidence suggests that Conduct Disorderoften mediates the Attention Deficit Hyperactivity Dis-order (ADHD)–PSUD relationship (Gittelman et al.,1985; Hechtman and Weiss, 1986; Barkley et al., 1990;Mannuzza et al., 1991; Babor et al., 1992; Biederman et* Corresponding author.

0376-8716/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved.PII: S 0 3 7 6 -8716 (99 )00003 -4

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176166

al., 1997). It is posited that these behavioral characteris-tics constitute a core disorder of behavioral self-regula-tion (BSR). BSR is defined herein as the degree towhich an individual can control their activity and reac-tivity to environmental challenges. Only recently hasthe extent to which BSR increases risk for PSUD andrelated behaviors been examined. Dawes et al. (1997),in an earlier study using the same subjects described inSection 2.1, demonstrated predictive validity of BSRfor family, peer, and school problems in young adoles-cence at 2-year follow-up. Disturbances in these threedomains of psychosocial functioning are posited toincrease the risk for substance abuse (Hawkins et al.,1992). Mezzich et al. (1997a,b), employing definitionsand procedures similar to those used by Martin et al.(1994), but in a separate sample of female adolescentsubstance abusers, developed a latent construct of be-havioral dysregulation that included measures of hyper-activity, impulsivity, and inattention. Mezzich et al.(1997a) showed behavioral dysregulation, negative af-fectivity, and family impairment influence violence insubstance abusing female adolescents. In a secondstudy, Mezzich et al. (1997b) demonstrated that behav-ioral dysregulation, negative affectivity, and childhoodvictimization predicted substance use and risky sexualbehavior in substance abusing female adolescents.Caspi et al. (1996), in a third study of a differentsample, reported that undercontrolled 3-year-old boyswere at greater risk of developing Antisocial PersonalityDisorder and Alcohol Dependence by age 21. Takentogether, the concurrent and predictive validity of mea-sures similar to BSR is supported by the three abovedescribed studies.

Johnson et al. (1992), in their review of the hormonaland behavioral homeostasis (Greek for ‘steady state’)literature, define ‘stress’ as a state of threatenedhomeostasis. Hormonal and behavioral homeostasiscan be perturbed by physical and psychological stres-sors, induced by family dysfunction, abusive parenting,and deviant peer affiliation (Johnson et al., 1992; Mosset al., 1995). Johnson et al. (1992) suggest that thesechronic contextual stressors can suppress both andro-gen and cortisol concentrations. The mechanisms bywhich chronic environmental stress influences circulat-ing levels of androgens and cortisol include direct mod-ulation by the Hypopituitary Gonadal Axis (HPG) andindirect modulation by the Hypopituitary Adrenal Axis(HPA) (Bambino and Hsueh, 1981; Francis, 1981;Collu et al., 1984; Sapolsky, 1991, 1992; Johnson et al.,1992). Moreover, previous experience (Archer, 1991;Rubinow and Schmidt, 1996), social interactions(Mazur, 1985), and social rank (Schaal et al., 1996) arethought to influence androgen (Archer, 1991; Rubinowand Schmidt, 1996) and cortisol (Buchanan et al., 1992;Susman et al., 1997) levels, as well as hormone–behav-ior associations. Studies on non-human primates and

adult humans have shown that both the HPG and HPAaxes, but particularly the HPA axis, are sensitive tophysical and psychological stress. Studies on humanyouths, however, have generally shown hyporesponsiv-ity of cortisol in chronic environmental stress situa-tions. In a small sample of prepubertal youth,Constantino et al., (1993) failed to find abnormal levelsof testosterone in aggressive subjects. Moss et al.(1995), in the same baseline assessment of preadolescentsample as described herein in Section 2.1, have shownthat decreased cortisol reactivity to an anticipated stres-sor in sons of substance abusing fathers is associatedwith Child Behavior Checklist (CBCL; Achenbach andEdelbrock, 1983) problem behaviors, and commissionerror scores on a computerized task (Schneider andDetweiler, 1987). Moreover, Moss et al. (in press), alsoin longitudinal follow-up of the same sample as de-scribed in Section 2.1, have reported that lower preado-lescent cortisol level prior to an anticipated stress wasassociated prospectively with regular monthly cigaretteand marijuana use, but not with regular alcohol useduring middle adolescence.

Cross-sectional studies on hormone–behavior rela-tions in peripubertal and pubertal youth have shownsignificant positive (Olweus, 1987), negative (Dabbs etal., 1991), and no (Susman et al., 1987; Inoff-Germainet al., 1988) associations. Positive associations havebeen shown between androgen concentration and levelof verbal (Olweus, 1987) and physical (Olweus, 1987)aggression, as well as peer-nominated dominance(Schaal et al., 1996). Testosterone has been associatedwith other behaviors that are posited to be linked toBSR in adolescents, including smoking, drinking, andsex (Udry, 1990). Dabbs et al. (1991) reported a signifi-cant interaction between testosterone and cortisol lev-els; that is, they found that the testosterone–aggressionassociation was greater among subjects having a lowcortisol level. Scerbo and Kolko (1994) did not confirmthis finding in a separate sample. The longitudinalrelations among testosterone–aggression and low corti-sol in these samples have not been reported. Inoff-Ger-main et al. (1988) and Susman et al. (1987), in a sampleof peripubertal youth, failed to observe a significantcorrelation between plasma androgen level and negativeaffect, maternal reports of delinquency and opposi-tional behavior, and direct observation measures ofirritability and assertiveness.

Longitudinal data suggest that the hormone reactiv-ity may be more sensitive to environmental stressors atparticular developmental transitions, such as theperipubertal period (Johnson et al., 1992; Susman et al.,1997). For example, Susman et al. (1997) show that ina small sample of healthy adolescents, over a 1-yearperiod, distress behavior for both sexes in a challengingsituation decreases, whereas, for girls cortisol level de-creases, while for boys, cortisol level increases. This

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176 167

study, however, does not relate the magnitude, timing,or chronicity of environmental stressors during thefollow-up period. Hence, interpretation of these sexdifferences in cortisol level at longitudinal follow-up isproblematic. In a separate sample of males, followedfrom ages 6 to 13, testosterone levels were positivelyassociated with high social dominance and social suc-cess, whereas males with a history of high physicalaggression had lower testosterone levels, compared toboys with no history of physical aggression (Schaal etal., 1996; Tremblay et al., 1997). Schaal et al. (1996)speculate that chronic activation of the adrenal axismay explain the relative suppression of the HPG axis inthis sample. This study also does not relate the magni-tude, timing, or chronicity of environmental stressorsduring the longitudinal follow-up. Although specula-tive, these chronically aggressive boys most probablymatured in environments where they experienced highdegrees of physical and psychological stressors, includ-ing family dysfunction, abusive parenting from angryand aggressive parents, and deviant peer affiliation.

From a multifactorial epigenetic perspective of etiol-ogy of substance abuse, inclusion of measures of behav-ioral and hormonal homeostastis, and of theenvironmental stressors that may perturb homeostasis,in a longitudinal study of sons and daughters of sub-stance abusing fathers is likely to help elucidate themechanisms leading to PSUD outcomes (Tarter andVanyukov, 1994; Vanyukov et al., 1994; Moss et al., inpress). The extent to which measures of hormonalprofile (e.g. androgens, cortisol) and hormonalhomeostasis (e.g. cortisol reactivity), interact with con-current environmental stressors (e.g. specific parentalaggressive antisocial personality characteristics, as wellas family and peer dysfunction), to modulate BSR inhigh risk youth (e.g. behavioral homeostasis) heretoforehas not been investigated in sons of substance abusingfathers. It is posited that measures of hormonal andbehavioral homeostasis have a greater magnitude ofcovariation in sons of substance abusing fathers, com-pared to normal control sons, during the peripubertalperiod. Empirical evidence has yet to document thepreadolescent covariation of hormonal and behavioralhomeostasis in sons of substance abusing fathers and incontrols, or the direction and magnitude of these asso-ciations in these comparison groups.

This investigation tested two cross-sectional hypothe-ses. The first hypothesis was that concentrations ofplasma testosterone, plasma dihydrotestosterone, andsalivary cortisol, as well as cortisol reactivity, werelower in preadolescent high average risk (HAR) boys,compared to preadolescent low average risk (LAR)boys; these associations are posited to be due in part tochronic homeostatic stress experienced from the familyand peer environment prior to baseline assessment. Thesecond hypothesis was that in these preadolescent boys,

cortisol reactivity would be negatively associated withBSR (e.g. low cortisol reactivity would be associatedwith high behavioral dysregulation), while parent anti-sociality, family dysfunction and deviant peer affiliationwould be significantly positively associated with BSR(e.g. high degree of environmental stressors would beassociated with high behavioral dysregulation).

2. Methods

2.1. Subjects

The sample consisted of baseline assessment of twogroups of 10- through 12-year-old boys, classified ac-cording to their biological father’s diagnostic status oflifetime DSM-III-R Psychoactive Substance Use Disor-der (PSUD). This baseline sample was accrued between1989 and 1997, and is a portion of the first wave on anongoing longitudinal study. One-hundred fifty high av-erage risk (HAR) boys had fathers who qualified forPSUD. Low average risk (LAR) boys (n=147) hadfathers who were not qualified for PSUD, and had noother adult lifetime Axis I or Antisocial PersonalityDisorder. Chronic neurological illness, acute neurologi-cal injury, organic brain syndrome requiring treatment,uncorrected sensory incapacity (vision and hearing),intelligence quotient less than 75, and schizophrenia orother psychotic illness were exclusionary criteria. Cur-rent or lifetime comorbid psychiatric disorder in thePSUD fathers, other than psychosis, did not disqualifythe son from the study. The two groups of boys werederived from intact, single parent, as well as reconsti-tuted families, so as to obtain a representative sampleof the range of family structures associated with PSUDin adult men. Recruitment sources of fathers includedlocal outpatient and inpatient substance abuse treat-ment programs; radio, television, local newspaper ad-vertisements; and other printed media. A marketresearch group was also employed. Employing thisrecruitment strategy affords the opportunity of maxi-mizing the generalizability of the HAR sample. Cashincentives were provided to participating fathers andfamily members who completed the protocol. The studyhas been approved by University of Pittsburgh MedicalCenter Institutional Review Board. Prior to entry, allparticipating parents granted informed consent andsons their assent.

In order to control for sibling order effects, the oldestboy between ages 10 and 12 years in each family wasselected. Comparison of differences in substance usepatterns between HAR and LAR boys (Dawes et al.,1997) revealed very low rates of substance use experi-mentation that were unlikely to significantly influencedifferences in hormone levels between risk groups, orprediction of both risk status and BSR. In the baseline

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176168

Table 1Demographics, Behavioral Self-Regulation (BSR), and Lifetime DSM-III-R Diagnoses in HAR and LAR boysa

LAR (n=147)Variable t-valueHAR (n=150) P-valueMean (S.D.)Mean (S.D.)

11.36 (0.96)Age −0.9111.26 (0.95) NS43.14 (13.46)SES −4.5736.14 (12.85) B0.001

112.25 (15.74) −4.28104.02 (15.59) B0.001Full Scale IQBSR 2.26 (0.29)2.40 (0.32) 3.81 B0.001

n (% of total) x2Ethnicity* P-valuen (% of total)

122 (41.2)Caucasian 15.9094 (31.8) 0.00120 (6.8)47 (15.9)African–American

8 (2.7)Other 5 (1.7)

n (%) x2Diagnosis** P-valuen (%)

ADHD 31 (10.5) 15 (5.1) 6.47 0.0110 (3.4)CD 2 (0.7) 5.50 0.02

7 (2.4) 7.6321 (7.1) B0.01ODD19 (6.4)Childhood anxiety disorders 11 (3.7) 2.32 NS

Depressive disorders 7 (4.7) 1 (0.7) 4.58 0.03

a BSR, Behavioral Self-Regulation; ADHD, Attention Deficit Hyperactivity Disorder; CD, Conduct Disorder; ODD, Oppositional DefiantDisorder.

* One missing value;** Two missing values; (%) is the percentage of subjects in each column, for HAR and LAR groups.

assessment used for these analyses, neither the HARnor the LAR boys reported a single DSM-III-R PSUD.

Differences between HAR and LAR groups for de-mographics, behavioral self-regulation, and lifetimeDSM-III-R Disorders are reported in Table 1. As canbe seen, HAR boys, compared to LAR boys, had lowersocioeconomic status (Hollingshead, 1990). HAR boysalso had lower WISC-III intelligence quotients (Wech-sler, 1991). These factors were thus controlled statisti-cally in the analyses.

The distribution of DSM-III-R lifetime psychiatricand PSUD disorders in fathers and mothers are re-ported in Tables 2 and 3. As can be seen, fathers hadmore extensive histories for PSUD and other comorbidpsychiatric disorders, compared to mothers.

2.2. Assessment procedure

The protocol reported herein is a component of a2-day comprehensive baseline evaluation in an ongoinglongitudinal study. In this report, the assessment isconducted on 10- through 12-year-old boys and theirnuclear families. Following informed consent from theparents, and assent from the boys, the protocol wasadministered in fixed order. Interviews were adminis-tered by trained masters level clinical associates. Demo-graphic information was recorded first. Next, theparents and their sons were administered the psychiatricinterviews. This was followed by completion of theself-report questionnaires. Thereafter, the boys sleptovernight on an inpatient adolescent psychiatric unit. A

fasting venipuncture was performed at about 07:00 h.Following breakfast, the protocol was continued. All ofthe questionnaires and rating scales were administeredand scored according to standard method. The boys,their parents, and their teachers were assessed using thefollowing measures.

2.3. Measures

2.3.1. DemographicsInformation about age and household socioeconomic

status (Hollingshead, 1990) was obtained using theCEDAR Demographic Form. Full scale intelligencequotient was obtained using the revised Wechsler Intel-ligence Scale for Children (WISC-III; Wechsler, 1991).

2.3.2. Family dysfunctionThe Dysfunctional Family Index (DFI) was obtained

from summation of sons’ responses to seven scales inthe General Section of the Family Assessment Measure(Skinner et al., 1983): Task Accomplishment, Role Per-formance, Communication, Affective Expression, Af-fective Involvement, Control, and Values and Norms.A high DFI score thus characterizes family dysfunctionacross a broad range of domains.

2.3.3. Parent characteristicsParents completed the Child Abuse Potential In6en-

tory (Milner, 1980). The Abuse Potential Scale mea-sured the parent’s propensity to employ severe punitivemethods on their son. The algorithm described in Mil-

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176 169

Table 2Lifetime DSM-III-R diagnoses of proband fathers in the PSUD (SA+) and control (SA−) groupsa

SA− (n=147)SA+ (n=149) P-valueDSM-III-R diagnoses*

(%) n (%)n

Psychoacti6e substance use disorders(4.0)Amphetamine abuse 06 (0) 0.03**(6.0)Amphetamine dependence 09 (0) 0.003**

(51.0) 3***76 (2.0)Alcohol abuse B0.001**Alcohol dependence (62.4)93 0 (0) B0.001**

(26.2) 039 (0)Cannabis abuse B0.001**(26.8) 0Cannabis dependence (0)40 B0.001**(12.1) 018 (0)Cocaine abuse B0.001**(32.2) 0Cocaine dependence (0)48 B0.001**(18.1) 627 (4.1)Nicotine dependence B0.001**

(2.7) 0Opioid abuse (0)4 NS(17.4) 026 (0)Opioid dependence B0.001**

Comorbid psychiatric disorders(26.2)Major depression 039 (0) B0.001**(11.4)Adult Anxiety Disorder 017 (0) B0.001**(18.8) 028 (0)Antisocial Personality Disorder B0.001**

(8.1) 1 (0.7)Attention Deficit Hyperactivity Disorder 0.003**12(8.7) 013 (0)Oppositional Defiant Disorder B0.001**

(34.9) 6 (4.1) B0.001**Conduct Disorder 52

a Adult Anxiety Disorder, Sum of Panic Disorder without Agoraphobia, Panic Disorder with Agoraphobia, Generalized Anxiety Disorder,Agoraphobia without history of Panic Disorder, Social Phobia, Obsessive Compulsive Disorder, Post-Traumatic Stress Disorder, AnxietyDisorder Not Otherwise Specified.

* One missing subject.** Significant Fisher’s Exact Tests, two-tail.*** These subjects had very mild alcohol abuse in young adulthood only, without any other psychiatric comorbidity.

ner (1980) was employed to obtain valid scores for theanalyses reported herein. Twenty-three fathers of HARsons (15.3% of substance abusing fathers) and ninefathers of LAR sons (6.1% of control fathers) wereremoved due to invalid scores. Twenty-eight mothers ofHAR sons (18.7% of sample) and 16 (10.9% of sample)were also removed due to invalid scores. The number oflifetime DSM-III-R Antisocial Personality DisorderSymptoms was obtained from the Structured ClinicalInterview for DSM-III-R (SCID; Spitzer et al., 1987).

2.3.4. Peer delinquencySons completed the Peer Delinquency Scale (Loeber,

1989, unpublished). This scale rates delinquent activityof peers. The Cronbach’s a was 0.84, consistent withresults reported in Loeber’s Pittsburgh Youth study(Loeber et al., 1998, p. 71).

2.3.5. Age-corrected Tanner stagingAssessment of sexual maturation was determined

during physical examination by a nurse practitioner.Staging of genital development employed the defini-tions of Marshall and Tanner (1970). Age-correctedTanner stage was defined as the average of TannerStage for pubic hair and genital development, multi-plied by 100, and divided by the boys’ ages in months.

2.3.6. Beha6ioral self-regulation scale (BSR; Dawes etal., 1997)

A continuous measure of BSR was created fromstandardized (z-scored) subscales that were summed todevelop aggregate observed measures of lifetime inat-tention, impulsivity/hyperactivity, and aggressivity.Higher scores on the construct of BSR indicated higherbehavioral dysregulation, with the highest BSR scoresmeeting DSM-III-R criteria for Attention Deficit Hy-peractivity Disorder (ADHD), Oppositional DefiantDisorder (ODD), and Conduct Disorder (CD) (Table1). The observed measures included the K-SADS-E(Orvaschel et al., 1982), the Dimensions of Tempera-ment Survey (DOTS-R, Windle, 1992), the DisruptiveBehavior Disorder Rating Scale (Pelham and Murphy,1987), and the Child Behavior Checklist, teacher ver-sion (Achenbach and Edelbrock, 1983). Specific items,and references for the observed measures have beenreported previously (Dawes et al., 1997). The Cron-bach’s a for inattention was 0.79, for impulsivity/hyper-activity was 0.66, and for aggressivity was 0.72. In theHAR group, the minimum value was 1.58, maximumwas 3.19, with a range of 1.60. For the LAR group, theminimum was 1.43, maximum was 3.03, with a range of1.59. Confirmatory factor analysis (CFA) was em-ployed to fit a first-order factor, providing a good fit ofthe data (Dawes et al., 1997).

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176170

Table 3Lifetime DSM-III-R diagnoses of mothers in the PSUD (SA+) and control (SA−) groupsa

DSM-III-R Diagnoses* SA+ (n=143) SA− (n=144) P-value

(%)n n (%)

Psychoacti6e substance use disorders(0.7) 0 (0) NSAmphetamine abuse 1(4.9) 27 (1.4)Amphetamine dependence NS

(17.5) 10 (6.9) 0.007**Alcohol abuse 25(19.6) 428 (2.8)Alcohol dependence B0.001**

(9.8) 2Cannabis abuse (1.4)14 0.002**(7.7) 311 (2.1)Cannabis dependence 0.03**(2.1) 1Cocaine abuse (0.7)3 NS(5.2) 015 (0)Cocaine dependence B0.001**(0.7) 1Opioid abuse (0.7)1 NS(4.9) 17 (0.7)Opioid dependence 0.04**(8.7) 8 (2.8) 0.002**Nicotine dependence 25

Comorbid psychiatric disorders(36.4)Major depression 3852 (26.4) 0.08(24.5)Adult Anxiety Disorder 2235 (15.3) 0.06

(2.1) 13 (0.7)Antisocial Personality Disorder NS(2.8) 0 (0)Attention Deficit Hyperactivity Disorder 0.064(2.1) 03 (0)Oppositional Defiant Disorder NS(9.8) 1 (0.7) B0.001Conduct Disorder 14

a Adult Anxiety Disorder, Sum of Panic Disorder without Agoraphobia, Panic Disorder with Agoraphobia, Generalized Anxiety Disorder,Agoraphobia without history of Panic Disorder, Social Phobia, Obsessive Compulsive Disorder, Post-Traumatic Stress Disorder, AnxietyDisorder Not Otherwise Specified;

* Ten missing subjects.** Significant Fisher’s Exact Tests, two-tail.

2.3.7. Determination of hormone concentrations in boysSalivary cortisol was obtained just prior to (at 09:00

h) and after (at 10:15 h) auditory evoked potential(ERP) testing, which is a mild anticipatory stressor formost subjects. The ERP task consisted of target (high)and standard (low) tones that were presented at 0.10probability in an active-response condition, employingan auditory ‘oddball’ paradigm. Subjects mentallycounted the number of target tones. Cortisol reactivitywas defined as the difference between salivary cortisolconcentrations after minus before ERP.

Salivary cortisol concentrations were measured usingdissociation-enhanced lanthanide fluoroimmunoassay(DELFIA) (Yao et al., 1999). Use of salivary cortisolavoids the potential induction of a stress response dueto venipuncture. Salivary cortisol is highly correlatedwith serum cortisol concentration. It is a reliable andvalid indicator of the unbound, biologically active frac-tion of circulating cortisol (Kirschbaum and Hellham-mer, 1994; Kiess et al., 1995). The majority of cortisolin blood is bound to plasma proteins, including albu-min and cortisol-binding protein. The biologically ac-tive fraction is not bound to plasma proteins.Intra-assay (within-run) coefficient of variation for sali-vary cortisol was 7.48 and 4.65% CV at 2.94 ng/ml(S.D.=0.22 ng/ml) and 6.23 ng/ml (S.D.=0.29 ng/ml),

respectively. Inter-assay (between-run)% CV was 7.49and 4.41 at 4.22 ng/ml (S.D.=0.09 ng/ml) and 5.49ng/ml (S.D.=0.24 ng/ml), respectively.

Plasma testosterone and dihydrotestosterone weredetermined by radioimmunoassay (RIA) using Amer-sham’s testosterone/dihydrotestosterone RIA kit. Thekit employed tritiated dihydrotestosterone and an anti-body that was specific to testosterone and dihy-drotestosterone. The amount of labeleddihydrotestosterone bound to antiserum was inverselyassociated with the amount of testosterone and dihy-drotestosterone available in the assay sample. Measure-ment of the antibody-bound radioactivity afforded theopportunity to quantify the amount of testosterone anddihydrotestosterone in the sample. This procedure pro-vided a simple, sensitive, specific, and reproduciblemethod for measurement of testosterone (T) and dihy-drotestosterone (DHT). The intra-assay coefficient ofvariation (% CV) for T was 5.2 at 356 pg/ml and forDHT was 5.0 at 393 pg/ml. The intra-assay precisionsfor T were 5.2 and 5.0% CV at 356 pg/ml (S.D.=12.3pg/ml) and 393 pg/ml (S.D.=13.0 pg/ml), respectively.The inter-assay precisions for T and DHT were 10.8and 9.4% CV at 347 pg/ml (S.D.=25.0 pg/ml) and 396pg/ml (S.D.=24.9 pg/ml), respectively.

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176 171

Table 4Differences in hormone levels between high average risk (HAR) and low average risk (LAR) boys, controlling for age-corrected pubertal status

LAR (mean (S.D.)) F-value dfHormone P-valueHAR (mean (S.D.))

1308.02 (1757.61) 4.22Testosterone1 (pg/ml) 1,2531026.39 (1335.41) 0.04Dihydrotestosterone1 (pg/ml) 238.43 (160.31) 263.10 (198.51) 4.44 1,253 0.04Salivary cortisol before ERP2 (ng/dl) 317.20 (161.30)262.57 (132.20) 10.51 1,230 0.001

261.93 (111.49) 1.28246.27 (108.21) 1,216Salivary cortisol after ERP2 (ng/dl) NSCortisol reactivity2,3 −52.43 (90.10)−9.31 (88.55) 13.13 1,222 B0.001

1 Simple factorial ANOVAs (Grouping Variable, Risk Group Status; Covariates, Age-Corrected Pubertal Status, Household SocioeconomicStatus, Full-Scale IQ).

2 Simple factorial ANOVA, controlling for Household Socioeconomic Status, and Full-Scale IQ; ERP, evoked related potential.3 Cortisol reactivity was measured as the difference between after and before ERP cortisol concentrations.

2.4. Statistical analyses

All positively skewed variables were logarithmictransformed to approximate normality.

The first hypothesis was to test whether concentra-tions of plasma testosterone, plasma dihydrotestos-terone, and salivary cortisol, as well as cortisolreactivity, were lower in high average risk (HAR)boys, compared to low average risk (LAR) boys, dueto chronic homeostatic stress from the family and peerenvironment. Multivariate analysis of variance(MANOVA) was first used to compare whether hor-mone concentrations and cortisol reactivity betweenrisk groups (HAR vs. LAR groups) were significantlydifferent, controlling for Household SocioeconomicStatus (SES) and age-corrected Tanner Stage. Simplefactorial analysis of variances (ANOVAs) for individ-ual hormone concentrations and cortisol reactivity be-tween risk groups were also employed. Fortestosterone and dihydrotestosterone as the dependentvariables, the factor was risk group, controlling forage-corrected Tanner stage, full-scale IQ, SES, familydysfunction, and deviant peer affiliation. For cortisolconcentrations and cortisol reactivity, the factor wasgroup status, controlling for full scale IQ, SES, familydysfunction and deviant peer affiliation.

For the second hypothesis, that cortisol reactivitywould be negatively associated with BSR, while parentantisociality, family dysfunction and deviant peeraffiliation would be significantly positively associatedwith BSR, a regression model was developed in whichbehavioral and hormonal homeostatic factors in-creased the proportion of variance explained in associ-ation with BSR. Blocks of variables were entered inthe following order, in order to model increasing lev-els of biological and homeostatic complexity (e.g.physiology, behavior, cognition, and environment), af-ter first controlling for demographics and risk groupstatus: (1) demographics and risk group; (2) hor-mones; (3) age-corrected Tanner stage; (4) parentalabuse potential and number of parental lifetime Anti-

social Personality Disorder symptoms; (5) family dys-function, and (6) peer delinquency. Interaction termsfor age-corrected Tanner stage and demographics,with the parental characteristics, family dysfunction,and peer delinquency were tested in univariate rela-tions with BSR.

3. Results

3.1. Test of differences in hormone le6els and riskgroup status

MANOVA of hormone concentrations and cortisolreactivity between risk groups was significant (Wilk’sl=0.93, F(5, 211)=3.28, P=0.007, h2=0.07), con-trolling for age-corrected Tanner stage and householdSES. Table 4 presents results for simple factorialANOVAs of differences in hormone levels in HARand LAR boys. Age-corrected Tanner genital statuswas significantly positively correlated with testosteronelevel (T; r=0.56, PB0.001) and dihydrotestosterone(DHT; r=0.57, PB0.001). Cortisol prior to ERP(r= −0.15, PB0.05) and cortisol after ERP (r= −0.15, PB0.05) were significantly negatively associatedwith family dysfunction. T (r=0.13, PB0.05) andDHT (r=0.16, PB0.05) were significantly positivelyassociated with deviant peer affiliation. Therefore, age-corrected Tanner genital stage, family dysfunction,and peer delinquency were originally entered as co-variates in the ANOVAs for testosterone and dihy-drotestosterone. Family dysfunction and peerdelinquency were also entered as covariates in the sim-ple factorial ANOVAs for cortisol concentration, andfor cortisol reactivity. Because family dysfunction andpeer delinquency were not significant in theseANOVAs, the covariates were removed in the finalmodels reported in Table 4. As can be seen, each ofthe hormone levels was lower for the HAR boys,compared to the LAR boys although salivary cortisolfollowing ERP failed to reach statistical significance.

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176172

Table 5Regression model of BSR. Order of entry of independent variables

R2 R2 change F-value change Significance of F-value changeBlock number Variables entereda

0.07 0.071. 3.64ETHNIC, SA, SES, FSIQ 0.0072. T, DHT, C–DIFF 0.07 B0.01 0.13 NS

0.07 B0.01 0.083. NSATANIND0.16 0.09ABUSEFA, ABUSEMO, ASPLFFA, ASPLFMO 4.774. 0.001

DFI5. 0.24 0.08 17.88 B0.0010.32 0.096. 22.72PDS B0.001

a ETHNIC, Ethnicity (dichotomized as Caucasian vs. Other); SA, (High Average Risk vs. Low Average Risk); SES, Head of HouseholdSocioeconomic Status; FSIQ, Full Scale Intelligence Quotient; DHT, dihydrotestosterone; T, testosterone; C–DIFF, Cortisol Reactivity;ATANIND, Age-corrected Tanner Stage; ASPLFFA, fathers’ number of lifetime DSM-III-R Antisocial Personality Disorder Symptoms;ASPLFMO, mothers’ number of lifetime DSM-III-R Antisocial Personality Disorder Symptoms; ABUSEFA, father’s physical abuse potential;ABUSEMO, mother’s physical abuse potential; DFI, Dysfunctional Family Index; PDS, Peer Delinquency Scale.

3.2. Regression model of hormonal and beha6ioralhomeostasis

Ordinary least squares regression was employed tomodel measures of hormonal and behavioral homeosta-sis predicting BSR (Table 5). Demographics and riskgroup status were entered in the first block of variables,with R2 of 0.7 and significant F change (P=0.007). Thenext two blocks of variables (hormones and age-cor-rected Tanner stage, respectively) did not produce sig-nificant changes in the R2. In the fourth block, entry ofparental abuse potential and parental Antisocial Per-sonality Disorder symptoms, produced a 0.09 change inR2 (F change=4.77, P=0.001). In the fifth block,entry of family dysfunction, R2 change increased 0.08(F change=17.88, PB0.001). In the final block, peerdelinquency was entered, with R2 change of 0.09 (Fchange=22.72, PB0.001). Only the interaction termfor the univariate relation between age-corrected Tan-ner stage and peer delinquency was significant (r=0.21,P=0.01). However, the interaction term between age-corrected Tanner stage and BSR was not significant inthe final model and was removed. The final modeloverall R2 was 0.32. All variation inflation factors wereless than 10, which is the generally accepted maximumfor this statistic (Neter et al., 1990).

As can be seen in the final model in Table 6, familydysfunction and peer delinquency were highly signifi-cant in association with BSR. Fathers’ abuse potentialwas also highly significant, with a negative associationwith BSR. Mothers’ number of lifetime Antisocial Per-sonality Disorder symptom were significantly associatedwith BSR, while mother’s abuse potential had a trendtowards significance.

4. Discussion

Our first hypothesis, that baseline assessment concen-trations of testosterone, dihydrotestosterone, cortisol,and cortisol reactivity would be significantly lower in

HAR boys, compared to LAR boys, was supported.Our second hypothesis, that cortisol reactivity, parentpersonality characteristics, family dysfunction, and peerdelinquency would be significantly associated with BSRwas only partially supported. These findings neverthe-less extend results reported by Vanyukov et al. (1993)and Moss et al. (1995) of a significant negative correla-tion between salivary cortisol level and number ofconduct disorder symptoms in HAR boys, by alsoexamining antisocial characteristics in both parents,while controlling for family dysfunction and peer delin-quency. Moreover, the findings reported herein revealedthat parental Antisocial Personality Disorder symptomsand parental abuse potential were strongly associatedwith both severity of family dysfunction and deviantpeer affiliation. To our knowledge, this is the firstreport of a cross-sectional regression model employingBSR as the dependent variable, with independent vari-ables of cortisol reactivity, and sex hormones, whilecontrolling for age-corrected Tanner stage, parentalabuse potential, parental Antisocial Personality Disor-der symptoms, family dysfunction, and peer delin-quency, in samples of sons of substance abusing fathersand controls. The findings reported herein are consis-tent with a multifactorial model of liability to PSUD(Tarter et al., 1998).

This study extends previous studies on androgens,cortisol reactivity, pubertal development, and external-izing behavior in preadolescent boys, by using a samplesize which afforded the opportunity to examine multi-ple measures of hormonal and behavioral homeostasis.Most previous studies of steroid hormones and problembehavior in children and adolescents have had smallersample sizes which allowed only for conducting univari-ate correlations or group comparisons (Buchanan et al.,1992; Rubinow and Schmidt, 1996).

The extant literature suggests that multiple homeo-static mechanisms may account for our results (Brannet al., 1995; Rubinow and Schmidt, 1996). Severalbiobehavioral factors can modulate the relations amongandrogen and cortisol concentrations, cortisol reactiv-

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176 173

Table 6Final regression model of BSR

SE Standardized b coefficient t-valueb Coefficient P-valueIndependent variablesa VIFb

FSIQ 0.01B0.01 0.03 0.43 NS 1.710.05 −0.08 −0.96−0.05 NSSA 2.03

B0.01SES B0.01 0.09 1.19 NS 1.390.06 0.07 0.84 NSETHNIC 1.700.050.06 −0.01 −0.13B0.01 NSDHT 3.360.04 0.05 −0.01T NS0.01 3.36

B0.01 B−0.01 −0.04B−0.01 NSC–DIFF 1.17−0.08ATANIND 0.09 −0.08 −0.93 NS 1.77

B0.01 0.04 0.52B0.01 NSASPLFFA 1.940.02ASPLFMO B0.01 0.17 2.32 0.02 1.40

0.04 −0.22 −2.83ABUSEFA 0.005−0.08 1.700.04 0.13 1.820.08 0.07ABUSEMO 1.41

B0.01 0.26 3.72 B0.001DFI 1.27B0.010.03 0.33 4.77 B0.0010.12 1.26PDS

a ETHNIC, Ethnicity (dichotomized as Caucasian vs. Other); SA, (High Average Risk vs. Low Average Risk); SES, Head of HouseholdSocioeconomic Status; FSIQ, Full Scale Intelligence Quotient; DHT, dihydrotestosterone; T, testosterone; C–DIFF, Cortisol Reactivity;ATANIND, Age-corrected Tanner Stage; ASPLFFA, fathers’ number of lifetime DSM-III-R Antisocial Personality Disorder Symptoms;ASPLFMO, mothers’ number of lifetime DSM-III-R Antisocial Personality Disorder Symptoms; ABUSEFA, father’s Physical Abuse Potential;ABUSEMO, mother’s Physical Abuse Potential; DFI, Dysfunctional Family Index; PDS, Peer Delinquency Scale.

b VIF, Variance Inflation Factor.

ity, and BSR. First, differential sensitivity of the hypo-pituitary–adrenal axis and hypopituitary–gonadal axisto physical and psychological stressors can result indifferent hormone profiles. Manifest behaviors mayrepresent the sum of individual steroid effects (Ru-binow and Schmidt, 1996), or sums of the effects ofindividual steroids and ratios (Susman et al., 1987) ofsteroids. Second, factors such as age (Simon et al.,1992) and circadian rhythm (Winters, 1991) can influ-ence androgen and cortisol levels. Third, previous expe-rience (Rubinow and Schmidt, 1996), environmentalstressors (Francis, 1981), social interactions (Mazur,1985), and social rank (Schaal et al., 1996) are thoughtto influence androgen (Rubinow and Schmidt, 1996)and cortisol (Buchanan et al., 1992; Susman et al.,1997) levels and their concurrent effects on behavior.Additional hormone concentrations, such as adrenalandrogens (Dorn and Chrousos, 1997), may influenceandrogen–behavior relationships directly or indirectly(Buchanan et al., 1992). Moreover, Dabbs et al. (1991)found that cortisol moderates the behavioral effects oftestosterone. Moderation is consistent with the findingof Cumming et al. (1983) that cortisol can lower testos-terone level. The specific neuroregulatory mechanismslinking the two hormone systems with BSR remain tobe elucidated.

Affect (Graber and Brooks-Gunn, 1995) and behav-ior (Paikoff and Brooks-Gunn, 1991) can influencehormone concentrations directly (e.g. from provokedaggressive behavior) or indirectly (e.g. through interper-sonal states such as negative affect). Moreover, chronicfamily stressors can result from some forms of child-hood psychiatric disorder (Lombroso et al., 1994) inter-

acting (Barkley et al., 1992; Anderson et al., 1994) orcorrelating (Scarr, 1992) with a harsh family environ-ment. These family chronic stressors can lead to sup-pression of androgen and cortisol concentrations(Johnson et al., 1992).

Two comments on the findings are indicated. First,the hypothesized relationship of a significant negativecorrelation between cortisol reactivity and BSR was notsupported. It should be noted, however, that cortisollevel prior to evoked potential was significantly nega-tively associated with BSR (r= −0.14, PB0.05). Thenegative finding in the final regression model may bedue in part to the fact that the BSR construct is forlifetime traits of inattention, impulsivity/hyperactivity,and aggressivity. A behavioral construct which mea-sures behavioral distress is more likely to covary withcortisol reactivity (Susman et al., 1997). Moreover,lower preadolescent anticipatory cortisol responseshave been shown to be significantly associated withregular cigarette use and regular marijuana use (Mosset al., in press). In summary, anticipatory cortisol re-sponses and cortisol reactivity appear to have greaterutility in explaining covariation with distress behaviorand other health risk behaviors, and possibly as apredictor of intergenerational transmission of substanceabuse liability.

Second, the finding that BSR was significantly nega-tively associated with fathers’ abuse potential, but hada trend toward significant positive association withmothers’ abuse potential was unexpected. Post-hocanalyses revealed that 24.2% of HAR boys had lived asignificant time with their mother only, whereas only7.5% of LAR boys had lived with their mother only

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176174

(x2=15.41, PB0.001). Moreover, logistic regressionanalysis predicting living with the mother only for asignificant period in the son’s lifetime revealed signifi-cant covariates of mother’s cocaine dependence (OddsRatio=1.20, confidence interval (1.04, 2.19)) and fa-ther’s opiate dependence (Odds Ratio=1.20, confi-dence interval (1.06, 1.83)). Although speculative, itmay be the case that son’s who have lived with bothparents their entire lives had the advantage of fatherswho had effective parenting and discipline skills butrated themselves as somewhat rigid and distressed.

Several caveats also need to be considered. First, thisstudy was limited to sons of substance abusing fathersand sons of nonsubstance abusing fathers. Recruitmentof daughters of PSUD fathers was initiated in 1994,and were not available in sufficient numbers to providethe statistical power needed to fulfill the aims of thisstudy at this time. Second, a small literature on inter-view techniques for children younger than age 12 sug-gests that their responses may be unreliable (Achenbachet al., 1987). The assessment procedures describedherein were designed to maximize the accuracy of theboys’ self-reports, by using trained interviewers and the‘best estimate’ procedure (Leckman et al., 1982). Third,the authors acknowledge that serotonin dysfunction ispresent in some impulsive, aggressive individuals (Bern-hardt, 1997; Coccaro et al., 1997a,b,c; Halperin et al.,1997; Pine et al., 1997; Brady et al., 1998), and thatcatecholamine dysfunction is present in some individu-als with disorders of inattention and impulsivity/hyper-activity (Pliszka et al., 1996; Pliszka and McCracken,1997; Tannock, 1998). However, peripheral measures ofthese neurotransmitter systems were not available forthe analyses presented herein. Lastly, as noted through-out this manuscript, the results of this report are basedon cross-sectional data. Hence, causal inferences at thispoint cannot be made regarding the mechanisms under-lying the associations between hormone levels, familydysfunction, peer affiliation, and BSR in high risk boysbased on the data reported herein. However, futurereports of longitudinal follow-up of these same boyswill allow causal inferences to be made.

These limitations notwithstanding, the findings hereinextend previous research by showing that boys’ percep-tions of family dysfunction and peers delinquency,along with parental reports of their abuse potential andAntisocial Personality Disorder symptoms, are stronglyassociated with sons’ BSR. Group differences withlower androgen concentrations, and lower cortisol leveland cortisol reactivity in HAR compared to LAR sonsare consistent with the hypothesis that these sons areadapted to chronic stress imposed from a very dysfunc-tional family system. Interventions to prevent worsen-ing of BSR should therefore address familydysfunction, deviant peer affiliation, as well as severityof BSR impairment. However, longitudinal research is

needed to elucidate the magnitude and timing of howparental personality characteristics influence develop-mental trajectories, to culminate in either good oradverse outcomes.

Acknowledgements

This work was supported in part by a center grantfrom the National Institute on Drug Abuse (DA05606), and a Mentored Clinical Scientist DevelopmentAward (1K08 DA-299) from the National Institute onDrug Abuse. We thank the families who participated inthis research. Special appreciation is expressed to DrGalina P. Kirillova for performing the hormone assaysand Brion Maher for his technical assistance.

References

American Psychiatric Association, 1987. Diagnostic and StatisticalManual of Mental Disorders, 3rd edn. American PsychiatricAssociation, Washington, DC.

Achenbach, T., Edelbrock, C., 1983. Manual for the Child BehaviorChecklist and Revised Child Behavior Profile. Achenbach,Burlington, VT.

Achenbach, T.M., McConaughy, S.H., Howell, C.T., 1987. Child/adolescent behavioral and emotional problems: Implications ofcross-informant correlations for situational specificity. Psychol.Bull. 10, 213–232.

Anderson, C.A., Hinshaw, S.P., Simmel, C., 1994. Mother–childinteractions in ADHD and comparison boys: Relationships withovert and covert externalizing behavior. J. Abnorm. Child Psy-chol. 22 (2), 247–265.

Archer, J., 1991. The influence of testosterone on human aggression.Br. J. Psychol. 82, 1–28.

Babor, T.F., Hofmann, M., DelBoca, F.K., et al., 1992. Types ofalcoholics, I. Evidence for an empirically derived typology basedon indicators for an empirically derived typology based on indica-tors of vulnerability and severity. Arch. Gen. Psychiatry 49, 599.

Bambino, T.H., Hsueh, A.J., 1981. Direct inhibitory effect of gluco-corticoids upon testicular luteinizing hormone receptor andsteroidogenesis in vivo and in vitro. Endocrinology 108 (6),2142–2148.

Barkley, R.A., Fischer, M., Edelbrock, C.S., Smallish, L., 1990. Theadolescent outcome of hyperactive children diagnosed by researchcriteria, I: An 8-year prospective follow-up study. J. Am. Acad.Child Adolesc. Psychiatry 29, 546–557.

Barkley, R.A., Anastopoulos, A.D., Guevremont, D.C., Fletcher,K.E., 1992. Adolescents with attention deficit hyperactivity disor-der: Mother–adolescent interactions, family beliefs and conflicts,and maternal psychopathology. J. Abnorm. Child Psychol. 20 (3),263–288.

Bernhardt, P.C., 1997. Influences of seratonin and testosterone inaggression and dominance: convergence with social psychology.Current Directions in Psychosocial Science 6 (2), 44–48.

Biederman, J., Farone, S., Milberger, S., Guite, J., et al., 1996. Aprospective 4-year follow-up study of attention-deficit hyperactiv-ity and related disorders. Arch. Gen. Psychiatry 53, 437–446.

Biederman, J., Wilens, T., Mick, E., et al., 1997. Is ADHD a riskfactor for Psychoactive Substance Use Disorder? Findings from afour-year prospective follow-up study. J. Am. Acad. Child Ado-lesc. Psychiatry 36 (1), 21–29.

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176 175

Brady, K.T., Myrick, H., Mcelroy, S., 1998. The relationship betweensubstance use disorders, impulse control disorders, and pathologicalaggression. Am. J. Addict. 7 (3), 221–230.

Brann, D.W., Hendry, L.B., Mahesh, V.B., 1995. Emerging diversitiesin the mechanism of action of steroid hormones. J. Steroid Biochem.52 (2), 113–133.

Brook, J.S., Whiteman, M., Finch, S., Cohen, P., 1996. Young adultdrug use and delinquency: Childhood antecedents and adolescentmediators. J. Am. Acad. Child Adolesc. Psychiatry 35 (12), 1584–1592.

Buchanan, C.M., Eccles, J.A., Becker, J.B., 1992. Are adolescents thevictims of raging hormones: Evidence for activational effects ofhormones on moods and behavior at adolescence. Psychol. Bull.111 (1), 62–107.

Caspi, A., Moffitt, T.E., Newman, D.L., Silva, P.A., 1996. Behavioralobservations at age 3 year predict adult psychiatric disorders:Longitudinal evidence from a birth cohort. Arch. Gen. Psychiatry53, 1033–1039.

Coccaro, E.F., Kavoussi, R.J., Hauger, R.L., Cooper, T.B., Ferris,CC.F., 1997a. Cerebrospinal fluid vasopressin levels: Correlateswith aggression and serotonin function in personality-disorderedsubjects. Arch. Gen. Psychiatry 55 (8), 708–714.

Coccaro, E.F., Kavoussi, R.J., Trestman, R.L., Gabriel, S.M., Cooper,T.B., Siever, L.J., 1997b. Serrotonin function in human subjects:Intercorrelations among central 5-HI indices and aggressiveness.Psychiatry Res. 73 (1–2), 1–14.

Coccaro, E.F., Kavoussi, R.J., 1997c. Fluoxetinne and impulsiveaggressive behaviour in personality-disordered subjects. Arch. Gen.Psychiatry 54 (12), 1–14.

Collu, R., Gibb, W., Ducharme, J.R., 1984. Effects of stress on gonadalfunction. J. Endocrinol. Invest. 7 (5), 529.

Constantino, J.N., Grosz, D., Saenger, P., Chandler, D.W., Nandi, R.,Earls, F.J., 1993. Testosterone and aggression in children. J. Am.Acad. Child Adolesc. Psychiatry 32 (6), 1217–1222.

Cumming, D.C., Quigley, M.E., Yen, S.S.C., 1983. Acute suppressionof circulating testosterone by cortisol in men. J. Clin. Endocrinol.Metab. 57, 671–673.

Dabbs, J.M., Jurkovic, G.J., Frady, R.L., 1991. Salivary testosteroneand cortisol among late adolescent male offenders. J. Abnorm.Child Psychol. 19 (4), 469–478.

Dawes, M.A., Tarter, R.E., Kirisci, L., 1997. Behavioral self-regula-tion: Correlates and 2-year follow-up for boys at risk for substanceabuse. Drug Alcohol Depend. 45, 165–176.

Dorn, L.D., Chrousos, G.P., 1997. The neurobiology of stress: Under-standing regulation of affect during female biological transitions.Semin. Reprod. Endocrinol. 15 (1), 19–35.

Francis, K.T., 1981. The relationship between high and low traitpsychological stress, serum testosterone, and serum cortisol. Expe-rientia 37, 1296–1297.

Gittelman, R., Mannuza, S., Shenker, R., Bonagura, N., 1985. Hyper-active boys almost grown up: I. Psychiatric status. Arch. Gen.Psychiatry 42, 937–947.

Gorrenstein, E., Newman, J., 1980. Disinhibitory psychopathology: Anew perspective and model for research. Psychol. Rev. 87, 301–315.

Graber, J.A., Brooks-Gunn, J., 1995. Biological and maturationalfactors in development. In: VanHasselt, V.B., Herson, M. (Eds.),Handbook of Adolescent Psychopathology: A Guide to Diagnosisand Treatment. Lexington, New York, pp. 66–101.

Halperin, J.M., Newcorn, J.H., Kopstein, I., McKay, K.E., Schwarz,S.T., Siever, L.J., Sharma, V., 1997b. Serotonin, aggression, andparental psychopathology in children with attention-deficit hyper-activity disorder. J. Am. Acad. Child Adol. Psychiatry 36 (10),1391–1398.

Hawkins, J.D., Catalano, R.F., Miller, J.Y., 1992. Risk and protectivefactors for alcohol and other drug problems in adolescence andearly adulthood: Implications for substance abuse prevention.Psychol. Bull. 112 (1), 64–105.

Hechtman, L., Weiss, G., 1986. Controlled prospective fifteen yearfollow-up of hyperactives as adults: Non-medical drug and alcoholuse and anti-social behaviour. Can. J. Psychiatry 31, 557–567.

Hollingshead, A., 1990. A Four-Factor Index of Social Status. NewHaven, CT.

Inoff-Germain, G., Snyder, A.G., Nottlemann, E.D., Susman, E.J.,Cutler, G.B. Jr, Chrousos, G.P., 1988. Relations between hormonelevels and observational measures of aggressive behavior of youngadolescents in family interactions. Dev. Psychol. 24, 129–139.

Johnson, E.O., Kamilaris, T.C., Chrousos, G.P., Gold, P.W., 1992.Mechanisms of stress: A dynamic overview of hormonal andbehavioral homeostasis. Neurosci. Biobehav. Rev. 16, 115–130.

Kandel, D., Simcha-Fagan, O., Davies, M., 1986. Risk factors fordelinquency and illicit drug use from adolescence to young adult-hood. J. Drug Issues 60, 67–90.

Kellam, S.G., Brown, H., 1982. Social Adaptational and PsychologicalAntecedents of Adolescent Psychopathology Ten Years Later.Johns Hopkins University, Baltimore, MD.

Kiess, W., Meidert, A., Dressendorfer, R.A., Schreiver, K., Kessler, U.,Konig, A., Schwarz, H.P., Strasburger, C.J., 1995. Salivary cortisollevels throughout childhood and adolescence: Relation with age,pubertal stage, and weight. Pediatr. Res. 37 (4), 502–506.

Kirschbaum, C., Hellhammer, D.H., 1994. Salivary cortisol in psy-choneuroendocrine research: Recent developments and applica-tions. Psychoneuroendocrinology 19 (4), 313–333.

Leckman, J.F., Scholomskas, D., Thompson, W.D., Belanger, A.,Weissman, M.M., 1982. Best estimate of lifetime psychiatric diag-noses: A methodological study. Arch. Gen. Psychiatry 39, 879–883.

Loeber, R., 1989. Peer Delinquenncy Scale. Pittsburgh Youth Study:Department of Psychiatry, University of Pittsburgh, Pittsburgh,PA. (Unpublished manuscript).

Loeber, R., Farrington, D.P., Stouthamer-Loeber, M., VanKammen,W.B., 1998. Antisocial behavior and mental health problems:Explanatory factors in childhood and adolescence. Lawrence Erl-baum Associates, Mahwah, NJ, p. 71.

Lombroso, P.J., Pauls, D.L., Leckman, J.F., 1994. Genetic mechanismsin childhood psychiatric disorders. J. Am. Acad. Child Adolesc.Psychiatry 33 (7), 921–938.

Mannuzza, S., Gittelman, K.R., Bonagura, N, et al., 1991. Hyperactiveboys almost grown up: V. Replication of psychiatric status. Arch.Gen. Psychiatry 48, 77–83.

Marshall, W.A., Tanner, J.M., 1970. Variations in pattern of pubertalchanges in boys. Arch. Dis. Child. 45, 13.

Martin, C.S., Earleywine, M., Blackson, T.C., Vanyukov, M.M., Moss,H.B., Tarter, R.E., 1994. Aggressivity, inattention, hyperactivity,and impulsivity in boys at high and low risk for substance abuse.J. Abnorm. Child Psychol. 22, 177–203.

Mazur, A., 1985. A biosocial model of status in face-to-face primategroups. Soc. Forces 64, 377–402.

Mezzich, A.C., Giancola, P.R., Tarter, R.E., Lu, S., Parks, S.M.,Barrett, C.M., 1997a. Violence, suicidality and drug/alcohol use infemale substance abusers. Alcoholism: Clin. Exp. Res. 21 (7),1300–1307.

Mezzich, A.C., Tarter, R.E., Giancola, P.R., Lu, S., Kirisci, L., Parks,S., 1997b. Substance use and risky sexual behavior in femaleadolescents. Drug Alcohol Depend. 44, 157–166.

Milner, J., 1980. Child Abuse Inventory: Manual. Psytec, Webster, NC.Moss, H.B., Vanyukov, M.M., Martin, C.S., 1995. Salivary cortisol

responses and the risk for substance abuse in prepubertal boys. Biol.Psychiatry 38, 547–555.

Moss et al., in press.Neter, J., Wasserman, W., Kutner, M.H., 1990. Applied Linear

Statistical Models: Regression, Analysis of Variance, and Experi-mental Design, 3rd edn. Irwin, Boston, MA, pp. 408–411.

Newman, J.P., Wallace, J.F., 1993. Diverse pathways to deficientself-regulation: Implications for disinhibitory psychopathology inchildren. Clin. Psychol. Rev. 13, 699–720.

M.A. Dawes et al. / Drug and Alcohol Dependence 55 (1999) 165–176176

Olweus, D., 1987. Testosterone and adrenaline: Aggressive antisocialbehavior in normal adolescent males. In: Mednick, S.A., Moffitt,T.E., Stack, S.A. (Eds.), The Causes of Crime: New BiologicalApproaches. Cambridge University Press, Cambridge, pp. 239–262.

Orvaschel, H., Puig-Antich, J., Cambers, W., Fabrizie, M., Johnson,R., 1982. Retrospective assessment of prepubertal major depres-sion with the Kiddie-SADS-E. J. Am. Acad. Child Adolesc.Psychiatry 21, 392–397.

Paikoff, R.L., Brooks-Gunn, J., 1991. Do parent–child relationshipschange during puberty? Psychol. Bull. 110 (1), 47–66.

Pelham, W., Murphy, D., 1987. The DED rating scale: a parent andteacher rating scale for the diruptive behavior disorders of child-hood in DSM-III-R. Department of Psychiatry, University ofPittsburgh, Pittsburgh, PA. (Unpublished manuscript).

Pine, D.S., Coplan, J.D., Wassarman, G.A., Miller, L.S., Fried, J.E.,Davies, M., Cooper, T.B., Greenhill, L., Shaffer, D., Parsons, B.,1997. Neuroendocrine response to fenfluramine challenge in boys:Associations with aggressive behavior and adverse rearing. ArchGen. Psychiatry 54 (9), 839–846.

Pliszka, S.R., McCracken, J.T., 1997. Catecholamines in ADHD: Apostscript. J. Am. Acad. Child Adolesc. Psychiatry 36 (7), 869–870.

Pliszka, S.R., McCracken, J.T., Maas, J.W., 1996. Catecholamines inAttention-Deficit Hyperactivity Disorder: Current perspectives. J.Am. Acad. Child Adolesc. Psychiatry 35 (3), 264–272.

Reich, W., Earls, F., Frankel, O., Shayka, J.J., 1993. Psychopathol-ogy in children of alcoholics. J. Am. Acad. Child Adolesc. Psychi-atry 32, 995–1002.

Robins, L.N., McEvoy, L., 1990. Conduct problems as predictors ofsubstance abuse. In: Robins, L.N., Rutter, M. (Eds.), Straight andDevious Pathways from Childhood to Adulthood. CambridgeUniversity Press, Cambridge, pp. 182–204.

Rubinow, D.R., Schmidt, P.T., 1996. Androgens, brain, and behav-ior. Am. J. Psychiatry 153 (8), 974–984.

Sapolsky, R.M., 1991. Testicular function, social rank and personal-ity among wild baboons. Psychoneuroendocrinology 16 (4), 281–293.

Sapolsky, R.M., 1992. Neuroendocrinology of the stress-response. In:Becker, J.B., Breedlove, S.M., Crews, D. (Eds.), Behavioral En-docrinology. MIT Press, Cambridge, MA, pp. 287–324.

Scarr, S., 1992. Developmental theories for the 1990s: Developmentand individual differences. Child Dev. 63, 1–19.

Scerbo, A.S., Kolko, D.J., 1994. Salivary testosterone and cortisol indisruptive children: Relationship to aggressive, hyperactive, andinternalizing behaviors. J. Am. Acad. Child Adolesc. Psychiatry33 (8), 1174–1184.

Schaal, B., Tremblay, R.E., Soussignan, R., Susman, E.J., 1996. Maletestosterone linked to high social dominance but low physicalaggression in early adolescence. J. Am. Acad. Child Adolesc.Psychiatry 35 (10), 1322–1330.

Schneider, W., Detweiler, M., 1987. A connectionist/control archi-tecture for working memory. In: Bower, G.H. (Ed.), The Psychol-ogy of Learning and Motivation, vol. 21. Academic Press, NewYork.

Simon, D., Preziosi, P., Barrett-Connor, E., Roger, M., Saint-Paul,M., Nahoul, K., Papoz, L., 1992. The influence of aging onplasma sex hormones in men: The Telecom study. Am. J. Epi-demiol. 135, 783–791.

Skinner, H.A., Steinhauer, P.D., Santa-Barbara, J., 1983. The familyassessment measure. Can. J. Community Ment. Health 2, 91–105.

Spitzer, R.L., Williams, B.W., Gibbon, M., 1987. Instruction Manualfor the Structured Clinical Interview for the DSM-III-R. NewYork State Psychiatric Institute, New York.

Susman, E.J., Inoff-Germain, G., Nottelmann, E.D., Loriaux, D.L.,Cutler, G.B., Chrousos, G.P., 1987. Hormones, emotional dispo-sition, and aggressive attributes in young adolescents. Child Dev.58, 1114–1134.

Susman, E.J., Dorn, L.D., Inoff-Germain, G., Nottlemann, E.D.,Chrousos, G.P., 1997. Cortisol reactivity, distress behavior, andbehavioral and psychological problems in young adolescents: Alongitudinal perspective. J. Res. Adolesc. 7 (1), 81–105.

Tannock, R., 1998. Attention Deficit Hyperactivity Disorder: Ad-vances in cognitive, neurobiological, and genetic research. J. ChildPsychol. Psychiatry Allied Discip. 39 (10), 65–99.

Tarter, R., Vanyukov, M., 1994. Alcoholism: A developmental disor-der. J. Consul. Clin. Psychol. 62 (6), 1096–1107.

Tarter, R., Alterman, A., Edwards, K., 1989. Neurobehavioral theoryof alcoholism etiology. In: Chaudron, C., Wilkinson, D. (Eds.),Theories of Alcoholism. Addiction Research Foundation,Toronto.

Tarter, R., Moss, H., Blackson, T., Vanyukov, M., Brigham, J.,Loeber, R., 1996. Disaggregating the liability to drug abuse. In:Wetherington, C., Falk, J. (Eds.), Laboratory Behavior Studies ofVulnerability to Drug Abuse. NIDA Monograph PHSPublication.

Tremblay, R.E., Schaal, B., Boulerice, B., et al., 1997. Male physicalaggression, social dominance and testosterone levels at puberty: Adevelopmental perspective. In: Raine, A. (Ed.), Biosocial Bases ofViolence, pp. 271–291.

Udry, J.R., 1990. Biosocial models of adolescent problem behaviors.Soc. Biol. 37, 1–10.

Vanyukov, M.M., Moss, H.B., Plail, J.A., Blackson, T., Mezzich,A.C., Tarter, R.E., 1993. Antisocial symptoms in preadolescentboys and their parents: Associations with cortisol. Psychiatry Res.46, 9–17.

Vanyukov, M.M., Moss, H.B., Tarter, R.E., 1994. Assortment for theliability to substance abuse and personality traits. Ann. New YorkAcad. Sci. 708, 102–107.

Wechsler, D., 1991. Wechsler Intelligence Scale for Children, Revised.The Psychological Corporation, 555 Ascademic Court, San Anto-nio, Texas.

Windle, M., 1992. Revised Dimensions of Temperament Survey(DOTS-R): Simultaneous group confirmatory factor analysis foradolescent gender groups. Psychol. Assess. 4 (2), 228–234.

Winters, S.J., 1991. Diurnal rhythm of testosterone and luteinizinghormone in hypogonadal men. J. Androl. 12, 185–190.

Yao, J.K., Moss, H.B., Kirillova, G.P., 1999. Determination ofsalivary cortisol by nonisotopic immunoassay. Clin. Biochem. 31,187–190.

.