ELSEVIER Drug and Alcohol Dependence 39 (1995) 253-261

The association between childhood irritability and liability to substance use in early adolescence: a 2-year follow-up study

of boys at risk for substance abuse

Ralph E. Tarter*“, Timothy Blackson”, Janet Brighama, Howard Mossa, Gian Vittorio Caprarab

‘Center for Education and Drug Abuse Research, Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O’Hara Street, Pittsburgh, PA 15213, USA

bDepartment of Psychology, University of Rome, 00185 Rome, Italy

Received 20 March 1994; accepted 26 July 1995

Abstract

The aim of this investigation was to determine whether irritability, defined as the propensity to experience and express anger following actual or perceived provocation, is a component of the liability to alcohol and drug abuse. Sons of substance abusing fathers (n = 40) and normal fathers (n = 56) were studied when they were lo- 12 years of age and followed-up 2 years later. Hierar- chical regression analysis revealed that resting salivary cortisol concentration, impulsivity and family discord measured when the subjects were lo-12 years of age explained 35% of the variance on a scale measuring irritability 2 years later. At follow-up, when the boys were 12-14 years of age, it was observed that irritability scale scores and family discord were the only variables that ac- counted for significant variance on a scale measuring coping via alcohol and drug use. Latency and amplitude of the Nl and P3 event-related potentials of an auditory oddball task, measured at age 10-12, were not associated with drug use at age 12-14. These results indicate that family dysfunction, stress state of the child, and low behavioral self-control additively account for a significant proportion of variance on irritability scale scores 2 years later, and that this trait, in conjunction with family discord, is associated with substance use as a coping response by early adolescence.

Keywordr: Drug abuse; Etiology; Event related potential; Family; Dysfunction; Child development

1. Introduction

Behavioral dysregulation has been implicated to com- prise an important component of the liability to sub- stance abuse. Empirical evidence (Pelham and Lang, 1993; Reich et al., 1993; Alterman et al., 1984) as well as theoretical reviews (Gorrenstein and Newman, 1980; Tarter et al., 1989; Moflitt, 1993) suggest that the behav- ioral features of dysregulation, such as high behavioral activity level, impulsivity, inattention, and aggressivity, are associated with an augmented risk for alcohol and drug abuse.

Other aspects of dysregulation, particularly its affec-

l Corresponding author.

tive correlates, have not been systematically researched. Whereas negative affect has been reported to predispose to alcohol and drug abuse (Merikangus et al., 1985; Kandel and Davies, 1986), the extenl to which this reflects a dispositional disorder or instead is circumsc- ribed to an inability to appropriately modulate emo- tional responses to environmental stressors remains poorly understood. Recent studies have documented an association between early age onset of alcohol and drug use and emotional reactivity (Chassin et al., 1993; Blackson et al., 1994). Furthermore, the constellation of traits comprising ‘difficult temperament’ has been found to presage early age onset substance use (Lemer and Vicary, 1994). The difficult temperament configuration is featured by susceptibility to emotional distress and

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254 R.E. Tarter et al. /Drug and Alcohol Dependence 39 (1995) 253-261

poor behavioral regulation. Complementing these latter Endings, it has been recently reported that the aggregate of traits comprising the ‘difficult affective temperament’ distinguishes prepubertal male offspring who have pat- ernal history of substance abuse from offspring of nor- mal fathers (Blackson et al., 1994). Considered together, the emerging findings implicate a core disorder in self- regulation encompassing behavioral and affective di- mensions (Tarter et al., 1989).

To date, almost all of the research has been directed at elucidating the behavioral concomitants of dysregula- tion. For example, Martin et al. (1994), employing a multi-trait multi-method strategy, derived the Behavior Dysregulation Scale (BDS) and observed that male children of substance abusers can be differentiated from children of normal parents on traits measuring ag- gressivity, attention and impulsivity. However, little is known about the affective component of dysregulation and its association with risk for substance abuse. In re- sponse to this lacuna, the present investigation sought to (1) clarify the developmental antecedents of affective dysregulation operationally defined herein as irritabili- ty, and (2) to determine whether affective dysregulation correlates with conjoint substance use and acting out be- havior as a coping response.

With respect to the first study aim, a biochemical indi- cator of stress reactivity, two electrophysiological mea- sures of information processing, three indicators of behavioral self-control, and severity of family dysfunc- tion were measured in late childhood (age, 10-12) to evaluate the extent to which they predict scores on a scale measuring irritability in early adolescence (age, 12-14). Each of the measures selected for study was based on previous research linking these variables to the risk for alcohol and drug abuse. Hence, within an epigenetic perspective (Tarter and Vanyukov, 1994), biochemical, electrophysiological, behavioral and in- terpersonal processes, were investigated to determine the extent to which they predict irritability which, in turn, was studied to determine its association with early age substance use and acting out behavior.

The trait of irritability was selected for study because it encompasses both the emotional and aggressive facets of dysregulation. Significantly, emotional reactivity and impulsive aggression have each been independently found to be related to alcohol and drug abuse (Moss et al., 1990; Tarter, 1991). The youth version of the Ir- ritability Scale (Caprara et al., 1985) captures both of these latter dimensions thereby comprising an appropri- ate indicator of emotional and behavioral dysregulation.

Stress reactivity, information processing efficiency, and behavioral control were studied at baseline (age, 10-12) to determine their individual and conjoint con- tribution to the development of irritability 2 years later. The rationale underlying selection of these specific vari-

ables was based on prior research demonstrating their association with the risk for alcohol and drug abuse. Cortisol concentration in saliva was used as a biochemi- cal indicator of stress reactivity. Low cortisol concentra- tion is associated with conduct disorder symptom counts and measures of impulsivity and aggression (Vanyukov et al., 1993; Moss et al., in press). In turn, these behavioral characteristics are consesually recog- nized to be strong risk factors for alcohol and other drug abuse.

The neurophysiological indicators of information processing were the Nl and P3 amplitude and latency response components in a conventional auditory event related potential (ERP) ‘oddball’ task. Evidence has been accrued indicating that the P3 amplitude measured in this paradigm may be an indicator of vulnerability for alcoholism based on family history for this disorder (Polich et al., 1994). An enhanced Nl wave has been shown to predict future criminality (Raine et al., 1990); this latter behavioral disposition is commonly associ- ated with alcohol and drug abuse. These waveforms are believed to reflect aspects of selective attention and short-term memory processes, respectively (Polich, 1993).

Three indicators of behavioral control were obtained: errors of commission to nontarget stimuli in a vigilance task (impulse errors), planning ability in solving maze problems, and capacity to execute a sustained slow motor response. Previous research conducted at our center has demonstrated that these variables are inter- correlated to reflect a disposition of behavioral disinhib- ition (Moss et al., 1993). This trait is well documented to be associated with the liability to substance abuse. In addition, the association between severity of family discord in late childhood and irritability level in early adolescence was measured because the quality of familial interactions has been shown to influence the risk for substance use among adolescents (Bennett et al., 1987; Blackson and Tarter, 1994; Blackson et al., 1994). Thus, individual variation (biochemical, elec- trophysiological, behavioral) measured in late childhood was investigated in relation to environmental context (family stability) to predict irritability in early adolescence.

The second aim of this study was directed at clarifying the extent to which irritability scores in early adoles- cence, when the boys were 12-14 years of age, covaried with behaviors that are firmly established to be pro- dromal to a Psychoactive Substance Use Disorder (American Psychiatric Association, 1987). Alcohol and drug use in early adolescence are associated with a heightened risk for developing a substance use disorder. The second aim of this study, therefore, was to clarify the extent to which irritability is associated with early age substance use as a coping response.

R. E. Tarter et al. /Drug and Alcohol Dependence 39 (1995) 253-261 255

2. Methods

2.1. Subjects

Two groups of lo- to 12-year-old boys were studied based on the presence (SA+) or absence (SA-) of a lifetime DSM-III-R diagnosis of Psychoactive Sub- stance Use Disorder (PSUD) in the proband fathers. The SA+ and SA- groups consisted of 40 and 56 families, respectively. Diagnosis of PSUD in the fathers (SA+) was based on information obtained from the Structured Clinical Interview for DSM-III-R (SCID) (Spitzer et al., 1987). Current or lifetime comorbid psychiatric disorder in the father, other than psychosis, did not disqualify the son from study. The pattern of PSUD diagnosis was heterogeneous such that 92.5% of the subjects had at least two substance use/dependence disorders. The most frequent diagnosis was alcohol de- pendence (70%) followed by alcohol abuse (Xl%), can- nabis abuse (37.5%) and dependence (37.5%), opioid dependence (30%) and cocaine dependence (27.5%). Table 1 summarizes the distribution of PSUD and com- orbid psychiatric diagnoses in the SA+ group.

To maximize representativeness of the sample, a psychiatric disorder in the spouse, other than psychosis, did not disqualify the family from study in either group. However, lifetime PSUD was an exclusionary criterion in the SA- group. In the SA+ group, 11 of the wives qualified for a lifetime diagnosis of PSUD; this high fre- quency of conjoint spousal PSUD is consistent with prior research pertaining to assortment and contagion in drug abuse (Vanyukov et al., 1994). SA+ probands were recruited from treatment programs and by advertise-

Table 1 Lifetime DSM-III-R diagnoses of SA+ fathers (n = 40)

DSM-III-R Diagnoses ?I Percentage

Psychoactive substance use disorders Alcohol dependence 28 70.0 Alcohol abuse 20 50.0 Cannabis dependence 15 37.5 Cannabis abuse 15 37.5 Cocaine dependence II 27.5 Cocaine abuse 3 7.5 Opioid dependence 12 30.0 Opioid abuse 1 2.5 Sedative dependence 6 15.0 Sedative abuse 3 7.5 Amphetamine dependence 7 17.5 Amphetamine abuse 5 15.0 Hallucinogen dependence 1 2.5 Comorbid psychiatric disorders Mood 18 45.0 Anxiety 10 25.0 Antisocial personality 12 30.0

Total > 100% because of dual PSUD diagnoses in 92.5% of group.

ment. The SA- probands were recruited by advertise- ment. A history of neurological injury or pathology, physical disability, or a full scale IQ below 80 in any family member were exclusionary criteria. The boys studied at follow-up consisted of 89% of the original sample investigated at baseline 2 years previously.

To control for sibling order effects, the oldest male in the sibship who was between 10 and 12 years old was selected for study. Some of the boys had exposure to alcoholic beverages outside of the home; however, con- sumption levels were very low and in all likelihood did not confound the results. None of the boys had used il- legal drugs.

Table 2 summarizes the personal and demographic characteristics of the SA+ and SA- groups. As can be seen, the boys in the SA+ group had lower socioecono- mic status. This is not surprising because of the downward social mobility in families when there is chronic alcohol and drug abuse (Dohrenwend et al., 1992). Full scale IQ was also lower in the boys in the SA+ group. The impact of SES and IQ is discussed in the Results section of this report.

2.2. Instrumentation

2.2.1. Cortisol concentration A saliva sample was obtained 15 min after the subjects

remained in a passive state. During this interval, the subjects sat in a sound attenuated room while paste elec- trodes were applied to the scalp in anticipation of the event-related potential study. The cortisol assay was conducted by a commercial laboratory using a standard radioimmunoassay procedure.

2.2.2. Event-related potentials The subjects performed a counting task during the ad-

ministration of an auditory ‘oddball’ task (Brigham et al., in press). High- and low-pitched tones were presen- ted in 0.10 probability condition (24 of 240) of target-to- probe ratio. During each task, tones (50 ms in duration, 64.5 dB SPL) were presented to subjects’ right and left ears via earphones, with one tone presented every 2 s. Tones were presented in the same random sequence to all subjects. Tone pitch was 1000 Hz for low (probe) tones and 2000 Hz for high (target) tones. Subjects were instructed to count the high-pitched tones only and were tested in discerning and counting high tones before any data were collected. After the block of stimuli was presented, the subject’s tone count was noted. Subjects who were accurate within three tones in their counting across all trials were included in the analysis. Using this criterion, none of the subjects initially recruited were deleted because of incapacity to count the tones. Sub- jects were instructed and monitored to keep their eyes closed during the testing.

256 R. E, Tarter et al. /Drug and Alcohol Dependence 39 (1995) 253-261

Table 2 Personal and demographic characteristics of boys having positive @A+) and negative (SA-) paternal history of psychoactive substance use disorder

Characteristic SA+ (N = 40)

Mean S.D.

SA- (N = 56)

Mean S.D.

r-Value P-value

Age Time 1 Time 2

Grade in school Time 1 Time 2

Socioeconomic status WISC-III IQ

10.9 1.0 11.1 0.8 1.32 NS 12.9 1.0 13.2 0.9 1.50 NS

4.2 1.1 4.8 1.2 2.51 0.014 6.2 1.4 6.9 1.3 2.75 0.007

37.8 13.2 48.8 12.4 4.12 0.001 169.7 12.5 118.0 12.5 3.21 0.002

n Percentage n Percentage

Euro-American 34 a5 52 92.9 African-American 4 10 2 3.6 Other 2 5 2 3.6

Auditory event-related potentials (AERPs) were re- corded with AglAgCl electrodes from five scalp sites (Fz, Cz, Pz, P3, and P4; Jasper, 1959), referring to linked ears, with forehead grounds. Bandpass was 0.01-30 Hz, with digitized samples obtained every 8 ms for a 1200- ms epoch beginning 200 ms prior to stimulus onset. Electrodes were placed at the outer canthus and supra- orbitally to the left eye for a bipolar recording of the electro-ocular (EOG) activity. Impedance for all record- ing sites was 5 kB or less. Artifacts were removed before averaging by processing all trials through a customized program which eliminated trials according to criteria of range and velocity. Additionally, all trials not rejected by the automated program were screened for artifacts. Average ERPs were calculated from trials considered free of artifacts. Averaging of ERPs was done separately for type of stimulus (target or probe).

ERP components were identified manually from a numerical output of the averaged waveforms. Peaks were determined by a trained rater blind to the diagnosis of the subjects. Peak amplitudes were calculated as the deviation from the mean voltage during the baseline period. The following components were measured: Pl, Nl, P2, N2, P3. These components, associated with suc- cessive stages of cognitive information processing, are identified by their order and polarity. Pl (latency 40-70 ms post-stimulus) is the first positive peak post- stimulus, P2 (150-200 ms) generally the second, and P3 (250-450 ms) the third. Nl (90-150 ms) and N2 (200-275 ms) are the first and second negative peaks, respectively. Data from target tones at Cz electrode site in the 0.10 probability condition were utilized in this analysis.

2.2.3. Behavioral control Three tasks were administered. Errors of commission;

that is, responses to nontarget stimuli, on a vigilance test

(Schneider and Detweiler, 1987) were recorded to index inhibitory control. Gn this test, the subject was required to respond whenever one of two target letters from among four stimuli appeared on the video monitor. The Porteus Maze Test was administered to evaluate plan- ning ability in solving maze problems. Motor inhibitory control was evaluated using the motor restraint test. On this task, the subject is instructed to trace the outline of a 180” arc as slowly as possible on the computer monitor using a lightpen.

2.2.4. Family disruption The dysfunctional family index, obtained from the

Family Assessment Measure, quantified magnitude of disharmony in the home. This instrument has well documented psychometric properties (Skinner et al., 1984). The Family Assessment Measure was ad- ministered as an interview to the boys.

2.2.5. Irritability scale The children’s version of the self-report Irritability

Scale (Caprara et al., 1985) was administered individual- ly to each subject. The questionnaire consists of 30 items which are rated on a six-point scale. Appendix A lists the items of the Irritability Scale. This instrument has been validated in a sample of Italian youth (Caprara et al., 1994). In our sample (N = 96) the internal reliability (Cronbach alpha) was 0.85. On this scale, the lower the score the greater the irritability disposition.

2.2.6. Drug use Three items from the Coping Inventory developed by

Wills (1986) were aggregated into a scale measuring alcohol and drug use. This scale was used to identify the prodromal indicators of a future substance use disorder, specifically the propensity to select abusable compounds as a coping response. Quantity and frequency of drug

R.E. Tarter et al. /Drug and Alcohol Dependence 39 (1995) 253-261 251

use at 12-14 years of age are not likely to be accurate for predicting a drug abuse disorder because of the relatively low levels of consumption at this age. Conse- quently, coping behavior involving substance use was deemed more relevant at this age. Emphasis is thus given to the motivational disposition for substance use rather than quantifying the topology of drug involvement. Responses are scored on a four-point scale ranging from never (0) to usually (4). This self-report consisted of the following items: “When Z Have Problems I... ” (1) Drink Beer or Wine, (2) Smoke Grass or Marijuana, and (3) Take Pills to Feel Better.

and discharged. The follow-up assessment was con- ducted 2 years later.

2.4. Statistical analysis

2.3. Procedure

The association between predictor and criterion vari- ables was examined using hierarchical multiple regres- sion analysis. Because socioeconomic status and IQ were significantly different between the groups, these variables were entered first and second, respectively into the regression analyses. Next, the variables were entered according to level of biological organization, beginning with the biochemical predictor followed by the physio- logical and behavioral variables

On the evening of day 1, the families reported to the Center for Education and Drug Abuse Research (CEDAR). After obtaining informed consent from the parents and their children, the research protocol was implemented. The first phase of the protocol involved administering the Structured Clinical Interview for DSM-III-R (SCID) by trained research associates (Spitzer et al., 1987). The SCID was used as the primary source of information for determining psychiatric diagnoses in the parents. The SCID employed at CEDAR was expanded from the original version in order to more fully document externalizing behavior disorders. The epidemiological version of the Kiddie Schedule for Affective Disorders and Schizophrenia (K- SADS-E) (Orvaschel et al., 1982) was administered to the children. In addition, the boys were tested for intelli- gence level using the WISC-III and the parents were in- terviewed to rule out a history of neurodevelopmental disability in the children. At the conclusion of this phase of the protocol, the boys slept overnight at the center. The research was resumed the next morning following breakfast. The protocol was administered in fixed order and within a tightly controlled schedule. At the conclu- sion of the baseline protocol, the families were debriefed

3. Results

Table 3 presents the means and standard deviations for the two groups on the predictor and criterion vari- ables. It can be seen that with the exception of commis- sion errors on the vigilance test, the boys in the SA+ and SA- groups were not discriminable. In effect, paternal history by itself did not distinguish high (SA+) from average risk (SA-) subjects on the biochemical measure of stress reactivity, electrophysiological measures of in- formation processing and the psychological indices of motor control, irritability and externalizing behavior.

The biopsychosocial predictors of irritability were in- vestigated using hierarchical regression analysis. Table 4 summarizes the results demonstrating that IQ, salivary cortisol concentration, motor restraint, Porteus Mazes test score, and the dysfunctional family index from the Family Assessment Measure obtained where the boys were lo- 12 years of age explained 35% of the score vari- ance on the Irritability Scale when the boys were 12-14 years of age (F = 5.13, P < 0.001). Socioeconomic status was not related to irritability scores.

Table 5 summarizes the results of hierarchical regres- sion analysis aimed at predicting scale score variance on

Table 3 Means, standard deviations and between group comparisons on protocol measures

Measure SA+

Mean S.D.

SA-

Mean SD.

t-Value P-value

Cortisol (ng/dl) 245.10 103.87 261.18 119.76 0.68 P3 Latency 378.20 54.39 365.61 54.14 1.12 P3 Amplitude 11.55 Il.07 13.81 13.11 0.89 Nl Latency 116.20 34.99 119.93 33.83 0.52 Nl Amplitude -8.20 6.56 -9.52 9.08 0.78 Motor restraints 99.52 39.51 118.10 92.81 1.19 Vigilance false alarms 0.012 0.012 0.006 0.005 2.80 Porteus Mazes test age 13.75 2.17 14.35 2.00 1.39 Dysfunctional Family Index 76.20 11.99 71.80 11.63 1.80 Irritability scale score 72.93 16.55 75.39 19.13 0.66 Dwtll= 7.43 2.5 7.19 2.0 0.53

NS NS NS NS NS NS 0.007 NS NS NS NS

258 R.E. Tarter et al. /Drug and Alcohol Depenaknce 39 (1995) 253-241

Table 4 Hierarchical regression analysis predicting irritability scores at time 2 from measures obtained 2 years previously when the boys were IO-12 years of age

Measure R2 F-value P-value Bf t-Value P-value

SES 0.001 0.13 NS -0.10 -1.04 NS WISC IQ 0.05 4.52 <0.04 0.13 1.28 NS Cortisol 0.14 10.01 co.01 0.25 2.62 <O.Oll N I Amplitude 0.15 0.23 NS -0.07 -0.77 NS P3 Amplitude -0.02 -0.24 NS Motor restraint 0.22 2.61 < 0.056 -0.22 -2.39 co.02 Vigilance -0.11 -1.11 NS Porteus Mazes 0.21 2.13 CO.04 Dysfunctional Family Index 0.35 17.59 <O.ool -0.38 -4.19 <O.ool

the drug use coping measure. As can be seen, at the 2- year follow-up, irritability scale score and the family dysfunction index accounted for significant variance on the Coping Questionnaire measuring drug/alcohol use as a coping response. The full model was significant (I; = 2.55, P c 0.01). The full model explained 23% of variance on the coping questionnaire.

Irritability measured at age 12-14 thus accounts for a modest but statistically significant proportion of var- iance on the coping questionnaire. Salivary cortisol concentration, impulsivity, and family dysfunction mea- sured 2 years previously predicted a significant propor- tion of variance on Irritability Scale scores. Neither paternal history of substance abuse nor the Nl and P3 components of the ERP explained significant variance on Irritability Scale scores.

An analysis was also conducted to determine whether irritability scores in the SA+ offspring were related to the comorbid presence of antisocial personality disorder (ASPD) in the fathers. It was found that boys whose fathers had comorbid PSUD and ASPD (n = 12) reported more irritability (mean = 65.1; S.D. = 16.9) than boys whose fathers had PSUD but no ASPD (n = 28) (mean = 76.3; S.D. = 15.5). It is noteworthy that high scores on this scale reflect low irritability. This subgroup difference is significant (t = -2.04; P < 0.05).

Thus, the demonstration that irritability may be pro- dromal to PSUD may be confined to the subgroup of boys where there is comorbid PSUD and ASPD in the father; this comorbid pattern has been referred to as the type 2 variant of substance abuse in genetic research (Cloninger et al., 1983).

4. Discussion

The results of this investigation indicate that irritabili- ty may be a component of the liability for PSUD. By early adolescence, irritability is associated with drug and alcohol use as a coping response to problems. It is also noteworthy that the results indicate that paternal history of substance abuse disorder may be less salient than dispositional factors, such as irritability, for predicting the development of drug abuse. However, the observa- tion that offspring of fathers with ASPD reported great- er irritability than offspring without antisocial fathers in the substance abuse group suggests that this contributor to liability may be related to familial stress or the com- ponent of liability associated with ASPD.

The trait of interest in this study was irritability. As previously discussed, irritability encompasses a disposi- tion of affective dysregulation accompanied by reactive aggression. Recently, Martin et al. (1994), employing a

Table 5 Hierarchical regression analysis predicting alcohol/drug use as a coping response at age 12-14

Measure R2 F-value P-value Bf t-Value P-value

SES 0.001 0.01 NS 0.02 0.15 NS WISC IQ 0.01 0.60 NS 0.02 0.17 NS c0rtis01 0.02 1.17 NS -0.06 -0.54 NS Nl Amplitude 0.02 0.28 NS 0.08 0.78 NS P3 Amplitude -0.06 -0.58 NS Motor restraint 0.05 0.75 NS -0.08 -0.71 NS Vigilance -0.18 -1.71 <0.09 Porteus Mares 0.03 0.23 NS Dysfunctional Family Index 0.15 10.03 <0.002 0.19 1.77 CO.08 Irritability Scale 0.23 9.08 co.OO3 -0.36 -3.01 < 0.003

R. E. Tarter et al. /Drug and Alcohol Dependence 39 (1995) 2S3-261 259

multitrait multimethod strategy, identified four behav- ioral components of dysregulation consisting of in- attention, hyperactivity, impulsivity and aggressivity. Preadolescent sons of substance abusers were disting- uishable from sons of normal fathers on this multi- dimensional trait. In this study, irritability did not distinguish offspring according to presence or absence of paternal history of PSUD. The reasons for this appar- ent discrepancy from the Martin et al. findings are unclear. It may be that irritability is a liability factor for only the subset of the population where the father has comorbid ASPD. It is salient to note in this regard that the male offspring of fathers without substance abuse self-report the same level of irritability as youths whose fathers have a PSUD but no ASPD. Significantly, Cot- tler et al. (1995) observed that irritable aggression is a more frequent feature of drug abusers who have childhood conduct disorder and adult ASPD compared to drug abusers who have ASPD but no childhood con- duct disorder. Thus, while the reasons for the difference between the present findings and those reported by Mar- tin et al. (1994) cannot be established for certain, it is plausible that irritability is a contributor to substance abuse liability in the subset of the population where there is early age behavioral deviancy.

It remains to be determined whether individuals with this putative diathesis to substance abuse experience a stronger reinforcing effect from alcohol and drugs than persons who are normative on the irritability trait. Greater reinforcement may derive from the dual effects of stabilizing an otherwise labile CNS by inducing a phasic but stable stimulating or sedating state in addi- tion to relief from the aversive subjective state of affec- tive and behavioral lability. In effect, drugs having abuse potential may simultaneously act as positive and negative reinforcers for persons whose liability to sub- stance abuse involves a high level of irritability. Evi- dence supporting this notion is admittedly limited and based on findings from psychopathic individuals (Mawson and Mawson, 1977), polydrug users who reg- ularly alternate stimulant and depressant drug use and the observation that alcohol is more stress attenuating in high risk young adults who have a propensity toward behavioral disinhibition (Sher and McCrady, 1984; Sher and Walitzer, 1986). In this context, it is noteworthy that irritability is among the most salient features of an antisocial personality disorder (Moss et al., 1990).

One hypothesis emanating from the results reported herein is that the teleological basis of drug seeking be- havior among individuals who develop abuse or depen- dence is to stabilize dysregulation of affect. Little is known about individual differences in response to drugs having abuse potential with respect to psychological traits. However, it is plausible to theorize that consump- tion of psychoactive compounds would be especially reinforcing among individuals in whom affective dys-

regulation is ameliorated pharmacologically. It is note- worthy that a ‘normalizing’ effect has been postulated to comprise an important factor determining alcohol use among alcoholics (Kissin and Hankoff, 1959). Also, it is pertinent to note that individuals scoring high on behav- ioral disinhibition experience a greater reinforcing effect of alcohol (Sher and Levenson, 1982). The findings presented herein provide a heuristic basis to determine how individual differences in affective self-regulation comprise a component of the liability to substance abuse with respect to the reinforcing actions of drugs.

Another line of research suggested by the findings points to an indirect etiological pathway to drug abuse involving an interaction between affective dysregulation and the social environment. For example, disruptive so- cial interactions concomitant to dispositional irritability are likely to result in marginalization by peers, diminu- tion of social opportunities, and social avoidance. As the opportunities for normative social interactions diminish, the remaining options become confined to socializing with deviant and marginalized individuals. Association with deviant peers, who tolerate as well as exhibit non-normative behavior fosters early age habit- ual drug and alcohol use along with other age-related non-normative behavior (e.g. truancy, sexual inter- course). Thus, affective dysregulation predisposes the youngster to early age drug exposure mediated by de- viant peer affiliations.

Several caveats regarding the results reported herein need to be noted. First, probands in this study who had comorbid psychiatric diagnoses were not excluded. The lifetime prevalence of psychiatric disorder is very high, thus to exclude such individuals would have resulted in a sample that is non-representative of the population. It is thus possible that the findings may not be specific to the risk for substance abuse, but rather are related to certain comorbid variants. In this regard, as noted previously, irritability was significantly greater in the male offspring of men who had both a Psychoactive Substance Use Disorder and Antisocial Personality Dis- order compared to sons whose fathers had a drug abuse disorder but no antisocial disorder. Thus, it may be that irritability is a liability trait for only the type 2 variant of substance abuse (Cloninger et al., 1983). Further re- search on a larger sample is required to disaggregate the specific contribution of substance abuse in the family from the spectrum of other psychiatric disorders.

Second, the offspring subjects in the substance abuse group had lower IQ scores. Other studies have reported lower IQ scores in children of substance abusers (Gabrielli and Mednick, 1983; Tarter et al., 1984). Also, the SA+ group had lower SES. This finding is not sur- prising in view of the observation of downward social mobility in substance abusers (Dohrenwend et al., 1992). It is recognized that these two factors could operate indirectly through pathways not measured in

260 R.E. Tarter et al. /Drug and Alcohol Dependence 39 (1995) 253-261

this study even though neither SES nor IQ contributed a significant proportion of variance on acting alco- hol/drug use as a coping response.

Third, it should be noted that this study was not strictly a prospective investigation. Irritability was not measured at baseline when the subjects were age lo- 12. Hence, it is possible that high irritability scores were present at time 1 and that the biochemical, behavioral and family dysfunction variables did not presage ir- ritability but rather were correlates of this trait.

Finally, caution must be exercised in generalizing the results of this study. As previously discussed, the pro- bands were volunteers. The results could therefore be potentialIy biased by characteristics of individuals who volunteer to participate in research projects. This is a general shortcoming of most investigations employing the high risk paradigm. Nonetheless, while the findings may not be extrapolated to the whole population, they underscore the importance of the irritability trait as a contributor to early age liability to PSUD inasmuch as less severe disturbance is likely to be present in volunteer probands.

In conclusion, stress reactivity, family discord and im- pulsivity in lO- to 12-year-old boys explains a significant proportion of the variation (35%) on irritability scale scores at age 12-14. Magnitude of irritability at age 12-14 covaries with drug and alcohol use as a coping strategy. These findings demonstrate the importance of affective dysregulation in early age onset drug and alco- hol use.

Acknowledgements

This work is supported by a center grant from the National Institute on Drug Abuse DA05605 to the Center for Education and Drug Abuse Research. CEDAR is a consortium between St. Francis Medical Center and the University of Pittsburgh.

Appendix A: Irritability Scale

1. I easily fly off the handle with those who don’t want to listen or understand.

2. I am often in a bad mood. 3. Usually when someone shows a lack of respect for me, I let it

80 by. 4. 1 have never been touchy. 5. It makes my blood boil to have somebody make fun of me. 6. I think I have a lot of patience. 7. When I am irritated I need to vent my feelings immediately. 8. When I am tired I easily lose control. 9. I think I am rather touchy.

10. When I am irritated, I can’t tolerate discussions. 11. I could not put anyone in their place, even if it were necessary. 12. I can’t think of any good reason for resorting to violence. 13. I often feel like a powder keg ready to explode. 14. I seldom strike back even if someone hits me first.

15. I can’t help being a little rude to people I don’t like. 16. Sometimes when I am angry I lose control over my actions. 17. I do not know of anyone who would wish to harm me. 18. Sometimes I really want to pick a tight. 19. I do not like to make practical jokes. 20. When I am right, I am right. 21. I never get mad enough to throw things. 22. When someone raises his voice 1 raise mine higher. 23. Sometimes people bother me just by being around. 24. Some people irritate me if they just open their mouth. 25. Sometimes I shout, hit and kick to let off steam. 26. I don’t think I am a very tolerant person. 27. Even when I am vary irritated I never swear. 28. It is others who provoke my aggression. 29. Whoever insults me or my family is looking for trouble. 30. It takes very little for things to bug me.

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