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Psychophysiological Responses in ADHD Boys With and Without Conduct Disorder: Implications for Adult Antisocial Behavior
Psychophysiological Responses in ADHD Boys With and Without Conduct Disorder: Implications for Adult Antisocial Behavior SABINE C. HERPERTZ, M.D., BRITTA WENNING, PH.D., BODO MUELLER, M.D., MUTAZ QUNAIBI, B.S., HENNING SASS, M.D., AND BEATE HERPERTZ-DAHLMANN, M.D.
ABSTRACT Objective: Several studies have demonstrated that the presence of attention-deficit/hyperactivity disorder (ADHD) in childhood increases the risk of antisocial behavior developing in adulthood. However, because previous research did not consider comorbid conduct disorder (CD), the question of whether ADHD by itself or only the association of ADHD with CD implies a risk of adult antisocial behavior developing is still under discussion. Method: Because several characteristics of psychophysiological response had been shown to be associated with future increased likelihood of adult antisocial behavior, autonomic arousal as well as electrodermal responses to orienting and aversive stimuli were assessed in 26 boys with ADHD+CD compared with 21 boys with ADHD alone and 21 controls. Results: Boys with a comorbid condition of ADHD+CD showed a decrement of autonomic responses and a more rapid habituation to orienting and aversive startling stimuli compared with age-matched children with ADHD alone. Conclusions: Boys with ADHD+CD show a psychophysiological response pattern that is very similar to that reported in antisocial personalities. These findings give further support for a high persistence of antisocial behavior from childhood to adulthood, while no evidence was found that ADHD itself is associated with a predisposition to antisocial behavior. J. Am. Acad. Child Adolesc. Psychiatry, 2001, 40(10):1222–1230. Key Words: attention-deficit/hyperactivity disorder, conduct disorder, antisocial behavior, psychophysiology.
Several studies have demonstrated that the presence of attention-deficit/hyperactivity disorder (ADHD) in childhood increases the risk of antisocial behavior developing in adulthood. Of all boys with ADHD, 20% to 30% show delinquent behavior as adults (Satterfield et al., 1982; Weiss and Hechtman, 1993). However, previous research on children with ADHD often did not consider Accepted April 10, 2001. Dr. Herpertz, Dr. Wenning, Mr. Qunaibi, and Dr. Sass are with the Department of Psychiatry and Psychotherapy, and Dr. Mueller and Dr. Herpertz-Dahlmann are with the Department of Child and Adolescent Psychiatry and Psychotherapy, Aachen Technical University, Aachen, Germany. This research was funded by the Interdisciplinary Center for Clinical Research of the Medical Faculty, RWTH Aachen and by the German Society for the Advancement of Scientific Research (DFG grant HE 2660/3-1). The authors thank Ulrich Schwenger for technical advice, Anette Schuerkens for statistical support, and Daniela Cardaci, Sabine Leger, Rebecca Loehrer, and Christiane Lichterfeld for their assistance during the examinations. Reprint requests to Dr. Herpertz, Department of Psychiatry and Psychotherapy, Aachen Technical University, Pauwelsstr. 30, 52074, Aachen, Germany; e-mail: [email protected]. 0890-8567/01/4010–1222䉷2001 by the American Academy of Child and Adolescent Psychiatry.
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comorbid conduct disorder (CD). Therefore, the question of whether ADHD by itself implies a risk of adult antisocial behavior (Mannuzza et al., 1998) or whether the association of ADHD in childhood and delinquent behavior in adulthood is rather a consequence of a high co-occurrence between ADHD and CD (Lilienfeld and Waldman, 1990) is still under discussion. Psychophysiological research has provided substantial data which demonstrate that low autonomic arousal and orienting may be correlates of future increased likelihood of delinquency. Prospective studies have shown that low arousal (assessed through resting heart rate and the number of nonspecific skin conductance responses) and small electrodermal orienting responses to neutral tones, taken at the age of 15, were related to delinquent behavior, assessed at the age of 24 (Raine et al., 1990a,b). The same psychophysiological characteristics have been reported for adult antisocial personalities since the 1970s (Hare, 1978; Siddle, 1977). Particularly psychopaths, who in addition to habitual antisocial behavior show typical characterological features (e.g., J . A M . AC A D . C H I L D A D O L E S C . P S YC H I AT RY, 4 0 : 10 , O C TO B E R 2 0 0 1
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fearlessness, selfishness, lack of empathy and remorse), were shown to be electrodermally hyporesponsive to aversive acoustic stimuli as well (Hare et al., 1978). In the realm of psychophysiological research, the concept of psychopathy is often preferred to the operationalization of the antisocial personality disorder, as found in DSM-IV, as it is not restricted to behavioral phenomena but includes enduring personality traits that are at the core of the habitual offender (Cleckley, 1976; Hare, 1978; Herpertz and Sass, 2000). A number of psychophysiological studies have already been performed with children who have ADHD that do not, however, give any information on comorbid conditions of CD. While the majority of authors reported decreased electrodermal responses and faster habituation in orienting paradigms in children with ADHD (Rosenthal and Allen, 1978; Schmidt et al., 1985), other authors failed to observe reduced autonomic orienting in hyperactive children (Delamater et al., 1981; Raine and Jones, 1987). Data on autonomic arousal in ADHD do not provide any consistent findings (Hastings and Barkley, 1978). Only a small number of studies used the startle paradigm in children. Whereas Shibagaki et al. (1993) found a decrement of the electrodermal component of the startle response in 6- to 12-year-old children with ADHD, Ornitz et al. (1992) reported no difference in startle eye-blink magnitude and habituation between children with ADHD and controls. Few studies exist comparing psychophysiological data of children who have CD with controls. Most authors reported lower baseline heart rates in children with conduct problems (Raine, 1996; Raine and Jones, 1987; Zahn and Kruesi, 1993); however, others did not (Garralda et al., 1991; Rogeness et al., 1990). Response data appear to suggest reduced skin conductance orienting (Raine, 1996) and lower electrodermal reactivity to high-intensity tones (Schmidt et al., 1985). Raine and Jones (1987) tried to compare children with CD and ADHD: although impairments in attention were found in both groups in a reaction-time task, only children with CD had lower autonomic arousal (Raine and Jones, 1987). To our knowledge, only one study differentiated between children with simple ADHD and those who additionally meet the diagnostic criteria of CD (ADHD+CD) (Zahn and Kruesi, 1993). The orienting and the startle response are two psychophysiological paradigms commonly used in the realm of antisocial behavior. They reflect two different compoJ . A M . AC A D . C H I L D A D O L E S C . P S YC H I AT RY, 4 0 : 10 , O C TO B E R 2 0 0 1
nents of attentional capacity: while orienting involves attentional engagement, startle represents the interruption of an ongoing activity (i.e., attentional disengagement) that is followed by avoidance or escape from an aversive stimulus (Lang et al., 1997; Turpin et al., 1999). Little orienting activity is thought to indicate a deficit in the allocation of attentional resources to a novel, however hardly motivating, external stimulus (Raine et al., 1990b). The most frequently used and most reliable measure of autonomic orienting is the change of skin conductance in response to neutral, low-intensity tone stimuli, typically a 60- to 70-dB tone. Startle response occurs to highintensity (90–110 dB), rapid-risetime stimuli (Turpin et al., 1999). According to the defense cascade hypothesis put forward by Lang et al. (1997), physiological responses to a threatening stimulus shift from selective attention/ heightened vigilance expressed by heart rate deceleration and skin conductance reactivity to a defensive action that, among others, is reflected in a priming of defensive reflexes, such as the eye-blink, the electromyographic (EMG) activity of the musculus orbicularis oculi. Therefore, in addition to changes of autonomic activity, the startle response subsumes behavioral components. The aim of our study was to investigate autonomic arousal, orienting, and startle response in boys aged 8 to 13 years with an exclusive diagnosis of ADHD, on the one hand, and with comorbid ADHD+CD, on the other hand, in comparison with age-matched controls. Our hypothesis was that boys with ADHD+CD but not with ADHD alone would show a psychophysiological response pattern similar to adult antisocial personalities and to the subtype of psychopaths in particular. With regard to the single response measures used in this study, it was expected that ADHD+CD boys—compared with ADHD and control subjects—would show lower electrodermal and cardiac arousal, a decrement of autonomic orienting, and reduced autonomic and behavioral (eye-blink) responses to a startling acoustic probe. METHOD Sample Boys aged between 8 and 13 years and with externalizing behavior problems who had been consecutively admitted to the inpatient and outpatient clinic of the Department of Child and Adolescent Psychiatry were screened for the study. Subjects who scored below 85 on Verbal and Performance IQ, measured with the German version of the Wechsler Intelligence Scale for Children (HAWIK-III) (Tewes et al., 1999), were excluded as were those with an additional mental (e.g., per-
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ing ADHD criteria. The DISYPS not only provides the number of criteria that have been fulfilled but also a severity score of each item ranging from 0 to 3. Severity scores entered statistical analyses in this study. To recruit homogeneous groups of ADHD and ADHD+CD children with a similar degree of dysfunction, subjects who fulfilled the criteria of oppositional defiant disorder were excluded from both diagnostic groups. Controls were also evaluated by the DISYPS to rule out psychiatric disorders. Parent and Teacher Rating Scales (Conners, 1973) were obtained for all children as well. To be included in one of the clinical groups, children had to fulfill the following criteria: a minimal parent or teacher score of ≥15 and a sum score of ≥30. In addition, the Child Behavior Checklist (CBCL) (Achenbach, 1991) was used, which has been shown to be a reliable and valid measure of externalizing and internalizing symptoms in childhood (Hofstra et al., 2000). To include a self-report questionnaire of aggressive behavior, we used the Assessment of Aggressive Behavior in Specific Situations (EAS-J), which consists of pictures presenting a variety of aggressive situations (Petermann and Petermann, 1996). Participant characteristics including age, IQ, and level of education are summarized in Table 1.
vasive developmental disorder, psychosis, tics, or a clinically significant anxiety or mood disorder) or medical disorder (particularly a neurological disorder). Exclusion criteria were assessed using a German standardized interview, the Diagnostic Interview for Psychiatric Disorders in Childhood and Adolescence (Kinder-DIPS) (Unnewehr et al., 1995). Of 60 patients tested for inclusion and exclusion criteria 21 boys with ADHD and 26 boys with ADHD+CD were included in the study in addition to 21 controls. Control boys were recruited by advertisement in local primary and secondary school centers. They had been free of any medication for a minimum of 72 hours at the time of testing and were found to have normal hearing. Children and their parents gave written consent for the children to participate after receiving a comprehensive description of the study. Diagnosis To be classified as having ADHD or ADHD+CD, children had to meet the severity and age-of-onset criteria outlined in DSM-IV. Diagnoses were based on the Diagnostic System for Psychiatric Disorders in Childhood and Adolescence (DISYPS) (Doepfner and Lehmkuhl, 1998). The DISYPS is a German questionnaire for parents that subsumes all items given in the diagnostic categories of the ADHD subtypes and of CD according to DSM-IV. For ADHD to be diagnosed, the child must have presented more than six of nine symptoms in either of the ADHD subtypes. For ADHD+CD to be diagnosed, the child has to have shown at least three symptoms of the DSM-IV diagnostic criteria of CD within the last 12 months in addition to fulfill-
Psychophysiological Recording Physiological measures of skin conductance and heart rate activity were recorded by a modular system (ZAK Medical Technics, Marktheidenfeld, Germany), and the startle reflex was measured with a commercial startle system (San Diego Instruments, San
TABLE 1 Diagnostic Data: Results From One-Way Analyses of Variance With Post Hoc Pairwise Comparisons of Group Means ADHD (n = 21) Age: mean (SD) IQ: mean (SD) Level of educationa Primary school Secondary school Lower level Intermediate level High level DISYPSb: mean (SD) Attention deficit Hyperactivity Impulsivity ODD behavior CD behavior Conners scalesb: mean (SD) Parents Teacher CBCLc: mean (SD) CBCL, Externalizing scale CBCL, Internalizing scale EAS-Jc
ADHD+CD (n = 26)
Controls (n = 21)
10.29 (1.92) 10.35 (1.89) 9.83 (1.55) 95.71 (11.08) 93.50 (7.97) 110.24 (11.77) 11
13
13
1 4 5
8 4 1
0 4 4
21.38 10.52 8.81 5.29 0.33
(3.29) 21.83 (3.10) (2.15) 10.37 (3.07) (2.65) 9.33 (2.27) (3.93) 17.00 (5.36) (0.79) 8.00 (4.38)
20.86 (5.20) 20.60 (5.50)
1.95 0.71 0.10 1.10 0.00
(1.88) (1.10) (0.30) (1.44) (0.00)
F (df = 2)
p
2.38 NS 17.44 .0001
342.81 127.43 110.56 96.20 63.14
.0001 .0001 .0001 .0001 .0001
Tukey-HSD Test ( p < .05) NS C > ADHD+CD; C > ADHD
ADHD+CD > C; ADHD > C ADHD+CD > C; ADHD > C ADHD+CD > C; ADHD > C ADHD+CD > ADHD > C ADHD+CD > ADHD; ADHD+CD > C
19.81 (6.44) 18.46 (6.02)
2.86 (3.79) 0.86 (1.38)
76.72 .0001 105.23 .0001
ADHD+CD > C; ADHD > C ADHD+CD > C; ADHD > C
66.48 (8.24) 71.73 (13.30) 66.76 (8.34) 69.54 (9.43) 50.01 (10.13) 52.15 (9.27)
49.33 (6.85) 52.90 (10.87) 45.17 (8.48)
29.76 .0001 19.17 .0001 3.34 .04
ADHD+CD > C; ADHD > C ADHD+CD > C; ADHD > C ADHD+CD > C
Note: ADHD = attention-deficit/hyperactivity disorder; CD = conduct disorder; C = controls; HSD = honestly significant difference; ODD = oppositional defiant disorder; DISYPS = Diagnostic System for Psychiatric Disorders in Childhood and Adolescence; CBCL = Child Behavior Checklist; EAS-J = Assessment of Aggressive Behavior in Specific Situations; NS = not significant. a Trinominal system of secondary school in Germany differentiating educational levels. b Sum scores. c T scores.
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Diego, CA). Physiological signals were recorded via 1-cm Ag-AgCl electrodes filled with electrolyte paste (Spectra 360). Impedances were kept below 5 kOhm. Skin Conductance. To record skin conductance activity, we centered electrodes on the thenar and hypothenar eminences of the nondominant hand; activity was sampled every 20 milliseconds, rectified, and integrated with a time constant of 0.3 seconds within a measuring range of 0 to 30 microseconds. Over a 3-minute rest period the number of nonspecific skin conductance responses (NS-SCRs) was recorded as a parameter of electrodermal arousal. NS-SCRs are spontaneously occurring SCRs that arise in the absence of a stimulus. The orienting paradigm consisted of a sequence of 10 pure tones of 1000Hz frequency, 25-millisecond rise and fall times, 65-dB intensity, 5second duration, and randomized interstimulus intervals (range: 25–40 seconds) (Raine et al., 1990a, 1995). A sequence of 10 tones of white noise was used as startle stimulus (100-dB intensity, 40-milliseconds duration, randomized interstimulus intervals between 22 and 28 seconds) (Turpin et al., 1999). Loudness of tones was calibrated using an artifical ear. Tones were delivered binaurally over a continuous 52dB background noise level to mask out extraneous sounds. The magnitude of the SCR was defined as the largest increase standardized to the intraindividual maximum within 0.9 and 4 seconds of the presentation of the stimulus. It was shown that range-corrected scores make SCR data more orderly and psychologically meaningful (Lykken et al., 1996). Finally, values were transformed logarithmically to improve the symmetry of the distribution curves. An amplitude exceeding 0.02 microseconds was taken as an elicited response (Turpin et al., 1999). A habituation measure consisted of the number of responses until habituation occurs. Habituation was defined as the number of trials that occur until at least three consecutive responses do not exceed 0.02 microseconds (Dawson et al., 2000). Eye-Blink Response. For measuring the eye-blink component of the startle reflex, the EMG activity of the left orbicularis oculi muscle was recorded through two electrodes, one placed under the left eye and the other below the outer canthus. The ground electrode was placed behind the left ear. The acoustic startle stimulus was the 50-millisecond burst of white noise, calibrated at 100 dB as described above. EMG activity was amplified by a factor of 10,000 with a 100- to 1,000-Hz band-pass filter, digitized at 1 kHz in a 10- to 150-millisecond time window from the start of the acoustic stimuli, then rectified and stored for off-line analysis. The software used for analysis stored the startle response values in arbitrary analog-digital units. A startle reflex was considered to have occurred when EMG activity surpassed the baseline by at least 10 units. The criterion for startle reflex nonresponders was defined as fewer than 25 units for the mean of response amplitudes (Braff et al., 1992). Heart Rate. Heart rate signals were recorded from the left forefinger by an infrared sensor over a rest period of 3 minutes with sample intervals consisting of the first and last 30 seconds of this period. The signals were sampled at 50 Hz, rectified, and integrated with a time constant of 0.3 seconds within a measuring range of 1 mV. Subjects were seated comfortably in a separate light- and soundattenuated laboratory where temperature and humidity levels were kept constant. Each subject was familiarized with the equipment, electrode application, and general nature of the experiment. Participants got instructions for each of the three experiments. For the first test the boys were told to relax for some minutes while nothing would happen. For the second test they were instructed to listen passively to a series of tones of moderate intensity and for the third test to a series of “beeps.” Data Analysis To detect group differences in clinical characteristics and symptom severity, the three diagnostic groups were compared by using one-way
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analysis of variance (ANOVAs) with post hoc tests (Tukey-honestly significant difference test controlling the type I error rate). For psychophysiological base rates and response parameters, multivariate one-way ANOVAs (MANOVAs) were performed. Response parameters included SCR amplitudes to orienting and startling stimuli as well as the number of responses until habituation occurred. Because of our specific hypotheses for the psychophysiological data, planned contrasts of ADHD+CD and controls and of ADHD+CD and ADHD were performed using one-tailed t tests, followed by Bonferroni-Holm type I error adjustment (Holm, 1979). In addition, all psychophysiological response measures were analyzed by using MANOVAs with repeated measures. Individual trial data were collapsed into three trial blocks, the first block consisting of four, the second and third block of three trials. The first trial was excluded if response was lower than in the second trial; this phenomenon of an early sensitization of response in repetitive stimulus presentation has been described by Schandry (1996). Repeated-measures MANOVAs were performed on the three diagnostic groups, with trial blocks as the repeated-measures factor. Finally, analyses of covariance were conducted to assess the effect of IQ on psychophysiological measures of attention. All statistical analyses were performed with SAS 6.12. RESULTS DIAGNOSTIC DATA
By design, significant overall group effects were found with regard to all subscales of the diagnostic instrument (DISYPS) assessing ADHD and CD symptoms. Post hoc group comparisons revealed that the ADHD and ADHD+CD groups did not differ in the severity of ADHD symptoms, but that they differed significantly in the severity of CD symptoms (p = .0001). Data assessed by means of the Conners scales for parents and for teachers also showed an overall group effect and confirmed that the two clinical groups were highly comparable with regard to the severity of ADHD symptoms. All boys with ADHD+CD fulfilled criteria of earlyonset CD. The CBCL revealed a significant group effect too: both ADHD groups (ADHD+CD and ADHD) scored significantly higher on the Externalizing and Internalizing scales of the CBCL compared with controls but, again, did not differ from each other. Regarding the results of the self-report aggression scale (EAS-J), a further group effect was found with a higher amount of aggressive behavior in the ADHD+CD group—but not the ADHD without CD group—compared with the control subjects (Table 1). PSYCHOPHYSIOLOGICAL DATA Arousal Measures
Electrodermal. One-way MANOVA on NS-SCRs produced a group effect (F = 3.54, df = 2, p = .03) with 1225
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planned group comparisons showing that the children with ADHD+CD had a significantly lower number of responses than the controls (T = –2.79, p = .008) but did not differ from children with ADHD alone (T = 0.76, df = 2, p = .42) (Table 2). Cardiovascular. There was no group effect for resting heart rate (F = 2.27, df = 2, p = .11).
Responses To Aversive Startling Stimuli
Electrodermal Responses. Data from one-way MANOVA showed an overall group effect (F = 3.22, df = 2, p = .04) in total SCR to 10 aversive startling stimuli. Planned contrasts revealed that comorbid subjects had significantly lower responses than ADHD subjects (T = 2.42, p = .03) and also showed a tendency to exhibit lower responses in comparison with control subjects (T = 1.94, p = .09). Repeated-measures MANOVA detected a group effect (F = 3.66, df = 2, 65, p = .03) in addition to a repeated-measures effect (F = 23.31, df = 2, 130, p < .001) but no interaction effect. Frequency of responses until habituation also revealed a significant main group effect (F = 4.47, df = 2, p = .01); planned contrasts indicated that ADHD+CD subjects showed an accelerated habituation compared with subjects with ADHD alone (T = 2.94, p = .005) and also habituated more quickly than controls (T = –1.77, p = .04). Figure 2 shows electrodermal responses (means, SEMs) of the three groups to each of the three trial blocks in addition to the mean total responses. Intelligence was shown to be no significant covariant of electrodermal response to orienting and startling stimuli (p ranging between .53 and .96). Electromyographic Eye-Blink Response. One subject with ADHD and one subject with ADHD+CD failed to show any eye-blink response. The three groups did not differ in the magnitude of eye-blink response (F = 0.40, df = 2, p =
Orienting Measure
Electrodermal. One-way MANOVA of total SCR to 10 orienting stimuli revealed a significant group effect (F = 3.22, df = 2, p = .04) with planned group comparisons indicating that children with ADHD+CD had significantly lower responses than children with ADHD alone (T = 2.45, p = .001) and controls (T = –2.04, p = .002). A repeated-measures MANOVA revealed a main group effect as well (F = 3.04, df = 2, 65, p = .05). As expected, electrodermal responses declined over the trial blocks in the overall group (F = 30.40, df = 2, 130, p < .001), with no group ⫻ trial block interaction. In addition, a further main group effect was found with regard to the frequency of electrodermal responses until habituation occurred (F = 3.59, df = 2, p = .03); planned contrasts showed that children with the comorbid condition showed a smaller number of responses than the ADHD (T = 2.14, p = .01) and control groups (T = –2.44, p = .01). Figure 1 presents the electrodermal data (means, SEMs) of the three groups in each of the three trial blocks in addition to the mean total responses.
TABLE 2 Psychophysiological Data: Results From One-Way Multivariate Analyses of Variance and Planned Pairwise Comparisons of Group Means ADHD (n = 21)
ADHD+CD (n = 26)
Controls (n = 21)
Mean (SD)
Mean (SD)
Mean (SD)
2.905 (3.97) 0.428 (0.20) 82.38 (12.41)
1.884 (2.25) 0.410 (0.20) 84.41 (11.72)
0.102 (0.07)
Total no. of SCRs Startle measures Total SCR amplitude Total no. of SCRs
Arousal measures Nonspecific SCRs Skin conductance level Resting heart rate Orienting measures Total SCR amplitude
Amplitude of EMG response
t Test a (p < .05)
F (df = 2)
p
4.666 (4.41) 0.370 (0.19) 89.73 (10.18)
3.54 1.49 2.27
.03 NS NS
ADHD+CD < C NS NS
0.049 (0.05)
0.101 (0.09)
3.22
.04
5.411 (2.85)
3.625 (2.46)
5.473 (2.45)
3.59
.03
ADHD+CD < C, ADHD+CD < ADHD ADHD+CD < C, ADHD+CD < ADHD
0.221 (0.12) 7.35 (2.53)
0.131 (0.12) 5.0 (2.75)
0.177 (0.10) 6.45 (2.68)
3.22 4.47
.04 .01
129.33 (84.07)
141.30 (91.20)
0.40
NS
152.83 (93.67)
ADHD+CD < ADHD ADHD+CD < ADHD, ADHD+CD < C NS
Note: ADHD = attention-deficit/hyperactivity disorder; ADHD+CD = comorbid condition of attention-deficit/hyperactivity disorder and conduct disorder; C = controls; SCR = skin conductance response; EMG = electromyographic; NS = not significant. a One-tailed t tests were followed by Bonferroni-Holm type I error adjustment.
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Fig. 1 Amplitudes of skin conductance response of the ADHD group, the ADHD+CD group, and the control group in the orienting paradigm (total amplitude and amplitudes in response to each of the three trial blocks). Means and SEMs (error bars). ADHD = attention-deficit/hyperactivity disorder; CD = conduct disorder.
Fig. 2 Amplitudes of skin conductance response of the ADHD group, the ADHD+CD group, and the control group in the startle paradigm (total amplitude and amplitudes in response to each of the three trial blocks). Means and SEMs (error bars). ADHD = attention-deficit/hyperactivity disorder; CD = conduct disorder.
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.68). EMG responses declined over the trial blocks in the overall group (F = 14.63, df = 2, 126, p < .001) with no significant group ⫻ trial block interaction effect. DISCUSSION
Our results support the hypothesis that boys with ADHD+CD show a decrement of autonomic responses to orienting and aversive startling stimuli compared with agematched children with ADHD alone and compared with controls. Psychophysiological findings were consistent because children with ADHD+CD were characterized by a lower amplitude of SCR and by more rapid habituation. Taking all results together, boys with ADHD+CD showed a psychophysiological response pattern that is very similar to that reported from studies with psychopathic antisocial personalities. These earlier studies provided good evidence for smaller orienting SCRs and for smaller electrodermal responses to aversive, startling acoustic stimuli in psychopathic adults (Hare et al., 1978). In addition, a deficit of autonomic orienting response in children was shown to be associated with a later development of criminal behavior (Raine et al., 1990a) as opposed to high autonomic reactivity, which is regarded as a protective factor against a criminal career (Raine et al., 1995). As in earlier studies, arousal measures did not provide as consistent findings as response measures to orienting and startling stimuli. The number of NS-SCRs was significantly reduced in children with ADHD+CD compared with control subjects. Resting heart rate was not found to be significantly lower in children with ADHD+CD compared with controls, although it tended to be lower. Contrary to earlier data reported by Zahn and Kruesi (1993), arousal measures did not differentiate between ADHD children with and without comorbid CD. However, there are some differences in the study design. Zahn and Kruesi (1993) recruited a group with the overall syndrome of disruptive behavior disorder and afterward made a differentiation between those with and without CD. Compared with our study, their sample was rather small and less homogeneous because 9 of 14 boys included in the ADHD without CD group had a mixed diagnosis with oppositional defiant disorder. Subjects with ADHD+CD did not exhibit significantly smaller eye-blink responses to a startling probe consistent with findings in adult criminal offenders (Herpertz et al., in press). Inconsistent with data assessed in psychopaths, the ADHD+CD group did not show a higher percentage 1228
of subjects without any eye-blink reflex, so-called nonresponders. On the whole, the magnitude of the defensive startle reflex appears to be no valuable correlate of an endangered development. Since autonomic responses to orienting and startling stimuli were decreased, children with ADHD+CD show a deficit of both attentional components; that is, they exhibit a deficit in the allocation of attentional resources to low-level, hardly motivating external stimuli, and they do not disengage from an ongoing activity when faced with a highly unexpected, potentially dangerous stimulus. As shown by our diagnostic data (DISYPS and Conners scales), children with ADHD alone exhibited equally severe behavioral symptoms of an attentional deficit as those with ADHD+CD. However, consistent with the findings of other authors (Delmater et al., 1981; Raine and Jones, 1987), children with ADHD failed to exhibit reduced SCRs in the orienting or startle paradigm. How can we explain this dissociation of behavioral and psychophysiological measures of attention? Decreased autonomic responses in the ADHD+CD children of our study may rather reflect the way a child allocates his attentional resources to a specific event or task than an irreversible deficit in information processing capacity (Raine and Jones, 1987). Children with ADHD+CD may have shown lower responses to the orienting task because it was boring and involved no active attention. This interpretation is supported by findings in psychopathic and antisocial individuals who showed enhanced attention under certain circumstances, particularly when the task at hand was motivating or even followed by reward (Jutai and Hare, 1983; Raine et al., 1990a). The decrement in electrodermal responses to the second passive attention task in our study—the startling probe—may reflect an insensitivity toward potentially frightening events and therefore may be indicative of low fear levels, which interfere with danger anticipation (Hare et al., 1978; Raine, 1996). Thus our data suggest that insufficient anticipatory fear may also be a feature boys with ADHD+CD have in common with antisocial adults (Herpertz et al., in press). The discrepancy in psychophysiological findings between ADHD subjects with and without comorbid CD must caution against any global claims for a strict overlap between ADHD and ADHD+CD (Cadesky et al., 2000). Earlier data on children with CD (Raine and Jones, 1987; Schmidt et al., 1985) and the similarity of the psychophysiological response pattern between antisocial adults and the ADHD+CD children in our study J . A M . AC A D . C H I L D A D O L E S C . P S YC H I AT RY, 4 0 : 10 , O C TO B E R 2 0 0 1
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support Schachar et al. (2000). They recently suggested that children with ADHD+CD might represent a symptomatic phenocopy of ADHD without common underlying deficits but exhibit ADHD-like behaviors as a reflection of their CD. This may be particularly true for children with the early-onset type of CD that were included in our study. The inclusion of children with CD alone in future studies would help to determine whether ADHD+CD is a variant of CD rather than of ADHD. Limitations
Some methodical limitations of our study need to be considered. First, we consider limitations related to characteristics of the sample: our cohort was rather small, but according to our results the diagnostic groups were homogeneous and representative in psychopathology. Differences in psychopathology between the two clinical groups were reflected by highly significant differences in diagnostic items (assessed by the DISYPS), but not in the CBCL scores. Particularly high scores on the Internalizing scale of the CBCL appear not to reflect fearfulness in the sense of a high anticipation of negative consequences of behavior that is thought to protect from antisocial development. As in other studies (Schachar et al., 2000), controls had a significantly higher IQ than both clinical groups, which was, however, shown to have no influence on group differences in psychophysiological measures. Second, although our finding of an accelerated habituation is supported by other studies in antisocial individuals, one cannot exclude the possibility that the initial level of response confounds the habituation criterion (Rosenthal and Allen, 1978). The latter was lower in ADHD+CD subjects and may have led sooner to a negligible SCR than in subjects with higher initial responses. Clinical Implications
In view of finding predictors of adult criminal behavior in childhood and adolescence, the identification of subtypes, as can be indicated by psychophysiological parameters, is of major relevance. Genetic studies show significant heritability for autonomic arousal and skin conductance responsivity (Venables, 1993). Raine et al. (1990a) suggested that the genetic predisposition to criminal behavior might find its expression—at least to some degree—through autonomic nervous system factors. However, chronic stress also influences psychophysiological responses because it can initiate a process of downregulating autonomic responses (Herpertz et al., 1999). J . A M . AC A D . C H I L D A D O L E S C . P S YC H I AT RY, 4 0 : 10 , O C TO B E R 2 0 0 1
This was supported by Carrey et al. (1995), who reported lower electrodermal responses in abused compared with nonabused children when these subjects viewed slides with everyday emotional or cognitive content. In summary, low autonomic responses to orienting and startle stimuli were observed in children with ADHD+CD but not in children with ADHD alone. Because low autonomic response is thought to be a marker for future increased likelihood of antisocial behaviors, further research should include longitudinal studies testing whether psychophysiological responses increase our ability to predict outcome of boys with extroversive disorders and thus may provide an opportunity for early intervention. REFERENCES Achenbach TM (1991), Manual for the Child Behavior Checklist (CBCL). German version by Melchers P, Doepfner M, Arbeitsgruppe Deutsche Child Behavior Checklist. Koeln: Arbeitsgruppe Kinder-, Jugendlichen-, und Familiendiagnostik, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne Braff DL, Grillon C, Geyer MA (1992), Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49:206–215 Cadesky EB, Mota CL, Schachar RJ (2000), Beyond words: how do children with ADHD and/or conduct problems process nonverbal information about affect? J Am Acad Child Adolesc Psychiatry 39:1160–1167 Carrey NJ, Butter HJ, Persinger MA, Bialik RJ (1995), Physiological and cognitive correlates of child abuse. J Am Acad Child Adolesc Psychiatry 34:1067–1075 Cleckley H (1976), The Mask of Sanity: An Attempt To Clarify Some Issues About The So-Called Psychopathic Personality, 5th ed. St Louis: Mosby Conners CK (1973), Rating scales for use in drug studies with children. Psychopharmacol Bull 9:24–84 Dawson ME, Schell AM, Filion DL (2000), The electrodermal system. In: Handbook of Psychophysiology, Cacioppo JT, Tassinary LG, Berntson GG, eds. Cambridge, England: Cambridge University Press Delamater A, Lahey M, Drake L (1981), Toward an empirical subclassification of “learning disabilities”: a psychophysiological comparison of “hyperactive” and “nonhyperactive” subgroups. J Abnorm Child Psychol 9:65–77 Doepfner M, Lehmkuhl G (1998), Diagnostic System for Mental Disorders in Child and Adolescence According to ICD-10 and DSM-IV (DISYPS-KJ). Bern, Switzerland: Huber Garralda ME, Connell J, Taylor DC (1991), Psychophysiological anomalies in children with emotional and conduct disorders. Psychol Med 21:947–957 Hare RD (1978), Psychopathy and electrodermal responses to nonsignal stimulation. Biol Psychol 6:237–246 Hare RD, Frazelle J, Cox DN (1978), Psychopathy and physiological responses to threat of an aversive stimulus. Psychophysiology 15:165–172 Hastings JE, Barkley RA (1978), A review of psychophysiological research with hyperkinetic children. J Abnorm Child Psychol 6:413–447 Herpertz S, Kunert HJ, Schwenger UB, Sass H (1999), Affective response in borderline personality disorder: a psychophysiological approach. Am J Psychiatry 156:1550–1556 Herpertz S, Sass H (2000), Emotional deficiency and psychopathy. Behav Sci Law 18:567–580 Herpertz SC, Werth U, Lukas G, Qunaibi BS, Schuerkens A, Sass H (in press), Emotion in criminal offenders with psychopathy and borderline personality disorder. Arch Gen Psychiatry Hofstra MB, van der Ende J, Verhulst FC (2000), Continuity and change of psychopathology from childhood into adulthood: a 14-year follow-up study. J Am Acad Child Adolesc Psychiatry 39:850–858 Holm S (1979), A simple sequentially rejective multiple test procedure. Scand J Stat 6:65–70
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Jutai JW, Hare RD (1983), Psychopathy and selective attention during performance of a complex perceptual motor task. Psychophysiology 20:146–151 Lang PJ, Bradley MM, Cuthbart BN (1997), Motivated attention: affect, activation, and action. In: Attention and Orienting: Sensory and Motivations Processes, Lang P, Simons R, Balaban M, eds. Mahwah, NJ: Erlbaum, pp 97–136 Lilienfeld SO, Waldman ID (1990), The relation between childhood attentiondeficit hyperactivity disorder and adult antisocial behavior reexamined: the problem of heterogeneity. Clin Psychol Rev 11:699–725 Lykken DT, Rose R, Luther B, Maley M (1966), Correcting psychophysiological measures for individual differences in range. Psychol Bull 66:481–484 Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M (1998), Adult psychiatry status of hyperactive boys grown up. Am J Psychiatry 155:493–498 Ornitz EM, Hanna GL, de Traversay J (1992), Prestimulation-induced startle modulation in attention-deficit hyperactivity disorder and nocturnal enuresis. Psychophysiology 29:437–451 Petermann F, Petermann U (1996), Assessment of Aggressive Behavior in Specific Situations, 3rd version. Göttingen, Germany: Hogrefe Raine A (1996), Autonomic nervous system factors underlying disinhibited, antisocial, and violent behavior. Ann N Y Acad Sci 794:46–59 Raine A, Jones F (1987), Attention, autonomic arousal, and personality in behaviorally disordered children. J Abnorm Child Psychol 15:583–599 Raine A, Venables PH, Williams M (1990a), Autonomic orienting responses in 15-year-old male subjects and criminal behavior at age 24. Am J Psychiatry 147:933–937 Raine A, Venables PH, Williams M (1990b), Relationships between CNS and ANS measures of arousal at age 15 and criminality at age 24. Arch Gen Psychiatry 47:1003–1007 Raine A, Venables PH, Williams M (1995), High autonomic arousal and electrodermal orienting at age 15 years as protective factors against criminal behavior at age 29 years. Am J Psychiatry 152:1595–1600 Rogeness GA, Cepeda C, Macedo CA, Fischer C, Harris WR (1990), Differences in heart rate and blood pressure in children with conduct disorder, major depression, and separation anxiety. Psychiatry Res 33:199–206
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Rosenthal RH, Allen TW (1978), An examination of attention, arousal, and learning dysfunctions of hyperkinetic children. Psychol Bull 85:689–715 Satterfield J, Hoppe C, Schell AM (1982), A prospective study of delinquency in 110 adolescent boys with attention deficit disorder and 88 normal adolescent boys. Am J Psychiatry 139:795–798 Schachar R, Mota VL, Logan GD, Tannock R, Klim P (2000), Confirmation of an inhibitory control deficit in attention-deficit/hyperactivity disorder. J Abnorm Child Psychol 28:227–235 Schandry R (1996), Textbook of Psychophysiology. Weinheim: Beltz PsychologieVerlagsUnion Schmidt K, Solanto MV, Bridger WH (1985), Electrodermal activity of undersocialized aggressive children. J Child Psychol Psychiatry 26:653–660 Shibagaki M, Yamanaka T, Furuya T (1993), Attention state in electrodermal activity during auditory stimulation of children with attention-deficit hyperactivity disorder. Percept Mot Skills 77:331–338 Siddle DA (1977), Electrodermal activity and psychopathy. In: Biosocial Bases of Criminal Behavior, Mednick SA, Christianson KO, eds. New York: Gardner Press Tewes U, Rossmann P, Schallberger U (1999), Wechsler Intelligence Test for Children, HAWIK-III, 3rd ed. Bern, Switzerland: Huber Turpin G, Schaefer F, Boucsein W (1999), Effects of stimulus intensity, risetime, and duration on autonomic and behavioral responding: implications for the differentiation of orienting, startle, and defense responses. Psychophysiology 36:453–463 Unnewehr S, Schneider S, Margraf J (1995), Diagnostic Interview for Psychiatric Disorders in Childhood and Adolescence. Berlin: Springer Venables PH (1993), Electrodermal indices as markers for the development of schizophrenia. In: Progress in Electrodermal Research, Roy JC, Boucsein W, Fowles DC, Gruzelier J, eds. New York: Plenum, pp 187–206 Weiss G, Hechtman T (1993), Hyperactive Children Grown Up: ADHD in Children, Adolescents, and Adults. New York: Guilford Zahn TP, Kruesi MJP (1993), Autonomic activity in boys with disruptive behavior disorders. Psychophysiology 30:605–614
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ABSTRACT Objective: Several studies have demonstrated that the presence of attention-deficit/hyperactivity disorder (ADHD) in childhood increases the risk of antisocial behavior developing in adulthood. However, because previous research did not consider comorbid conduct disorder (CD), the question of whether ADHD by itself or only the association of ADHD with CD implies a risk of adult antisocial behavior developing is still under discussion. Method: Because several characteristics of psychophysiological response had been shown to be associated with future increased likelihood of adult antisocial behavior, autonomic arousal as well as electrodermal responses to orienting and aversive stimuli were assessed in 26 boys with ADHD+CD compared with 21 boys with ADHD alone and 21 controls. Results: Boys with a comorbid condition of ADHD+CD showed a decrement of autonomic responses and a more rapid habituation to orienting and aversive startling stimuli compared with age-matched children with ADHD alone. Conclusions: Boys with ADHD+CD show a psychophysiological response pattern that is very similar to that reported in antisocial personalities. These findings give further support for a high persistence of antisocial behavior from childhood to adulthood, while no evidence was found that ADHD itself is associated with a predisposition to antisocial behavior. J. Am. Acad. Child Adolesc. Psychiatry, 2001, 40(10):1222–1230. Key Words: attention-deficit/hyperactivity disorder, conduct disorder, antisocial behavior, psychophysiology.
Several studies have demonstrated that the presence of attention-deficit/hyperactivity disorder (ADHD) in childhood increases the risk of antisocial behavior developing in adulthood. Of all boys with ADHD, 20% to 30% show delinquent behavior as adults (Satterfield et al., 1982; Weiss and Hechtman, 1993). However, previous research on children with ADHD often did not consider Accepted April 10, 2001. Dr. Herpertz, Dr. Wenning, Mr. Qunaibi, and Dr. Sass are with the Department of Psychiatry and Psychotherapy, and Dr. Mueller and Dr. Herpertz-Dahlmann are with the Department of Child and Adolescent Psychiatry and Psychotherapy, Aachen Technical University, Aachen, Germany. This research was funded by the Interdisciplinary Center for Clinical Research of the Medical Faculty, RWTH Aachen and by the German Society for the Advancement of Scientific Research (DFG grant HE 2660/3-1). The authors thank Ulrich Schwenger for technical advice, Anette Schuerkens for statistical support, and Daniela Cardaci, Sabine Leger, Rebecca Loehrer, and Christiane Lichterfeld for their assistance during the examinations. Reprint requests to Dr. Herpertz, Department of Psychiatry and Psychotherapy, Aachen Technical University, Pauwelsstr. 30, 52074, Aachen, Germany; e-mail: [email protected]. 0890-8567/01/4010–1222䉷2001 by the American Academy of Child and Adolescent Psychiatry.
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comorbid conduct disorder (CD). Therefore, the question of whether ADHD by itself implies a risk of adult antisocial behavior (Mannuzza et al., 1998) or whether the association of ADHD in childhood and delinquent behavior in adulthood is rather a consequence of a high co-occurrence between ADHD and CD (Lilienfeld and Waldman, 1990) is still under discussion. Psychophysiological research has provided substantial data which demonstrate that low autonomic arousal and orienting may be correlates of future increased likelihood of delinquency. Prospective studies have shown that low arousal (assessed through resting heart rate and the number of nonspecific skin conductance responses) and small electrodermal orienting responses to neutral tones, taken at the age of 15, were related to delinquent behavior, assessed at the age of 24 (Raine et al., 1990a,b). The same psychophysiological characteristics have been reported for adult antisocial personalities since the 1970s (Hare, 1978; Siddle, 1977). Particularly psychopaths, who in addition to habitual antisocial behavior show typical characterological features (e.g., J . A M . AC A D . C H I L D A D O L E S C . P S YC H I AT RY, 4 0 : 10 , O C TO B E R 2 0 0 1
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fearlessness, selfishness, lack of empathy and remorse), were shown to be electrodermally hyporesponsive to aversive acoustic stimuli as well (Hare et al., 1978). In the realm of psychophysiological research, the concept of psychopathy is often preferred to the operationalization of the antisocial personality disorder, as found in DSM-IV, as it is not restricted to behavioral phenomena but includes enduring personality traits that are at the core of the habitual offender (Cleckley, 1976; Hare, 1978; Herpertz and Sass, 2000). A number of psychophysiological studies have already been performed with children who have ADHD that do not, however, give any information on comorbid conditions of CD. While the majority of authors reported decreased electrodermal responses and faster habituation in orienting paradigms in children with ADHD (Rosenthal and Allen, 1978; Schmidt et al., 1985), other authors failed to observe reduced autonomic orienting in hyperactive children (Delamater et al., 1981; Raine and Jones, 1987). Data on autonomic arousal in ADHD do not provide any consistent findings (Hastings and Barkley, 1978). Only a small number of studies used the startle paradigm in children. Whereas Shibagaki et al. (1993) found a decrement of the electrodermal component of the startle response in 6- to 12-year-old children with ADHD, Ornitz et al. (1992) reported no difference in startle eye-blink magnitude and habituation between children with ADHD and controls. Few studies exist comparing psychophysiological data of children who have CD with controls. Most authors reported lower baseline heart rates in children with conduct problems (Raine, 1996; Raine and Jones, 1987; Zahn and Kruesi, 1993); however, others did not (Garralda et al., 1991; Rogeness et al., 1990). Response data appear to suggest reduced skin conductance orienting (Raine, 1996) and lower electrodermal reactivity to high-intensity tones (Schmidt et al., 1985). Raine and Jones (1987) tried to compare children with CD and ADHD: although impairments in attention were found in both groups in a reaction-time task, only children with CD had lower autonomic arousal (Raine and Jones, 1987). To our knowledge, only one study differentiated between children with simple ADHD and those who additionally meet the diagnostic criteria of CD (ADHD+CD) (Zahn and Kruesi, 1993). The orienting and the startle response are two psychophysiological paradigms commonly used in the realm of antisocial behavior. They reflect two different compoJ . A M . AC A D . C H I L D A D O L E S C . P S YC H I AT RY, 4 0 : 10 , O C TO B E R 2 0 0 1
nents of attentional capacity: while orienting involves attentional engagement, startle represents the interruption of an ongoing activity (i.e., attentional disengagement) that is followed by avoidance or escape from an aversive stimulus (Lang et al., 1997; Turpin et al., 1999). Little orienting activity is thought to indicate a deficit in the allocation of attentional resources to a novel, however hardly motivating, external stimulus (Raine et al., 1990b). The most frequently used and most reliable measure of autonomic orienting is the change of skin conductance in response to neutral, low-intensity tone stimuli, typically a 60- to 70-dB tone. Startle response occurs to highintensity (90–110 dB), rapid-risetime stimuli (Turpin et al., 1999). According to the defense cascade hypothesis put forward by Lang et al. (1997), physiological responses to a threatening stimulus shift from selective attention/ heightened vigilance expressed by heart rate deceleration and skin conductance reactivity to a defensive action that, among others, is reflected in a priming of defensive reflexes, such as the eye-blink, the electromyographic (EMG) activity of the musculus orbicularis oculi. Therefore, in addition to changes of autonomic activity, the startle response subsumes behavioral components. The aim of our study was to investigate autonomic arousal, orienting, and startle response in boys aged 8 to 13 years with an exclusive diagnosis of ADHD, on the one hand, and with comorbid ADHD+CD, on the other hand, in comparison with age-matched controls. Our hypothesis was that boys with ADHD+CD but not with ADHD alone would show a psychophysiological response pattern similar to adult antisocial personalities and to the subtype of psychopaths in particular. With regard to the single response measures used in this study, it was expected that ADHD+CD boys—compared with ADHD and control subjects—would show lower electrodermal and cardiac arousal, a decrement of autonomic orienting, and reduced autonomic and behavioral (eye-blink) responses to a startling acoustic probe. METHOD Sample Boys aged between 8 and 13 years and with externalizing behavior problems who had been consecutively admitted to the inpatient and outpatient clinic of the Department of Child and Adolescent Psychiatry were screened for the study. Subjects who scored below 85 on Verbal and Performance IQ, measured with the German version of the Wechsler Intelligence Scale for Children (HAWIK-III) (Tewes et al., 1999), were excluded as were those with an additional mental (e.g., per-
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ing ADHD criteria. The DISYPS not only provides the number of criteria that have been fulfilled but also a severity score of each item ranging from 0 to 3. Severity scores entered statistical analyses in this study. To recruit homogeneous groups of ADHD and ADHD+CD children with a similar degree of dysfunction, subjects who fulfilled the criteria of oppositional defiant disorder were excluded from both diagnostic groups. Controls were also evaluated by the DISYPS to rule out psychiatric disorders. Parent and Teacher Rating Scales (Conners, 1973) were obtained for all children as well. To be included in one of the clinical groups, children had to fulfill the following criteria: a minimal parent or teacher score of ≥15 and a sum score of ≥30. In addition, the Child Behavior Checklist (CBCL) (Achenbach, 1991) was used, which has been shown to be a reliable and valid measure of externalizing and internalizing symptoms in childhood (Hofstra et al., 2000). To include a self-report questionnaire of aggressive behavior, we used the Assessment of Aggressive Behavior in Specific Situations (EAS-J), which consists of pictures presenting a variety of aggressive situations (Petermann and Petermann, 1996). Participant characteristics including age, IQ, and level of education are summarized in Table 1.
vasive developmental disorder, psychosis, tics, or a clinically significant anxiety or mood disorder) or medical disorder (particularly a neurological disorder). Exclusion criteria were assessed using a German standardized interview, the Diagnostic Interview for Psychiatric Disorders in Childhood and Adolescence (Kinder-DIPS) (Unnewehr et al., 1995). Of 60 patients tested for inclusion and exclusion criteria 21 boys with ADHD and 26 boys with ADHD+CD were included in the study in addition to 21 controls. Control boys were recruited by advertisement in local primary and secondary school centers. They had been free of any medication for a minimum of 72 hours at the time of testing and were found to have normal hearing. Children and their parents gave written consent for the children to participate after receiving a comprehensive description of the study. Diagnosis To be classified as having ADHD or ADHD+CD, children had to meet the severity and age-of-onset criteria outlined in DSM-IV. Diagnoses were based on the Diagnostic System for Psychiatric Disorders in Childhood and Adolescence (DISYPS) (Doepfner and Lehmkuhl, 1998). The DISYPS is a German questionnaire for parents that subsumes all items given in the diagnostic categories of the ADHD subtypes and of CD according to DSM-IV. For ADHD to be diagnosed, the child must have presented more than six of nine symptoms in either of the ADHD subtypes. For ADHD+CD to be diagnosed, the child has to have shown at least three symptoms of the DSM-IV diagnostic criteria of CD within the last 12 months in addition to fulfill-
Psychophysiological Recording Physiological measures of skin conductance and heart rate activity were recorded by a modular system (ZAK Medical Technics, Marktheidenfeld, Germany), and the startle reflex was measured with a commercial startle system (San Diego Instruments, San
TABLE 1 Diagnostic Data: Results From One-Way Analyses of Variance With Post Hoc Pairwise Comparisons of Group Means ADHD (n = 21) Age: mean (SD) IQ: mean (SD) Level of educationa Primary school Secondary school Lower level Intermediate level High level DISYPSb: mean (SD) Attention deficit Hyperactivity Impulsivity ODD behavior CD behavior Conners scalesb: mean (SD) Parents Teacher CBCLc: mean (SD) CBCL, Externalizing scale CBCL, Internalizing scale EAS-Jc
ADHD+CD (n = 26)
Controls (n = 21)
10.29 (1.92) 10.35 (1.89) 9.83 (1.55) 95.71 (11.08) 93.50 (7.97) 110.24 (11.77) 11
13
13
1 4 5
8 4 1
0 4 4
21.38 10.52 8.81 5.29 0.33
(3.29) 21.83 (3.10) (2.15) 10.37 (3.07) (2.65) 9.33 (2.27) (3.93) 17.00 (5.36) (0.79) 8.00 (4.38)
20.86 (5.20) 20.60 (5.50)
1.95 0.71 0.10 1.10 0.00
(1.88) (1.10) (0.30) (1.44) (0.00)
F (df = 2)
p
2.38 NS 17.44 .0001
342.81 127.43 110.56 96.20 63.14
.0001 .0001 .0001 .0001 .0001
Tukey-HSD Test ( p < .05) NS C > ADHD+CD; C > ADHD
ADHD+CD > C; ADHD > C ADHD+CD > C; ADHD > C ADHD+CD > C; ADHD > C ADHD+CD > ADHD > C ADHD+CD > ADHD; ADHD+CD > C
19.81 (6.44) 18.46 (6.02)
2.86 (3.79) 0.86 (1.38)
76.72 .0001 105.23 .0001
ADHD+CD > C; ADHD > C ADHD+CD > C; ADHD > C
66.48 (8.24) 71.73 (13.30) 66.76 (8.34) 69.54 (9.43) 50.01 (10.13) 52.15 (9.27)
49.33 (6.85) 52.90 (10.87) 45.17 (8.48)
29.76 .0001 19.17 .0001 3.34 .04
ADHD+CD > C; ADHD > C ADHD+CD > C; ADHD > C ADHD+CD > C
Note: ADHD = attention-deficit/hyperactivity disorder; CD = conduct disorder; C = controls; HSD = honestly significant difference; ODD = oppositional defiant disorder; DISYPS = Diagnostic System for Psychiatric Disorders in Childhood and Adolescence; CBCL = Child Behavior Checklist; EAS-J = Assessment of Aggressive Behavior in Specific Situations; NS = not significant. a Trinominal system of secondary school in Germany differentiating educational levels. b Sum scores. c T scores.
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Diego, CA). Physiological signals were recorded via 1-cm Ag-AgCl electrodes filled with electrolyte paste (Spectra 360). Impedances were kept below 5 kOhm. Skin Conductance. To record skin conductance activity, we centered electrodes on the thenar and hypothenar eminences of the nondominant hand; activity was sampled every 20 milliseconds, rectified, and integrated with a time constant of 0.3 seconds within a measuring range of 0 to 30 microseconds. Over a 3-minute rest period the number of nonspecific skin conductance responses (NS-SCRs) was recorded as a parameter of electrodermal arousal. NS-SCRs are spontaneously occurring SCRs that arise in the absence of a stimulus. The orienting paradigm consisted of a sequence of 10 pure tones of 1000Hz frequency, 25-millisecond rise and fall times, 65-dB intensity, 5second duration, and randomized interstimulus intervals (range: 25–40 seconds) (Raine et al., 1990a, 1995). A sequence of 10 tones of white noise was used as startle stimulus (100-dB intensity, 40-milliseconds duration, randomized interstimulus intervals between 22 and 28 seconds) (Turpin et al., 1999). Loudness of tones was calibrated using an artifical ear. Tones were delivered binaurally over a continuous 52dB background noise level to mask out extraneous sounds. The magnitude of the SCR was defined as the largest increase standardized to the intraindividual maximum within 0.9 and 4 seconds of the presentation of the stimulus. It was shown that range-corrected scores make SCR data more orderly and psychologically meaningful (Lykken et al., 1996). Finally, values were transformed logarithmically to improve the symmetry of the distribution curves. An amplitude exceeding 0.02 microseconds was taken as an elicited response (Turpin et al., 1999). A habituation measure consisted of the number of responses until habituation occurs. Habituation was defined as the number of trials that occur until at least three consecutive responses do not exceed 0.02 microseconds (Dawson et al., 2000). Eye-Blink Response. For measuring the eye-blink component of the startle reflex, the EMG activity of the left orbicularis oculi muscle was recorded through two electrodes, one placed under the left eye and the other below the outer canthus. The ground electrode was placed behind the left ear. The acoustic startle stimulus was the 50-millisecond burst of white noise, calibrated at 100 dB as described above. EMG activity was amplified by a factor of 10,000 with a 100- to 1,000-Hz band-pass filter, digitized at 1 kHz in a 10- to 150-millisecond time window from the start of the acoustic stimuli, then rectified and stored for off-line analysis. The software used for analysis stored the startle response values in arbitrary analog-digital units. A startle reflex was considered to have occurred when EMG activity surpassed the baseline by at least 10 units. The criterion for startle reflex nonresponders was defined as fewer than 25 units for the mean of response amplitudes (Braff et al., 1992). Heart Rate. Heart rate signals were recorded from the left forefinger by an infrared sensor over a rest period of 3 minutes with sample intervals consisting of the first and last 30 seconds of this period. The signals were sampled at 50 Hz, rectified, and integrated with a time constant of 0.3 seconds within a measuring range of 1 mV. Subjects were seated comfortably in a separate light- and soundattenuated laboratory where temperature and humidity levels were kept constant. Each subject was familiarized with the equipment, electrode application, and general nature of the experiment. Participants got instructions for each of the three experiments. For the first test the boys were told to relax for some minutes while nothing would happen. For the second test they were instructed to listen passively to a series of tones of moderate intensity and for the third test to a series of “beeps.” Data Analysis To detect group differences in clinical characteristics and symptom severity, the three diagnostic groups were compared by using one-way
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analysis of variance (ANOVAs) with post hoc tests (Tukey-honestly significant difference test controlling the type I error rate). For psychophysiological base rates and response parameters, multivariate one-way ANOVAs (MANOVAs) were performed. Response parameters included SCR amplitudes to orienting and startling stimuli as well as the number of responses until habituation occurred. Because of our specific hypotheses for the psychophysiological data, planned contrasts of ADHD+CD and controls and of ADHD+CD and ADHD were performed using one-tailed t tests, followed by Bonferroni-Holm type I error adjustment (Holm, 1979). In addition, all psychophysiological response measures were analyzed by using MANOVAs with repeated measures. Individual trial data were collapsed into three trial blocks, the first block consisting of four, the second and third block of three trials. The first trial was excluded if response was lower than in the second trial; this phenomenon of an early sensitization of response in repetitive stimulus presentation has been described by Schandry (1996). Repeated-measures MANOVAs were performed on the three diagnostic groups, with trial blocks as the repeated-measures factor. Finally, analyses of covariance were conducted to assess the effect of IQ on psychophysiological measures of attention. All statistical analyses were performed with SAS 6.12. RESULTS DIAGNOSTIC DATA
By design, significant overall group effects were found with regard to all subscales of the diagnostic instrument (DISYPS) assessing ADHD and CD symptoms. Post hoc group comparisons revealed that the ADHD and ADHD+CD groups did not differ in the severity of ADHD symptoms, but that they differed significantly in the severity of CD symptoms (p = .0001). Data assessed by means of the Conners scales for parents and for teachers also showed an overall group effect and confirmed that the two clinical groups were highly comparable with regard to the severity of ADHD symptoms. All boys with ADHD+CD fulfilled criteria of earlyonset CD. The CBCL revealed a significant group effect too: both ADHD groups (ADHD+CD and ADHD) scored significantly higher on the Externalizing and Internalizing scales of the CBCL compared with controls but, again, did not differ from each other. Regarding the results of the self-report aggression scale (EAS-J), a further group effect was found with a higher amount of aggressive behavior in the ADHD+CD group—but not the ADHD without CD group—compared with the control subjects (Table 1). PSYCHOPHYSIOLOGICAL DATA Arousal Measures
Electrodermal. One-way MANOVA on NS-SCRs produced a group effect (F = 3.54, df = 2, p = .03) with 1225
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planned group comparisons showing that the children with ADHD+CD had a significantly lower number of responses than the controls (T = –2.79, p = .008) but did not differ from children with ADHD alone (T = 0.76, df = 2, p = .42) (Table 2). Cardiovascular. There was no group effect for resting heart rate (F = 2.27, df = 2, p = .11).
Responses To Aversive Startling Stimuli
Electrodermal Responses. Data from one-way MANOVA showed an overall group effect (F = 3.22, df = 2, p = .04) in total SCR to 10 aversive startling stimuli. Planned contrasts revealed that comorbid subjects had significantly lower responses than ADHD subjects (T = 2.42, p = .03) and also showed a tendency to exhibit lower responses in comparison with control subjects (T = 1.94, p = .09). Repeated-measures MANOVA detected a group effect (F = 3.66, df = 2, 65, p = .03) in addition to a repeated-measures effect (F = 23.31, df = 2, 130, p < .001) but no interaction effect. Frequency of responses until habituation also revealed a significant main group effect (F = 4.47, df = 2, p = .01); planned contrasts indicated that ADHD+CD subjects showed an accelerated habituation compared with subjects with ADHD alone (T = 2.94, p = .005) and also habituated more quickly than controls (T = –1.77, p = .04). Figure 2 shows electrodermal responses (means, SEMs) of the three groups to each of the three trial blocks in addition to the mean total responses. Intelligence was shown to be no significant covariant of electrodermal response to orienting and startling stimuli (p ranging between .53 and .96). Electromyographic Eye-Blink Response. One subject with ADHD and one subject with ADHD+CD failed to show any eye-blink response. The three groups did not differ in the magnitude of eye-blink response (F = 0.40, df = 2, p =
Orienting Measure
Electrodermal. One-way MANOVA of total SCR to 10 orienting stimuli revealed a significant group effect (F = 3.22, df = 2, p = .04) with planned group comparisons indicating that children with ADHD+CD had significantly lower responses than children with ADHD alone (T = 2.45, p = .001) and controls (T = –2.04, p = .002). A repeated-measures MANOVA revealed a main group effect as well (F = 3.04, df = 2, 65, p = .05). As expected, electrodermal responses declined over the trial blocks in the overall group (F = 30.40, df = 2, 130, p < .001), with no group ⫻ trial block interaction. In addition, a further main group effect was found with regard to the frequency of electrodermal responses until habituation occurred (F = 3.59, df = 2, p = .03); planned contrasts showed that children with the comorbid condition showed a smaller number of responses than the ADHD (T = 2.14, p = .01) and control groups (T = –2.44, p = .01). Figure 1 presents the electrodermal data (means, SEMs) of the three groups in each of the three trial blocks in addition to the mean total responses.
TABLE 2 Psychophysiological Data: Results From One-Way Multivariate Analyses of Variance and Planned Pairwise Comparisons of Group Means ADHD (n = 21)
ADHD+CD (n = 26)
Controls (n = 21)
Mean (SD)
Mean (SD)
Mean (SD)
2.905 (3.97) 0.428 (0.20) 82.38 (12.41)
1.884 (2.25) 0.410 (0.20) 84.41 (11.72)
0.102 (0.07)
Total no. of SCRs Startle measures Total SCR amplitude Total no. of SCRs
Arousal measures Nonspecific SCRs Skin conductance level Resting heart rate Orienting measures Total SCR amplitude
Amplitude of EMG response
t Test a (p < .05)
F (df = 2)
p
4.666 (4.41) 0.370 (0.19) 89.73 (10.18)
3.54 1.49 2.27
.03 NS NS
ADHD+CD < C NS NS
0.049 (0.05)
0.101 (0.09)
3.22
.04
5.411 (2.85)
3.625 (2.46)
5.473 (2.45)
3.59
.03
ADHD+CD < C, ADHD+CD < ADHD ADHD+CD < C, ADHD+CD < ADHD
0.221 (0.12) 7.35 (2.53)
0.131 (0.12) 5.0 (2.75)
0.177 (0.10) 6.45 (2.68)
3.22 4.47
.04 .01
129.33 (84.07)
141.30 (91.20)
0.40
NS
152.83 (93.67)
ADHD+CD < ADHD ADHD+CD < ADHD, ADHD+CD < C NS
Note: ADHD = attention-deficit/hyperactivity disorder; ADHD+CD = comorbid condition of attention-deficit/hyperactivity disorder and conduct disorder; C = controls; SCR = skin conductance response; EMG = electromyographic; NS = not significant. a One-tailed t tests were followed by Bonferroni-Holm type I error adjustment.
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Fig. 1 Amplitudes of skin conductance response of the ADHD group, the ADHD+CD group, and the control group in the orienting paradigm (total amplitude and amplitudes in response to each of the three trial blocks). Means and SEMs (error bars). ADHD = attention-deficit/hyperactivity disorder; CD = conduct disorder.
Fig. 2 Amplitudes of skin conductance response of the ADHD group, the ADHD+CD group, and the control group in the startle paradigm (total amplitude and amplitudes in response to each of the three trial blocks). Means and SEMs (error bars). ADHD = attention-deficit/hyperactivity disorder; CD = conduct disorder.
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.68). EMG responses declined over the trial blocks in the overall group (F = 14.63, df = 2, 126, p < .001) with no significant group ⫻ trial block interaction effect. DISCUSSION
Our results support the hypothesis that boys with ADHD+CD show a decrement of autonomic responses to orienting and aversive startling stimuli compared with agematched children with ADHD alone and compared with controls. Psychophysiological findings were consistent because children with ADHD+CD were characterized by a lower amplitude of SCR and by more rapid habituation. Taking all results together, boys with ADHD+CD showed a psychophysiological response pattern that is very similar to that reported from studies with psychopathic antisocial personalities. These earlier studies provided good evidence for smaller orienting SCRs and for smaller electrodermal responses to aversive, startling acoustic stimuli in psychopathic adults (Hare et al., 1978). In addition, a deficit of autonomic orienting response in children was shown to be associated with a later development of criminal behavior (Raine et al., 1990a) as opposed to high autonomic reactivity, which is regarded as a protective factor against a criminal career (Raine et al., 1995). As in earlier studies, arousal measures did not provide as consistent findings as response measures to orienting and startling stimuli. The number of NS-SCRs was significantly reduced in children with ADHD+CD compared with control subjects. Resting heart rate was not found to be significantly lower in children with ADHD+CD compared with controls, although it tended to be lower. Contrary to earlier data reported by Zahn and Kruesi (1993), arousal measures did not differentiate between ADHD children with and without comorbid CD. However, there are some differences in the study design. Zahn and Kruesi (1993) recruited a group with the overall syndrome of disruptive behavior disorder and afterward made a differentiation between those with and without CD. Compared with our study, their sample was rather small and less homogeneous because 9 of 14 boys included in the ADHD without CD group had a mixed diagnosis with oppositional defiant disorder. Subjects with ADHD+CD did not exhibit significantly smaller eye-blink responses to a startling probe consistent with findings in adult criminal offenders (Herpertz et al., in press). Inconsistent with data assessed in psychopaths, the ADHD+CD group did not show a higher percentage 1228
of subjects without any eye-blink reflex, so-called nonresponders. On the whole, the magnitude of the defensive startle reflex appears to be no valuable correlate of an endangered development. Since autonomic responses to orienting and startling stimuli were decreased, children with ADHD+CD show a deficit of both attentional components; that is, they exhibit a deficit in the allocation of attentional resources to low-level, hardly motivating external stimuli, and they do not disengage from an ongoing activity when faced with a highly unexpected, potentially dangerous stimulus. As shown by our diagnostic data (DISYPS and Conners scales), children with ADHD alone exhibited equally severe behavioral symptoms of an attentional deficit as those with ADHD+CD. However, consistent with the findings of other authors (Delmater et al., 1981; Raine and Jones, 1987), children with ADHD failed to exhibit reduced SCRs in the orienting or startle paradigm. How can we explain this dissociation of behavioral and psychophysiological measures of attention? Decreased autonomic responses in the ADHD+CD children of our study may rather reflect the way a child allocates his attentional resources to a specific event or task than an irreversible deficit in information processing capacity (Raine and Jones, 1987). Children with ADHD+CD may have shown lower responses to the orienting task because it was boring and involved no active attention. This interpretation is supported by findings in psychopathic and antisocial individuals who showed enhanced attention under certain circumstances, particularly when the task at hand was motivating or even followed by reward (Jutai and Hare, 1983; Raine et al., 1990a). The decrement in electrodermal responses to the second passive attention task in our study—the startling probe—may reflect an insensitivity toward potentially frightening events and therefore may be indicative of low fear levels, which interfere with danger anticipation (Hare et al., 1978; Raine, 1996). Thus our data suggest that insufficient anticipatory fear may also be a feature boys with ADHD+CD have in common with antisocial adults (Herpertz et al., in press). The discrepancy in psychophysiological findings between ADHD subjects with and without comorbid CD must caution against any global claims for a strict overlap between ADHD and ADHD+CD (Cadesky et al., 2000). Earlier data on children with CD (Raine and Jones, 1987; Schmidt et al., 1985) and the similarity of the psychophysiological response pattern between antisocial adults and the ADHD+CD children in our study J . A M . AC A D . C H I L D A D O L E S C . P S YC H I AT RY, 4 0 : 10 , O C TO B E R 2 0 0 1
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support Schachar et al. (2000). They recently suggested that children with ADHD+CD might represent a symptomatic phenocopy of ADHD without common underlying deficits but exhibit ADHD-like behaviors as a reflection of their CD. This may be particularly true for children with the early-onset type of CD that were included in our study. The inclusion of children with CD alone in future studies would help to determine whether ADHD+CD is a variant of CD rather than of ADHD. Limitations
Some methodical limitations of our study need to be considered. First, we consider limitations related to characteristics of the sample: our cohort was rather small, but according to our results the diagnostic groups were homogeneous and representative in psychopathology. Differences in psychopathology between the two clinical groups were reflected by highly significant differences in diagnostic items (assessed by the DISYPS), but not in the CBCL scores. Particularly high scores on the Internalizing scale of the CBCL appear not to reflect fearfulness in the sense of a high anticipation of negative consequences of behavior that is thought to protect from antisocial development. As in other studies (Schachar et al., 2000), controls had a significantly higher IQ than both clinical groups, which was, however, shown to have no influence on group differences in psychophysiological measures. Second, although our finding of an accelerated habituation is supported by other studies in antisocial individuals, one cannot exclude the possibility that the initial level of response confounds the habituation criterion (Rosenthal and Allen, 1978). The latter was lower in ADHD+CD subjects and may have led sooner to a negligible SCR than in subjects with higher initial responses. Clinical Implications
In view of finding predictors of adult criminal behavior in childhood and adolescence, the identification of subtypes, as can be indicated by psychophysiological parameters, is of major relevance. Genetic studies show significant heritability for autonomic arousal and skin conductance responsivity (Venables, 1993). Raine et al. (1990a) suggested that the genetic predisposition to criminal behavior might find its expression—at least to some degree—through autonomic nervous system factors. However, chronic stress also influences psychophysiological responses because it can initiate a process of downregulating autonomic responses (Herpertz et al., 1999). J . A M . AC A D . C H I L D A D O L E S C . P S YC H I AT RY, 4 0 : 10 , O C TO B E R 2 0 0 1
This was supported by Carrey et al. (1995), who reported lower electrodermal responses in abused compared with nonabused children when these subjects viewed slides with everyday emotional or cognitive content. In summary, low autonomic responses to orienting and startle stimuli were observed in children with ADHD+CD but not in children with ADHD alone. Because low autonomic response is thought to be a marker for future increased likelihood of antisocial behaviors, further research should include longitudinal studies testing whether psychophysiological responses increase our ability to predict outcome of boys with extroversive disorders and thus may provide an opportunity for early intervention. REFERENCES Achenbach TM (1991), Manual for the Child Behavior Checklist (CBCL). German version by Melchers P, Doepfner M, Arbeitsgruppe Deutsche Child Behavior Checklist. Koeln: Arbeitsgruppe Kinder-, Jugendlichen-, und Familiendiagnostik, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne Braff DL, Grillon C, Geyer MA (1992), Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49:206–215 Cadesky EB, Mota CL, Schachar RJ (2000), Beyond words: how do children with ADHD and/or conduct problems process nonverbal information about affect? J Am Acad Child Adolesc Psychiatry 39:1160–1167 Carrey NJ, Butter HJ, Persinger MA, Bialik RJ (1995), Physiological and cognitive correlates of child abuse. J Am Acad Child Adolesc Psychiatry 34:1067–1075 Cleckley H (1976), The Mask of Sanity: An Attempt To Clarify Some Issues About The So-Called Psychopathic Personality, 5th ed. St Louis: Mosby Conners CK (1973), Rating scales for use in drug studies with children. Psychopharmacol Bull 9:24–84 Dawson ME, Schell AM, Filion DL (2000), The electrodermal system. In: Handbook of Psychophysiology, Cacioppo JT, Tassinary LG, Berntson GG, eds. Cambridge, England: Cambridge University Press Delamater A, Lahey M, Drake L (1981), Toward an empirical subclassification of “learning disabilities”: a psychophysiological comparison of “hyperactive” and “nonhyperactive” subgroups. J Abnorm Child Psychol 9:65–77 Doepfner M, Lehmkuhl G (1998), Diagnostic System for Mental Disorders in Child and Adolescence According to ICD-10 and DSM-IV (DISYPS-KJ). Bern, Switzerland: Huber Garralda ME, Connell J, Taylor DC (1991), Psychophysiological anomalies in children with emotional and conduct disorders. Psychol Med 21:947–957 Hare RD (1978), Psychopathy and electrodermal responses to nonsignal stimulation. Biol Psychol 6:237–246 Hare RD, Frazelle J, Cox DN (1978), Psychopathy and physiological responses to threat of an aversive stimulus. Psychophysiology 15:165–172 Hastings JE, Barkley RA (1978), A review of psychophysiological research with hyperkinetic children. J Abnorm Child Psychol 6:413–447 Herpertz S, Kunert HJ, Schwenger UB, Sass H (1999), Affective response in borderline personality disorder: a psychophysiological approach. Am J Psychiatry 156:1550–1556 Herpertz S, Sass H (2000), Emotional deficiency and psychopathy. Behav Sci Law 18:567–580 Herpertz SC, Werth U, Lukas G, Qunaibi BS, Schuerkens A, Sass H (in press), Emotion in criminal offenders with psychopathy and borderline personality disorder. Arch Gen Psychiatry Hofstra MB, van der Ende J, Verhulst FC (2000), Continuity and change of psychopathology from childhood into adulthood: a 14-year follow-up study. J Am Acad Child Adolesc Psychiatry 39:850–858 Holm S (1979), A simple sequentially rejective multiple test procedure. Scand J Stat 6:65–70
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