عملکرد اجرایی شناختی در توسعه اختلال شخصیت ضد اجتماعی

Abstract The present study examined the association of cognitive–executive abilities to two risk factors for alcoholism, i.e., antisocial behaviors and a family history (FH+) of alcohol dependence. A sample of 91 right-handed, non-substance-dependent, young male adults recruited from the community were classified into three groups: (1) a control group of n=32 men with no history of DSM-III-R childhood conduct disorder (CD) or antisocial personality disorder (ASPD); (2) n=25 men who met criteria for a DSM-III-R childhood CD diagnosis, but did not meet diagnostic criteria for ASPD (i.e., CD/ASPD−); and (3) n=34 men who met DSM-III-R criteria for ASPD. They were further divided into those with and without a positive family history of alcoholism. A two-way (Antisocial Profile (3)×Family History of Alcoholism (2)) ANOVA was used to compare several neuropsychological measures of executive–cognitive functioning (ECF) ability. Verbal abstraction ability was found to be significantly lower in ASPD subjects compared with controls and CD-only subjects, inversely related to antisocial behavior severity (as measured by symptom count). CD-only and control subjects' abstraction ability were statistically indistinguishable. FH+ was associated with increased errors in planning performance on the Porteus Maze Test and diminished performance on Luria's simple alternate-tapping motor tasks. The effect was more pronounced when inhibition of prepotent motor planning was required. Results are consistent with previous work examining ECF ability in antisocial samples that find subtle differences in ECF ability compared to controls. The findings suggest that normal versus abnormal behavioral outcome for children with conduct problems may be influenced by cognitive ability profile, perhaps because of varying maturational processes.

Introduction The consequences of childhood conduct disorder (CD) and its continuation into adulthood as antisocial personality disorder (ASPD) can represent tremendous societal and medical costs. CD and ASPD have been linked to various behavioral, social, and health problems, including aggression, criminal behavior, and substance disorder Jordan et al., 1996, Lewis et al., 1983, Moeller et al., 1998 and Patrick & Zempolich, 1998. Previous work highlights the role of CD and ASPD as a risk factor for substance dependence (Hesselbrock, Meyer & Hesselbrock, 1992), showing that adults with ASPD have a three- to fourfold greater likelihood of developing substance dependence compared to adults without ASPD. The widely noted association between alcoholism and ASPD has led to several theories proposing an “antisocial alcoholic” subtype (Babor et al., 1992; Cloninger et al., 1981; Jellinek, 1960), possibly with different etiological and developmental mechanisms than other subtypes. Antisocial behavior shows heterogeneity of onset and expression across childhood and adolescence Feehan et al., 1994, Hinshaw et al., 1993, Lahey & Loeber, 1994, Lahey et al., 1995, Lahey et al., 1998, Loeber, 1991 and Moffitt, 1993. These differences have complicated investigators' search to identify those factors that operate during maturation, which may be associated with ASPD. Longitudinal studies estimate at least one in four CD youth continues to display antisocial behaviors in adulthood (Robins, 1966). This raises the question of what factors operate to result in adult ASPD, or act to prevent the majority of problem-behavior youth from developing ASPD. A related question is whether the same factors also predispose youth to substance abuse and later alcohol dependence. While environmental factors unquestionably play a role in the development of ASPD (Farrington, 1986), some researchers have examined neuropsychological test performance in an attempt to determine whether various neurobehavioral deficits predispose youth to ASPD. One approach has been to examine the relationship between executive–cognitive functioning (ECF) abilities and ASPD. ECF is thought to represent higher-order abilities involved in planning, initiation, and regulation of goal-directed behavior (Luria, 1980). ECF deficits in alcoholics include abstract reasoning, set shifting, set persistence, attention, verbal/categorical fluency, concept generation, persistence, temporal organization, sequencing, supervisory motor control, hypothesis formation testing, and cognitive flexibility (Giancola & Moss, 1998). The unifying element of these multifaceted abilities is that they are believed to have the majority of their primary neurological substrates in the prefrontal cortex (PFC) and its connections to other cortical and subcortical areas (Fuster, 1997 and Luria, 1980). Research has begun to address whether ECF ability in CD youth Moffitt, 1993 and Pennington & Ozonoff, 1996 or ASPD adults (Kandel & Freed, 1989; Gorenstein, 1987; Gorton, Swirsky-Sacchetti, Sobel, Samuel, & Goron, 1999) differs from healthy controls. In general, results favorably support the idea that deficits on neuropsychological tests of ECF can be found in these groups, as shown in a recent meta-analysis (Morgan & Lilienfeld, 2000). However, it remains unresolved if these deficits are solely attributable to executive function, or if impairments of other neuropsychological abilities are implicated. Despite the encouraging results, no published studies to date have examined whether ECF ability varies with changes in antisocial behavior between adolescence and early adulthood. Such work would address the hypothesis that ECF impairment is associated with the onset and/or stability of disruptive problem behavior. Previously, we investigated this issue by examining relationships between ECF ability and CD/ASPD diagnoses for substance-dependent inpatients (Stevens et al., in press). We found that patients who met the criteria for ASPD had lower vocabulary and verbal abstraction ability compared to both normal controls and to patients who had CD as children, but not ASPD as adults. However, we did not control for possible attention-deficit hyperactivity problems. It has been suggested that ECF deficits in CD groups may only be present in comorbid CD/ADHD groups (Pennington & Ozonoff, 1996). When considering the relationship of ECF ability and CD/ASPD, an important related issue is the risk for substance dependence inherent in antisocial behavior disorders. Giancola and Moss (1998) suggest that ECF deficits are the most consistent and predominant of all the cognitive deficits found in alcoholics. These abilities are believed to be related to processes of reinforcement, learning, and motivation Fuster, 1989, Iversen & Mishkin, 1972 and Rolls et al., 1994, which may influence the development of substance use. Predicated on presumed biological predisposition to alcoholism Schuckit, 1987 and Tarter, 1988, studies have examined ECF ability in both youth at-risk for alcohol disorder because of a positive family history of alcoholism (Schuckit, 1987). Reviews of early studies showed that the evidence for a relationship between ECF and a positive family history (FH+) of alcoholism was mixed Schuckit, 1987, Searles, 1990 and Tarter et al., 1990. ECF deficits found in ASPD adults (Gorenstein, 1987) and CD youth (Moffitt, 1993), along with electrophysiological evidence Bauer, 1997, Bauer & Hesselbrock, 1993, Bauer et al., 1994 and O'Connor et al., 1994 are consistent with some investigators' suggestion that the cognitive performance differences found in earlier FH+ studies are likely due to a high prevalence of CD and/or ASPD in the samples, rather than family history status (Gillen & Hesselbrock, 1992 and Malloy et al., 1989). The etiological relationships among, FH+, CD/ASPD, and ECF have yet to be disentangled. The field of developmental neuropsychology has emerged in recent years to examine cognitive ability from a perspective that includes central nervous system maturation. Research has emerged to characterize cognitive development in various groups of youth, using studies of human (Diamond & Goldman-Rakic, 1985), animal Diamond, 1988 and Diamond et al., 1987, and psychopathological youth whose abnormal behavior is thought to stem from suspected or identified brain injury, or problems with brain maturation Cattelani et al., 1998 and Pennington & Ozonoff, 1996. This research not only seeks to describe the development of specific cognitive abilities, but also the development of different brain systems and their changes at later ages (Welsh & Pennington, 1988). Our current understanding of ECF development posits that age-appropriate forms of ECF ability are present in early childhood, but then ECF shows a protracted course of full maturation (Welsh & Pennington, 1988), extending into late adolescence and early adulthood. In this context, it is plausible that a developmental ECF abnormality may underlie antisocial behavior in some groups of youth and adolescents. Although others have speculated that deficits or maturational lags in self-governing ECF ability development may influence the expression of problem behavior in some youth (Hill et al., 1999, Hogan, 1999 and Smith et al., 1992), it is not known whether ECF abilities causally influence the expression of antisocial behavior. This is partly because of our incomplete understanding of frontal lobe maturation and ECF development (Smith et al., 1992). The present study examined whether remission of antisocial behavior after adolescence is associated with normal ECF development, when compared with normal controls and youth whose antisocial behaviors do not remit. The study has three objectives: First, the study used formal diagnostic classification criteria (i.e., CD and ASPD diagnoses determined from retrospective self-report) to examine whether adult executive–cognitive abilities differ according among three profiles of antisocial behavior development (i.e., young adults with no history of antisocial behavior, CD-only subjects, or subjects with ASPD). It was predicted that young adult ASPD+ subjects would show lower ECF ability than either normal controls or CD-only subjects, while CD-only and controls would be comparable. Second, we were interested in whether FH+ enhances or reduces neuropsychological test performance among the three antisocial behavior groups. Third, to account for the possible confound of childhood ADHD, correlational analyses examined the relationships between ECF ability and disruptive behavior severity occurring prior to age 12.

Results 3.1. Demographic information for antisocial profiles The demographic features, general intelligence estimates, and monthly alcohol consumption of the three antisocial groups were compared. No significant differences among the three groups for age, education, WAIS-R Performance IQ score, MAST score, or average amount of absolute alcohol consumed in the past 6 months. WAIS-R Verbal IQ was significantly different (P=.036) among the three groups. Post hoc testing revealed that only normal control subjects differed from CD/ASPD−. The means, standard deviations, percentages, and significant differences among groups are displayed in Table 1. Table 1. Demographic differences by antisocial behavior classification All continuous variables used one-way ANOVA to test for significant differences. Paternal alcoholism history differences tested by Pearson chi-square. Variable Normal controls (n=32) CD/ASPD− (n=25) CD/ASPD+ (n=34) P Mean (S.D.) Mean (S.D.) Mean (S.D.) Age (years) 22.5 (1.34) 23.2 (1.53) 23.4 (1.75) n.s. Education (years) 15.4 (1.31) 15.3 (1.57) 14.7 (1.55) n.s. WAIS Verbal IQ 113.0 (12.97) 104.1 (13.36) 107.5 (12.53) .036 WAIS Performance IQ 105.4 (14.54) 100.0 (13.69) 103.0 (11.19) n.s. MAST score 3.2 (3.25) 4.2 (2.97) 5.9 (6.55) n.s. Alcohol last 6 months (oz.) 45.5 (44.9) 60.0 (80.0) 82.3 (103.2) n.s. Paternal alcoholism history 46.4% 50.0% 41.4% n.s. Table options 3.2. Antisocial profile and ECF results The means, standard deviations, and significance levels for comparisons of ECF test performance for each diagnostic classification category are displayed in Table 2. There was a significant main effect of antisocial profile for WAIS-R Similarities [F(2,79)=4.171, P<.05]. Table 2. ECF by antisocial behavior classification Variable Controls (n=32) CD/ASPD− (n=25) CD/ASPD+ (n=34) P Mean (S.D.) Mean (S.D.) Mean (S.D.) WAIS Similarities* 22.4 (2.78) 21.3 (2.70) 19.9 (4.08) .019 WAIS Information 22.2 (4.32) 20.2 (40.03) 21.7 (3.53) n.s. WAIS Digit span* 19.3 (4.21) 16.9 (4.02) 19.2 (4.16) .070 WAIS Picture Arrangement* 14.7 (2.08) 12.8 (2.97) 14.3 (2.91) .094 WCST Categories achieveda 5.4 (1.41) 5.5 (1.22) 5.6 (1.03) .028 WCST Perseverative Errors 11.2 (8.75) 8.5 (5.46) 10.7 (7.18) n.s. Porteus highest year without errorb 10.8 (3.25) 9.2 (4.86) 9.5 (4.08) .045 Trails Aa 20.8 (4.40) 22.5 (9.51) 21.2 (5.83) .031 Trails Bb 46.4 (24.21) 48.6 (15.87) 50.0 (15.00) .094 Verbal fluency 55.6 (7.42) 54.5 (9.43) 54.6 (9.42) n.s. LMT No. 22 Tap right hand twice 19.1 (5.94) 17.8 (5.65) 17.2 (5.82) n.s. LMT No. 22 Extraneous errors* 0.9 (1.34) 0.7 (0.92) 1.5 (1.81) .082 LMT No. 23 Tap left hand twicea 16.8 (5.34) 14.8 (5.13) 15.6 (4.99) .021 LMT No. 23 Extraneous errors 0.8 (1.13) 1.1 (1.26) 1.2 (1.65) n.s. * CD/ASPD effect at least P<.10. a CD/ASPD×Family History interaction effect at least P<.10 (means not shown). b Family history effect at least P<.10 (means not shown). Table options Trend levels of significance were found for WAIS-R Digit Span [F(2,79)=2.755, P<.10], Picture Arrangement [F(2,79)=2.442, P<.10], and for Luria Motor Task No. 22 Extraneous Errors [F(2,79)=2.579, P<.10]. No other ECF measure was significantly different across antisocial groups. Planned comparison results indicate that the difference in Similarities scores is primarily due to the significant difference (P<.01) between normal controls and CD/ASPD+. A significant linear effect was detected across the groups with Similarities score decreasing as antisocial severity increased. Planned comparisons showed that CD/ASPD− subjects had significantly lower Digit Span performance than normal controls (P<.05) or ASPD+ subjects (P<.05). There was no statistical difference between normal controls and ASPD+ subjects on Digit Span scores. A similar pattern was found for Picture Arrangement scores. There was a significant difference between normal controls and CD/ASPD− (P<.05) and a trend difference between CD and ASPD+ (P<.10) for Picture Arrangement scores. Furthermore, there was no difference between ASPD+ and normal controls on Picture Arrangement scores. The mean number of LMT No. 22 Extraneous errors showed a significant difference (P<.05) between CD/ASPD− and CD/ASPD+ subjects, but not for any other pairs of contrasts. 3.3. Family history and ECF results Table 2 also indicates significant effects for FH on ECF test results. In the analysis of covariance controlling for the influence of Verbal IQ, a main effect of family history status was found for Porteus Maze highest year without error score, F(1, 82)=4.128, P<.05. This Porteus Maze score was higher for family history negative subjects by an average of approximately 2 years in each antisocial profile category. Trails B also tended to be different [F(1,82)=2.869, P<.10]. No other ECF measure was significantly different between FH groups. 3.4. Antisocial Profile×Family History interaction The interaction of Antisocial Profile and FH was examined in relation to ECF. Significant interactions were found for three ECF measures. Trails A completion time revealed a significant Antisocial Profile (3)×FH (2) interaction [F(2,79)=3.619, P<.05]. Total Categories achieved on the WCST also showed a significant interaction [F(2,79)=4.154, P<.05]. There was a significant interaction for Luria Motor Task No. 23 (tap left hand twice/right hand once) [F(2,79)=4.084, P<.05]. These significant interactions are also indicated in Table 2. Therefore, each of the components of these 3×2 interactions were retested as a series of three 2×2 interaction contrasts. For Trails A completion time, the significant components of the FH×Antisocial Profile interaction were between normal controls and CD/ASPD+ [F(1,60)=3.278, P<.10] and between CD/ASPD− and CD/ASPD+ [F(1,53)=6.196, P<.05] (Fig. 1). For WCST Total Categories, there was a significant interaction between normal controls and CD/ASPD− [F(1,53)=3.845, P<.10] and between CD/ASPD− and CD/ASPD+ [F(1,52)=9.000, P<.01] (Fig. 2). For LMT No. 23, interaction component was significant between normal controls and CD/ASPD+ [F(1,60)=7.619, P<.01] and between CD/ASPD− and CD/ASPD+ [F(1,53)=4.290, P<.05] (Fig. 3). FH×Antisocial Behavior Classification interaction: Trails A (s). Control vs. ... Fig. 1. FH×Antisocial Behavior Classification interaction: Trails A (s). Control vs. CD/ASPD−, n.s.; control vs. CD/ASPD+, P=.075; CD/SAPD− vs. CD/ASPD+, P=.016. Figure options FH×Antisocial Behavior Classification interaction: WCST Total Categories ... Fig. 2. FH×Antisocial Behavior Classification interaction: WCST Total Categories achieved. Control vs. CD/ASPD−, P=.055; control vs. CD/ASPD+, n.s.; CD/SAPD− vs. CD/ASPD+, P=.004. Figure options FH×Antisocial Behavior Classification interaction: Luria Motor Task comparison. ... Fig. 3. FH×Antisocial Behavior Classification interaction: Luria Motor Task comparison. Control vs. CD/ASPD−, n.s.; control vs. CD/ASPD+, P=.008; CD/ASPD− vs. CD/ASPD+, P=.043. Figure options 3.5. Association of disruptive childhood behavior with ECF In order to determine whether various disruptive behaviors influenced test scores, the intercorrelation of neuropsychological test scores and symptoms counts of childhood hyperactivity, impulsivity, inattention, and childhood and adulthood conduct problems were computed (see Table 3). Table 3. Zero-order correlation of ECF test measures with disruptive behavior symptoms Impulsivity Inattention Hyperactivity CD symptoms ASPD symptoms WAIS Full Scale IQ −.264* −.204 −.196 −.180 −.026 WAIS Verbal IQ −.303** −.292** −.276** −.207 .033 WAIS Similarities −.164 −.206 −.203 −.199 −.275** WAIS Information −.249* −.306** −.225* −.182 .075 WAIS Digit Span −.014 −.202 −.048 −.041 .197 WAIS Picture Arrangement −.330** −.223* −.181 −.112 .060 WCST Categories achieved −.039 −.138 −.049 .037 −.009 WCST Perseverative Errors .009 .120 .140 −.060 −.035 Porteus highest year without error .200 .151 .081 −.096 −.043 Trails A −.005 .058 .099 .089 .195 Trails B .127 .113 .082 .105 −.020 Verbal fluency −.038 −.001 .012 −.048 .028 LMT No. 22 Tap right hand twice −.095 −.062 −.212* −.101 .039 LMT No. 23 Tap left hand twice −.031 −.110 −.092 −.175 .081 Impulsivity 1.000 .515** .658** .394** .139 Inattention .515** 1.000 .567** .300** .116 Hyperactivity .658** .567** 1.000 .405** .189 CD symptoms .3936** .300** .405** 1.000 .393** ASPD symptoms .139 .116 .189 .393** 1.000 * P<.05. ** P<.01. Table options Significant associations were found between Impulsivity and WAIS-R Full Scale IQ, Verbal IQ, and the WAIS Information and Picture Arrangement subtests. A significant association was also found between Inattention symptoms and WAIS-R Verbal IQ, Information, and Picture Arrangement. Hyperactivity was significantly associated with Verbal IQ and Luria Motor Task No. 22 (tap right hand twice/left hand once). Childhood CD symptom count severity was uncorrelated to adult ECF performance. However, the number of adult ASPD symptoms was associated with WAIS-R Similarities scores. As would be expected, Impulsivity, Inattention, and Hyperactivity were all significantly intercorrelated. Childhood CD symptoms were also significantly intercorrelated with these problem behavior symptoms counts. However, adult ASPD symptom count was correlated only to the number of childhood CD symptoms. These findings suggest that childhood behaviors indicative of ADHD might have been a factor in neuropsychological performance for at least some of the subjects, but was not a widespread confound.