Hyperactive and aggressive behaviors in childhood as related to low platelet monoamine oxidase (MAO) activity at adult age: A longitudinal study of male subjects

Pergamon Per,son. individ. Difl Vol. 19, No. 3. 373-383, 1995 pp.

Copyright 0 1995 Elsewer Science Ltd

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HYPERACTIVE AND AGGRESSIVE BEHAVIORS IN CHILDHOOD AS RELATED TO LOW PLATELET

MONOAMINE OXIDASE (MAO) ACTIVITY AT ADULT AGE: A LONGITUDINAL STUDY OF MALE SUBJECTS

Britt af Klinteberg’** and Lars Oreland ‘Department of Psychology, Stockholm University and ‘Department of Pharmacology,

University of Uppsala, Sweden

(Received I9 March 1994; received for publication 25 April 1995)

Summary-Aspects of childhood behavior were explored in relation to platelet monoamine oxidase (MAO) activity, which is considered a biological marker of vulnerability for disinhibition and psychosocial deviances, at adult age. Data were obtained from a group of 75 male subjects as ( I) teacher ratings of behavior at ages 10 and 13 yr with respect to Motor Restlessness and Concentration Difficulties, the sum of which was used as an indicator of Hyperactive Behavior, and Aggressiveness, supposed to be concomitants in the developmental process behind later disinhibitory tendencies and different forms of psychosocial deviances, and (2) platelet MAO activity, used as an indirect indicator of central serotonergic activity, at age 26-27 yr. A pattern analysis (Configural Frequency Analysis, CFA) was applied. For the combination of being high in persistent Hyperactive Behavior and high in persistent Aggressiveness at an early age, and being low in platelet MAO activity at adult age, a highly significant type was obtained. Furthermore, results of loglinear modelling of Hyperactive Behavior and Aggressiveness in childhood and adult platelet MAO activity indicated a positive relationship between Hyperactive Behavior and Aggressiveness, and a negative association between Hyperactive Behavior and platelet MAO activity; those interactions were significant and contributed to a good model fit. There was no significant interaction effect between Aggressiveness and platelet MAO activity. The results of the analyses were used as a basis for some theoretical and methodological conclusions.

INTRODUCTION

In an earlier study within the longitudinal project ‘Individual Development and Adjustment’ (Magnusson, 1988) of the present group of males, results indicated that hyperactive behavior is closely linked to later alcohol problems and violent offending in the same individuals (af Klinteberg, Andersson, Magnusson & Stattin, 1993). This finding focuses the interest on underlying mechanisms to which these maladjustment problems might be linked and stresses the importance of investigating the continuous processes of interaction between biological, psychological and social aspects of individual functioning. A crucial point is then to understand the interacting factors which ‘activate’ biological vulnerability in the developing process of psychological disturbances and antisocial behavior (Magnusson & ijhman, 1987; Asberg, Schalling, Traskman-Benz & Wagner, 1987). Individual differences in stability and change of antisocial behavior during the life-course were recently discussed and highlighted (Magnusson, af Klinteberg & Stattin, 1994; Moffitt, 1993). The central question of the present study concerns the possibility of an underlying constitutional biological vulnerability manifested in subtle childhood behavior problems. In biological studies of psychosocial vulnerability, relationships between excretion levels of stress hormones and personality traits and conduct have been reported. In a study of the present group, hyperactive and aggressive behaviors on the one hand, and persistent criminal behavior on the other, were found to be related to low urinary adrenaline excretion in normal and stressful situations (af Klinteberg & Magnusson, 1989; Magnusson et al., 1994). Furthermore, in a group of criminal psychopaths low levels of adrenaline excretion were found as well as low adrenergic reactivity to stress (Lidberg, Levander, Schalling & Lidberg, 1978; Levander, Mattson, Schalling & Dalteg, 1987), and results suggesting low autonomic nervous system reactivity in disruptive boys were recently reported by Zahn and Kruesi (1993).

A biological marker of great interest in connection with antisocial behavior is the enzyme monoamine oxidase (MAO E.C. 1.4.3.4). In several studies impulsive-aggressive and disinhibited

*To whom all correspondence should be addressed.

373

314 Britt af Klinteberg and Lars Oreland

behaviors have been associated with low serotonergic activity in the central nervous system (CNS) (Linnoila, Virkkunen, Scheinin, Nuutila, Rimon & Goodwin, 1983; Linnoila, DeJong & Virkkunen, 1989). The activity of MAO in blood platelets, which is supposed to reflect central serotonergic function (Oreland, 1993; Oreland & Shaskan, 1983), is a more accessible biological indicator and has been found to be of particular interest in the understanding of biological bases for antisocial behavior and psychosocial disorders. MAO is a mitochondrial enzyme present in all tissues and is responsible for the oxidative deamination of the endogenous monoamine neurotransmitters as well as of exogenous monoamines. Levels of MAO activity within individuals have been found to be quite stable over time (Murphy, Belmaker, Buchsbaum, Martin, Ciaranello & Wyatt, 1977; Murphy, Wright, Buchsbaum, Nichols, Costa & Wyatt, 1976) with a heritability of about 0.75 as revealed by twin studies (Pedersen, Oreland, Reynolds & McClearn, 1993).

The notion that platelet MAO activity reflects central serotonergic activity is supported by the findings of a positive correlation between cerebral spinal fluid (CSF) levels of 5hydroxyindoleacetic acid (5HIAA) and platelet MAO activity (Oreland, Wiberg, Asberg, Trbkman, Sjostrand, Thoren, Bertilsson & Tybring, 198 1). In support of a positive correlation between platelet MAO and central serotonergic activity are also recent findings in volunteers of a significant negative relationship between platelet MAO activity and number of failed inhibitions in a computerized reaction time task with auditory signals for response inhibition (af Klinteberg, Oreland, Hallman, Wirsen, Levander & Schalling, 1991). In similar tasks, deficient performance has been strongly associated with serotonergic depletion in animal studies (Soubrie, 1986) and with non-conformity in human Ss (Newman, Widom & Nathan, 1985). Further evidence for a connection between low central serotonin turnover and low platelet MAO activity are findings of low levels of 5-HIAA in the CSF in violent offenders (Virkkunen & Linnoila, 1993) and in type II alcoholics (Virkkunen & Linnoila, 1993; von Knorring, Hallman, von Knorring & Oreland, 199 1; Devor, Cloninger, Hoffman & Tabacoff, 1993), and of a changed responsivity to a serotonin receptor agonist (m-chlorophenylpiperazin, m-CPP) in males exhibiting antisocial personality disorder with substance abuse (Moss, Jeffrey & Panzak, 1990). Thus, these categories of individuals also have low platelet MAO activity (see Belfrage, Lidberg & Oreland, 1992). The exact mechanism for the association between central serotonergic activity and platelet MAO activity is not known. The fact that the serotonergic neuron, in contrast to other monoaminergic neurons, but similar to the thrombocytes, contains the ‘wrong type’ of the enzyme, i.e. MAO-B (Levitt, Pintar & Breakfield, 1982), which is relatively ineffective in metabolizing serotonin, as well as the presence of a variety of other serotonergic functions in the thrombocyte (Pletscher, 1987), support the notion that platelet MAO activity and central serotonergic activity or capacity are regulated by a common factor. Possible mechanisms for such a common regulation, on the molecular level, have recently been reviewed (Oreland & Hallman, in press). A low or qualitatively weak serotonergic turnover, in several studies, has been found to be related to certain personality traits such as sensation seeking and impulsivity in both normal Ss and psychiatric patients (see Zuckerman, 1991; Oreland, 1993). Accordingly, low platelet MAO activity has been used as a biological indicator for vulnerability to disinhibitory psychopathology present in different forms of psychosocial disorders and evidenced as psychopathy, violent suicide attempts, hyperactivity and alcoholism (see Oreland, 1993). Interestingly, low platelet MAO activity was earlier found also in relatives of alcoholics (Alexopoulos, Lieberman & Frances, 1983), supporting the notion of an underlying vulnerability. Disinhibitory syndromes are characterized by an impaired control of impulses and reduced ability to anticipate negative consequences of behavior (Gorenstein & Newman, 1980). Of particular relevance for the present study are recent results that in a group of males, who had committed crime before the age of 15 yr, those who continued to commit crimes displayed significantly lower platelet MAO activities than those who had no continued criminality (Alm, Alm, Humble, Leppert, Sorensen, Lidberg & Oreland, 1994).

Findings supporting the assumption that hyperactive behavior and aggressiveness have additive effects on severity of adult maladjustment outcome have been reported at some length (Loney, Langhome & Patemite, 1978; Fanington, Loeber & van Kammen, 1990; Taylor, Sandberg, Thorley & Giles, 199 1). With reference to these results, the problem under examination will be elucidated by analyses of data for persistent hyperactive behavior, measured as the combination of concentration difficulties and motor restlessness, and persistent aggressiveness, from the ages of 10 and 13 yr, and of platelet MAO activity, from the age of 26-27 yr. It was hypothesized that a behavior pattern of

Childhood behaviors and adult platelet MAO activity 375

combined hyperactive and aggressive behaviors in childhood is related to low serotonergic activity in the same individuals. To examine this hypothesized linkage, configural frequency and loglinear analyses were applied, using prospective longitudinal data.

METHOD

In the longitudinal research program ‘Individual Development and Adjustment’, an age cohort of children in a Swedish community attending grade three (about 10 yr of age) at the time of the first data collection, comprising about 1100 Ss, have been prospectively studied (Magnusson, Dun& & Zetterblom, 1975; Magnusson, 1988). The purpose of the research program is to study individual development and adjustment from an interactionistic perspective. Within this program, a sample of 5s (‘the biological investigation sample’), considered to be representative of all school children in the community, have been prospectively and intensively studied from childhood to adulthood. Data for the study presented here refer to this sample.

Subjects

The specific investigation group employed in the following analyses is defined as those boys from whom behavioral data were obtained at the ages of 10 and 13 yr as well as biological measures at the adult age. A biological investigation was completed on 84 male Ss at age 2627 yr and of them 75 Ss had complete data from all three occasions in time. A study of the drop out at adult age has not indicated any drop-out bias (Bergman & Magnusson, 1983).

Behavior ratings

Ratings of behavior at the ages of 10 and 13 yr were obtained from the teachers, who most often had followed the Ss for 3 yr. Different teachers performed the ratings at each age level, which means that the ratings were made by independent raters at the two age levels. Behavior was rated on seven-point scales with verbal descriptions of the extreme manifestations as follows.

Motor Restlessness. (1) They have no difficulty at all in satisfying even great demands on silence and quietness. (7) They find it very difficult to sit still during lesssons. They fidget uneasily in their seats or wish to move about in the classroom, even during lessons. They may also be talkative and noisy.

Concentration Difficulties. (1) They have a marked ability to concentrate on a task and persevere with it. They never allow themselves to be distracted, and do not give up as long as a task suits their level of intelligence. (7) They cannot concentrate on their work, but are occupied with irrelevant things, or sit daydreaming. For a few moments they may work but are soon lost in other thoughts again. They usually give up quickly, even when the work is suited to their level of intelligence.

The reliability for the rating variables is conservatively estimated at 0.80 (Magnusson et al., 1975). In earlier studies within the research project, the teacher ratings have demonstrated high validity (Backteman & Magnusson, 1981).

Persistent Hyperactive Behavior. In the analyses presented here, the sum of ratings of Motor Restlessness and Concentration Difficulties was used as an indicator of Hyperactive Behavior. Ratings for these two variables pooled across the two age levels of 10 and 13 were combined to yield an indicator of persistent Hyperactive Behavior. Boys with sum scores of 20 5 were classified as ‘high’ and those with scores < 20 as ‘low’ on the persistent Hyperactive Behavior variable.

Persistent Aggressiveness. In the present analyses, ratings of Aggressiveness over the two age levels of 10 and 13 were combined to yield an indicator of persistent Aggressiveness. Boys with sum scores of 10 5 were classified as ‘high’ and those with scores < 10 as ‘low’ on the persistent Aggressiveness variable.

Determination of platelet MAO activity

Blood samples were obtained in the morning at a hospital-based laboratory for determination of MAO activity in thrombocytes. MAO activity was analyzed in platelet-rich plasma according to the procedure described by Eckert, Gottfries, von Knorring, Oreland, Wiberg and Winblad (1980). Two substrates were used, 14C-labelled P-phenyl-etylamine (B-PEA) and tryptamine, which may be


assumed to assess the same kind of MAO activity (Fowler, Ekstedt, Egashira, Kinemuchi & Oreland, 1979). Activity is expressed as nanomoles of substrate oxidized per 10” platelets per minute.

Treatment of data

Configural Frequency Analyses [CFA (von Eye, 1990; Bergman & Magnusson, 1984; Krauth & Lienert, 1982)] were applied to test the existence of syndromes. The CFA compares the observed frequencies of all possible variable combinations to the expected frequencies under the null hypothesis of independence among the variables. A pattern that occurs more often than could be expected by chance is a significant configurational ‘type’, and a pattern that occurs less often than could be expected by chance is a significant ‘antitype’. The level of significance was adjusted by multiplying the nominal significance level by the number of all possible variable combinations in the present design. Since there was a significant (rX, = 0.79), though not as high correlation as could be expected between the two MAO substrates (cf. af Klinteberg et al., 199 l), results from the CFA performed on both the P-PEA and the tryptamine substrates are presented. Finally, for the study of the relative contribution of the behavior variables to the prediction of platelet MAO activity, a logistic regression analysis with persistent Hyperactive Behavior and persistent Aggressiveness as independent variables and adult platelet MAO activity as the dependent variable, as well as loglinear analyses with all three variables as additive factors and their possible interactions were performed (Bishop, Fienberg & Holland, 1975).

RESULTS

Relationships of persistent Hyperactive Behavior and Aggressiveness in childhood to adult platelet MAO activity

Patterns of persistent hyperactive behavior and aggressiveness from the ages of 10 and 13 and platelet MAO activity at adult age were examined. The behavior measures of persistent Hyperactive Behavior and persistent Aggressiveness were dichotomized and coded as ‘low’ ( < 20 and < 10, respectively) and ‘high’ (20 5 and 10 I, respectively). The platelet MAO activity was dichotomized using the mean as cutoff point: platelet MAO < mean was coded as ‘low’ and platelet MAO L mean was coded as ‘high’. The combination of (a) high or low persistent Hyperactive Behavior, (b) high or low persistent Aggressiveness, and (c) high or low platelet MAO activity yields eight groupings of the 75 males for whom complete data are available. In order to test which of the eight patterns occurred more or less often than could be expected from a random model, the CFA was applied. The results of the analyses are presented in Tables 1 and 2.

In line with expectations, a significant excess of cell frequencies (‘types’) was found for the pattern of (1) high persistent Hyperactive Behavior, high persistent Aggressiveness, and low platelet MAO activity for the B-PEA substrate (see Table 1). Furthermore, there was a tendency for the combination of being (2) high in persistent Hyperactive Behavior, low in persistent Aggressiveness, and high in platelet MAO activity, to occur less often than could be expected by chance (forming an ‘antitype’) for the /?-PEA substrate. Seven out of the 75 males were expected according to a random model. However, only one male S was obtained for that pattern.

The results of the pattern analyses correspond to what was expected from variable oriented analyses (Shekim, Hodges, Horwitz, Glaser, Davis & Bylund, 1984; Kruesi, Hibbs, Zahn, Keysor, Hamburger, Bartko & Rapoport, 1992). In the present study, 12 males belonged to the group of male Ss characterized by high persistent Hyperactive Behavior and high persistent Aggressiveness in childhood. For the combination of being high in persistent Hyperactive Behavior and high in persistent Aggressiveness at an early age, and low in platelet MAO activity at adult age, 2.3 out of the 75 male Ss were expected (for the P-PEA substrate) according to a random, model. As is seen in Table 1, eight males were obtained for that pattern, forming a highly significant ‘type’.

The results of the analysis based on the MAO P-PEA data presented in Table 1 were cross-validated by a pattern analysis based on the platelet MAO tryptamine substrate data, and the results are presented in Table 2.

The same significant result pattern was obtained for the MAO tryptamine data in the CFA analysis


Table 1. Configurations of dichotomized persistent Hyperactive Behavior and Aggressiveness variables based upon ratings at age IO and 13 yr, and a dichotomized biochemical variable, platelet monoamine oxidase (MAO) activity (substrate P-PEA) for a group of

normal male 5s at the age of 27 yr (n = 75)

Hyperactive

Pattern Size Level of sign

Type/ Behavior Aggressiveness MAO-B Obtained Expected z Adjusted level antitype

Low Low Low 23 23.10 - 0.03 Low Low High 28 20.21 2.03 LOW High Low 3 6.71 - 1.52 Low High High 2 5.92 - 1.68 High Low Low 6 7.84 - 0.69 High Low High

: 6.87 - 2.35 0.10 at

High High Low 2.30 3.82 0.005 t High High High 4 2.01 I .42

The level of significance was adjusted by multiplying the nominal significance level by eight (the number of all possible variable combinations in the present design).

as for the MAO P-PEA data. These findings from a pattern approach underscore that findings obtained in variable based approaches are robust.

In a logistic regression analysis with persistent Hyperactive Behavior and persistent Aggressiveness as independent variables and adult platelet MAO activity as the dependent variable, Hyperactive Behavior contributed significantly (P < 0.05, one-tailed test) to the prediction of adult platelet MAO activity, whereas there was no significant contribution of Aggressiveness for the present group.

Results of loglinear modelling of persistent Hyperactive Behavior and Aggressiveness in childhood and adult platelet MAO activity

The distribution of scores in the behavior variables and platelet MAO activity was dichotomized as described above in the presentation of the results of the CFA and the logistic regression analysis. Since the relationship with platelet MAO was shown to be in the expected direction, it was of interest to further study the main effects of the persistent Hyperactive Behavior and Aggressiveness, and the platelet MAO activity variables in loglinear analyses with all three variables as additive factors and their possible interactions. Results are presented in Table 3. The main effect’s model gave a poor fit (Likelihood ratio = 27.3, d.f. = 4, P < 0.000). Inclusion of the interaction between Hyperactive Behavior and Aggressiveness gave a significantly better model fit (Likelihood ratio = 5.7, d.f. = 3, P < 0.13). The final model chosen included also the interaction between Hyperactive Behavior and platelet MAO activity, which gave a good fit (Likelihood ratio = 1.3, d.f. = 2, P < 0.52). The final model (5) was chosen since it gave a significantly better fit than the model with only one interaction included (4). The difference between the iikelihood ratio (G’) for model 4 and G* for model 5 has an asymptotic x2 distribution with degrees of freedom d.f.(4)+l.f.(5) = 1 (x2 = 4.39, d.f. = 1, P < 0.05). The model with all three interactions was not significantly better than the chosen model.

Table 2. Configurations of dichotomized persistent Hyperactive Behavior and Aggressiveness variables based upon ratings at age 10 and 13 yr, and a dichotomized biochemical variable, platelet monoamine oxidase (MAO) activity (substrate tryptamine) for a group

of normal male 5s at the aee of 27 vr (n = 75)

Hyperactive

Pattern Size Level of sign

Type/ Behavior Aggressiveness MAO-rrypt Obtained Expected 2 Adjusted level antitype

Low Low Low 26 24.83 0.29 Low Low High 25 18.48 I .-I5 Low High Low 3 7.28 - 1.67 Low High High 2 5.42 - 1.53 High Low Low 6 8.42 - 0.89 High Low High I 6.27 - 2.20 Hieh High Low 8 2.47 3.58 0.005 t High High High 4 I .83 I .62

The level of significance was adjusted by multiplying the nominal significance level by eight (the number of all possible variable combinations in the present design).


Table 3. Likelihood ratios (G*). degrees of freedom (d.f.). and P-values of the nine possible hierarchical models in a loglinear analysis with all three variables, persistent Hyperactive Behavior (I) and Aggressiveness (2) based upon ratings at age IO and 13 yr, and platelet MAO activity (3). entered as additive factors, and their possible interactions, for a group of normal male Ss at age 27 yr

(n = 75)

Model Variables G2 d.f. f-value

: [I] [2] [3] [I 31 27.3 22.9 4 3 0.000 0.000 3 [2 31 26.1 3 0.000 4 [I 21 5.7 3 0.13

i [I [I 2][23] 21 [I 31 4.5 1.3 2 2 0.52 0.10 7 [I 3][23] 21.7 2 0.000

[I 21 [I 31 [2 31 1.3 [I231 0

:, 0.26 I

The model including the interaction term between Aggressiveness and platelet MAO activity and the interaction between Hyperactive Behavior and Aggressiveness did not give a significantly better fit than the model including only the interaction between Hyperactive Behavior and Aggressiveness.

The two interaction terms were both significant. The interaction term for Hyperactive Behavior and Aggressiveness was positive and the one for Hyperactive Behavior and platelet MAO activity negative. There was no significant interaction effect between Aggressiveness and platelet MAO activity.

Coefficients of the estimates, standard errors, and P-values for the final loglinear model are presented in Table 4. The main effect of Aggressiveness was positive and significant (P < 0.01); for Hyperactive Behavior the main effect tended to be significant (PcO.06); and for platelet MAO activity there was no significant main effect-all in accordance with the cut-off points yielding the groupings. Observed and expected frequencies in the main effect’s model and the final loglinear model of the behavior rating variables and the platelet MAO activity variable are given in Table 5.

Concluding remarks. The critical pattern of interest from the hypothesis, supported by the results in the CFA analyses, was that of high persistent Hyperactive Behavior, high persistent Aggressiveness and low adult platelet MAO activity. The final loglinear model indicated for that pattern a positive relationship between Hyperactive Behavior and Aggressiveness, and a negative association between Hyperactive Behavior and platelet MAO activity. Both interactions were significant and contributed with positive effects to the model fit. The interesting parts of the model are the interaction effects between those additive factors, resulting in an excess of individuals for that cell, indicated in the CFA, by forming a significant ‘type’, and in the main effect’s model, by showing a very bad fit.

DISCUSSION

In the present study from the longitudinal project Individual Development and Adjustment (IDA), hyperactive and aggressive behaviors in childhood were found to be related to low platelet MAO

Table 4. The coefficients of the estimates, standard errors, and P-values for the final loglinear model (Likelihood ratio = I .3, d.f. = 2, P < 0.52) of dichotomized persistent Hyperactive Behav- ior (Hyp) and Aggressiveness (Agg) variables based upon ratings at age 10 and 13 yr, and a dichotomized biochemical variable, platelet monoamine oxidase (MAO) activity (substrate /?-PEA),

for a group of normal male Ss at the age of 27 yr (n = 75)

Variable

HYP Agg MAO Hyp*Agg Hvo*MAO

Estimate Standard error P-value

0.340 0.178 0.056 0.446 0.167 0.008 0.222 0.147 0.130 0.715 0.167 0.000

- 0.293 0.147 0.045

Childhood behaviors and adult platelet MAO activity

Table 5. Observed and expected frequencies in the main effect’s (El ) model and in the final (E2) loglinear model in patterns of dichotomized persistent Hyperactive Behavior and Aggressiveness variables based upon ratings at age 10 and 13 yr. and a dichotomized biochemical variable, platelet monoamine oxidase (MAO) activity (substrate /I-PEA), for a group of normal male Ss at the age of 27 yr (n = 75); and results of the models in terms of

likelihood ratios, degrees of freedom (d.f.), and P-values

379

Hyperactive Behavior

Pattern

Aggressiveness MAO-/I

Frequencies

Observed E I E2

Low LOW LOW Low Low High Low High High Low High Low High High High High

Likehhood ratio d.f. P-value

Low High Low High Low High Low High

23 23.10 23.68 28 20.21 21.32

3 6.17 2.32 2 5.92 2.68 6 7.84 5.16 I 6.86 I .84 8 2.30 8.84 4 2.01 3.16

27.3 I .29 4 2 O.OCiI 0.52

activity at adult age (26-27 yr) in the same Ss. In an earlier study on the present group of normal males, surprisingly high relationships were found between hyperactive behavior and aggressiveness in childhood on the one hand and an Impulsive Sensation-seeking Psychopathy factor at adult age (mean age 27 yr) (af Klinteberg, Schalling & Magnusson, 1990). In studies of associations between platelet MAO activity and personality scales, low platelet MAO activity has been found to be connected to extraverted, impulsive, sensation seeking-relat?d traits (Schalling, Asberg, Edman & Oreland, 1987; af Klinteberg, Schalling, Edman, Oreland & Asberg, 1987). Furthermore, low MAO Ss have been found to have higher use of tobacco and alcohol, to display more signs of possible alcohol dependence and more drug abuse (von Knorring, Oreland & Winblad, 1984). The integrating biology of hyperactive and aggressive symptoms might primarily concern the personality trait impulsivity and associated biological indicators (Shapiro, 1965; Eysenck & Eysenck, 1978; Schalling, Edman & &berg, 1983; Barratt & Patton, 1983; Zuckerman, 199 1). In an earlier study from the present project, hyperactive behavior in childhood was found to be highly related to adult impulsivity (af Klinteberg, Magnusson & Schalling, 1989), connected with criminal behavior, alcohol abuse, and other psychosocial disorders at adult age (Schalling, &berg, Edman & Levander, 1984; Rydelius, 1983). With regard to antisocial behavior, biological (Magnusson, Stattin & Dun&, 1983; Magnusson, 1987; Kruesi et al., 1992; Brennan, Mednick & Mednick, 1993; Smith & Hucker, 199 1) as well as genetical linkages have been demonstrated (Mednick, Gabrielli & Hutchings, 1984; for a review, see Mednick, Moffitt, Gabrielli & Hutchings, 1986).

Research results have indicated relationships between impulsive and aggressive behaviors and signs of a weak serotonergic turnover in the central nervous system (Virkkunen & Linnoila, 1993), impulsive and outacting aggressive personality traits, and low platelet MAO activity (Schalling et al., 1987; af Klinteberg et al., 1987). Furthermore, there are studies suggesting a more genetically related alcoholism (von Knorring, Bohman, von Knorring & Oreland, 1985; von Knorring et al., 199 1; Devor er al., 1993) to be negatively associated with platelet MAO activity. Interestingly, in a study of violent offenders it was found that Ss with alcoholic fathers had lower levels of the cerebrospinal fluid serotonin metabolite concentration and were more impulsive than Ss without alcoholic fathers (Linnoila et al., 1989). These results suggest that there may exist a familial vulnerability trait associated with early onset alcohol abuse, impulsive and violent criminal behavior, low central serotonergic turnover and low platelet MAO activity, supporting the notion about platelet MAO as being a genetic marker for central serotonergic activity (Oreland, 1993; Oreland & Shaskan, 1983). Furthermore, these findings are in line with the connection found in our earlier study on the present group between childhood hyperactive behavior, and alcohol problems and violent offending before the age of 25-26 yr in the same individuals (af Klinteberg et al., 1993). Another finding supporting the above reasoning of an underlying genetically linked vulnerability for disinhibitory tendencies is


that probands of males, diagnosed as hyperactives in childhood, were found to display significantly higher rates than comparisons of attention deficit hyperactivity disorder (ADHD) symptoms, antisocial personality disorders, and drug abuse disorders (Mannuzza, Klein, Bessler, Malloy & LaPadula, 1993).

In the examination of developmental issues, in a Swedish follow-up study of young male criminals and controls (see af Klinteberg, Humble & Schalling, 1992), childhood hyperactive behavior Ss were found to be significantly overrepresented among Ss in the upper 25% of the sample distribution of scores on the Psychopathy Check List [PCL (Hare, 1991)] at adult age. In studying the specific contribution of hyperactive behavior and aggressiveness to the development of psychopathy-related traits, childhood hyperactive behavior and aggressiveness, respectively, and PCL scores at adult age in the same Ss, were examined. Preliminary results indicate that Ss with hyperactive behavior symptoms and Ss with a combination of hyperactive behavior and aggressiveness, but not Ss with aggressive symptoms only, had significantly higher PCL scores at adult age than Ss with no childhood hyperactive or aggressive symptoms (af Klinteberg, in preparation). This relationship is noteworthy, in the light of the present results of childhood hyperactive and aggressive behaviors together being connected significantly more often than could be expected by chance with low platelet MAO activity at adult age. Subsequently, it is of specific interest to note that in the loglinear modelling of additive factors, the unique interaction effects of the present two aspects of externalizing behaviors indicated hyperactive behavior to be related to an underlying biological vulnerability in terms of low serotonergic turnover, and aggressiveness to be strongly associated with hyperactive behavior, assumingly worsening the developmental outcome of the deficiency. The recent findings of Alm and coworkers (1994), that individuals who continued committing crimes after 15 yr of age had significantly lower platelet MAO activities than individuals who did not continue to commit crimes after this age, are in notable consonance with these findings. Low platelet MAO activity was also related to psychopathy in groups of criminals (Lidberg, Modin, Oreland, Tuck & Gillner, 1985) and to violence in mentally disordered non-psychotic offenders (Belfrage et al., 1992). Moreover, reduced central serotonergic function was reported to be associated with impulsive aggression in a group of personality disorder patients (Coccaro, Siever, Klar, Maurer, Cochrane, Cooper, Mohs & Davis, 1989), and interestingly, in an examination of alcoholic, violent offenders and controls, to be primarily associated with impulsivity aspects ofbehavior (Virkkunen, Rawlings, Tokala, Poland, Guidotti, Nemeroff, Bissette, Kalogeras, Karonen & Linnoila, 1994).

Conclusion

The analyses in the present study suggest a possible underlying biological indicator of vulnerability to psychosocial disturbances to be connected to childhood problem behaviors such as hyperactive and aggressive behaviors in the same individuals, prominently persistent hyperactive behavior. The critical pattern of interest from the hypothesis, supported by the results in the configural frequency analyses, was that of high persistent hyperactive behavior, high persistent aggressiveness and low adult platelet MAO activity. The results of the final loglinear model indicated for that pattern a positive relationship between hyperactive behavior and aggressiveness, and a negative association between hyperactive behavior and platelet MAO activity. Both interactions were significant and contributed with positive effects to the excess of individuals for that specific variable combination. The empirical results and the approach of performing the analyses emphasize the importance of an interactionistic theoretical perspective on individual development and its methodological implications (Magnusson, 1990). In an interactionistic perspective, individual development is understood as a continuously ongoing process in which psychological and biological factors in the individuals, and factors in the environment are involved in the overriding theoretical framework (Magnusson, 1988), as has been the case in the research program from which the present data stem.

Acknowledgemenrs-This research was supported by grants from the Swedish Council for Planning and Coordination of Research, the Bank of Sweden Tercentenary Foundation, and the Swedish Medical Research Council. Valuable comments on an earlier version and constructive collaboration with Professor D. Magnusson and Dr S. E. Johansson concerning statistical methods are gratefully acknowledged.


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