Journal of Child Psychology and Psychiatry 43:4 (2002), pp 417–434
Annotation: The role of prefrontal deficits, low
autonomic arousal, and early health factors
in the development of antisocial and
aggressive behavior in children
University of Southern California, USA
Background: This article selectively reviews the biological bases of antisocial and aggressive behavior in
children with a focus on low autonomic functioning, prefrontal deﬁcits, and early health factors.
Results: Low resting heart rate is thought to be the best-replicated biological correlate of antisocial and
aggressive behavior in child and adolescent populations and may reﬂect reduced noradrenergic
functioning and a fearless, stimulation-seeking temperament. Evidence from neuropsychological,
neurological, and brain imaging studies converges on the conclusion that prefrontal structural and
functional deﬁcits are related to antisocial, aggressive behavior throughout the lifespan. A prefrontal
dysfunction theory of antisocial behavior is advanced. This argues that social and executive function
demands of late adolescence overload the late developing prefrontal cortex, giving rise to prefrontal
dysfunction and a lack of inhibitory control over antisocial, violent behavior that peaks at this age. Birth
complications and minor physical anomalies are selectively associated with later violent behavior,
especially when combined with adverse psychosocial risk factors for violence. Cigarette smoking during
pregnancy may increase the risk for antisocial and violent behavior in later life by disrupting
noradrenergic functioning and enhancement of cholinergic receptors that inhibit cardiac functioning.
Malnutrition during pregnancy is associated with later antisocial behavior and may be mediated by
protein deﬁciency. Conclusions: It is argued that early health intervention and prevention studies may
provide the most effective way of reversing biological deﬁcits that predispose to antisocial and aggressive
behavior in children and adults. Keywords: Aggression, antisocial behavior, brain imaging, health,
There is no doubt that genetic processes play an lessness, executive functions, head injury, and
etiological role in childhood antisocial and aggressive neurological processes. The last process, early
behavior (Eley, Lichenstein, & Stevenson, 1999; Ge health factors, is more broadly construed and in-
et al., 1996; Slutske et al., 1997). What is much less cludes discussion of birth complications, minor
clear are the precise physiological mechanisms and physical anomalies, exposure to smoking, and mal-
pathways through which these genetic processes nutrition.
exert their inﬂuence in predisposing towards anti- There are different reasons for highlighting each of
social behavior. In addition, it is well known that these three processes. Heart rate is highlighted be-
non-genetic, environmental processes produce cause it is the best-replicated biological correlate of
physiological changes in both CNS and ANS antisocial and aggressive behavior in children. Pre-
functioning in a way that can predispose to antisocial frontal deﬁcits are selected because brain imaging
and aggressive behavior (Suomi, 2000; Raine, 1997). research is becoming an increasing source of new
There are therefore strong reasons to believe that discovery on biology – antisocial relationships, and
biological processes play a key role in the etiology of because they highlight the importance of future
antisocial and violent behavior in both children and imaging studies in antisocial child populations.
adults, but what are the most important of these Health factors are underscored because of the in-
processes, and what are their mechanisms of action? creasing focus on early biological processes that are
This selective review focuses on just three biolo- amenable to change. Nevertheless, these are not the
gical processes, low resting heart rate, prefrontal only biological processes that are of importance with
deﬁcits, and early health factors, an approach taken respect to antisocial behavior, and readers are re-
to focus on some of the most promising avenues of ferred to Davidson, Putnam, and Larson (2000),
future research. The ﬁrst two processes are highly Fishbein (2001), Henry and Mofﬁtt (1997), Lahey,
speciﬁc, but their coverage incorporates discussion McBurnett, Loeber, and Hart (1995), Raine (1993),
of vagal tone, noradrenergic functioning, right Susman and Ponirakis (1997), and Volavka (1999)
hemisphere functioning, stimulation seeking, fear- for reviews of other biological processes.
Ó Association for Child Psychology and Psychiatry, 2002.
Published by Blackwell Publishers, 108 Cowley Road, Oxford OX4 1JF, UK and 350 Main Street, Malden, MA 02148, USA
418 Adrian Raine
some way cause low heart rate (Wadsworth, 1976;
Autonomic underarousal and low resting heart rate
Farrington, 1987; Mofﬁtt & Caspi, 2001; Raine et al.,
Of the many psychophysiological processes that 1990, 1997a). One of these studies shows that
have been studied, low autonomic arousal has been resting heart rate at early as age 3 years relates to
most repeatedly related to antisocial, criminal, and aggressive behavior at age 11 years (Raine et al.,
violent behavior in both child and adult samples 1997a).
(Fishbein et al., 1989a; Fowles, 1993; Lahey, Hart, 4. Low heart rate is diagnostically speciﬁc. An
Pliszka, & Applegate, 1993; Raine, 1993; Patrick, unusual and important feature of the relationship is
1994; Volavka, 1995). While most studies have as- its diagnostic speciﬁcity. While conduct disorder has
sessed antisocial behavior in general without differ- been associated with low resting heart rate (e.g.,
entiating aggressive from non-aggressive forms, Rogeness, Cepeda, Macedo, Fischer, & Harris,
studies that have assessed violence have conﬁrmed 1990a), no other psychiatric condition appears to
that relatively low resting heart rate characterizes have been linked to low heart rate. Other psychiatric
aggressive and violent behavior (Farrington, 1997; conditions, including alcoholism, depression, schizo-
Raine, Reynolds, Venables, & Mednick, 1997d; phrenia, and anxiety disorder, have, if anything,
Raine, Reynolds, Venables, & Mednick, & Farring- been linked to higher (not lower) resting heart rate. In
ton, 1998a; Pitts, 1997; Wadsworth, 1976). Although contrast, other biological markers of childhood an-
there are multiple and not always consistent psy- tisocial behavior such as low cortisol and low sero-
chophysiological correlates of aggressive, antisocial, tonin are also found in other childhood disorders.
and violent behavior (Fishbein, Lozovosky, & Jaffe, 5. Findings have been replicated in at least 6 dif-
1989b; Volavka, 1995; Raine, 1993; Patrick, Zem- ferent countries. Low heart rate is a robust marker
polich, & Levenston, 1997; Lahey et al., 1995; Sus- independent of cultural context, with the relation-
man, Granger, Murowchick, Ponirakis, & Worrall, ship having been established in England (e.g., Far-
1996; Dettling, Gunnar, & Donzella, 1999), low rington, 1987), Germany (Schmeck & Poustka,
resting heart rate is chosen for focused attention in 1993), New Zealand (Mofﬁtt & Caspi, 2001), the US
this review for the following reasons: (e.g., Rogeness et al., 1990a), Mauritius (Raine et al.,
1. It is the best-replicated biological correlate of 1997a), and Canada (Mezzacappa et al., 1997).
antisocial behavior in child and adolescent samples. 6. Low heart rate is an independent predictor of
In a meta-analysis incorporating 29 independent violence. Low heart rate is predictive of later violence
samples, the average effect size was calculated at .56 independent of all other psychosocial and family risk
(Raine, 1996). This averaged effect size from these 29 factors. In a series of six regression analyses aimed
samples is robust in that it is found in female (d ¼ at establishing the best independent predictors of
.63) as well as in male samples (d ¼ .50), and is just convictions for violence in the Cambridge Study in
as strong as when heart rate is taken from a pulse Delinquent Development (Farrington, 1997), out of
reading (d ¼ .49) as when it is measured from a 48 family, socioeconomic, attainment, and person-
Grass polygraph (d ¼ .53) (Raine, 1996). As argued ality predictors, only two risk factors were inde-
by Rutter, Giller, and Hagell (1998, p. 161) there is pendently related to violence (i.e., independent of all
now extensive evidence from both cross-sectional other risk factors) in all six analyses – low resting
and longitudinal studies that antisocial, aggressive heart rate and poor concentration. Indeed, low heart
individuals have lower resting heart rates than con- rate was more strongly related to both self-report
trols (although see Van Hulle, Corley, Zahn-Waxler, and teacher measures of violence than having a
Kagan, & Hewitt, 2000, for a recent failure to ﬁnd criminal parent. These ﬁndings led Farrington
this effect in twins). (1997) to conclude, ‘These results suggest that
2. The relationship is not artifactual. Studies have low heart rate may be one of the most important
repeatedly ruled out potential artifacts such as explanatory factors for violence’ (p. 99).
height, weight, body bulk, physical development, 7. The relationship is consistent with gender
and muscle tone (Raine, Venables, & Mednick, differences in antisocial behavior. There are robust
1997a; Wadsworth, 1976; Farrington, 1997), poor gender differences in resting heart rate, with males
scholastic ability and low IQ (Raine, Venables, & being lower than females (Voors, Webber, & Beren-
Williams, 1990; Farrington, 1997), excess motor son, 1982), a gender difference in the same direction
activity and inattention (Raine et al., 1997a; Far- as gender differences in antisocial behavior. Fur-
rington, 1997), drug and alcohol use (Raine et al., thermore, this gender difference in heart rate is in
1997a), engagement in physical exercise and sports place at age 3 years (mean difference ¼ 6.1 beats/
(Wadsworth, 1976; Farrington, 1997), and low social minute, d ¼ .36, p < .0001), just before age 4 years
class, divorce, family size, teenage pregnancy, and when gender differences in antisocial, aggressive
other psychosocial adversity (Raine et al., 1990; behavior begin to emerge (Shaw & Winslow, 1997).
Wadsworth, 1976; Farrington, 1997). Because gender difference is one of the most salient
3. The relationship is conﬁrmed in prospective de- features of adult violence, any compelling develop-
signs. Five prospective studies rule out the possi- mental account of such behavior has ultimately to
bility that living a delinquent way of life could in account for this effect. The strong and replicated
Prefrontal deﬁcits and antisocial behavior 419
gender difference in resting heart rate provides such responses relative to Criminals. Thus, particularly
an explanatory avenue. high heart rate may act as a protective factor in those
8. Low heart rate is heritable, and the offspring of predisposed to adult crime.
criminal parents have low resting heart rates. Twin 13. Low heart rate characterizes aggression in
studies of heart rate have repeatedly found sub- animals. Eisermann (1992) reported that rabbits
stantial heritability for resting heart rate, with her- who are more aggressive and dominant have lower
itabilities in the .65 to .82 range (Ditto, 1993; resting heart rates than subordinate, nonaggressive
Boomsma & Plomin, 1986; Boomsma, Van-den- rabbits. Furthermore, when dominance is experi-
Bree, Orlebeke, & Molenaar, 1989; Theorell, de- mentally manipulated, heart rate reduces as domi-
Faire, & Fagrell, 1978). Intriguingly, studies have nance increases. Similar relationships have been
also found that the offspring of criminal parents have found in macaques, baboons, and tree-shrews
low resting heart rates (Farrington, 1987; Venables, (Cherkovich & Tatoyan, 1973; Holst, 1986).
1987). Given the facts that (a) there is signiﬁcant
heritability for childhood aggression and adult anti-
social behavior and (b) there is intergenerational
Mechanisms by which low heart rate may
transmission of antisocial behavior, low heart rate
predispose to aggressive and antisocial behavior
could turn out to be one of the genetic mechanisms
that helps account for the transmission of antisocial Low resting heart rate represents one of the best
behavior from one generation to the next. replicated, most easily measured, most promising,
9. Low heart rate characterizes life-course per- yet perhaps least understood, biological correlates of
sistent antisocial individuals in particular. Mofﬁtt antisocial and aggressive behavior in child and
and Caspi (2001) have recently found that low adolescent samples. What are the mechanisms
resting heart rate assessed at ages 7, 9, and 11 whereby low resting heart rate predisposes to anti-
years is particularly characteristic of life-course social behavior? Low arousal, stimulation seeking,
persistent offenders, a group who has been hypo- fearlessness, increased vagal tone/vagal passive
thesized as having early neurobiological deﬁcits coping, reduced noradrenergic functioning, and re-
(Mofﬁtt, 1993). duced right hemisphere functioning represent sev-
10. Low heart rate characterizes female as well as eral of the possible processes which, either by
male antisocial individuals. Several studies, inclu- themselves or in combination, may predispose a
ding two that are prospective, have now established child to aggression. Physiological explanations of the
that within females, low heart rate is linked to heart rate–antisocial relationship consist of arousal
antisocial behavior (Rogeness, Javors, Mass, & theory, vagal tone, norepinephrine, and right hemi-
Macedo, 1990b; Maliphant, Hume, & Furnham, sphere dysfunction.
1990; Raine et al., 1997a; Mofﬁtt & Caspi, 2001).
This further demonstrates the generalizability of the Low arousal. The most obvious and simple physio-
relationship. logical explanation is that heart rate is a measure of
11. Heart rate interacts with psychosocial risk autonomic arousal, and that low physiological
factors. Boys with low resting heart rates are more arousal in general is a predisposition to antisocial
likely to become violent adult offenders if they also and criminal behavior (Eysenck, 1987; Raine et al.,
have a poor relationship with their parent, and if 1990). In support of this relatively simple theory,
they come from a large family (Farrington, 1997). which also invokes stimulation-seeking (see below),
Furthermore, boys with low heart rate are especially there is growing evidence that other measures of
likely to be rated as aggressive by their teachers if autonomic and central nervous system functioning,
their mother was a teenage parent, they come from a including resting EEG (Raine et al., 1990), skin
low SES family, or they were separated from a parent conductance activity (Fowles, 1993; Raine et al.,
by age 10 (Farrington, 1997). 1990), and cortisol (McBurnett et al., 1991; Susman
12. High heart rate protects against crime devel- & Petersen, 1992; van Goozen et al., 1998) are re-
opment. Raine, Venables, and Williams (1995) report lated to antisocial and conduct disordered behavior
on a 14-year prospective study from England in in children.
which autonomic and CNS measures of arousal, On the other hand there appears to be no unitary
orienting, and conditioning were taken in 101 un- arousal system, as intercorrelations between these
selected 15-year-old male schoolchildren. Of these, different measures of arousal are low or even non-
17 antisocial adolescents who desisted from adult existent in the general population (e.g., Raine et al.,
crime (Desistors) were matched on adolescent anti- 1990). However, it is conceivable that an extreme
social behavior and demographic variables with 17 (antisocial) group within this general population
antisocial adolescents who had became criminal by does have low arousal on multiple arousal measures.
age 29 (Criminals), and with 17 non-antisocial, non- Some evidence does exist for underarousal on at
criminals (Controls). Desistors had signiﬁcantly least two separate physiological measures of arousal
higher resting heart rates, higher skin conductance in antisocial child and adolescent samples (e.g., van
(SC) orienting, and higher SC conditioned orienting Goozen et al., 1998; Raine et al., 1990).
420 Adrian Raine
Stimulation seeking theory. Stimulation-seeking (1996) found reduced, not increased, vagal tone was
theory argues that low arousal represents an un- associated with aggressive behavior in children. If
pleasant physiological state; antisocial individuals reduced vagal tone does prove a systematic correlate
seek stimulation in order to increase their arousal of antisocial behavior, it will indicate that the resting
levels to an optimal or normal level (Eysenck, 1997; heart rate–antisocial relationship is driven by par-
Quay, 1965; Raine et al., 1997a). Antisocial behavior ticularly strong sympathetic underarousal which is
is thus viewed as a form of stimulation-seeking, in powerful enough to overcompensate for the lack of
that committing a burglary, assault, or robbery parasympathetic inﬂuences (low vagal tone) which
could be stimulating for some individuals. would otherwise be expected to increase heart rate in
In support of this theory, El-Sheik, Ballard, and antisocial children.
Cummings (1994) found that preschool boys who
chose to watch videotapes depicting intense anger Reduced noradrenergic functioning. Strong un-
had lower heart rates than controls, and also that derarousal of the sympathetic nervous system would
low resting heart rate was associated with external- support a neurochemical explanation of the heart
izing problems. This indicates some support for the rate–antisocial relationship based on reduced nor-
view that low heart rate characterizes both stimula- adrenergic functioning. The monoamine norepi-
tion-seeking and antisocial behavior. Similarly, nephrine, found in autonomic nervous system
resting heart rate at age 3 years has been found neurons and produced in the locus coeruleus, is
to characterize stimulation-seeking behavior at centrally involved in attention and vigilance and
3 years, as well as aggressive behavior at 11 years forms one of the four arousal systems in the brain-
(Raine et al., 1997a, 1998a). stem.
While studies of peripheral measures of norepi-
Fearlessness theory. Fearlessness theory argues nephrine in antisocial children have found weak
that low levels of arousal during mildly stressful positive or null effects (Berman, Kavoussi, & Coc-
psychophysiological test sessions are markers of low caro, 1997), a meta-analytic review found a signiﬁ-
levels of fear (Raine, 1993, 1997). For example, cant negative effect size of .41 between reduced
particularly fearless individuals such as bomb dis- central (cerebrospinal ﬂuid) measures of norepi-
posal experts who have been decorated for their nephrine and increased antisocial behavior (Raine,
bravery have particularly low heart rate levels and 1993). Furthermore, Rogeness et al. (1990a, b) found
reactivity (Cox, Hallam, O’Connor, & Rachman, both reduced heart rate and reduced noradrenaline
1983; O’Connor, Hallam, & Rachman, 1985), as do in conduct disordered children.
British paratroopers decorated in the Falklands war
(McMillan & Rachman, 1987). Reduced right hemisphere functioning. Poor right
Antisocial and violent behavior (e.g., ﬁghts and hemisphere functioning could underlie the low heart
assaults) requires a degree of fearlessness to exe- rate–antisocial relationship. The right hemisphere is
cute, and lack of fear of socializing punishments in dominant for the control of autonomic functions,
early childhood would contribute to poor fear con- including heart rate (Lane & Jennings, 1995) and
ditioning and lack of conscience development (Raine, both lesion and intracarotid amobarbital studies
1993). Fearlessness theory receives support from the conﬁrm that reduced heart rate is associated with
fact that low heart rate also provides the underpin- decreased right hemisphere functioning (Zamrini
ning for a fearless or uninhibited temperament in et al., 1990; Yokoyama, Jennings, Ackles, Hood, &
infancy and childhood (Scarpa, Raine, Venables, & Boller, 1987). In turn, although left hemisphere
Mednick, 1997; Kagan, 1994). dysfunction has frequently been implicated in viol-
ence and crime (Raine, 1993), poor right hemisphere
Vagal tone. Another physiological mechanisms to functioning has also been found in antisocial and
account for the heart rate–antisocial relationship is violent populations as measured by functional
increased vagal tone. Raine and Venables (1984) ﬁrst magnetic resonance imaging (fMRI – Raine et al.,
suggested that the low heart rate recorded in anti- 2001a), computerized tomography (CT – Hucker
social individuals may be a function of increased et al., 1988), neuropsychological tests (Day & Wong,
vagal tone and reﬂect a passive coping response to 1996), spatial IQ measures (Raine, Yaralian, Rey-
mildly stressful situations (i.e., so-called ‘resting nolds, Venables, & Mednick, in press), EEG deﬁcits
states’ prior to some other experimental manipula- (Evans & Park, 1997), and event-related potentials
tion). (ERPs – Drake, Pakalnis, Brown, & Hietter, 1988).
Data since then have not supported this hypo- Poor right hemisphere functioning (particularly
thesis, favoring instead increased parasympathetic the anterior regions) has been associated with deﬁ-
activity in antisocial individuals. For example, Mez- cits in the withdrawal system, a system that pro-
zacappa et al. (1997) found that antisocial 15-year- motes retreat from aversive and dangerous
old boys were characterized by low resting heart situations (Davidson, Eckman, Saron, Senulis, &
rates, but also found evidence for reduced, not in- Friesen, 1990; Davidson, 1998). Furthermore, pa-
creased, vagal functioning. Furthermore, Pine et al. tients with right hemisphere lesions, compared to
Prefrontal deﬁcits and antisocial behavior 421
those with left hemisphere lesions, have been shown Mofﬁtt & Caspi, 2001; Wadsworth, 1976; Raine
to have reduced heart rate and skin conductance et al., 1997a).
responses to ﬁlms depicting negative emotions (e.g.,
anger) (Zoccolotti, Caltagirone, Benedetti, & Gain-
otti, 1986). Reduced right hemisphere functioning Frontal deficits and antisocial/violent behavior
and a consequent weaker withdrawal system could
make children less averse to dangerous, risky situ- Perhaps the main difference between human and
ations that increase the probability of antisocial animal brains is the massive development of the
behavior. prefrontal cortex in the former. It is likely that this
prefrontal development has allowed humans to de-
velop a social system that emphasizes close co-
Conclusions on heart rate operation, reciprocal altruism, and close living in
Of the positions outlined above, stimulation-seek- groups. Such behavior requires a particularly efﬁ-
ing, fearlessness, and reduced noradrenergic func- cient system of aggression regulation. The following
tioning may ultimately be shown to be the most section explores the notion that the prefrontal cortex
likely partial explanations of the heart rate–antiso- plays a key role in the regulation of anger and
cial behavior relationship. Nevertheless, it is prob- violence, and that deﬁcits in prefrontal structure or
able that no one of the above processes by function can result in dysregulated, aggressive
themselves can explain the link between low heart behavior in adults and children.
rate and antisocial behavior. Furthermore, other
processes may play a signiﬁcant role. For example,
Frontal functional deﬁcits in adults
low heart rate may also index a lack of empathy in
children, which in turn could predispose to exter- Over the past decade brain imaging studies have
nalizing behavior problems (Zahn-Waxler, Cole, begun to converge on the conclusion that antisocial
Welsh, & Fox, 1995). Instead, it is likely that several and violent offenders have functional impairments to
of the explanations, in part or in combination, are the prefrontal region of the brain. Reviews of brain
relevant in explaining the relationship. The reason imaging studies of violent and psychopathic popu-
why low heart rate is a robust marker for antisocial lations conducted up to 1994 have been reviewed by
behavior may be because it is a broad, global con- Raine (1993), Raine and Buchsbaum (1996), and
struct that taps into multiple physiological and Henry and Mofﬁtt (1997). These reviews, while
psychological processes of relevance to antisocial showing variability in ﬁndings across studies, con-
behavior. cur in indicating that violent offenders have func-
The next generation of research in this area needs tional deﬁcits to the anterior regions of the brain,
to identify the speciﬁc cardiovascular processes particularly the frontal region.
(e.g., sympathetic versus parasympathetic) that are Since these reviews, at least seven more recent
active in shaping the relationship between low heart studies support this key ﬁnding of anterior brain
rate and antisocial/aggressive behavior. There is dysfunction. Goyer et al. (1994), using positron
also a need to assess whether manipulations of emission tomography (PET) in an auditory activation
resting heart rate cause changes in antisocial be- condition, showed that an increased number of ag-
havior. For example, stimulants act by increasing gressive impulsive acts were associated with reduced
both norepinephrine and dopamine (dopamine be- glucose in the frontal cortex of 17 personality-
comes norepinephrine through the attachment of disordered patients. Volkow et al. (1995), using PET
the enzyme dopamine b-hydroxylase). Stimulants in a non-activation, eyes open, resting state,
have also been found to increase heart rate (Wachtel observed reduced glucose metabolism in both pre-
& de Wit, 1999) as well as to reduce the symptoms frontal and medial temporal regions in 8 psychiatric
of conduct disorder independent of any effect of patients (3 with schizophrenia) with a history of
hyperactivity (Klein et al., 1997). Further research is violence. Kuruoglu, Arikan, Karatas, Arac, and Isik
needed, too, into the developmental context of the (1996), using single photon emission computerized
heart rate–antisocial relationship. Studies of adult tomography (SPECT) in a resting state, found that 15
psychopaths have failed to ﬁnd resting heart rate alcoholics with antisocial personality disorder
differences (Raine, 1993) but these studies have al- showed signiﬁcantly reduced frontal regional cere-
most exclusively compared psychopaths to crimi- bral blood ﬂow (rCBF) compared to 4 alcoholics with
nals who are not psychopaths, leaving open the other personality disorders and 10 nonalcoholic
possibility that both these groups may have lower controls. Intrator et al. (1997), using SPECT, showed
heart rates than non-criminal controls. The fact that that 8 drug-abusing psychopaths compared to 9
low heart rate in childhood and adolescence predicts non-psychopaths had increased rCBF bilaterally in
antisocial and criminal behavior in adulthood sug- fronto-temporal regions during the processing of
gests that low heart rate is of etiological signiﬁcance emotional words (see also Hirono, Mega, Dinov,
for adult criminal behavior as well as child antiso- Mishkin, & Cummings, 2000 below). Soderstrom,
cial behavior (Raine et al., 1990; Farrington, 1997; Tullberg, Wikkelsoe, Ekholm, & Forsman (2000),
422 Adrian Raine
also using SPECT, found reduced blood ﬂow in both during a social stressor task in which subjects had to
frontal and temporal lobes of 21 individuals convic- prepare and give a speech about their worst faults.
ted of impulsive violent offences. Using magnetic As argued by Damasio (2000), this is a task that is
resonance spectroscopy, Critchley et al. (2000) found particularly well suited to eliciting secondary emo-
lower prefrontal concentrations of N-acetyl aspartate tions such as shame, guilt, and embarrassment,
and creatine phosphocreatine in 10 mildly retarded which are thought to be mediated by the ventrome-
repetitively violent offenders compared to controls. dial prefrontal cortex. In a logistic regression in
These studies have been very variable with respect which the Antisocial group was compared to Con-
to subject population (e.g., murderers, violent trols, the three prefrontal and autonomic variables
schizophrenics, drug-abusing psychopaths) and (prefrontal gray/whole brain, heart rate, skin con-
measure of frontal functioning (blood ﬂow, glucose, ductance) predicted 50.8% of the variance and pre-
N-acetyl aspartate) and it should be noted that dicted group membership with an accuracy of
sample sizes are generally small. However, the fact 76.9%.
that they all observe anterior, frontal deﬁcits in as- These results are consistent with ﬁndings on pa-
sociation with violent, aggressive, antisocial beha- tients with neurological disorders in both single case
vior suggests that frontal dysfunction is a broad (Damasio, 1994) and group studies (Damasio, Tra-
predisposition to generalized antisocial and violent nel, & Damasio, 1990; Stuss & Benson, 1986). This
behavior. Frontal deﬁcits are not universally found, research demonstrates that those who have suffered
however; at least two studies (Seidenwurm, Pounds, signiﬁcant damage to the prefrontal region of the
Globus, & Valk, 1997, using PET in a non-activation, brain proceed to acquire an antisocial, psychopath-
eyes open, resting state, and Raine et al., 2001a ic-like personality. These patients also show auto-
using fMRI to a working memory challenge task) nomic arousal and attention deﬁcits to socially
have failed to ﬁnd frontal deﬁcits. Furthermore, it is meaningful events (Damasio, 1994, Damasio et al.,
clear that the prefrontal cortex is but one of a num- 1990), a ﬁnding consistent with the role played by
ber of brain structures implicated in neural circuits the prefrontal cortex in modulating emotion, arou-
underlying violence (Davidson et al., 2000). Never- sal, and attention (Stuss & Benson, 1986; Davidson,
theless, the overall body of brain imaging research 1993). These patients have major structural deﬁcits
clearly implicates frontal dysfunction in violent to the prefrontal cortex, and the relevance of such
offenders. ﬁndings to the majority of antisocial, psychopathic
In our own research, we found reduced prefrontal individuals in both society and prison could be
glucose metabolism in 41 murderers compared to 41 questioned. The fact that antisocial, psychopathic-
age, sex, and schizophrenia matched normal con- like individuals drawn from society also show a
trols (Raine, Lencz, Bihrle, Lacasse, & Collette, subtle but signiﬁcant volume reduction in the
1997). Furthermore, these deﬁcits particularly prefrontal cortex (Raine et al., 2000) supports the
characterized affective, impulsive murderers as op- relevance of these neurological studies for under-
posed to predatory, instrumental murderers (Raine standing antisocial behavior in society.
et al., 1998b). Nevertheless, three important ques- The speciﬁc subregion of the prefrontal cortex that
tions remain unanswered from this increasingly is structurally impaired in antisocial and aggressive
large body of research. First, are frontal deﬁcits individuals is still open to question. Data based on
speciﬁc to selected populations of institutionalized acquired damage to the prefrontal cortex in the form
offenders, or are they also found in community of gross lesions in civilians (Damasio, 1994) and
samples of violent offenders? Second, do violent off- damage incurred through warfare in soldiers (Graf-
enders have a physical, structural deﬁcit in this man et al., 1996) implicate the ventromedial and
region of the brain? Third, are prefrontal structural orbitofrontal sub-regions. Alternatively, impair-
and functional deﬁcits found in psychopathic forms ments to the dorsolateral region, which is critically
of antisocial behavior? involved in cognitive ﬂexibility and response per-
severation, cannot be ruled out because recidivistic
antisocial behavior can be conceptualized as
Prefrontal structural deﬁcits in adult antisocial
perseverative, unmodifyable behavior in the face of a
repeatedly punished response. Future research in
Findings from a recent structural MRI study provide non-neurological antisocial populations using ana-
answers to these questions above. Twenty-one indi- tomical MRI and segmentation of gray matter within
viduals recruited from the community with a diag- the prefrontal cortex is critically needed to resolve
nosis of antisocial personality disorder (APD) and this issue.
high psychopathy scores were shown to have an 11% What are the mechanisms and processes through
reduction in the volume of gray matter in the pre- which prefrontal and autonomic deﬁcits could pre-
frontal cortex, compared to both normal controls and dispose to antisocial personality disorder? There are
a substance dependence control group (Raine et al., at least three routes. First, patients with prefrontal
2000). The APD group also showed lower autonomic damage fail to give anticipatory autonomic responses
activity (both skin conductance and heart rate) to choice options that are risky, and make bad
Prefrontal deﬁcits and antisocial behavior 423
choices even when they are aware of the more ad- delinquents speciﬁcally have a deﬁcit with respect to
vantageous response option (Bechara, Damasio, executive functions, i.e., self-regulation and inhibi-
Tranel, & Damasio, 1997). This inability to reason tory control, concept-formation, abstract reasoning,
and to take appropriate decisions in risky situations problem-solving behavior, ﬂexible behavior respon-
is likely to contribute to the impulsivity, rule- sive to external contingencies, sustained attention,
breaking, and reckless, irresponsible behavior that planning, and organization. The frontal cortex is the
make up four of the seven traits of DSM-IV antisocial brain structure that has been most consistently im-
personality disorder. Second, the prefrontal cortex is plicated in executive function deﬁcits, although it
part of a neural circuit that plays a central role in should be noted that executive function deﬁcits do
fear conditioning and stress responsivity (Hugdahl, not always go hand-in-hand with frontal structural
1998; Frysztak & Neafsey, 1991). Poor conditioning deﬁcits. While Teicher and Golden (2000) argue that
is theorized to be associated with poor conscience evidence for executive function deﬁcits in antisocial
development (Raine, 1993), and individuals who are children is variable, a recent meta-analysis of exe-
less autonomically responsive to aversive stimuli cutive dysfunction and antisocial behavior by Mor-
such as social criticism during childhood would be gan and Lilienfeld (2000) shows signiﬁcant effect
less susceptible to socializing punishments, and sizes (Cohen’s d) of .40 for conduct disorder and .86
hence become predisposed to antisocial behavior. for juvenile delinquency, thus supporting Mofﬁtt’s
Experiments have repeatedly conﬁrmed that anti- position. There is debate, however, as to whether
social groups show poor fear conditioning (Raine, these effects are carried entirely by comorbid atten-
1993). Third, the prefrontal cortex is involved in the tion-deﬁcit disorder in antisocial children (e.g., see
regulation of arousal (Dahl, 1998; Hellige, 1993), Clark, Prior, & Kinsella, 2000), or whether executive
and as outlined earlier, deﬁcits in autonomic and function deﬁcits exist in aggressive children after
central nervous system arousal in antisocials have controlling for hyperactivity (see e.g., Seguin, Bou-
been viewed as facilitating a stimulation-seeking, lerice, Harden, Tremblay, & Pihl, 1999). On balance,
antisocial behavioral response to compensate for it seems likely that (a) conduct disordered children
such underarousal. comorbid for attention-deﬁcit disorder have the
severest executive functional deﬁcits; (b) conduct
disordered children without attention-deﬁcit have a
Frontal deﬁcits in antisocial children
less strong, but signiﬁcant form of executive function
Brain imaging and neurological studies, combined deﬁcits; (c) evidence for executive function deﬁcits
with the substantial neuropsychological and EEG supports the notion of frontal lobe deﬁcits in anti-
literature on antisocial and criminal behavior (Vola- social children.
vka, 1995; Raine, 1993), place beyond reasonable While structural brain imaging studies of conduct
doubt the fact that there is a link between prefrontal disordered children are lacking, there are studies of
deﬁcits and antisocial, violent behavior in adults. the behavioral sequelae that follow head injuries in
But are these same links found in children? And is children. Overwhelmingly, these studies ﬁnd that
there evidence that damage to the prefrontal region conduct disorder and externalizing behavior prob-
of the brain actually causes antisocial, aggressive lems are common after head trauma (Hux, Bond,
behavior in children? Skinner, Belau, & Sanger, 1998; Max et al., 1998;
The question of whether there are links between Butler, Rourke, Fuerst, & Fisk, 1997; Mittenberg,
prefrontal structural/functional deﬁcits and anti- Wittner, & Miller, 1997). It is also clear that some
social behavior in children would be most directly children develop internalizing rather than external-
answered by imaging research. Although there is a izing behavior problems after head injury (e.g., Max
growing literature on other externalizing disorders et al., 1998), while others remain relatively unaffec-
such as hyperactivity, which inconsistently impli- ted. When the problem is approached from the other
cates frontostriatal systems (Filipek, 1999), there direction, by looking at base rates of head injury in
appears to have been no studies conducted on con- delinquents and non-delinquents, rates are not too
duct disorder, aggression, or antisocial behavior in dissimilar, but parents of delinquent children are
children (although see Amen and Carmichael, 1997, much more likely to report that behavior problems
for a report of increased anterior medial frontal blood began to develop after head trauma compared to
ﬂow as assessed by SPECT in sixty-four 6–17-year- parents of non-delinquents (Hux et al., 1998).
olds with oppositional deﬁant disorder but lacking in Studies of children with lesions to the prefrontal
conduct disorder). Instead, one must turn to tradi- cortex early in life lend further evidence to the view
tional neuropsychological studies to answer the that head (and therefore brain) trauma can directly
question of functional deﬁcits in antisocial children. lead to antisocial and aggressive behavior. Anderson,
Reviews of this evidence in child and adolescent Bechara, Damasio, Tranel, and Damasio (1999)
samples indicate that antisocial behavior is charac- reported on two cases (one female, one male)
terized by neuropsychological impairments (Mofﬁtt, who suffered selective lesions to the prefrontal
1993; Raine, 1993). More speciﬁcally, Mofﬁtt (1990, cortex in the ﬁrst 16 months of life (bilateral
1993) has argued that antisocial children and polar and ventromedial in the female, and right
424 Adrian Raine
polar-medial- dorsal in the male). Both showed early control, and inhibit a growing sex drive, deal with
antisocial behavior that progressed into delinquency threats and challenges to their social status that
in adolescence and criminal behavior in adulthood, arise within their peer groups, and plan and organize
and included impulsive aggressive and nonaggressive for a future career. They need to sustain increasing
forms of antisocial behavior. Both had autonomic attention to school performance in order to maximize
deﬁcits, poor decision-making skills, and deﬁcits on career prospects. Those leaving school at 18 for a job
learning from feedback. Pennington and Bennetto in the real world lose the social structure and sup-
(1993) report on nine other cases of children suffering port systems that they have grown used to, and must
frontal lesions in the ﬁrst 10 years of life. They noted adapt their behavior to the more variable contin-
that all nine suffered behavioral problems after the gencies, incentives, and disincentives that drive
injuries, with 7 of the 9 being conduct disordered, economic life. In addition, they must plan and de-
and the remaining two exhibited either impulsive, velop strategies for attracting a partner (or choosing
labile, behavior or uncontrollable behavior. These between possible partners), and they may need to
cases when taken together strongly suggest that make early parenting decisions. Throughout this
damage to the prefrontal cortex can directly lead to period, they must evaluate and assess competing
antisocial, aggressive, and criminal behavior. life-course strategies and engage in complex decision
making. At the same time the normative rebellious
spirit and antisocial behavior that have character-
Developmental processes, frontal functions,
ized most adolescence (Mofﬁtt, 1993) must be in-
and antisocial behavior
hibited and suppressed in order to succeed in life
Brain imaging, neuropsychological, and neurological and make way for new, more adaptive behavioral
studies all suggest that damage or dysfunction to the strategies.
prefrontal cortex is a signiﬁcant predisposition to The prefrontal cortex bears the burden of this
antisocial behavior. These ﬁndings are based pre- magniﬁed cognitive load that requires multiple exe-
dominantly on studies focusing on children and cutive functions – sustained attention, behavioral
adolescents, or adults up to the mid-30s, but there is ﬂexibility to changing contingencies, working mem-
also recent evidence that aggression and antisocial ory, self-regulation and inhibition, abstract decision
behaviour in elderly demented patients is particu- making, planning and organization. Yet the pre-
larly associated with deﬁcits to the anterior and frontal cortex is relatively late to mature and this
frontal regions of the brain (Hirono et al., 2000; processing load occurs at a time when this structure
Miller, Darby, Benson, & Cummings, 1997; Mega is still developing, with myelination of the frontal
et al., 2000). Combined with studies showing that cortex continuing into the early 20s and even 30s. A
damage to the prefrontal cortex in the beginning of minority of individuals with early damage or dys-
life produces antisocial and aggressive behavior, and function of the prefrontal cortex would be particu-
imaging studies showing correlations between viol- larly likely to suffer an information overload during
ent offending and reduced prefrontal structure/ this time period, resulting in further dysfunction of
function in early to mid-adulthood, they together the prefrontal cortex, less regulatory control, and
make a compelling case for the notion that prefrontal further, life-long, antisocial behavior. Others with an
deﬁcits can cause antisocial and aggressive behavior intact but particularly late-maturing prefrontal cor-
throughout the lifespan. tex may be antisocial during childhood and adoles-
Adequate theories of antisocial and violent be- cence, but with further maturation of the frontal
havior need to explain why criminal offending peaks lobes in early adulthood may eventually discontinue
in the late teens, a phenomenon that has been called their antisocial behavior. Others may have frontal
‘at once the most robust and least understood dysfunction, but may be protected from antisocial
empirical observation in the ﬁeld of criminology’ behavior by having more social support or fewer
(Mofﬁtt, 1993, p. 675). The adolescent-limited per- social-transitional demands placed on them. Yet
spective of Mofﬁtt (1993) in which social norms make another group of late-onset offenders (Hamalainen &
antisocial, rebellious behavior during adolescence a Pulkkinen, 1996; Ishikawa & Raine, 2001) may not
normative but transient phenomenon is one per- evidence antisocial behavior until early adulthood
suasive account. It is argued here that a prefrontal when life stressors at this time overload a prefrontal
dysfunction theory of crime can also contribute in cortex with latent functional impairments.
part to understanding this crime–age relationship. In summary, the fact that children, adolescents,
Prior to adolescence, children live in a relatively adults, and elderly patients with prefrontal deﬁcits
structured environment where complex, life-chan- are characterized by antisocial, aggressive behavior
ging planning and decision making is not the norm. makes a compelling lifespan case for a prefrontal
In contrast, late adolescence is a stage in life where dysfunction theory of antisocial, aggressive beha-
enormous social demands are being placed on the vior. It is hypothesized that the social and executive
rapidly growing teenager, a load that calls on re- function demands of late adolescence place an
sources of the frontal cortex and its associated exe- overload on the late-developing prefrontal cortex,
cutive functions. Such adolescents need to regulate, giving rise to prefrontal dysfunction and a lack of
Prefrontal deﬁcits and antisocial behavior 425
inhibitory control over antisocial, aggressive beha- no interaction between perinatal insult and family
vior at this age. This prefrontal overload is hypo- adversity was found for a smaller sample of German
thesized to be particularly likely in individuals with children (N ¼ 322) where outcome was restricted to
developmental delays in prefrontal maturation or in follow-up at age 8 years (Laucht et al., 2000).
hyperactive children with pre-existing prefrontal The Copenhagen sample of 4,269 was reassessed
deﬁcits. Furthermore, persistence into adulthood of for violence outcome at age 34 years (Raine, Bren-
antisocial behavior is thought to be especially likely nan, & Mednick, 1997). The results indicate that the
in those who have suffered head trauma and which biosocial interaction previously observed holds for
may prevent a maturational catch-up of the pre- violent but not non-violent criminal offending. Fur-
frontal cortex in adulthood. thermore, the interaction was found to be speciﬁc to
more serious forms of violence and not threats of
violence. The interaction held for early onset but not
Early health factors late onset violence, and was not accounted for by
psychiatric illness in the mothers. Rearing in a
The question of whether brain deﬁcits exist in anti- public care institution in the ﬁrst year of life and
social, violent individuals is no longer a useful one. It attempt to abort the fetus were the key aspects of
is now beyond doubt that brain deﬁcits contribute in maternal rejection found to interact with birth com-
some way to antisocial and aggressive behavior. The plications in predisposing to violence. In a more de-
more important question concerns ‘What early fac- tailed assessment of a random 10% of this sample,
tors can signiﬁcantly increase the probability that a those with both early neuromotor deﬁcits (including
growing child will suffer impaired brain functioning birth complications) and unstable family environ-
and consequent antisocial behavior?’. This section ments had higher rates of teenage behavior problems
brieﬂy outlines early health factors that may con- and adult criminal and violent offending compared to
tribute to brain impairment, and consequently those with only social or biological risk factors
autonomic dysregulation and antisocial/aggressive (Raine, Brennan, Mednick, & Mednick, 1996). The
behavior. biosocial group with both sets of risk factors ac-
counted for 70.2% of all violence committed by the
Birth complications such as anoxia (lack of oxy-
Several studies have shown that babies who suffer gen), forceps delivery, and pre-eclampsia (hyperten-
birth complications are more likely to develop con- sion leading to anoxia) are thought to contribute to
duct disorder, delinquency, and commit impulsive brain damage, and they may be just one of a number
crime and violence in adulthood when other psy- of early sources of brain dysfunction observed in
chosocial risk factors are present. Speciﬁcally, ob- child and adult antisocial groups. On the other
stetric factors interact with psychosocial risk factors hand, as indicated above, birth complications may
in relation to adult violence. Raine, Brennan, and not by themselves predispose to crime, but instead
Mednick (1994) prospectively assessed birth com- may require the presence of negative environmental
plications and maternal rejection at age 1 year in circumstance to trigger later adult crime and viol-
4,269 live male births in Copenhagen, Denmark. ence. Furthermore, while they are likely to contrib-
Birth complications signiﬁcantly interacted with ute to prefrontal damage, their effects would not be
maternal rejection of the child in predicting violent speciﬁc to this brain area but would impact on
offending at age 18 years. Only 4% of the sample had multiple brain sites, including the hippocampus.
both birth complications and maternal rejection, but
this small group accounted for 18% of all the violent
Minor physical anomalies
crimes committed by the entire sample.
This ﬁnding from Denmark has been replicated in Minor physical anomalies (MPAs) have been associ-
several other studies. Piquero and Tibbetts (1999), in ated with disorders of pregnancy and are thought to
a prospective longitudinal study of 867 males and be a marker for fetal neural maldevelopment towards
females from the Philadelphia Collaborative Perina- the end of the ﬁrst three months of pregnancy. As
tal Project, found that those with both pre/perinatal such, they may be viewed as an indirect marker of
disturbances and a disadvantaged familial environ- abnormal brain development. MPAs are relatively
ment were much more likely to become adult violent minor physical abnormalities consisting of such
offenders. Pregnancy complications interacted with features as low-seated ears, adherent ear lobes, and
poor parenting in predicting adult violence in a large a furrowed tongue. While MPAs may have a genetic
Swedish sample (Hodgins, Kratzer, & McNeil, 2001). basis, they may also be caused by environmental
Similarly, perinatal risk interacted with being an factors acting on the fetus such as anoxia, bleeding,
only child in raising the odds of adult violent off- and infection (Guy, Majorski, Wallace, & Guy, 1983).
ending by a factor of 4.4 in a sample of 5,587 Fin- Minor physical anomalies have also been found to
nish males (Kemppainen, Jokelainen, Jaervelin, characterize pre-adult antisocial behavior and tem-
Isohanni, & Raesaenen, 2001). On the other hand, perament. Paulus and Martin (1986) found more
426 Adrian Raine
MPAs in aggressive and impulsive pre-school boys, a birth cohort of 4,169 males, found a twofold in-
while Halverston and Victor (1976) also found higher crease in adult violent offending in the offspring of
levels of MPAs in boys showing problem behaviors in mothers who smoked 20 cigarettes a day. Rasanen et
elementary school. MPAs have even been linked to al. (1999) again found a twofold increase of violent
peer aggression as early as age 3 years (Waldrop, criminal offending in the offspring of women who
Bell, McLaughlin, & Halverson, 1978). Although smoked during pregnancy. Weissman, Warner,
MPAs have generally characterized behavior disor- Wickramaratne, and Kandel (1999) found a fourfold
ders in children drawn from the normal population increase in conduct disorder in boys of mothers who
(see Pomeroy, Sprafkin, & Gadow, 1988 for a review), smoked 10 cigarettes a day during pregnancy, while
at least one study failed to observe a link between Wakschlag et al. (1997) found more than a fourfold
MPAs and conduct disorder within a mixed group of increase in conduct disorder in the offspring of
emotionally disturbed children (Pomeroy et al., mothers who smoked 10 cigarettes a day. Fergusson,
1988). Woodward, and Horwood (1998) also found a doub-
Mednick and Kandel (1988) studied MPAs, as- ling of risk for conduct disorder in the offspring of
sessed by an experienced pediatrician, in a sample of maternal smokers, while Day, Richardson, Golds-
129 12-year-old boys. MPAs were found to be related chmidt, and Cornelius (2000) found an increase of
to violent offending as assessed nine years later 6 points in behavior problems in three-year-olds
when subjects were aged 21 years, though not to exposed to smoking during the third trimester.
property offenses without violence. However, when Importantly, a number of the above studies have
subjects were divided into those from unstable, non- controlled for many third factors that could account
intact homes versus those from stable homes, a for the smoking–antisocial relationship. Low SES,
biosocial interaction was observed. MPAs only pre- low maternal education level, mother’s age at birth,
dicted violence in those individuals raised in un- family size, poor childrearing behaviors, bad par-
stable home environments. Similarly, Brennan, enting, obstetric complications, birth weight, family
Mednick, and Raine (1997), in a study of 72 male problems, parental psychiatric diagnoses, offspring
offspring of psychiatrically ill parents, found that smoking, and other drug use during pregnancy were
those with both MPAs and family adversity had es- controlled for in one or more of the above studies.
pecially high rates of adult violent offending. This One important third factor, criminality and anti-
interaction was conﬁrmed by Pine, Shaffer, Schon- social personality in the parents, was controlled for
feld, and Davies (1997) who found that MPAs in in the studies of Brennan et al. (1999), Weissman et
7-year-olds combined with environmental risk in al. (1999), and Wakschlag et al. (1997), although
predisposing to conduct disorder at age 17. These Hill, Lowers, Locke-Wellman, and Shen (2000) found
ﬁndings are similar to those on birth complications no relation between maternal smoking and conduct
reported above: thus the presence of a negative disorder after controlling for parental antisocial
psychosocial factor is required to ‘trigger’ the biolo- personality disorder. Taken together with the dose–
gical risk factor, and in both cases the effects are response relationship also established in several of
speciﬁc to violent offending. In a study conﬁrming the studies, these ﬁndings suggest (but do not prove)
speciﬁcity of MPAs to violence, Arseneault, Tremb- a causal relationship between smoking during
lay, Boulerice, Seguin, and Saucier (2000) found that
´ pregnancy and later antisocial and violent behavior.
MPAs assessed at age 14 predicted violent delin- Some interaction effects were observed between
quency at age 17 in 170 males, but not to nonviolent smoking and other factors. For example, Brennan
delinquency. In this study, effects were independent et al. (1999) found a much stronger link between
of family adversity. smoking during pregnancy and adult violent off-
ending in those who had suffered delivery compli-
cations – there was no such link in those lacking
Nicotine during pregnancy
delivery complications. Rasanen et al. (1999) simi-
The effect of fetal exposure to alcohol in increasing larly found interaction effects between birth compli-
risk for conduct disorders is well known (e.g., Fast, cations and teenage pregnancy, single-parent family,
Conry, & Loock, 1999; Olsen et al., 1997; Streiss- unwanted pregnancy, and developmental motor
guth et al., 1999), but recently a spate of studies has lags. Combined with other interaction effects for
established beyond reasonable doubt a signiﬁcant birth complications and MPAs noted above, these
link between smoking during pregnancy and later interaction effects for nicotine support a biosocial
conduct disorder and violent offending. A number of interaction conceptual framework for understanding
these studies are impressive in terms of their size, biology–antisocial relationships (Raine et al., 1997b)
the prospective nature of data collection, long-term and underline the need to test for interaction effects
outcome, and control for third factors. Rantakallio, in future studies.
Laara, Isohanni, and Moilanen (1992) found that the Maternal smoking during pregnancy may be an
offspring of mothers who smoked were twice as likely important contributory factor to the brain deﬁcits
to have a criminal record by age 22 in a sample of that have been found in adult offenders. Animal
5,966. Brennan, Grekin, and Mednick (1999), using research has clearly demonstrated the neurotoxic
Prefrontal deﬁcits and antisocial behavior 427
effects of two constituents of cigarette smoke – carb- towns for several months. Women who were preg-
on monoxide (CO) and nicotine (see Olds, 1997 for a nant at this time were exposed to severe malnutrition
detailed review). Prenatal nicotine exposure, even at at different stages of pregnancy. The male offspring
relatively low levels, disrupts the development of the of these women were followed up into adulthood to
noradrenergic neurotransmitter system (Levin, ascertain rates of antisocial personality disorder,
Wilkerson Jones, Christopher, & Briggs, 1996), and and were compared to controls who were not ex-
interferes with neuronal development in the cere- posed to malnutrition. The adult offspring of preg-
bellum which in turn is implicated in cognitive nant women who suffered signiﬁcant nutritional
functioning. Similarly, CO has been found to damage deﬁcits during the ﬁrst and/or second (but not third)
the basal ganglia, cerebral cortex, and cerebellar trimester of pregnancy had 2.5 times the rates of
cortex, as well as decrease levels of norepinephrine. antisocial personality disorder compared to controls
These effects of smoking exposure on noradren- (Neugebauer, Hoek, & Susser, 1999).
ergic neurotransmitter functioning may be of par- There is also initial evidence for relationships be-
ticular signiﬁcance in the context of autonomic tween zinc and protein deﬁciency and aggression in
deﬁcits in antisocial individuals outlined earlier. animals (Tikal, Benesova, & Frankova, 1976; Halas,
Reduction of noradrenergic functioning caused by Reynolds, & Sandstead, 1977). There is extensive
smoking would be expected to disrupt sympathetic experimental evidence in animals that the offspring
nervous system activity, consistent with evidence of rats fed a diet containing marginal levels of either
outlined earlier for reduced sympathetic arousal in zinc or protein throughout pregnancy and lactation
antisocial individuals (Raine, 1996). Furthermore, showed impaired brain development (Oteiza, Hurley,
when pregnant rats are exposed to nicotine at the Lonnerdal, & Keen, 1990; Bennis-Taleb, Remacle,
levels found in human smokers, the offspring show Hoet, & Reusens, 1999). In humans, zinc deﬁciency
an enhancement of cardiac M2-muscarinic cholin- in pregnancy has been linked to impaired DNA, RNA,
ergic receptors, receptors that inhibit autonomic and protein synthesis during brain development,
functions (Slotkin, Epps, Stenger, Sawyer, & Seidler, and to congenital brain abnormalities (Pfeiffer &
1999). This would help explain the well-replicated Braverman, 1982; King, 2000). The amygdala, which
ﬁnding of low resting heart rate in antisocial indi- also shows abnormal functioning in PET imaging of
viduals outlined above (Raine, 1993). Further evi- violent offenders (Raine, Buchsbaum, & LaCasse,
dence supporting this perspective is the ﬁnding that 1997c; Raine et al., 1998b; Davidson et al., 2000) is
beta-adrenergic agonists that increase cognitive densely innervated by zinc-containing neurons
performance in normal rats fail to have such effects (Christensen & Frederickson, 1998), and males with
on nicotine-exposed rats (Levin, Briggs, Christopher, a history of assaultive behavior have been found to
& Rose, 1993), again indicating disruption of this have lower zinc relative to copper ratios in their blood
neurotransmitter system that regulates both auto- compared to non-assaultive controls (Walsh, Isaac-
nomic and cognitive functions. son, Rehman, & Hall, 1997). While prenatal zinc
supplementation trials have failed to document
consistent effects, initial data suggest a beneﬁcial
effect of prenatal zinc supplementation on infants’
Although deﬁciency in nutrition itself has been rarely neurobehavioural development (Shah & Sachdev,
studied in relation to childhood aggression, several 2001). Furthermore, smoking during pregnancy,
studies have demonstrated the effects of related which is also associated with violence in the off-
processes, including food additives, hypoglycemia, spring, can impair the transportation of zinc from
and more recently cholesterol, on human behavior the mother to her fetus (King, 2000).
(Rutter et al., 1998; Raine, 1993; Fishbein & Pease, Protein provides essential amino acids for the ra-
1994). In addition, some studies have shown asso- pid growth of fetal tissue, and protein deﬁciency has
ciations between over-aggressive behavior and vita- been recently linked to antisocial behavior problems.
min and mineral deﬁciency (Breakey, 1997; For example, malnutrition at age 3 years (including
Wereback, 1995). Furthermore, one study (Rosen, protein deﬁciency) has recently been associated with
1996) claimed that nearly a third of a population of increased externalizing behavior problems at ages 8,
juvenile delinquents (mostly males) showed evidence 11 and 17 years (Liu, Raine, Venables, Dalais, &
of iron deﬁciency. Nevertheless, these ﬁndings re- Mednick, 2002). Furthermore, positron emission
main both conﬂicting and controversial (Rutter et al., tomography (PET) studies of violent offenders have
1998). revealed deﬁcits to the prefrontal cortex and corpus
One intriguing and important study illustrates the callosum (Raine et al., 1997c; Volkow et al., 1995).
potentially causal role of malnutrition as early as Of interest, too, is the ﬁnding that the offspring of
pregnancy in predisposing to antisocial behavior. rats fed a low-protein diet during pregnancy show a
Towards the end of World War II when Germany was speciﬁc impairment to the corpus callosum (Wain-
withdrawing from Holland, they placed a food wright & Stefanescu, 1983) and reduction in DNA
blockade on the country that led to major food concentration in the forebrain (Bennis-Taleb et al.,
shortages and near-starvation in the cities and 1999). Consequently, protein and zinc deﬁciency
428 Adrian Raine
may both contribute to the brain impairments shown initial reports of the possible efﬁcacy of using
in violence offenders, which in turn are thought to biofeedback to increase physiological arousal in
predispose to violence, although the empirical basis hyperactive children (Lubar, 1989), and it is con-
for such a conclusion requires further substanti- ceivable that biofeedback training as part of a larger
ation from future studies. multi-modal treatment package could help to reduce
antisocial and violent behavior in adolescents. Nev-
ertheless, rigorous experimental studies on the
efﬁcacy of biofeedback on antisocial behavior are
Future research and intervention implications
currently lacking and are needed before clinical
Despite the progress that has been made in recent application is justiﬁed.
years in identifying biological risk factors for anti- Findings that prefrontal brain deﬁcits predispose
social and aggressive behavior, there are still major to antisocial and aggressive behavior suggest that
lacunae in this knowledge base. Which of these risk interventions that tackle the source of brain deﬁcits
factors are speciﬁc to aggression and violence, and may be successful in reducing antisocial and
which reﬂect a more general predisposition to anti- aggressive behavior. One of the most promising
social behavior? Are there speciﬁc biological corre- approaches to reducing the impact of brain deﬁcits
lates of reactive versus proactive aggression, lies in early health interventions (Liu & Raine, 1999).
life-course persistent versus adolescent limited If factors such as smoking and malnutrition during
antisocial behavior, and hyperactive versus non- pregnancy cause antisocial behavior, then interven-
hyperactive subgroups of antisocial children? What tions aimed at reducing these should help reduce
biological factors protect against the development of antisocial behavior. In this context, Olds et al.
antisocial and aggressive behavior? Are biological (1998), in a methodologically strong randomized
risk factors for antisocial behavior in children controlled trial, showed that an average of nine
attributable to genetic or environmental processes? nurse home visitations during pregnancy, which
These are just some of the central questions that improved the quality of pregnant mothers’ prenatal
need urgent attention in future studies. For example, diet and reduced fetal exposure to smoking, also
it has been suggested that affective, impulsive reduced offspring criminal and antisocial behavior
aggression may be more clearly linked to frontal 15 years later. Similarly, Lally, Mangione, and Honig
impairments (Ishikawa & Raine, 2001), but conclu- (1988) showed that advice to pregnant women on
sive statements cannot be drawn due to the lack of good nutrition, health, and child-rearing lead to a
sufﬁcient empirical data. reduction in juvenile delinquency at age 15 years.
These issues notwithstanding, what intervention These studies provide more support to the notion
implications if any can be drawn from risk research that poor nutrition and smoking play a causal role in
on autonomic arousal, prefrontal dysfunction, and the development of childhood aggression and that
early health factors? First and foremost, the trans- early attempts to reduce these risk factors can be
lation of knowledge from risk research to prevent successful in reducing antisocial behavior. In addi-
research must be undertaken with prudence and tion, because birth complications have been linked
due circumspection. At the same time, it is also im- to adult violence, it is possible that providing better
portant to ask how prevention and intervention re- antenatal and perinatal health care to poor mothers
search can be informed by knowledge of autonomic may help reduce birth complications, and thus
underarousal, prefrontal deﬁcits, and early health reduce violence. Stress management during preg-
risk factors for antisocial behavior. nancy could reduce pregnancy-induced hyperten-
With respect to the physiological underarousal– sion and hypoxia to the fetus. Breast-feeding during
antisocial link, if low arousal causes antisocial be- the postnatal period has also been shown to increase
havior, increasing arousal may help reduce anti- cognitive functioning in childhood, and this too
social behavior. As outlined earlier, methylphenidate needs to be further encouraged.
both increases arousal and reduces conduct disor- In addition to these prevention efforts, intervention
der (Klein et al., 1997; Wachtel and de Wit, 1999). An programs to reduce existing levels of antisocial
alternative to drug therapy may be environmental behavior may be more successful if they incorporate
manipulations. For example, there is initial evidence strategies that tackle brain deﬁcits. Safety education
that positive environmental manipulations are cap- programs and programs that tackle physical abuse
able of producing long-term shifts in arousal and may be expected to reduce rates of head trauma (and
psychophysiological information processing. In a thus brain dysfunction) in children. Cognitive
study in which children were randomly assigned to remediation programs that target executive func-
experimental and control conditions and matched on tions may conceivably help to reduce antisocial and
early psychophysiological functioning, a nutritional, aggressive behavior in the subgroup of conduct dis-
physical exercise, and educational enrichment pro- ordered children with prefrontal deﬁcits.
gram from ages 3–5 years resulted in increased In conclusion, biological factors clearly contribute
psychophysiological arousal and orienting at age 11 to childhood antisocial and aggressive behavior. In-
years (Raine et al., 2001b). There have been some terventions to reduce such behavior in children are
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