Jonathan Hill
Introduction
It is evident from many chapters in this volume that the origins and mainten-ance of conduct problems in childhood entail transactional processes between the individual and the environment (see also Caspi & Moffitt, 1995). Equally it is clear that many of the children who are at highest risk have problems that appear early and are remarkably predictive of antisocial behaviour in adoles-cence and early adult life, which suggests that stable individual vulnerabilities may be important. These have been characterized in terms of genetic influen-ces (Simonoff, chapter 8, this volume), neuropsychological deficits (Lynam &
Henry, chapter 9, this volume) perceptual processes (Pettit et al., chapter 11, this volume) and attachment status (DeKlyen & Speltz, chapter 12, this vol-ume). At this stage we cannot be sure to what extent these accounts reflect different processes that might contribute independently or in combination to risk, or overlapping processes viewed from different standpoints. If they are different, and they do contribute independently, we need models of the way in which this might happen, and one route is via consideration of biosocial and biopsychological processes.
The distinction between the ‘bio’ and the ‘social’ is in many respects artificial. There is nothing intrinsically less biological about social interactions than physiological processes (Bolton & Hill, 1996). We will take ‘biological’ to refer principally to neuroanatomy, neurochemistry and neurophysiology, and
‘social’ to family, peer and wider social processes. Psychological processes may be seen as mediating between the biological and the social.
The purpose of this chapter is to link some of the perspectives reviewed in other chapters to the development of the brain and influences on it, and then to consider some findings on the psychobiology of conduct problems. Reference will be made to features of neuroanatomy and neurochemistry that are covered in more detail in the preceding chapter (Herbert & Martinez, chapter 4) and illustrated in the figures in that chapter.
The outcomes assessed in the studies to be reviewed have varied
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considerably, ranging from scores on behaviour checklists in children to offi-cially recorded crime in young adults. Two key points reviewed extensively by Angold & Costello (chapter 6, this volume) should be borne in mind. Firstly different antisocial behaviours seen at different ages may reflect the same underlying processes, and equally similar behaviours may reflect different processes. Secondly it is likely that conduct problems, including those that are currently subsumed within particular diagnostic categories are likely to be heterogeneous. Age of onset of antisocial behaviours, associated comorbid conditions and gender are three sources of heterogeneity that have received considerable attention. It follows that there may be substantial variability in the extent and nature of biosocial influences on antisocial behaviours in relation to these factors.
Key issues in the development of the brain Background
There is growing evidence that events early in development are related to persistent conduct problems, and that therefore an understanding of factors that influence early brain development will be important. For instance an increased risk associated with smoking in pregnancy may result from an effect of nicotine on brain development (Fergusson et al., 1998; Wakschlag et al., 1997). The association of the temperamental characteristic ‘lack of control’ at age 3 years with the likelihood of violent convictions at age 18, suggests that early childhood variations in the functioning of the relevant neural systems may influence vulnerability (Henry et al., 1996).
Identification of early causes and indicators of altered neuronal function that might contribute to conduct problems requires an understanding of the devel-opment of normal structures. It is becoming increasingly clear that the young brain is a dynamic structure in which there are spurts and plateaux of develop-ment which are influenced by a complex interplay of genetic and social influences. The impact of biological or social risk factors is likely to be affected by preceding vulnerability, timing and additive or interactional effects of other risk or protective factors. Some influences on neural systems appear to have transient effects whilst others are more persistent, some are reversible and others more permanent.
Brain development
The central nervous system is composed of neurones and glial cells. Neurones are cells that transmit information along their axons in the form of electrical
impulses. Information is transmitted from one neurone to another at synapses via neurotransmitters. Dendrites are specialized branches of the neurone that receive information from other neurones. Most neurones have around 1000 contacts with other neurones, although the elaborate dendritic network of the cerebellar Purkinje cells receive around 150 000 contacts through their den-drites. Glial cells serve predominantly a physical and nutritional support role, although they also have a role in the re-uptake of neurotransmitters.
Most of the specialized structures of the brain outlined in the previous chapter (Martinez & Herbert, chapter 4) can be identified in the human brain during gestation. The formation of the structures entails division of neuronal precursor cells, followed by migration and the formation of selective connec-tions. Selective connections occur in two ways, through cellular competition and death, and through ‘process elimination’. Neuronal competition and death involves immature neurones early in prenatal development (Hamburger &
Oppenheim, 1982). Neurites (precursors of axons and dendrites) are sent out to target cells which secrete a trophic substance that promotes neuronal survival.
Cells that do not compete successfully for the trophic substance from the target cell either obtain it from another target cell or die. The neurites of successful cells establish synaptic connections with target cells. Process elimination occurs in the late prenatal period and extends into the postnatal period as neurones develop extensive dendrites and axons (Carlson et al., 1988). Dendrites and axons extend towards other target cells apparently guided by a combination of processes intrinsic to the neurone and extrinsic factors. More synapses are formed than survive in the mature brain, and the consolidation or elimination of synapses in development appear to be related to the extent of synaptic activity. It is thought that the selective loss of synapses fine tunes the develop-ing brain structure. In humans this process continues throughout childhood.
For instance in the frontal cortex synaptic density peaks in the early postnatal period and then declines up to the age of 16 years (Huttenlocher, 1979).
The interplay between brain development and experience
It seems likely that in some brain structures synaptic formation and loss are uninfluenced by environmental stimuli, and in others these are powerful. The interaction between genetically programmed synaptic developments and envir-onmental experiences provide the basis for plasticity and fine tuning. Clear evidence for an effect of experience on synapse formation and dendritic growth comes from studies of the visual system. In the mature visual cortex there are alternating columns of cells that respond preferentially to one eye or the other.
These columns develop through pruning of dendrites which is driven by visual
experience. If one eye is blocked the stripes in the column corresponding to the blocked eye become narrower, and those linked to the unblocked eye become wider (Shatz, 1990). This effect is seen only over a certain critical period. If visual input is blocked after that period there is no effect, and if it is unblocked before the critical period there is no effect. It is likely that this is a widespread mechanism whereby ‘the normal development of the nervous system unfolds as a series of timed genetic events whose expression depends on properly timed and delivered environmental stimuli’ (Ciaranelo et al., 1995).
Such interactions at the cellular level between genetically timed events and experience are mirrored in physiological and behavioural processes. A physio-logical example is provided by spontaneously hypertensive rats (SHR); strains in which hypertension is passed from one generation to another. If SHR rat pups are raised by normal rat mothers they do not develop hypertension, and if SHR rat mothers rear non-SHR rat pups they do not develop hypertension (Myers et al., 1989). It appears therefore that SHR rat mothers confer a genetic risk to their offspring, which is manifest only when the pup is also exposed to the SHR mother’s behaviour. A similar point is made in relation to aggressive behaviours in a series of studies carried out by Cairns and colleagues. Selective breeding produced two lines of mice, one that was highly aggressive and one that had a strong tendency to freeze upon social contact (Gariepy et al., 1988).
In the low aggressive line, dopamine concentrations were lower in the caudate nucleus and nucleus accumbens which are associated with emotional respon-ding, motivational states and initiation of action. (See also Herbert & Martinez, chapter 4, this volume.) As we shall see later in this chapter dopaminergic pathways from the ventral tegmental area of the brain stem to the nucleus accumbens have been implicated in models of a ‘Behavioural Activation System’ (Gray, 1987). However in a series of experiments involving social contact with other mice, many of the low aggressive mice could achieve dominance over the high aggressive mice, and this was accompanied by an increase in dopaminergic activity (Gariepy, 1996). Thus, notwithstanding marked genetic differences accompanied by predictable differences in neuro-transmitter levels, there were profound effects of social experience on patterns of behaving. The extent to which such processes occur in humans is not known, however given the prolonged period of fine tuning through synapse elimination in human development, it seems that they may be important.
Sex differences
Sex differences in rates of aggression and disruptive behaviours within the normal range and at the extremes are very striking, and a biosocial model of
conduct disorder will have to account for these. Neurobiological differences may have an effect directly by increasing risk, or through a general vulnerabil-ity to physical or psychological stressors, or through particular features which add to risk through transactional processes with environmental factors.
Differences between the brains of males and females appear to be governed by the action of circulating sex hormones (androgens and oestrogens) on neurones, and are not primarily the result of genetic differences acting within nerve cells. These hormones affect nerve cell division, migration and survival.
Males and females are morphologically indistinguishable until the sixth week of in utero development, when in males the testes start to secrete testosterone. In humans testosterone levels reach peaks at between 3–5 months of gestation and in the first six weeks postnatally, when they are several times higher than in the adult male. As Herbert & Martinez (chapter 4, this volume) point out there are androgen receptors in areas of the limbic system including the anterior hypothalamus, the medial amygdala and the septum, and these structures have been implicated in aggression. If there are links between hormonally mediated sex differences in these structures and aggression, these could operate either through hormonal effects on structure, or hormonal activation of these struc-tures. There is evidence that both mechanisms occur. Specific areas of the mammalian nervous system are thought to be sensitive to gonadal hormones during critical developmental periods before birth and in infancy, resulting in relatively permanent organizational changes in neural structure that are not dependent on hormonal stimulation (Todd et al., 1995). Intriguingly it has been argued that prenatal testosterone may contribute to the increased risk of language delay in boys, either through interfering with neuronal development (Geschwind & Galaburda, 1985), or through reduction of selective neuronal death (Galaburda et al., 1987). Given the links between language delay and conduct problems (Lynam & Henry, chapter 9, this volume), this might provide a mechanism linking effects of testosterone on the developing brain structure to antisocial behaviours in childhood. Other structures, notably female hypothalamic cells are very sensitive to changes in levels of oestrogen.
In spite of the presence of these mechanisms, the evidence for an effect of androgens on aggression is conflicting, and complex. Herbert & Martinez review the recent evidence in chapter 4, this volume. In relation to aggression in adolescence they refer to the work of Tremblay and colleagues showing that at age 13 testosterone levels were associated with social status and not with aggressiveness (Schaal et al., 1996). By age 16 there appeared to be a strong association between aggression and testosterone levels, suggesting that there may be a developmental change in the role of testosterone (Tremblay et al.,
1997). As Herbert & Martinez comment, there appears to be a triangular relationship between social structure, testosterone and aggression in male primates, and this relationship may change over time.
Sex differences in risk may also arise from a more general vulnerability to physical insult or stressor in the immature male central nervous system (Goodman, 1991). For instance as we shall see, the long-term impact of maternal smoking in pregnancy on the risk of later antisocial behaviours appears to be stronger in males than in females (Fergusson et al., 1998).
Whilst the structural differences in the brains of males and females may contribute directly to an increased risk of conduct problems, they may also lead to gender differences in the normal range, which in turn contribute to vari-ations in responses from parents and caretakers, and hence lead to differences in risk through interactional and transactional processes. For instance in mon-keys testosterone increases rough and tumble play (Herbert & Martinez, chapter 4, this volume), and such an effect in humans in conjunction with family stress may increase the likelihood of inconsistent or harsh parenting and hence affect the risk of oppositional or aggressive behaviours.
Psychobiological theories of risk Temperament
With these neurodevelopmental considerations in mind we turn to some specific theories of relevance to the development of antisocial behaviours in childhood. Individual differences in infancy that might contribute to subse-quent risk of psychopathology were conceptualized by Thomas and Chess in terms of temperament. Their pioneering work in the New York Longitudinal Study (NYLS) indicated that individual differences were predictive of subse-quent adaptation (Thomas et al., 1968). In general cross-sectional studies of parent-reported temperament and parent-reported behavioural problems have found associations (e.g. Barron & Earls, 1984, Prior et al., 1987). However these studies are difficult to interpret for a variety of reasons including the possibility that items referring to behaviour problems and to aspects of tem-perament are confounded, because they are measured at the same time. A major strength of the New York Longitudinal Study was that it attempted to predict behaviour problems longitudinally. However Cameron (1978) in a reanalysis of the NYLS data found that difficult temperament in the first year predicted only mild behavioural problems subsequently and paradoxically, in boys, scores reflecting less difficult temperament were associated with subse-quent more severe problems. Bates et al. (1985) did not find a relationship
between home observations of temperament in infancy and mother-reported behaviour problems at age 3, and Amaziadae et al. (1989) found no association between mothers’ ratings of infant temperament and behaviour problems at 4 years of age.
One reason that temperament has proved an inconsistent predictor may be that the dimensions of temperament identified by Thomas and Chess included a wide range of qualities with substantial conceptual overlap, many of which are highly correlated (Rothbart et al., 1995). Subsequent studies have identified a smaller group of factors and have attempted to link them to possible underlying neural systems. The aim of this work has been to identify processes that, separately or in combination, are adaptive or maladaptive, and to relate these processes to brain structures and neurochemistry. We will focus on behavioural activation and inhibition, attention and affect regulation.
Approach and inhibition
The successful regulation of approach behaviours to rewarding stimuli and avoidance of harmful stimuli has been central to the evolutionary success of most living organisms (Schneirla 1959). The idea that humans vary in the extent to which approach or avoidance predominate has a long history going back at least to Hippocrates and Galen (Windle, 1995). Recent formulations of an appetitive/approach system that mobilises approach behaviour to stimuli that predict positive events, are known variously as the Behavioural Activation System (Gray, 1987), Behavioural Facilitation System (Depue & Iacono, 1989), the Expectancy Foraging System (Panksepp, 1992) and Novelty Seeking (Cloninger, 1986). Depue & Iacono also have proposed that this system promotes irritative aggression when goals are blocked. The neural system associated with these processes is believed to comprise areas of the basolateral amygdala that respond to reward-related inputs by activating dopaminergic neurones within the brain stem’s ventral tegmental area, which in turn projects to the nucleus accumbens where they facilitate approach responses. Relatively stable individual differences in the propensity to approach objects are evident from around 6 months (Rothbart, 1988).
Gray (1987) has proposed that a Behavioural Inhibition System motivates responses to signals that predict punishment or threats, including inhibition of ongoing motor activity, increase of arousal, and direction of attention toward relevant information in the environment. This is very similar to Cloninger’s concept of Harm Avoidance (Cloninger, 1986). The neuronal circuitry is thought to involve the hippocampus, and the lateral nucleus of the amygdala, both of which are involved in labelling fearful stimuli (Davis, 1992; LeDoux,
1995, 1996; Herbert & Martinez, chapter 4 and Fig. 4.2, this volume). Further circuits connect eventually to the brain stem to regulate aspects of fearful behaviour including freezing, facial and vocal expression and heart rate changes, and to reticular and cortical circuits to regulate attention. Regulation of the behavioural inhibitory system appears to be both noradrenergic and serotonergic (Rogeness & McLure, 1996). Individual differences in fearful inhibition appear towards the end for the first year, and stability from the second to eighth years of life has been shown (Kagan et al., 1988).
Cloninger (1986) has proposed a third motivational system which he has termed Reward Dependence. This refers to the extent to which the individual is motivated by rewards, including social interactions and approval from others.
Cloninger has hypothesized that reward dependence is associated with norad-renergic activity.
Attention
Attentional systems are critical to responses to rewarding or aversive stimuli.
Accurate appraisal requires adequate attention and, equally, prolonged atten-tion to a stimulus may lead to an overestimate of its significance or to failure to gather information from other relevant sources. There is evidence that the Posterior Attentional System involving the mid brain superior colliculus, the thalamus and the parietal lobe is responsible for influencing the extent of focus on particular aspects of experiences (Derryberry & Rothbart, 1997). The analogy of the zoom lens of a camera has been used. If attention is limited to a particular location in visual space considerable detail is seen, however this is at the expense of the bigger picture. Disruption to the effective functioning of this system could lead to failure to appraise stimuli in enough detail, or of overem-phasis of some stimuli at the expense of others. Either could lead to inaccurate appraisal of potentially rewarding or threatening stimuli (Posner & Raichle, 1994). Whilst the posterior attentional system is thought to operate uncon-sciously, the Anterior Attentional System, associated with the anterior cingu-late cortex (Fig. 4.2, this volume) has been hypothesized to influence conscious
‘effortful control’ of behaviour. Derryberry and Rothbart used a test of ability to use a rule to inhibit a response as an index of this attentional system in children between the ages of 27 and 36 months. Children who performed well on this task were described by their parents as more skilled at attentional shifting and focusing, less impulsive and less prone to frustration reactions (Gerardi et al., 1996).
Possible links with conduct problems
The role of these motivational and attentional systems in the genesis of conduct problems is inevitably in many respects speculative. However the general principles make links with areas covered in other chapters of the book.
Derryberry & Rothbart (1997) have hypothesized that there is an interaction between the neural systems referred to earlier which mainly involve the limbic system and brain stem (their Figures 2 and 3), and cortical structures and the environment. Cortical processes involving perception and cognition provide representations of the physical and social world to the subcortical motivational systems. These representations also refer to the self in relation to others. In turn these representations are influenced by appetitive and defensive needs. In the presence of a supportive environment with clear and consistent reinforcers the quality of the information provided by the cortical structures is likely to improve with age, thus leading to increasingly effective regulation of the motivational systems. For instance a child who has a strong appetitive/
approach system is likely to develop a well socialized outgoing personality provided complementary inhibition in relation to inappropriate approaches has been established. This depends not only on the activation of behavioural systems, but also on the establishment of representational links between punishment and those aspects of the environment for which approach is not appropriate, and these are likely to result from effective learning.
Equally, combinations of threatful or confusing environmental experiences may contribute to inaccurate information processing and to extreme activation or frustration of motivational systems leading to emotional or behavioural disturbances. For instance inconsistent parenting may lead to failure to associ-ate inhibition of reward seeking with objects that do not belong to the child and hence increase the risk of stealing. In turn the relative strengths of the reward seeking and the behavioural inhibition systems might also affect the way the child represents situations, and his/her capacity to anticipate various conse-quences. ‘If a child’s representations emphasise rewards at the expense of punishment, it will be easy to anticipate the positive consequences of approach behaviour but more difficult to predict the negative outcomes that might occur’ (Derryberry & Rothbart, 1997).
The relationship of motivational systems to aggression is complex because, as Herbert & Martinez (chapter 4, this volume) outline, ‘aggression, unlike some other behaviours, has no biological functional purpose in isolation’. Gray (1987) has argued that predatory or instrumental aggression is a function of the appetitive system. Clearly the question arises as to why emotions such as anger should be associated with a motivational system that is oriented towards
stimuli that predict positive events. One possibility is that where there is a strong approach motivation that is frustrated this leads to distress involving frustration and anger. This is supported by the findings that aggression in 6–7-year-olds is related both to activity and smiling and to anger/frustration in infancy (Rothbart et al., 1994). Alternatively aggressive behaviours may result from a failure of the inhibitory system to control aggression (Quay, 1993), and support for this comes from studies reviewed later in the chapter.
Consideration of the role of attentional systems leads to further predictions regarding the representation of the external world and motivational systems.
The response to high and persistent levels of threat may be important to the origins of conduct problems for some children. Pettit et al. (chapter 11, this volume) have reviewed the evidence that children who have been physically abused are more likely to perceive threats in everyday experiences than those who have not. This suggests that the child will give high salience to threatening aspects of the environment and hence will have difficulty shifting attention either through the posterior or the anterior attentional systems to other aspects of the environment. The child may then be unable to assess situational sources of relief and safety, and self-concepts relating to success and efficacy, with the result that the behavioural inhibition system may be overwhelmingly activated leading to withdrawn or anxious behaviour. Alternatively the child may use an avoidant strategy, disengaging attention from the threatening situation without attending to sources of relief and coping options. This may reduce fear leaving the appetitive/aggressive system uninhibited, thus leading to an aggressive response to actual or perceived threats.
Frontal cortex
Herbert & Martinez (chapter 4, this volume) have referred to the intimate connection between the frontal lobe and the amygdala and the hypothalamus, and its role in the control of aggression. More generally a range of functions including sustaining attention, goal formation, anticipation and planning, self-monitoring and self-awareness, often referred to under the heading ‘executive functions’ are subserved by the frontal lobe and its connections to the limbic structures (Stuss & Benson, 1986). Lynam & Henry (chapter 9, this volume) have reviewed the evidence for specific deficits in frontal lobe functioning in relation to conduct problems. Here we refer briefly to the role of frontal activity in relation to the regulation of emotions and temperamental character-istics. Fox and colleagues (Fox et al., 1996) have proposed that the combination of reactivity to novelty and the expression of negative affect puts infants at risk for subsequent externalizing problems. They argue that areas in the right
frontal lobe are involved in the expression of negative affect and in the left frontal lobe with positive affect. This is based on evidence from studies of localized brain lesions, affective reactions of patients undergoing sodium amytal examination, and electrical activity patterns in clinical populations. In support of this hypothesis Fox et al. (1995) found that 4-year-old children with resting right frontal asymmetry on EEG were more likely to exhibit reticent and anxious behaviour during a peer play session compared with children exhibiting greater left frontal asymmetry. Links with serious conduct problems remain to be established, however in a low risk sample Fox et al. (1996) found that externalizing problems were predicted by the combination of high sociabil-ity and greater right frontal lobe activation on EEG, whilst there were no elevations of scores for externalizing behaviours in groups that had right activation and were not highly sociable, nor those who were sociable and had left activation.
Neurotransmitters Background
Considerable attention has been paid to the possibility that alterations in neurotransmitter levels underpin psychiatric conditions such as depression and attention deficit hyperactivity disorder (ADHD). As Herbert & Martinez (chap-ter 4, this volume) make clear neurotransmit(chap-ters in the brain serve many contrasting and interacting functions, and frequently measures of their levels are crude indicators of activity. The interdependence of neurotransmitter systems suggests that the balance among them, as much as the absolute levels of transmitters, may be important to the regulation and expression of behav-iour. Nevertheless the investigation of neurotransmitter function is of rel-evance to an understanding of neural systems, and the interplay between the developing child and the environment. In this chapter we focus on the biogenic amines, dopamine, noradrenaline and serotonin (5HT). As we saw earlier Gray has postulated that the behavioural activation system is associated with dopamine and the behavioural inhibition system with noradrenalin and serotonin activity. Cloninger in outlining a parallel model proposed that novelty seeking is associated with dopamine activity, reward dependence with noradrenalin, and harm avoidance with serotonin. Significant genetic influen-ces on levels of all three monoamines have been demonstrated in studies of monkeys and humans (Clarke et al., 1995; Higley et al., 1993; Oxenstierna et al., 1986). Equally there is substantial evidence that there are neurotransmitter–
environment interactions.
Monamines,development and experience
The developmental patterns of activity of noradrenalin (NA), dopamine (DA) and serotonin (5HT) are different. Levels of metabolites of dopamine decrease with age, and the density of dopamine receptors (D1 and D2) rises from birth to 2 years, and then declines through childhood (Rogeness & McClure, 1996;
Seeman et al., 1987). By contrast levels of the enzyme dopamine--hydroxylase which is involved in the conversion of dopamine to noradrenalin increases in activity from birth to around 7 years of life, when it reaches adult levels (Weinshilboum, 1983). It is tempting to conclude that this increase in norad-renalin activity relative to dopamine activity may be associated with an in-creased role for behavioural inhibition in relation to behavioural activation, and hence increased behavioural control, as development proceeds.
Clear effects of early social and maternal deprivation on the development of the brain biogenic amine system in rats and monkeys have been demonstrated (Kraemer et al., 1991). Studies in rats have demonstrated that stress in preg-nancy has persistent behavioural effects in the offspring, and these are asso-ciated with altered dopamine levels (Fride & Weinstock, 1988). Schneider et al.
(1998) compared the behavioural responses and CSF concentrations of biogenic amines following social isolation at age 8 months, of monkeys derived from either stressed or undisturbed pregnancies. Those who had experienced stressed pregnancies showed behavioural differences when reunited with their peers, and had altered levels of CSF metabolites of brain monoamines. As we saw earlier genetically determined dopamine levels associated with low aggres-sion in mice are altered following social experience. In monkeys maternal deprivation appears to be associated specifically with altered noradrenaline activity and with altered patterns of correlation among neurotransmitter levels.
Studies by Kraemer and colleagues have indicated that the effects may be persistent and stress related. They compared monkeys who were mother deprived during infancy with monkeys who were socially reared. By 36 months there were no behavioural differences and the measures of CSF neurotransmit-ter metabolites did not differ. However, afneurotransmit-ter administration of d-ampheta-mine, deprived monkeys showed more clinging, submission and aggression, and higher levels of CSF noradrenalin (Kraemer et al., 1984). Kraemer et al.
conclude that following deprivation the noradrenalin system apparently ma-tures but remains vulnerable to stressors.
Possible associations with conduct problems
Rogeness and colleagues (Rogeness & McClure, 1996) have provided some evidence that in children referred for psychiatric treatment, levels of