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Contents lists available at ScienceDirect

Neuroscience and Biobehavioral Reviews

journal homepage: www.elsevier.com/locate/neubiorev

Review article

Mapping the developmental pathways of child conduct problems

through the neurobiology of empathy
Caroline Moul , David J. Hawes, Mark R. Dadds
School of Psychology, University of Sydney, 2006, Australia

a r t i c l e i n f o a b s t r a c t

Article history: The notion that antisocial behavior reects failures of empathy has a long history in the clinical literature,
Received 13 February 2016 yet only recently has evidence emerged to support neuroscientic accounts of empathy and the develop-
Received in revised form 27 March 2017 ment of child conduct problems. Much of this evidence has come from research into callous-unemotional
Accepted 29 March 2017
traits, which correspond to the affective component of psychopathy and therefore encompass decits in
Available online xxx
empathy within a broader cluster of emotional impairments. In this review we integrate current evi-
dence concerning the biobehavioral bases of empathy and callous-unemotional traits, and discuss how
Keywords:
it may inform models of heterogeneous subgroups of individuals with early onset conduct problems. We
Empathy
Callous-unemotional
argue that somewhat distinct failures of empathy map onto distinct risk pathways to early onset conduct
Conduct problems problems, and that these pathways may be best understood by examining empathy in terms of cognitive
Emotion-recognition and environmental prerequisites and the various neurochemical systems implicated therein.
Attention 2017 Elsevier Ltd. All rights reserved.
Socio-environmental
Oxytocin
Serotonin
Testosterone
Cortisol
Dopamine

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2. Current conceptualisations of conduct problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3. Current conceptualisations of empathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4. A developmental perspective on empathy and conduct problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
5. Empathic processes: development course, underpinnings, and interplay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
6. Neurocognitive models of CU traits and associated empathic decits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
7. Neurochemical systems and the development of empathy and CU traits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
7.1. Neuropeptides: oxytocin and vasopressin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
7.2. Serotonin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
7.3. Cortisol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
7.4. Testosterone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
7.5. Dopamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
8. Summary of neurochemical correlates of empathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
9. Conclusion and future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

Corresponding author.
E-mail addresses:
caroline.moul@sydney.edu.au (C. Moul), david.hawes@sydney.edu.au (D.J. Hawes),
mark.dadds@sydney.edu.au (M.R. Dadds).

http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
0149-7634/ 2017 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
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1. Introduction
Models of persistent child and adolescent conduct problems
have evolved considerably in recent decades, as research has
revealed an increasingly complex picture of the processes through
which they are shaped across development. Some of the earliest
clinical descriptions of children with conduct problems suggested
that a lack of empathy could be found among the core features of
the presentation. For example, Redl and Wineman (1951), known
for their seminal therapeutic work with wayward boys in residen-
tial facilities, characterized these children as decient in the skill
of guring out how another person may feel about us (p. 122). The
idea that empathy decits underlie conduct problems has often
been echoed since. Indeed, antisocial and aggressive behavior by
denition can be seen to imply a failure to respond empathically
to the needs of others. It is somewhat striking then that the lack
of empathy widely assumed to characterize such individuals has
often not been seen when examined under scientic conditions.
Systematic and meta-analytic reviews of empathy in relation
to various forms of conduct problems across the lifespan have
highlighted much inconsistency in the evidence. The rst such
review, comprising 30 studies of children, adolescents, and adults,
found a low-to-moderate negative association between empathy
and aggression, externalizing and antisocial behaviors (Miller and
Eisenberg, 1988). Like those that followed, it also emphasised that
support for this relationship varied signicantly depending on the
measure of empathy employed. For example, aggression on the
whole was found to be associated with questionnaire measures
of empathy, but not methods involving picture/story measures,
facial/gestural reactions, or experimental inductions of empathy
(Miller and Eisenberg, 1988). Jolliffe and Farrington (2004) later
examined this relationship with regard to distinct components
of empathy, albeit in relation to criminal offences specically. A
stronger negative relationship was found between offending and
cognitive empathy (e.g., emotion labeling), whereas only a weak
negative relationship was found between offending and affective
empathy (e.g., arousal to emotional cues). Interestingly, decits in
empathy were also found to be signicantly stronger in adolescent
samples (d = 0.39) than adult samples (d = 0.17). A subsequent
systematic review of 17 studies investigating affective empathy
and aggression in children and adolescents concluded that evidence
was largely inconsistent (Lovett and Shefeld, 2007). A more recent
meta-analysis of 86 adult studies likewise found only a small neg-
ative correlation between empathy and aggression (Vachon et al.,
2014).
The discrepant ndings that have marked this literature have
likely arisen from both methodological and conceptual issues.
The measures traditionally used to investigate empathy among
children and adolescents with conduct problems have generally
fallen into four categories (Miller and Eisenberg, 1988). Most
common have been picture/story methods in which participants
are presented with narratives and visual stimuli depicting an
emotionally-provocative scenario, and asked to report on the emo-
tional responses of the protagonist (e.g., Feshbach & Roes, 1968).
Second is experimental paradigms designed to induce empathy
in participants, by means such as encouraging them to imagine
how another individual feels or to objectively observe them (e.g.,
Feshbach, 1978). A third category involves the coding of childrens
facial affect/gestural reactions to the emotions of others depicted in
lms or picture/story stimuli, which has been seen as particularly
advantageous for use with young children as it does not rely on
verbal self-reports of emotional states (e.g., Marcus et al., 1985).
Finally, self-report questionnaires have been commonly used to
index empathy in young children, often based on adaptations
of measures originally developed for adults (e.g., Bryants, 1982;
Dadds et al., 2008; Litvack-Miller et al., 1997). Furthermore, most
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
studies have either operationalized empathy as a global unitary
construct or have focused exclusively on specic facets of empa-
thy. As such, relatively little is known about the unique associations
between antisocial behavior and distinct components of empathy
emphasised in current neurocognitive models, and even less about
how these associations develop over time.
The aim of this review is to integrate current knowledge regard-
ing the biobehavioral bases of empathy decits that appear to
confer risk for conduct problems. In contrast to previous reviews
that have often focused on global associations between empathy
and conduct problems at a single level of analysis, we examine the
neurobiological systems that underlie empathy, as they map onto
the cognitive, affective, and behavioral features that characterize
heterogeneous forms of conduct problems. In recent years, much of
the evidence that has been particularly informative in this regard
has come from research into callous-unemotional traits. As out-
lined in the sections that follow, these traits represent a cluster of
features that include various decits in empathy alongside broader
emotional impairments, and it is now apparent that this phenotype
of CU traits may be more predictive of risk pathways than compo-
nents of empathy in isolation. We argue that somewhat distinct
failures of empathy map onto risk pathways to child conduct prob-
lems associated with high versus low levels of CU traits, and that
these risk pathways may be best understood by examining the cog-
nitive and environmental prerequisites for these capacities, and the
various neurochemical systems implicated therein.
2. Current conceptualisations of conduct problems
Violence and conduct problems have been a consistent and cen-
tral feature of human history, and attempts to understand their
causes, manifestation, and remediation have spanned sociological,
medical, legal, and ethological elds. In this review we draw on
the emerging tools of neuroscience and psychology, and present a
speculative discussion of one particular type of violence and anti-
social behavior, which characterizes the individual life histories of
a small but signicant number of people, usually males, in all soci-
eties. In other words, a chronic pattern of self-interested behavior
that offends against the rights of, and thus causes harm to, others
and society in general. The natural history of such behavior pat-
terns is quite well known, often beginning early in childhood as
repetitive oppositional tantrums, impulsivity and aggression, often
in environments typied by violence and instability (Loeber and
Farrington, 2000). The developmental trajectory of such behavior
generally progresses through a series of predictable milestones,
such as school failure, drug use and criminal involvement, and
once established, such a pattern is largely intractable to the efforts
of juvenile justice and psychiatric systems. Thanks to decades of
research much is now known about how to identify these problems,
and there exist well characterized and evaluated interventions that
can successfully remediate and prevent chronic outcomes when
delivered during childhood.
A major aim of research in recent decades has been to charac-
terize the signicant heterogeneity that is seen among individuals
with conduct problems, and various conceptualizations of this het-
erogeneity have been proposed (see Frick and Nigg, 2012; Hawes,
2014). These have included distinctions based on age of onset, with
considerable evidence to indicate that early (childhood) onset pre-
sentations are often more chronic and severe than those that rst
emerge during adolescence, and are further associated with dis-
tinct neurocognitive and family-based risk factors (Piquero and
Moftt, 2014). Evidence of distinct developmental pathways has
also supported distinctions between individuals with aggressive
versus nonaggressive subtypes of conduct problems (e.g., Burt and
Neiderhiser, 2009). Furthermore, aggression itself has been asso-
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ciated with distinct correlates when characterized in terms of
proactive versus reactive forms (e.g., Dickson et al., 2015), and
physical versus relational forms (e.g., Murray-Close et al., 2014).
Evidence regarding this heterogeneity is likewise reected in
the current diagnostic criteria for classifying conduct problems in
the Diagnostic and Statistical Manual of Mental Disorders (DSM5;
American Psychiatric Association, 2013). Here, persistent patterns
of conduct problems in childhood and adolescence are dened in
terms of oppositional deant disorder (ODD) and conduct disor-
der (CD). In DSM-5 the symptoms of ODD are grouped into three
dimensions, emphasising the notion that distinct symptom pat-
terns may provide clinically meaningful information in addition
to overall number of symptoms. These dimensions comprise (1)
angry/irritable mood (e.g., Often loses temper), (2) argumen-
tative/deant behavior (e.g., Often actively dees or refuses to
comply with requests from authority gures or with rules), and
(3) vindictiveness (Has been spiteful or vindictive at least twice
within the past 6 months). Compared to ODD, the symptoms of CD
include a greater emphasis on aggression and serious rule violations
(e.g., Often initiates physical ghts; Is often truant from school).
Furthermore, formulations of CD include age-based (childhood-
onset/adolescent-onset) subtyping, and a diagnostic specier for
individuals who meet full criteria for the disorder in addition to
exhibiting limited prosocial emotions, more commonly referred
to as callous-unemotional (CU) traits (i.e., lack of remorse or guilt,
callousnesslack of empathy, shallow or decient affect, and lack
of concern about performance in important activities). US-based
research has indicated that between 10% and 50% of youth with CD
would be designated with the CU specier, which is understood to
reect the affective component of psychopathy (Kahn et al., 2012).
The construct of psychopathy most commonly applied to
adult populations of antisocial offenders has provided an infor-
mative framework for re-examining empathy as it relates to
childhood conduct problems. Here, decits in empathy have been
investigated extensively in the context of the broader pheno-
type of CU traits (Frick et al., 2014). In Hares (1991) two-factor
model of psychopathy, the affective component of psychopa-
thy is differentiated from a behavioral component comprising
an impulsive/irresponsible antisocial/deviant lifestyle, and is held
to distinguish the high-risk psychopathic subgroup of antisocial
offenders from non-psychopathic offenders. The application of
the psychopathy construct to children has drawn understandable
scrutiny, but also recognition that the investigation of such char-
acteristics in childhood is essential to a developmental perspective
on conduct problems, and developmentally informed strategies for
early intervention and prevention of the most severe antisocial
outcomes (Rutter, 2012).
Evidence regarding developmental aspects of these character-
istics has grown rapidly, aided by measurement research that
has replicated a similar factor structure in child and adolescent
populations. For example, in a factor analytic study with a large rep-
resentative sample of children (n = 1359) aged 49 years, CU traits
were positively associated with severity of conduct problems, while
at the same time predicting prospective growth in conduct prob-
lems independent of baseline severity in such problems (Dadds
et al., 2005). There is now extensive support for the subtyping of
child and adolescent conduct problems based on the presence of
high versus low levels of CU traits (see Frick et al., 2014). Among
children and adolescents with conduct problems, those with high
levels of CU traits exhibit a particularly severe and chronic tra-
jectory of antisocial behavior. They are also characterized by high
levels of proactive or instrumental aggression and a range of unique
social-cognitive and neurobiological correlates related to the pro-
cessing of emotional stimuli and reinforcement learning. Evidence
of these correlates has been reported not only in samples of children
and adolescents with CD, but also those with oppositional deant
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
3
disorder (ODD), and in studies that have examined distributions of
CU traits in community samples (Frick et al., 2014).
Thus, as evidence regarding heterogeneity among children with
conduct problems has grown, it has become increasingly apparent
that risk processes related to empathy are of particular importance
to the subgroup of children characterized by high levels of CU traits.
It is this distinction based on high versus low levels of CU traits that
we draw on to examine the biobehavioral underpinnings of empa-
thy as they related to conduct problems in the following sections.
Before doing so, however, it is important to examine the construct
of empathy in its own right, which is itself now understood to be
complex and heterogeneous.
3. Current conceptualisations of empathy
The construct of empathy has been of enduring interest to
researchers across diverse philosophical and scientic elds, and
has often been viewed from competing theoretical positions
therein. In clinical literature, the concept of empathy has often
been applied somewhat globally, as a unitary process. However,
in recent years social cognitive neuroscience has come to provide a
unique perspective on empathy through growing research into the
characteristics and ontogeny of its putative components (Gonzalez-
Liencres et al., 2013).
There are various approaches to differentiating features and
subcomponents of empathy in this literature, and the large num-
ber of empathy-related concepts (see Batson, 2009). Blair (2005a,b)
proposed that empathy could be conceptualised as a collection of
partially dissociable neurocognitive systems, with key divisions
made between cognitive empathy (or Theory of Mind), motor
empathy (i.e., mirroring the motor responses of an observed actor),
and emotional empathy (i.e., responses to facial/bodily affective
cues, as well as emotional stimuli). Alternatively developmentalists
have often drawn the distinction between cognitive understand-
ing of anothers emotions or distress, versus the enactment of
an empathic response. This perspective assumes that fully devel-
oped empathy also includes the urge to act on such responses
by providing comfort and support to a victim when appropri-
ate. As such, cognitive and affective/emotional empathy may or
may not be transformed into prosocial actions intended to alle-
viate distress in another (e.g., Hoffman, 2000; Roberts and Strayer,
1996). More recently, it has been argued that accounts of empa-
thy can be enhanced by recognizing the role of motivation. That is,
although empathic responding is often highly reexive in nature,
such responding can also be somewhat context dependent, waxing
and waning based on the motives that guide ones willingness to
avoid or approach engagement with others emotions (Zaki, 2014).
In recent years the distinction between affective and cognitive
empathy has been receiving growing attention by cognitive neuro-
scientists (e.g., Adolphs, 2003; Decety and Jackson, 2004; Singer,
2006; Walter, 2012), and this distinction has been particularly
informative in conceptualising risk processes related to empathy
in relation to current models on conduct problems and the hetero-
geneity represented therein.
Affective empathy refers to the sharing of someone elses
emotional state, with common denitions typically describing an
affective response more appropriate to (Hoffman, 1984) or congru-
ent with (Eisenberg and Fabes, 1990) anothers situation than to
ones own. These affective reactions may nonetheless vary consid-
erably in quality, with the most basic form being emotion mimicry,
which involves an automatic, synchronization of emotional behav-
ior, such as affective expressions or postures with those of others.
The concept of emotional contagion has often been applied to
capture the involuntary or reexive nature by which affective
responses may occur by mere association with others. When some-
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one smiles at us we smile back automatically, catching a warm
feeling in the process, just as feelings of panic may quickly spread
through a crowd of people (Vreeke and van der Mark, 2003).
Cognitive empathy involves an explicit understanding of
anothers mental state, but is not necessarily accompanied by a
specic affective state. It refers to the ability to intellectually take
the role or perspective of another person, and involves the decod-
ing and labeling of emotions and their situational cues (Gladstein,
1983). As such, cognitive empathy is understood to reect the
capacity to represent the internal states of others. Some deni-
tions of cognitive empathy also encompass the metalizing abilities
associated with Theory of Mind (ToM) those abilities underlying
the attribution of propositional attitudes including beliefs, desires,
and intentions, to another person (e.g., Blair, 2005a,b). The over-
lap between empathy and ToM has further been conceptualised
with respect to the distinction between cognitive theory of mind
(i.e., metalizing about cognitive states) and affective theory of mind
(i.e., metalizing about affective states) (Walter, 2012).
Support for the distinction between cognitive and affective
empathy as dissociable processes has been compelling, but does
not imply that either occurs in isolation. In day-to-day social inter-
actions, attending to and metalizing about the emotional cues of
others (cognitive empathy) may lead to the experience of similar
affective states in oneself (affective empathy), just as emotion trig-
gered by visual signals such as facial expressions (e.g., crying) may
lead to metalizing about the emotions of others (Walter, 2012). As
such, current conceptualisations of empathy emphasise both the
differentiation and interplay of cognitive and affective processing
and behavioral responses.
4. A developmental perspective on empathy and conduct
problems
The role that a lack of empathy may play in conferring risk
for conduct problems, and aggressive behavior in particular, has
been the subject of numerous theoretical accounts. The need for
a developmental perspective on this issue has become increas-
ingly apparent in recent decades, as evidence has grown regarding
the complex interplay between biological and environmental
inuences that unfolds over time among individuals with hetero-
geneous forms of conduct problems. Decits in empathy and its
subcomponents can be seen to reect deviations from the typi-
cal developmental trajectories of the neurocognitive systems upon
which empathy relies; deviations that, in turn, interfere with adap-
tive development in other domains, across subsequent periods of
development. Developmental models have traditionally empha-
sised that vicariously experiencing the distress of others facilitates
an appreciation for the internal state of others, and in turn promotes
prosocial behavior. Conversely, the failure to know or experience
the emotions of others interferes with social and moral develop-
ment (Eisenberg and Miller, 1987). At the same time, models based
on learning theory have emphasised that empathic responses to the
distress expressed by victims of antisocial and aggressive behavior
are typically experienced as highly aversive. As such, individuals
with healthy levels of empathy nd their own aggressive behav-
ior to be vicariously punishing, and are understood to inhibit such
behavior as a result of stimulus-reinforcement learning (Blair and
Blair, 2009).
Research based on the subgrouping of children with conduct
problems characterized by high versus low levels of CU traits
has been particularly informative with regard to such theoreti-
cal accounts in recent years, providing compelling support for the
notion that distinct decits in empathy map onto these subgroups.
It has long been known that decits in language development and
verbal intelligence are common among children with conduct prob-
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
lems, however current evidence indicates that they are somewhat
specic to those with low levels of CU traits (Salekin et al., 2004;
Munoz et al., 2008). Evidence also suggests that for these children
representations of emotional states are easily and frequently acti-
vated by inappropriate (ambiguous) emotional cues, resulting in
the mislabelling of these cues (e.g., a peers benign expression is
attributed to anger) (Dodge et al., 1997; Dodge and Pettit, 2003;
Waldman, 1996). This prole describes a child who has difculty
verbalising the nuances of emotion and intensions in others (poor
cognitive empathy), yet experiences frequent and intense, perhaps
even heightened automatic emotional contagion (intact affective
empathy). In contrast, children with conduct problems and high
levels of CU traits appear to be characterized by an under-arousal
to cues of distress and threat that suggests a primary decit in
affective empathy. Conversely, the relatively intact verbal abilities
of these children would be expected to facilitate the development
of cognitive empathy. This prole describes a child who explicitly
understands the emotional states and thoughts of others (intact
cognitive empathy), but is unmoved by this understanding (poor
affective empathy).
Dadds et al. (2009) examined the unique associations between
callous-unemotional traits and the cognitive and affective com-
ponents of empathy, and explored how these associations are
transformed across development in a community sample of chil-
dren aged from 3 to 13 years (n = 2760; 1393 male, 1367 female).
Those with the highest level represented children in the highest
ranges on both CU traits and conduct problems. As predicted, high
levels of CU traits were found to be associated with lower parent
ratings of affective empathy across all age periods; however this
association was unique to males. It is also noteworthy that asso-
ciations between CU traits and empathy were moderated by age.
Specically, boys and girls with high levels of CU traits exhibited
decits in cognitive empathy across childhood, whereas high-CU
boys demonstrated a clear recovery to comparatively normal levels
of cognitive empathy by 912 years of age, despite ongoing impair-
ments in affective empathy. In contrast, high-CU girls showed no
such recovery in cognitive empathy. Further research is needed
to understand the developmental effects suggested by these nd-
ings. It is possible that for boys, the formal verbal operations that
develop with adolescence perform a compensatory function, even-
tually supporting the development of cognitive empathy albeit
through (abnormal) processes that are somewhat distinct from
those involved at earlier developmental periods (when cognitive
empathy appears to rely somewhat more directly on those pro-
cesses associated with automatic affective empathy) (Dadds et al.,
2009).
Findings from experimental studies have suggested that adult
offenders with psychopathic traits and antisocial children with
CU traits demonstrate similar patterns on indices that have been
used to operationalise cognitive and affective empathy. It should be
noted, however, that although there is evidence that CU traits may
increase risk for later adult psychopathy, these childhood traits do
not equate to psychopathy. Care should therefore be taken when
generalising the adult literature and term psychopathy to children.
Perhaps the most common method used to examine empathy
in relation to conduct problems and CU traits has been emotion-
recognition paradigms. Emotion-recognition tasks vary in the
stimuli they use and in the experimental design but, in general, the
participant is presented with images of faces expressing an emotion
(e.g. happy, sad, angry, fearful, and neutral) and asked to categorize
that emotion. Most tasks use simple, broad categories such as those
listed above but others, such as the Reading the Mind in the Eyes
task (Baron-Cohen et al., 2001) use images of the eye-region only
and provide four options of more nuanced emotions (e.g. playful,
comforting, irritated, bored).
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It is important to note that emotion-recognition speaks to abil-
ities in two domains of empathy. Clearly, the ability to correctly
label an emotion implies a certain level of cognitive understand-
ing; the person must have sufcient vocabulary and experience
with that emotional expression in order to categorize it. In addition,
emotion-recognition requires the person to attend to the relevant
features of the facial expression. For example, a fear expression
can only be reliably identied by attending to the widened-eyes.
Thus emotion-recognition requires both a sufcient basic level of
cognitive empathy and a prerequisite of affective empathy: the
appropriate allocation of visual attention.
There are two patterns of deviant responding in emotion-
recognition tasks that may be associated with empathy decits in
the context of antisocial behavior. The rst is a bias to overinter-
pret hostility (e.g. anger) in non-hostile expressions (e.g. neutral or
sad). As described previously, this pattern of responding is asso-
ciated with children with conduct problems and low levels of CU
traits (Dodge et al., 1997; Dodge and Pettit, 2003; Waldman, 1996).
The second is a failure to correctly identify emotions that should
elicit sympathy (sadness and fear).
Experimental paradigms have shown that offenders with psy-
chopathy exhibit a poor recognition of emotional states in others
that includes, but is not limited to, expressions of fear and sadness
(Dawel et al., 2012; Marsh and Blair, 2008). In children and adoles-
cents, CU traits have likewise been associated with poor recognition
of emotional states, which some studies have found to be partic-
ularly apparent for fear and sadness (Blair and Coles, 2000; Blair
et al., 2001; Bowen et al., 2013; Dadds et al., 2006; de Ridder et al.,
2001; Woodworth and Waschbusch, 2008). Similarly, high-CU chil-
dren have been found to demonstrate fear/sadness blindness to
emotional vocal tones (Blair et al., 2005; Stevens et al., 2001).
The impact of poor recognition of fear and sadness in another
individual on empathic responding and antisocial behavior may be
two-fold. In the rst instance, a child who fails to see that their
behavior towards another child has resulted in that child being
scared or upset is unable to learn to modify their behavior in the
future. The high CU child would be unable to learn to associate their
own behavior with a negative social outcome simply because that
outcome is not observed. Over repeated experience of neglecting
to observe the aversive social outcome of their own behavior, how-
ever, a child with CU traits may begin to lag behind their peers
in other aspects of empathy development. Emotion recognition is
a necessary building block for higher order empathy understand-
ing and empathic behaviors; a decit at this low level can have
deleterious effects resulting in an effective developmental delay in
empathy development.
Interestingly, the mechanism driving this fear/sadness emotion
recognition decit has been investigated and evidence suggests
that it is due to a decit in the automatic allocation of attention to
the socially-salient stimuli (e.g. fearfully-widened eyes displayed
in a fear face). Research in boys with conduct problems has shown
that those with high levels of CU traits fail to attend to the eye
region of fearful faces and have poor fear recognition accordingly
(Dadds et al., 2008; Dadds et al., 2006). However, when boys with
high CU traits were explicitly instructed to attend to the eye-
region of the emotional expressions their fear recognition decits
were normalised (Dadds et al., 2006). It should be noted that there
is evidence that the attentional decits associated with high CU
traits have been shown to occur with respect to any stimuli that is
not central to the immediate motivational goals of the individual,
and are not limited to socio-emotional cues (Dawel et al., 2015;
Newman et al., 2010). The apparent automatic, bottom-up nature
of this attentional decit has led to recent theoretical models of
psychopathy and CU traits to argue for a biologically-based, sub-
cortical substrate for this mechanism (Moul et al., 2012).
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
5
Before concluding this section, it is worth noting that studies
using Theory of Mind paradigms have generally reported little evi-
dence of impairment in this aspect of cognitive empathy in adults or
children with CU traits (Blair et al., 1996; Jones et al., 2010; Richell
et al., 2003; van Zwieten et al., 2013; Waller et al., 2015; Widom,
1976). On the whole, such ndings to date suggest that although
decits in cognitive empathy may be more pronounced and perva-
sive among individuals with CU traits than previously thought, it
is the domain of affective empathy, and its associated prerequisite
cognitive mechanisms, in which such individuals demonstrate the
most severe impairments, beginning early in life.
As seen here, attempts to identify global decits in empathy
among children with conduct problems have been largely unsuc-
cessful, whereas the notion that decits in subcomponents of
empathy may be key to understanding heterogeneous pathways to
antisocial behavior has received growing support in recent years.
As outlined in the following section, evidence regarding the typi-
cal development of, and interplay between, these subcomponents
has likewise grown, and in our view stands to inform models of
antisocial behavior based on this perspective.
5. Empathic processes: development course,
underpinnings, and interplay
Emerging accounts of the risk processes that shape conduct
problems among individuals with CU traits have emphasised a
complex interplay between neurobiological and environmental
contributions. Before we address such processes, it is important to
rst address current evidence regarding the neurodevelopmental
foundations of empathy and related capacities in healthy individ-
uals.
Given that the construct of empathy itself can be broken down
into discrete subcategories it follows that the neurology of empa-
thy is similarly subdivided. In his 2012 review paper, Walter (2012)
provides a concise account of the brain regions involved in empathy
and ToM. He divides brain regions into those activated by bottom-
up affective signals (affective empathy) and those activated by
top-down cognitive information (cognitive theory of mind). The
brain regions ascribed to affective empathy include the anterior
insular, the cingulate cortex and the amygdala. These limbic and
para-limbic structures constitute what has variously been referred
to as the emotional brain (Dolan, 2002; Le Doux, 1998) or parts
of the social brain (Adolphs, 2009). In contrast, cognitive theory
of mind is described as being strongly associated with activation
of parts of the dorsolateral prefrontal cortex, posteromedial cortex,
superior temporal sulcus and temporo-parietal junction. The ven-
tromedial prefrontal cortex is specically associated with cognitive
empathy and acts as a conduit between affective and cognitive
processing (Shamay-Tsoory, 2011; Walter, 2012).
Current developmental models of empathy suggest that cog-
nitive and affective empathy may follow somewhat distinct
ontogenetic trajectories that reect the differential maturation of
these respective brain structures. Broadly speaking, it appears that
those structures underlying the automatic ability to share emo-
tions were not only early to evolve phylogenetically, but are early
to develop in ontogeny. In contrast, those structures underlying the
capacity to reectively understand mental states emerged late in
phylogeny and are also among those to mature latest in fetal devel-
opment (Singer, 2006). However while highlighting the distinct
developmental trajectories of cognitive and affective empathy, cur-
rent perspectives also emphasise functional interactions between
these trajectories. Therein the capacities underlying one form of
empathy are seen to contribute to the development and quality of
another. In particular, early capacities for affective empathy appear
to feed into the emergence of subsequent capacities for cognitive
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empathy, with negative arousal motivating explanatory activity
and promoting associated skills.
Typical developmental trajectories for cognitive and affective
empathy differ most saliently in terms of the ages at which differ-
ent facets emerge, with the abilities underlying reective cognitive
empathy developing considerably later than those associated with
automatic affective empathy. Indeed, the beginnings of affective
empathy appear to be demonstrated soon after birth when new-
born infants selectively respond to the cries of other infants by
themselves crying (e.g., Martin and Clark, 1987). This empathic cry-
ing apparent well before infants demonstrate self-awareness and
the capacity to distinguish self and others is seen as an elementary
form of affect sharing, and often regarded as the foundation for the
increasingly complex forms of empathy that follow (e.g., Hoffman,
2000; Vreeke and van der Mark 2003).
It is only toward the end of the rst year that infants demon-
strate a more active response to peer distress; however at this time
the child acts to reduce his/her own empathic distress rather than
that of the victim. For example the child who observes a friend
fall down and cry may cry in response, and engage in self-soothing
behaviors such as thumb sucking. By 13 or 14 months infants may
no longer exhibit signs of their own distress, but show the rst
steps toward prosocial actions approaching, touching, and pat-
ting the distressed individual. It is only once the capacities for
self-awareness and the distinction between self and other develop,
beginning at around 18 months, that classic prosocial behavior is
demonstrated (Decety and Jackson, 2004). At this time a child may
respond to a distressed individual by bringing objects to him/her,
making suggestions about what to do, expressing sympathy in
words, seeking help from a third party, or even attempting to pro-
tect the distressed other (Harris, 1989).
Just as the development of automatic affective empathy pre-
cedes that of reective cognitive empathy, the implicit attribution
of intentions and other mental states to others also precedes
explicit forms of emotion understanding and metalizing. These
implicit processes include the ability of the infant to direct his/her
attention/gaze towards the attentional focus of his/her mother
(joint attention), which develops at around the age of 1218
months or even earlier. It is only later that explicit forms of cog-
nitive empathy emerge, which are thought to coincide with the
emergence of conscious representations of ones own mental states,
allowing for statements such as I feel sad or jealous (Singer, 2006).
These capacities are also thought to develop in relation to ones
own experience of (and representation of) feeling states. For exam-
ple, Singer (2006) suggests that the capacity to understand other
peoples feelings when there is congruency between ones own
feelings and those of another person precedes the capacity to
understand others feeling in the absence of any representation
of this feeling state in oneself. Once again, these differences likely
reect the differential maturation of underlying neural architec-
tures, with the former relying primarily on limbic structures and
the latter on pre-frontal and temporal structures.
Current perspectives on the development of empathy and its
component processes further assume that early environments play
a critical role in potentiating the neurobiological underpinnings
of these capacities (Knafo and Uzefovsky, 2013; Tone and Tully,
2014). Here, primary importance has generally been placed on
sensitive, responsive, and supportive caregiving (Eisenberg and
Valiente, 2002; Knafo and Plomin, 2006; Strayer and Roberts, 2004).
Although studies of these parenting inuences has often focused
on global empathy constructs or specic components of empathy
in isolation, those that have distinguished between cognitive and
affective empathy have found sensitive parenting to contribute
to the emergence of capacities in both domains (Eisenberg and
McNally, 1993; Soenens et al., 2007). Such caregiving has been
found to promote young childrens proclivity to take others per-
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
spectives (Farrant et al., 2012) and to predict increased empathic
concern and perspective taking in adolescence (Miklikowska et al.,
2011). It has likewise been shown to predict increases in childrens
levels of prosocial behavior toward peers (e.g., Hastings et al., 2007).
Among the theoretical perspectives that have emerged to
account for the mechanisms through which such caregiving may
promote and transform capacities related to empathy, social
learning theory accounts have emphasised the role that support-
ive parents play in modelling empathic skills to their offspring
(Barnett, 1987; Eisenberg et al., 2006). Alternatively, attachment
theorists have argued that conditions that foster a secure attach-
ment, sensitive and contingent caregiving frees children from
self-preoccupation and allows them to fully engage in empathic
exchanges (Hoffman, 2000; Sroufe, 2005; Sroufe and Fleeson,
1986). At the same time, the role that social environments play
in shaping the maturing brain structures and circuitry that support
empathy is understood to vary over time, with some developmental
periods thought to constitute critical windows for the acquisition or
expression of specic socioemotional functions (Nelson and Guyer,
2011). Subcortical regions such as the hippocampus, for example,
appear to be particularly vulnerable to environmental insults such
as psychical maltreatment during the preschool period, whereas
the prefrontal cortices may be more profoundly affected by mal-
treatment during adolescence (Andersen et al., 2008).
In recent years, neurodevelopmental accounts of empathy have
been informed signicantly by conceptualisations of caregiving
and the parent-child relationship based on the notion of syn-
chrony, as reected in mutually responsive behaviors such as joint
gaze. Synchrony has been argued to build on the infants biolog-
ical rhythms, extending them to social exchanges (Lester et al.,
1985; Tronick et al., 1980; Wolff, 1967). It is assumed that syn-
chrony plays a key role in the maturation of the social brain,
impacting on the development of self-regulation, symbol use, and
empathy across childhood (Feldman, 2007a). Conceptualisations of
synchrony emphasise systemic processes, involving co-regulatory
experiences within attachment relationships that provide the foun-
dation for a childs emerging capacity for intimacy, as well as
empathy and the ability to read the intentions of others. These
experiences are thought to promote, among other things, adap-
tive orientation to the external environment, and development of
limbic-mediated capacities such as those implicated in emotional
signalling and affect sharing that emerge at 3- to-6-months of age
(Levitt, 2003; Porges, 2003). Some of the most impressive support
for the importance of synchrony has come from long-term longitu-
dinal research. One such study followed infants from 3 months to 13
years of age, nding that synchrony during infancy was associated
with capacities for empathy and moral orientation in adolescence
(Feldman, 2007b).
Consistent with the dyadic conceptualisation of synchrony,
and multidimensional bioecological models of child development
(Belsky, 1984; Bronfenbrenner and Ceci, 1994), both parent-driven
and child-driven inuences have been emphasised in literature on
precursors to empathy and subsequent outcomes. The capacity to
engage in temporally-matched interactions is based on physiolog-
ical mechanisms, including attachment-related hormones such as
oxytocin (Feldman, 2007a,b). Factors including a childs disposi-
tions, the parents personality and psychopathology, and the nature
of the social context, are thought to inuence not only the char-
acteristics of synchrony for a dyad, but also the developmental
outcomes of synchrony. For example, more biologically regulated
children elicit more reciprocal interactions from their care-givers,
but are also likely to develop self-regulatory and social-adaptive
competencies. Likewise, mothers who effectively attend to their
infants communications are often less anxious and depressed. Sim-
ilarly, certain environments may be more or less conducive to
optimal synchrony (Feldman, 2007a,b).
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In the domain of cognitive neurodevelopment, the allocation
of attention to social stimuli is a clear prerequisite for the devel-
opment of empathy. An infants ability to attend to, and form
associations with, social stimuli such as facial expressions and
vocalizations enables him/her to recognize, and emotionally res-
onate, with other peoples emotions. This then facilitates the higher
order abilities of categorization, labeling and understanding. Exper-
imentally, the appropriate allocation of attention to socially salient
stimuli is indexed via emotion-recognition tasks. As described pre-
viously, it is likely that it is the inappropriate allocation of attention
that is the driving force behind the specic emotion-recognition
decits demonstrated by children and adolescents with conduct
problems and CU traits. As opposed to the pattern of responding
typically seen in children with conduct problems and low CU traits,
in which a cognitive/affective bias results in non-hostile (neutral)
expressions being mistaken for angry or aggressive, a decit in the
identication of fear/sadness has been associated with insufcient
allocation of attention to the salient features of the expression (i.e.
the fearfully widened eyes that signify fear) (Dadds et al., 2008;
Moul et al., 2012).
Emotion-recognition tasks alone only allow the researcher to
infer that there may be attention decits that result in incorrect
labeling of emotions. There are, of course, alternative explanations
such as an inadequate vocabulary or a lack of experience observing
specic emotions. In order to try and elucidate whether attentional
issues are associated with poor performance on these tasks some
research has used an eye-tracker to monitor the gaze of the par-
ticipant while performing the task. There are two components of
eye gaze that are important to consider in the context of emotion-
recognition. The rst is the number of relevant gaze shifts the
movement of gaze towards salient, emotion-identifying features
of the stimulus. The second component is the gaze duration the
length of time that the salient features are attended to. If the rst
component is compromised then it is plausible that the partici-
pant would not correctly identify the expression due to the neglect
of relevant cues. If the second component is too short or too long
then the participant may under, or over-, interpret, the expression
conveyed.
Of course, the allocation of attention is also critical for com-
ponents of social learning such as joint attention and synchrony
as described previously. Decits in attending to socially-relevant
stimuli (such as the eyes of others) may have a negative impact
on the development of the parent-child relationship. This effect
is not a trivial one as we know that the early caregiving environ-
ment has a signicant inuence on the development of empathy.
As such, attentional decits early in life may represent double jeop-
ardy for the development of empathy decits: once through their
direct effects on stimulus processing and again via the child-driven
inuences on the social environment.
As outlined here, the emergence of empathy across develop-
ment involves a complex interplay between affective and cognitive
subcomponents, in which a range of distinct neurocognitive capac-
ities are implicated. Environmental inputs in the form of early
caregiving appear to play a critical role in shaping these forms of
empathy and the neurocognitive capacities upon which they rely,
as do biological factors. It is these neurocognitive capacities and
their related biology that we turn to next.
6. Neurocognitive models of CU traits and associated
empathic decits
Given the fairly recent rise of CU traits in children as a research
area distinct from that of adult psychopathy, comprehensive neu-
rocognitive models for CU traits have not been developed. However,
a number of theories of the etiology of adult psychopathy can be
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
7
translated downwards to provide a solid base for understanding the
neurocognitive and biological correlates of CU traits. It is beyond
the scope of this article to review all the models that hold promise;
instead, three viewpoints are presented that provide a framework
with which to map decits in empathy and related neurochemical
systems onto CU traits.
Emotion-based models of psychopathy (Blair, 2004; Kiehl, 2006)
emphasise the hypoactivity of; the amygdala, the orbitofrontal cor-
tex, and the connectivity between the two (Motzkin et al., 2011), as
central to the disorder. Blairs Integrated Emotions System (IES)
model (Blair, 2005a,b) argues that dysfunction of the amygdala
impairs the processing of affective cues and reduces the associa-
bility between these cues and the appropriate response. In other
words, the IES suggests that children with high levels of CU traits
fail to inhibit antisocial and un-empathic behavior because they are
less able to learn the association between their own behaviors and
the affective responses of others. In this regard, the neural regions
involved in the empathy decits associated with CU traits (affec-
tive empathy) t well with this account. The amygdala is critically
involved in stimulus-reinforcement association formation. Thus,
dysfunction in this region could well impair a persons ability to
learn the appropriate social responses and to inhibit inappropriate
antisocial acts.
Attention-based accounts of psychopathy (Patterson and
Newman, 1993) argue that an emotion-based account is not suf-
cient as it does not explain the apparent context-specic nature
of decits associated with the disorder. For example, the nding
that when boys with CU traits were verbally instructed to attend to
the socially salient feature of the stimuli (in this case, the eye-region
of the face), their previously diminished fear-recognition abilities
normalised (Dadds et al., 2006). The fear-recognition decit was
dependent on the participants allocation of attention and thus,
arguably, does not represent a true deciency in the processing
of affective stimuli. Attention-based accounts (e.g. (Patterson and
Newman, 1993)) suggest that CU traits develop primarily as a result
of a difculty in shifting the allocation of attention from a primary
focus to non-dominant cues in the environment. Of course, should
there be global decits in the automatic allocation of attention
in children with conduct problems and CU traits then this should
be apparent in more than just experimental emotion-recognition
tasks. Indeed, more naturalistic research has found just that; boys
with high CU traits demonstrate reduced eye-gaze towards their
parents when engaged in dyadic communication (Dadds et al.,
2014a, 2011). This result is an illustration of the crosstalk between
cognitive and socioenvironmental risk factors for empathy devel-
opment.
Importantly, the amygdala plays a critical role in attention pro-
cesses with the basolateral amygdala (BLA), and connectivity to
the PFC, associated with the automatic allocation of attention, and
the central amygdala (CeA) associated with sustained attention to
salient cues (Moul et al., 2012). Thus, amygdala dysfunction, as
demonstrated in psychopathic and high CU samples (Anderson and
Kiehl, 2012; Hyde et al., 2013), could result in insufcient alloca-
tion of attention to socially salient cues and a resultant decit in
emotion-recognition, reciprocal eye-gaze, and affective empathy.
The Differential Amygdala Activation Model (DAAM) (Moul
et al., 2012) is the rst model to predict an association between
the dysfunction of specic neurochemical systems and amyg-
dala activation in the etiology of CU traits. The DAAM integrates
emotion-based and attention-based accounts into a single frame-
work and, in order to do so, makes a distinction between the
function of the BLA and CeA. The DAAM argues that the BLA is
underactive while the CeA is functioning normally, or indeed is
overactive, in people with high CU traits. The DAAM suggests that
the BLA is underactive as a result of reduced serotonergic system
activation and that the CeA may be overactive as a result of reduced
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oxytocin-induced inhibition. In support of this theoretical model,
recent research examined the connectivity proles of the BLA and
CeA in juvenile offenders with, and without, high levels of CU traits;
the results demonstrated differential connectivity of these amyg-
dala sub-regions in the offenders with high CU traits (Aghajani et al.,
2016).
Common elements of these models include an emphasis on
attention and responsiveness to salient emotion and contextual
stimuli and how these relate to emotional regions (amygdala)
and higher order control regions of the frontal cortex. As we see
in the next section, considerable evidence is mounting that the
neurochemical and hormonal systems of oxytocin, vasopressin,
serotonin, cortisol, testosterone, and dopamine, are involved
in these neurocognitive capacities that appear to underlie the
empathic decits associated with high levels of CU traits.
7. Neurochemical systems and the development of
empathy and CU traits
In line with a growth in the appreciation of the importance
of understanding the etiology of empathy and its role in conduct
problems there has been a considerable increase in the amount
of research dedicated to investigating the neurochemical bases of
empathy. This research has taken multiple forms, including genetic
association studies and measurement of saliva and blood levels,
and has used a variety of samples comprising; adults, children,
healthy and disordered populations. This recent urry of research
activity has identied a number of neurochemical systems that are
likely involved with the mechanisms of empathy. These neuro-
chemical targets are; cortisol, dopamine, testosterone, serotonin
and the neuropeptides oxytocin and vasopressin. As described pre-
viously, there are arguably two processes without which empathy
would cease to develop and be expressed; 1) social learning and
2) emotion-recognition. Given the importance of these processes
for the development and maintenance of empathic behaviors and
attitudes we will next consider the evidence to implicate these
neurochemical targets in; empathy itself, social learning, emotion-
recognition, and in empathy decits in the context of conduct
problems (CU traits). We will review the evidence to implicate
these neurochemical systems in order of perceived relevance; start-
ing with the neuropeptides then moving on to consider serotonin,
cortisol, testosterone and dopamine.
7.1. Neuropeptides: oxytocin and vasopressin
The past decade has seen a dramatic rise in the amount of
research dedicated to testing the role of the neuropeptides in the
mechanisms of empathy. Most notably, the neuropeptide oxytocin
(OT), has achieved popular status due to research to demonstrate
its effects on prosocial and empathogenic behaviors and attitudes
(Liu et al., 2012).
Animal models have shown that the early caregiving environ-
ment can inuence the function of the neuropeptides (Champagne
et al., 2001; Lukas et al., 2010). In some cases these changes are
thought to be life-long epigenetic changes to the genome that
alter the future functionality of the neurochemical system. For
example Murgatroyd et al. (2009) found that mice exposed to
early-life stress had increased AVP expression in the paraventric-
ular nucleus as adults. On the other hand, animal studies have
also shown that the neuropeptides can have transient inuences
on social neurocognition: oxytocin facilitates social approach with
new conspecics, memory for conspecics, and bond formation
(see (Liu et al., 2012) and (Lim and Young, 2006) for a summary
and review respectively). Studies using human participants show a
converging pattern of results. Oxytocin has been found to; encour-
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
age social approach to strangers and reduce the stress response to
social threat (Baumgartner et al., 2008; Kirsch et al., 2005), increase
trust and cooperative behaviors (Kosfeld et al., 2005), and increase
both the memory-for and the evaluation-judgments of strangers
(Guastella et al., 2008b; Theodoridou et al., 2009).
There is mounting evidence to suggest that oxytocin neurotrans-
mission plays a role in emotion-recognition. Research has found
signicant associations between single nucleotide polymorphisms
of the oxytocin receptor gene (OXTR) and emotion-recognition
scores (Lucht et al., 2013; Melchers et al., 2013). Tests of the effect
of acute intranasal administration of oxytocin have also found sig-
nicant associations with overall emotion-recognition accuracy
(Shahrestani et al., 2013), fear (Fischer-Shofty et al., 2010), and
happiness (Schulze et al., 2011).
It is of note that a substantial amount of the research that has
been conducted into the association between OT and emotion-
recognition has used samples with autism spectrum disorder
(ASD). The evidence to demonstrate an effect of OT on emotion-
recognition in these samples is mixed with some research nding
signicant positive effects (Domes et al., 2014) and other research
nding no signicant effect of OT on any aspects of emotion-
recognition (Guastella et al., 2015). Given the need to develop more
effective treatments for ASD, and the difculties sufferers can expe-
rience in the realms of social engagement and cognitive empathy,
the focus on this population is understandable. However, some
researchers have suggested that OT may only be associated with
emotion-recognition in those with emotion-recognition decits
and not associated with normal variations in emotion-recognition
ability. Indeed, Campbell et al. (2014) demonstrated an effect of
OT nasal spray on the emotion-recognition abilities of older (>60)
males (a sample characterized by diminished emotion-recognition
accuracy) but no effect of OT on older females or on young males
or females.
The evidence attesting to the inuence of oxytocin on the allo-
cation of attention and on gaze patterns in emotion-recognition
is mixed. Some research has found signicant effects of intranasal
oxytocin; increased number of gaze shifts to relevant features of
a face (e.g. eyes) (Gamer et al., 2010; Guastella et al., 2008a) and
longer gaze durations (Guastella et al., 2008a). However, other
research has failed to nd effects of intranasal oxytocin (Guastella
et al., 2009; Lischke et al., 2012). Research has also suggested that
the effect of oxytocin on eye-gaze may be emotion specic e.g.
associated with increased duration of gaze to neutral and happy
faces, but reduced gaze duration to negative faces (Domes et al.,
2013); and increased orienting to happy and fearful faces but not
to neutral faces (Tollenaar et al., 2013).
Over the past ve years a number of studies have looked into the
association between the oxytocin system and CU traits in children
and adolescents with conduct problems. Not without exception
(Malik et al., 2012) research has found as association between
callous-unemotional traits and; the oxytocin receptor gene (OXTR)
SNPs (Beitchman et al., 2012; Dadds et al., 2014d), methylation of
OXTR (Cecil et al., 2014; Dadds et al., 2014c); and levels of salivary
oxytocin (Levy et al., 2015).
Given the research demonstrating direct associations between
oxytocin system function and CU traits and the ndings to link oxy-
tocin neurotransmission with emotion-recognition, the evidence
suggests that oxytocin is an important component of the etiol-
ogy of empathy and that the function of the oxytocin system is
likely diminished in children and adolescents with conduct prob-
lems and high levels of CU traits. As such, this neuropeptide is a
sensible target for further research and as a basis for biological
accounts of CU traits. There are, however, reasons for caution. Not
all studies nd signicant associations between OT and empathy
(Gonzalez-Liencres et al., 2013) or effects of intranasal adminis-
tration (Dadds et al., 2014b; Guastella et al., 2015). Furthermore,
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there is research to indicate that in some circumstances OT may
reduce prosocial and empathic behaviors. For example, Bartz et al.
(2011) found that OT administration reduced trust and coopera-
tion in borderline patients. Furthermore, some antisocial effects of
nasally-administered OT have been observed such as an increase
in envy and schadenfreude (Shamay-Tsoory et al., 2009) and an
in-group bias (De Dreu et al., 2010).
Arginine vasopressin (AVP) is very similar in molecular structure
to OT but is more commonly associated with aggression (Heinrichs
and Domes, 2008). More recently, however, research interest has
turned towards the potential association between AVP and empa-
thy. To date there are only a few studies that have tested this
association but the results lend initial support to the inclusion
of AVP as an important neuropeptide in the etiology of empathy.
For example, Wu et al. (2015), tested the association between a
polymorphism of the vasopressin 1B receptor (AVP1B) gene and
cognitive and affective empathy in a large sample of Chinese men.
The results showed that carriers of the minor allele scored signi-
cantly higher than non-carriers in a self-report measure of affective
empathy. As with the inuence of OT on empathic behaviors and
attitudes, there is evidence to demonstrate that the effect of AVP
may be tied to specic sample characteristics. For example, vaso-
pressin has been found to be associated with decits in judgments
of negative emotions by men but only for same-sex judgements
(Uzefovsky et al., 2012).
Tabak et al. (2015) used a randomized, double-blind, placebo
controlled, between-subjects design to test the association
between intranasal administration of vasopressin or oxytocin and
empathic responding to a distress-inducing video clip. Interestingly
(and supporting the suggestion that OT may only be associated with
the alleviation of empathy decits), the results revealed that vaso-
pressin, but not oxytocin, was associated with increased empathic
concern. However, this relationship only held true for participants
who had experienced high, as opposed to low, levels of pater-
nal warmth during childhood. The authors draw on research to
describe the epigenetic effects of early parenting practices on OT
and AVP expression (e.g. Champagne et al., 2001; Lukas et al., 2010)
to provide a potential explanation for this nding. In other words, it
is possible that suboptimal early caregiving practices permanently
alter the neural architecture of empathy which is then differentially
susceptible to uctuations in vasopressin neurotransmission.
Thus, research suggests that the neuropeptides of oxytocin and
vasopressin may have an important role to play in the etiology
of empathy development. Given their known roles in very early
caregiving experiences (Champagne et al., 2001, 2003; Lukas et al.,
2010) it is not surprising that deviations in parenting experiences
(e.g. increased parent warmth) seems to have a long lasting inu-
ence on the future responsivity of the neuropeptide systems. There
is evidence for functionally-relevant genetic differences between
children with, and without, CU traits. The critical question which
remains unanswered is whether children with conduct problems
and CU traits have a purely biologically-based alteration in the func-
tion of their OT system, which then impacts their ability to form
reciprocal bonds with caregivers and to allocate attention appropri-
ately to socially-relevant stimuli; or whether very early caregiving
experiences serve to alter the function of the OT system via epige-
netic processes (e.g. methylation). The answer to this question has
signicant implications for our understanding of the etiology of CU
traits and for developing effective interventions.
7.2. Serotonin
Serotonin (5-HT) is a monoamine that has been implicated in
social behavior and mood states for decades. It is only relatively
recently, however, that its role in empathy has become apparent.
There is evidence from animal studies to suggest that the early care-
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
9
giving environment has an inuence on serotonin system function
(Arborelius and Eklund, 2007; Ognibene et al., 2008; Wankerl et al.,
2014). However, the vast majority of research relating serotonin
to empathy development in humans concerns; genetic association
studies, drug administration studies, and emotion recognition.
Gene association studies have also provided evidence to support
the role of serotonin in the mechanisms of empathy. Gyurak et al.
(2013) examined the relationship between a functional polymor-
phism of the serotonin transporter gene (5-HTTLPR) and individual
differences in emotional reactivity. One study used lms of other
people in distress to provoke empathic responding and physiolog-
ical reactivity. It was found that individuals with the s/s genotype
(two short alleles) of 5-HTTLPR showed greater levels of empathic
responding (more personal distress and higher levels of physiolog-
ical responses) in response to the lms than participants with long
alleles. However, an opposite result was found by Pelka-Wysiecka
et al. (2012) who used personality measures in a healthy sample
of Caucasian adults to demonstrate that participants with the s/s
genotype had the lowest levels of self-reported empathy.
The serotonin 2A receptor gene (HTR2A) has also been associ-
ated with empathy-related behaviors and abilities; for example,
social communication (Murphy et al., 2006), and prosocial orien-
tation (Gerretsen et al., 2010). Gong et al. (2015) looked at the
association between the serotonin receptor 2A gene (HTR2A) and a
single feature of empathy perspective taking in a large sample
of Chinese people. The results showed that the functional polymor-
phism (rs6313) of HTR2A was signicantly associated with scores in
perspective taking; supporting the suggestion that serotonin neu-
rotransmission is important for the process of empathic perspective
taking.
Serotonin has also been shown to be associated with prosocial
behaviors and attitudes. For example, Crockett et al. (2010) admin-
istered participants with citalopram (a selective serotonin reuptake
inhibitor: SSRI) before asking them to make moral judgments on a
set of moral dilemmas. The results demonstrated that enhancing
serotonin had prosocial effects; harmful actions were more likely
to be judged as morally unacceptable. The authors also found that
the prosocial effects of citalopram varied as a function of trait empa-
thy; participants high in trait empathy showed stronger effects of
citalopram on moral judgments than those low in traits empathy.
The association between serotonin neurotransmission
and empathy has also been investigated via the drug 3,4-
Methylenedioxymethamphetamine (MDMA, ecstasy). Users
accounts of the effects of the drug include an increased positivity,
prosocial attitudes and behaviors, and increased empathy. MDMA
is also known to increase the release of brain serotonin and nore-
pinephrine. As such, considerable research has been conducted to
test the mechanisms by which MDMA has its empathogenic effects.
Hysek et al. (2014) examined the acute psychological and hor-
monal effects of MDMA using a placebo-controlled, double-blind,
random-order, cross-over design in 32 healthy volunteers. MDMA
was found to enhance implicit and explicit affective empathy but
showed no effect on cognitive empathy but also impaired the
identication of negative emotions. MDMA administration was
found to increase plasma levels of cortisol and prolactin, which
are markers of serotonergic and noradrenergic activity, and of
oxytocin, which has also been associated with prosocial behavior.
A similar result was found by Kuypers et al. (2014) who showed
in a sample of 20 healthy MDMA users that MDMA selectively
inuenced affective empathy and left cognitive empathy, trust and
reciprocity unaffected.
A review of the evidence to implicate serotonergic modulation
of emotion-recognition was conducted by Del-Ben et al. (2008).
The review included; research that evaluated the effects of acute
manipulation of the serotonin system (e.g. tryptophan ingestion,
SSRIs), studies of the chronic treatment effects of serotonin, and the
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immediate and delayed effect of a single dose of MDMA. As exam-
ples, studies by Harmer et al. (2003) and Attenburrow et al. (2003),
respectively, found that acute administration of a serotonin selec-
tive reuptake inhibitor (SSRI) and ingestion of tryptophan improved
recognition of both fear and happiness. From their review, Del-Ben
et al. (2005) concluded that serotonin neurotransmission facilitates
the recognition of fearful faces and reduced serotonin neurotrans-
mission impairs fear recognition.
Other research has found similar results. Both Antypa et al.
(2011) and Defrancesco et al. (2011) found that the short allele in
a polymorphisms of the serotonin transporter gene (5HTTLPR) was
associated with enhanced fear recognition abilities and that this
effect was most evident in females. The evidence, however, is not
yet conclusive. Hysek et al. (2014), found that acute use of MDMA
(known to increase serotonin release) impaired the recognition of
negative emotions, including anger, sadness and fear. Again, this
result was most evident in females.
Given the evidence base to implicate serotonin neurotransmis-
sion in emotion-recognition recent research has moved on to try
and elucidate the mechanism of this action. The majority of this
research has used genetic association studies. Research into the
promotor region of the serotonin transporter gene (5HTTLPR) has
found that, in children, the s allele is associated with shorter looking
time to the eye-region of the face than the l allele. In adult samples
the results are more complicated. It has been found that partici-
pants with the low-expressing alleles (s and lG ) show faster xation
changes and shorter overall face xation durations (Boll and Gamer,
2014); no differences in gaze patterns but slower responding for
fearful faces (Miu et al., 2012); and longer xation times and a
greater number of xations for positive stimuli (Beevers et al.,
2011).
Research by Jonassen et al. (2015) tested the effects of a single
dose of SSRI on gaze patterns in a sample of healthy women. It was
found that women given SSRI, as compared with placebo, displayed
shorter saccade times and shorter gaze durations in addition to a
reduction in gaze orientation to the eye-region of the emotional
expression. It appears that there is an effect of serotonin neuro-
transmission on eye-gaze but that its manner of action is not yet
understood.
As such, serotonin neurotransmission appears to be important
for the pattern of emotion-recognition decits that specically
characterize children with high CU traits (poor fear recognition).
Conversely, serotonin does not appear to be involved in the hos-
tility bias (incorrect interpretation of neutral faces as displaying
anger) that is demonstrated by children with conduct problems
and low levels of CU traits. As such, the heterogeneity of conduct
problems, and the empathy decits that characterize them, seems
to be evident at the neurochemical level.
A reduced function of the serotonergic system has long been
implicated in the etiology of aggressive behaviors (Moore et al.,
2002; Stadler et al., 2004). More recently, research has suggested
that serotonin may play a role in antisocial personality disorder
and psychopathy (Cuartas Arias et al., 2011; Dolan and Anderson,
2003). It is only in the last few years that evidence has accumulated
to implicate serotonin system function with CU traits in children
and adolescents.
Genetic association studies have found links between CU traits
and functional polymorphisms in the serotonin 2A receptor gene
(HTR2A) and in the serotonin 1B receptor gene (HTR1B) (Moul et al.,
2013) in boys with conduct problems. A gene x environment inter-
action was discovered by Sadeh et al. (2010) in which CU traits
increased as socioeconomic status decreased but only among youth
who were homozygous for the long allele of the serotonin trans-
porter gene. Serum serotonin levels have also been found to be
lower in conduct problem boys with high levels of CU traits than
in those with low levels (Moul et al., 2013); and methylation of the
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
promotor region of HTR1B has also been found to be associated with
CU traits (Moul et al., 2015).
Thus, despite the limited amount of research into the association
between serotonin and CU traits in child and adolescent samples,
the data so far converge to paint a picture of reduced serotonergic
system function which would be concordant with the evidence to
associate reduced serotonin neurotransmission with poor recog-
nition of fear. In this regard, serotonin appears to play the most
signicant role in the etiology of empathy decits that are specic
to CU traits and the emotion-recognition pathway.
7.3. Cortisol
Cortisol is a steroid hormone that is produced within the adrenal
glands and is regulated by the hypothalamic-pituitary-adrenal
(HPA) axis. The HPA axis plays a vital role in maintaining homeo-
stasis in critical physiological processes such as the cardiovascular
system and immune system (Lightman and Conway-Campbell,
2010). The HPA axis is also known to be integral to the modula-
tion of the fear, and stress, responses (Herman and Cullinan, 1997).
While some theories posit that the fear/stress response may be
associated with the impulsive and risky behaviors often demon-
strated by psychopaths (Benning et al., 2005; Patrick, 1994), the
possible link between the fear/stress response and empathy itself
is less clear and so will not be discussed further. There is, however,
substantial evidence from animal models (see Curley et al. (2011)
for summary) to demonstrate effects of the early environment on
HPA axis function (Champagne et al., 2003; Snchez et al., 1998).
The function of the HPA axis can be both immediately, and
permanently, altered in response to suboptimal early caregiving
experiences. Seminal work pioneered by Michael Meaney and his
colleagues used animal models to demonstrate that caring mater-
nal behaviors of mice (licking and grooming of pups) within the
rst 10 days of life resulted in adult mice that had reduced corti-
costerone responses to stress and altered HPA axis RNA expression
(Liu et al., 1997). Similar effects have been found in humans. For
example, maternal depression/anxiety during the third trimester of
pregnancy has been shown to be associated with increased methy-
lation of the glucocorticoid receptor gene in the newborn infants
and with altered HPA stress reactivity in early infancy (Oberlander
et al., 2008). In all, research suggests that early maternal care
has a critical impact on HPA axis function (Francis and Meaney,
1999) and, is such, a potential neurochemical candidate to explain
the association between the early caregiving environment and the
development of empathy.
The direct evidence to support the role of cortisol and the
HPA axis in CU traits in children with conduct problems is mixed.
Research has found CU traits to be associated with low levels of
salivary cortisol (Loney et al., 2006); a blunted HPA-axis response
to stress (Stadler et al., 2011); a diminished cortisol awakening
response (Von Polier et al., 2013); and, at diurnal cortisol rhythms
(low variation) (Gostisha et al., 2014). However, other research has
failed to nd a signicant association between cortisol and CU traits
(Feilhauer et al., 2013); (Poustka et al., 2010).
The evidence presented so far has supported the role of cor-
tisol in the effects of the early caregiving environment and with
CU traits. There is also some research to demonstrate an associa-
tion between cortisol and empathy in healthy populations. Johnson
et al. (2014) investigated the association between empathy and
the cortisol awakening response (the change in salivary cortisol
levels between upon awakening and 30 min after waking). This
study found, in a sample of university students, that lower lev-
els of affective empathy were associated with diminished cortisol
awakening response increases (a result supporting the associations
found between diminished HPA axis function and CU traits in chil-
dren with conduct problems).
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Engert et al. (2014) found that increases in circulating cortisol
are associated with empathic stress (stress experienced as a result
of observing another person undergoing a stressful experience).
Engert and colleagues demonstrated that when one member of a
dyad underwent a psychosocial stressor 26% of observing partners
had a physiologically signicant increase in cortisol levels. This
effect was most profound for dyads which included intimate (as
opposed to unfamiliar) dyads. This nding lends support to the idea
that cortisol continues to serve an important function in the forma-
tion and maintenance of reciprocal bonds well into adulthood.
Thus, the research evidence converges on the idea that there is
a positive relationship between levels of circulating cortisol (and
reactivity of the HPA axis) and empathy; low levels of cortisol and
diminished HPA axis response is associated with less empathy and
increased CU traits. The main conceptual difculty regarding the
role of cortisol in the etiology of CU traits is differentiating between
cause and effect. The research looking into the effects of the prenatal
and early environment on the function of the HPA axis strongly
suggests that empathy circuitry may be altered. However, it is not
clear whether the link between cortisol and CU traits is driven by
the effects of diminished cortisol on empathy circuitry or whether
it is driven by the emotional and behavioral effects of high levels
of CU traits. In other words, altered HPA-axis function may be a
symptom, not a cause, of CU traits. If someone is less concerned
with the thoughts and feelings of others then they may also be less
stressed, less anxious and less responsive to psychosocial stressors.
7.4. Testosterone
Research suggests that testosterone plays a dual role in the eti-
ology of empathy. Fetal testosterone, most commonly indicated
by a proxy measure: the ratio of the lengths of the second and
fourth digits on the left hand (2D:4D), is thought to be associ-
ated with permanent organizational effects on the human brain
(Lombardo et al., 2012). Prenatal testosterone exposure is sexually
differentiated, with male fetuses being exposed to higher levels of
testosterone than female fetuses, and is thought to be important
in the development of systemizing and empathizing circuits in the
brain (Baron-Cohen, 2009). In this regard, it has been argued that
testosterone plays an important role in conditions that are associ-
ated more commonly with males and with low levels of empathy:
namely autism spectrum disorder and CU traits.
There is considerable empirical evidence to support the associa-
tion between high levels of fetal testosterone and empathy decits
(Chapman et al., 2006; Knickmeyer et al., 2006). The majority of
research has demonstrated evidence for an association between
fetal testosterone and cognitive empathy skills (Chapman et al.,
2006; Durdiakov et al., 2015). However, some studies have found
evidence for an association between fetal testosterone and affec-
tive empathy (Chapman et al., 2006; Kempe and Heffernan, 2011)
while other research has failed to replicate signicant associa-
tions at all (Voracek and Dressler, 2006) or only as a distinction
between healthy samples and those with autism spectrum disorder
(Hnekopp, 2012). As such, the precise nature of the relationship
between prenatal testosterone exposure, as indexed via the 2D4D
ratio, and empathy remains unclear.
One study used a longitudinal design to test a causal associ-
ation between directly measured levels of fetal testosterone in
amniotic uid and measures of empathy in early childhood (age
68) (Chapman et al., 2006). The study found a signicant negative
correlation between levels of fetal testosterone and both question-
naire measures of empathy and scores on the Reading the Mind in
the Eyes Task (Baron-Cohen et al., 2001). As such, it appears that
pre-natal exposure to testosterone may indeed have an effect on
empathy-related brain circuitry.
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
11
It is also argued that testosterone has an inuence on empa-
thy abilities post-natally. Research by Pascual-Sagastizabal et al.
(2013) tested the relationship between salivary testosterone levels
and scores on Bryants Empathy Index (Bryant, 1982) in a sam-
ple of 123 9 year old children. An interaction effect was discovered
such that girls with high testosterone levels scored lower in cog-
nitive empathy than girls with low testosterone. This pattern of
results, however, was not found for boys or for affective empathy.
Other studies have used experimental designs to test the effect of
testosterone on empathy skills. Hermans et al. (2006) used a double
blind placebo controlled trial in which 20 females were adminis-
tered a dose of either testosterone or placebo and were then tested
on a facial mimicry task using facial electromyography. Testos-
terone administration was associated with a general decrease in
facial mimicry, a marker of affective empathy. Interestingly a sim-
ilar result was found for the effects of testosterone administration
on cognitive empathy. Young women who were administered a
dose of testosterone were signicantly impaired in their cognitive
empathy ability however this effect was found to be predicted by
2D4D ratio (prenatal testosterone) (Van Honk et al., 2011).
Thus, it is fair to suggest that the impact of testosterone on
empathy may be two-fold; rst, through initial organization of
empathy-related circuitry in the brain, and second, dynamically
via the impact of uctuations in circulating testosterone levels
on the cognitive empathy-related cortical circuits. While there is
considerable evidence to support the role of testosterone early
in the etiology of empathy its relevance for CU traits specically
remains unknown. Given that the majority of evidence supports a
role for testosterone in cognitive empathy (shown to be decient
in children with ASD) as opposed to affective empathy (decient in
children with conduct problems and CU traits) (Jones et al., 2010)
it may not have a role in the mechanisms that underpin empathy
decits specic to children with high CU traits.
7.5. Dopamine
The evidence to support a role for dopamine in empathy and CU
traits is sparse and limited to non-clinical samples. However, recent
research speaks to the role of dopamine in empathy development
specically in the context of the early caregiving environment. Ani-
mal models have demonstrated effects of the early environment
on the function of the dopaminergic system (Ognibene et al., 2008;
Zhang et al., 2005) suggesting that dopamine may play a role in the
relationship between the early caregiving environment and empa-
thy development. Direct evidence for the role of dopamine in the
etiology of empathy is mainly concerned with the Dopamine D4
Receptor (DRD4) (Walter, 2012). A polymorphic region in the third
exon of DRD4 has been associated with a range of social behaviors
such as aggression (Schmidt et al., 2002) and negative emotionality
(Holmboe et al., 2011). This region includes a 7-repeat polymor-
phism that has been associated with the inuence of the quality of
child-care on child outcomes (Belsky and Pluess, 2013) and, as such,
is considered to have effects in an environment-sensitive manner.
For example, Knajo and Uzefovsky (2013) found that 7-repeat car-
riers were more susceptible to suboptimal parenting than 4-repeat
carriers; only in children with 7-repeats was empathic concern
lower when their mothers showed a higher degree of negativity.
This differential susceptibility suggests that, similar to the func-
tion of the HPA axis, early caregiving experiences may inuence
later empathy development for people with certain genotypes. This,
in turn, highlights the importance of simultaneously considering
both environmental (early experiences) and individual (genetic and
cognitive) factors in the etiology of empathy development and CU
traits.
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8. Summary of neurochemical correlates of empathy
In sum, there is a substantial body of research looking into the
neurochemical bases of empathy and a number of likely candi-
dates have been identied. In line with the different brain regions
proposed to be associated with affective empathy (amygdala and
ventral areas), cognitive empathy (vmPFC), and cognitive theory of
mind (dmPFC and cortical regions) (Walter, 2012) the neurochem-
ical correlates seem similarly distinguished. Cognitive empathy
appears most strongly associated with dopamine and testos-
terone; an association that is plausible given the heavy presence
of dopamine receptors in the prefrontal cortex (Meador-Woodruff
et al., 1996). In contrast, the inuences of serotonin, oxytocin and
vasopressin appear to be predominantly associated with more basic
level, bottom up aspects: affective empathy and its underlying
mechanisms.
The second distinction that is brought to bear is that there
appears to be a dynamic interplay between the long-lasting, even
permanent, effects of the early caregiving environment on the
function of neurochemical systems and the responsivity of these
same systems to transient changes in neurotransmission. These
early-environmental effects seem to be associated with the whole
gamut of empathy; from associations with affective and cognitive
empathy skills in healthy populations to interactions with spe-
cic genotypes, and responses to articial manipulations via drug
administration. This general association between the early environ-
ment and empathy development is, of course, potentially relevant
for explaining the deviant development of empathy found in chil-
dren with conduct problems and CU traits. However, the specicity
of the emotion-recognition decits found in CU traits, and their
associated pattern of decient attention allocation, suggest that an
additional, and potentially independent, cause of empathy decits
is present in these children. As predicted by the Differential Amyg-
dala Activation Model (Moul et al., 2012), the social neuropeptide,
oxytocin, and the serotonin system appear to be most strongly
implicated.
The question that remains is: can a comprehensive account of
the biobehavioral basis of conduct problems characterized by high
levels of CU traits be provided that brings together the current evi-
dence regarding the neurochemical and behavioral correlates? In
short, the answer is no. Research into the neurological and neuro-
chemical correlates of empathy decits in conduct problems and
CU traits is still in its early days. The data we have, so far, aids in
directing future research; to elucidate the roles of neurochemicals
in empathy decits, and to better understand the developmental
trajectory of CU traits and conduct problems within the childs
burgeoning sense of self and ability to empathize.
In all, while it is clear that no single account is sufciently
comprehensive to account for the complex interplay between neu-
rological, neurochemical and behavioral correlates of empathy
decits in conduct disorder and CU traits, research is beginning
to close in on brain regions and psychological processes that may
underpin their etiology. The amygdala and vmPFC are structures
strongly associated with empathy and with the basic cognitive
functions (e.g. allocation of attention) found to be decient in
psychopathic and high CU samples. Serotonin and oxytocin are
implicated with empathy, emotion-recognition skills and with CU
traits themselves. While a discrete approach to researching these
factors may be an oversimplication of the complexity of the
etiology of empathy decits in conduct problems an integrated
approach that takes more of a developmental stance may prove
more fruitful.
Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016
9. Conclusion and future directions
It is now apparent that attempts to implicate a global construct
of empathy in the general development of child conduct problems
have largely failed. On the contrary, the mapping of subcompo-
nents of empathy and their interplay early in life, onto more specic
pathways into conduct problems, has led to a more robust evi-
dence base. These subcomponents of empathy are known to be
characterized by specic neurocognitive capacities that may be
impaired in the particularly high risk group of children with con-
duct problems and high CU traits. These capacities and impairments
are associated with individual differences in attention and respon-
siveness to emotionally salient stimuli that can be understood in
based on neurochemical and hormonal function in specic neural
systems. Compelling evidence suggests that among such systems,
those related to neuropeptides (oxytocin and vasopressin), sero-
tonin, cortisol, testosterone, and dopamine, play a role in shaping
the neurocognitive capacities underlying empathy that mark the
pathway to conduct problems followed by these children.
We also noted that interplay between the various neurocog-
nitive capacities underlying the development of healthy empathy
begins very early in life, likely before they are often studied in
the context of conduct problems and callous-unemotional traits.
Just as the concept of empathy decits in conduct problems has
been extended from adult psychopathy down to CU traits in chil-
dren and adolescents, there is a clear need to further extend
research into younger, non-clinical samples, in order to better
understand the earliest socioenvironmental, cognitive and neuro-
chemical foundations of empathy. There is now strong evidence to
show that mechanisms of visual attention, eye-gaze and associated
attachment processes, and each of their correlated neurochemical
systems are critical components in the development of empathy.
There is also evidence that early life experiences and very basic
attention processing decits can have long-term, profound, and
dynamic effects on each other and on the neurochemical sys-
tems required for empathy development. The evidence is calling
for large scale longitudinal research that interrogates the interac-
tions between these behavioral and biological systems. We need to
understand when critical periods of epigenesis occur. We need to
know whether deviant patterns in an infants allocation of atten-
tion are driving parent-child interaction problems or vice versa. We
need to look at the building blocks of empathy in order to under-
stand how to rebuild the foundations for children who are suffering
from conduct problems characterized by CU traits.
Encouragingly, novel approaches to treatment for children with
conduct problems and high levels of CU traits have already begun
to think about this evidence and some positive results have already
been demonstrated (Hawes, Price, & Dadds, 2014). For instance
Dadds et al. (2012) found that an intervention designed for children
with ASD that focused on teaching children to recognize emotions
resulted in a signicant reduction in conduct problem symptoms
for children with high levels of CU traits. Hubble et al. (2015) found
tantalizing evidence that such training reduced subsequent crime
in youth offenders. In the adult literature, treatments trials that
have focused on cognitive decits have had similarly encouraging
results (Baskin-Sommers et al., 2015). A better understanding of the
roles of the neurochemical substrates of empathy decits in con-
duct problems may also pave the way for new treatment options.
While the jury is still out on the efcacy of OT nasal spray as an
empathy-enhancing drug both OT and serotonin may prove suit-
able targets for pharmacological intervention. However, a better
understanding of the sample characteristics and modes of action
that link empathy with these neurochemicals will be necessary
before real advances can be made.
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Please cite this article in press as: Moul, C., et al., Mapping the developmental pathways of child conduct problems through the
neurobiology of empathy. Neurosci. Biobehav. Rev. (2017), http://dx.doi.org/10.1016/j.neubiorev.2017.03.016