Neurobiological basis of psychopathy

1. #. JAMES #. Blair, PhD

Author AIIiliations
1. Unit on Affective Cognitive Neuroscience, Mood and Anxiety Program, National Institute
of Mental Health, 15K North Drive, Bethesda, MD 20892, USA

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To understand a psychiatric disorder we need to know why the pathology causes the behavioural
disturbance, the neural structures implicated in the pathology and the cause oI the dysIunction in
the neural structures. With regard to psychopathy, we have clear indications regarding why the
pathology gives rise to the emotional and behavioural disturbance and important insights into the
neural systems implicated in this pathology. What remains unclear is why these neural systems
are dysIunctional.
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WHAT IS PSYCHOPATHY?
Psychopathy is a disorder, deIined by Hare's Psychopathy Checklist #evised (PCL# and
characterised in part by a diminished capacity Ior remorse and poor behavioural controls ( Hare,
1991. ClassiIications oI psychopathy are not synonymous with diagnoses oI conduct disorder or
antisocial personality disorder ( American Psychiatric Association, 1994 but represent an
extension. These psychiatric diagnoses are poorly speciIied and concentrate on the antisocial
behaviour. Because oI this imprecision, the diagnostic rate oI conduct disorder is 16 oI boys in
mainstream education ( American Psychiatric Association, 1994 and over 80 Ior antisocial
personality disorder in adult Iorensic institutions ( Hart & Hare, 1996. In contrast, psychopathy
is deIined not only by antisocial behaviour but also by emotional impairment such as the lack oI
guilt. Only onethird oI those who are diagnosed with antisocial personality disorder meet criteria
Ior psychopathy ( Hart & Hare, 1996. Moreover, a diagnosis oI psychopathy, unlike antisocial
personality disorder, is inIormative regarding a patient's Iuture risk ( Hare, 1991.
A striking Ieature oI much oI the antisocial behaviour shown by individuals with psychopathy is
that it is mostly instrumental in nature, i.e. goal-directed towards achieving money, sexual
opportunities or increased status ( Cornell et al, 1996. This suggests that the pathology
associated with psychopathy interIeres with socialisation. It is well known that empathy-
inducing, positive parenting practices give rise to less antisocial behaviour than punishment-
based, negative parenting practices. This relationship is shown in healthy developing children as
well as in children with conduct disorder who do not present with the emotional dysIunction oI
psychopathy. However, Ior children with conduct disorder who do present with emotional
dysIunction, there is no relationship between parenting behaviours and level oI antisocial
behaviour ( Wootton et al, 1997. In other words, the emotional impairment Iound in individuals
with psychopathy interIeres with socialisation such that the individual does not learn to avoid
antisocial behaviour.
Socialisation involves aversive conditioning and instrumental learning. In order to learn that
hitting another is bad, this thought must be associated with an aversive unconditioned stimulus
(e.g. the distress oI the victim. Similarly, learning to avoid committing moral transgressions
involves committing a moral transgression and then being punished` by the aversive response oI
the victim's distress ( Blair, 1995. Individuals with psychopathy present with severe diIIiculties
in both aversive conditioning and instrumental learning ( Patrick, 1994; Blair, 2001. Moreover,
they have particular diIIiculties processing the IearIulness and sadness oI others ( Blair, 2001.
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THE NEURAL BASIS OF PSYCHOPATHY
The amygdala is involved in aversive conditioning and instrumental learning ( LeDoux, 1998. It
is also involved in the response to IearIul and sad Iacial expressions ( Blair et al, 1999. The
amygdala is thus involved in all the processes that, when impaired, give rise to the Iunctional
impairments shown by individuals with psychopathy. It is thereIore suggested that amygdala
dysIunction is one oI the core neural systems implicated in the pathology oI psychopathy (
Patrick, 1994; Blair et al, 1999.
Interestingly, two recent neuroimaging studies have conIirmed that amygdala dysIunction is
associated with psychopathy ( Tiihonen et al, 2000; Kiehl et al, 2001. Thus, Tiihonen et al (
2000 used volumetric magnetic resonance imaging (M#I to explore the relationship between
amygdaloid volume and degree oI psychopathy in violent oIIenders as measured by the PCL-#.
They Iound that high levels oI psychopathy were associated with reduced amygdaloid volume.
Kiehl et al ( 2001 used Iunctional M#I to examine neural responses in individuals with high
(~28/40 and low (23/40 scores on the PCL-# during an emotional memory task where the
participant processed words oI neutral and negative valence. Kiehl et al Iound a reduced
amygdala response in the high-scoring group, relative to the low-scoring group, during the
processing oI words oI negative valence.
There have been suggestions that other neural systems are dysIunctional in individuals with
psychopathy. Thus, on the basis oI neuropsychological and neuroimaging Iindings Ior violent
oIIenders, it has been argued that the Irontal cortex could be dysIunctional ( Morgan &
LilienIield, 2000; Soderstrom et al, 2000. However, all oI these studies, with the exception oI
one by ( #aine et al, 2000, have been with violent oIIenders rather than individuals with
psychopathy. This is noteworthy as there are crucial diIIerences between the general population
oI violent oIIenders and these individuals. Indeed, neuropsychological work with individuals
with psychopathy, unlike work with individuals who are violent, has repeatedly Iound Irontal
Iunctioning to be intact ( Kandel & Freed, 1989.
The volumetric M#I study conducted by #aine et al ( 2000 did assess individuals scoring highly
on the PCL-#. This study reported reduced preIrontal grey, but not white, matter volume in these
individuals. However, #aine et al were unable to diIIerentiate between grey matter Irom
diIIerent regions oI the Irontal cortex. This is unIortunate, as although it appears clear that there
is no generalised Irontal cortical dysIunction in individuals with psychopathy there is one region
oI the Irontal cortex that could be impaired, i.e. the orbitoIrontal cortex (OFC.
The OFC, especially the medial OFC, receives extensive projections Irom, and sends extensive
projections to, the amygdala. Moreover, the medial OFC is involved in instrumental learning and
response reversal both oI which Iunctions are impaired in individuals with psychopathy (
LaPierre et al, 1995. In addition, there have been attempts to link the disorder oI psychopathy
with the neurological condition oI acquired sociopathy` Iollowing lesions oI the OFC (
Anderson et al, 1999. Patients with acquired sociopathy` can present with socially
inappropriate behaviour and aggression Iollowing their lesion. However, iI aggression is seen it
is almost exclusively reactive (i.e. Irustration/threat-induced in nature and not the instrumental
goal-directed aggression shown by individuals with psychopathy. Indeed, it has been argued that
the extensive damage seen in those patients with acquired sociopathy` who present with reactive
aggression includes regions oI the lateral OFC that are implicated in modulating basic brain-stem
mechanisms that mediate the Iight-Ilight response to threat ( Blair, 2001. This modulatory
Iunction, and by implication this region, oI the OFC is not thought to be dysIunctional in
individuals with psychopathy.
Thus, it is suggested that the neural structures implicated in psychopathic pathology include the
amygdala and OFC. The basic causes oI the pathology remain unclear; however, there are
interesting possibilities. One is that pathology in the noradrenergic system can lead to the
observed amygdala dysIunction. Certainly, administration oI the -adrenergic blocker
propranolol, as well as amygdala damage, blocks the improvement in episodic memory Ior
emotionally arousing events, as well as disrupting the processing oI sad Iacial expressions (
Harmer et al, 2001. A second possibility concerns the potential value oI genetic inIormation and
mouse models. Many mouse models oI aggression concentrate on a heightened reactively
aggressive response to an intruder. However, a recent mouse model has been developed without
a Iunctional tailless` protein. The gene tailless is a member oI the super-Iamily oI genes that
encode transcription Iactors oI the ligand-activated nuclear receptor type, and is expressed in the
invertebrate and vertebrate brain. Interestingly, mice lacking a Iunctional tailless protein show
reduced amygdaloid volume. Moreover, they show heightened aggression even to litter-mates
and the Iemales lack normal maternal instincts ( Monaghan et al, 1997. Although it is diIIicult
currently to extrapolate Irom these data to an understanding oI psychopathy, the study oI such
animals should allow a molecular approach to understanding the genetic architecture oI the
Iorebrain. These data will undoubtedly be invaluable in Iurthering our understanding oI
psychopathy.
It is important to make one Iinal point. The liIestyle oI the individual with psychopathy may
exacerbate any neurobiological impairments. One Ieature associated with psychopathy is
substance misuse. This could be contributing to apparent impairments. For example chronic
amphetamine misuse has been shown to lead to disturbance in Iunctions mediated by the OFC (
#ogers et al, 1999. In this context, it is interesting to note that although perIormance on
measures thought to require amygdala involvement is impaired substantially in both adults with
psychopathy and children with psychopathic tendencies, perIormance on measures thought to
require the OFC is impaired substantially only in the adults ( Blair et al, 2001. This, oI course,
could reIlect the developmental course oI the disorder. However, alternatively, it could reIlect
the liIestyle oI the individual with psychopathy where substance misuse has interacted with the
Iundamental pathology to produce additional OFC pathology.
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CONCLUSIONS
The suggestion is that the pathology oI individuals with psychopathy detrimentally aIIects two
processes that are required Ior socialisation, i.e. aversive conditioning and instrumental learning.
This is thought to result Irom amygdala dysIunction potentially compounded by OFC
dysIunction. However, the reasons Ior this dysIunction remain unknown. The noradrenergic
system could be implicated but why this system should be dysIunctional is, again, unknown. An
answer is likely to Iollow an understanding oI the genetic architecture and morphogenesis oI the
Iorebrain.
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