Review article

Neurobiology of borderline personality disorder (BPD)

and antisocial personality disorder (APD)
Anna Buchheima, Gerhard Rothb, Günter Schiepekc, Oliver Pogarelld, Susanne Karchd
a
Institut für Psychologie, Universität Innsbruck, Austria
b
Institut für Hirnforschung, Universität Bremen, Germany
c
Institut für Synergetik und Psychotherapieforschung, Paracelsus Medizinische Privatuniversität, Salzburg, Austria
d
Klinik für Psychiatrie und Psychotherapie, Ludwig-Maximilians-Universität, München, Germany

Funding / potential competing interests: No financial suppor t and no other potential conflict of interest relevant to this ar ticle was repor ted.
Authors’ contribution: AB and GR contributed equally to the manuscript, which is based on a recent common publication (Roth G, Buchheim A.
Neurobiology of personality disorders. In: Clarkin JF, Fonagy P, Gabbard GO (eds). Psychodynamic Psychotherapy For Personality Disorders.
A Clinical Handbook. Washington DC, Arlington: American Psychiatric Publishing Inc; 2010. p. 89–124.)

Summary patients with co-morbid PTSD and BPD patients without

PTSD showed that the traumatic events were related to
Affective disorders and personality disorders are associated with a combina- reduced hippocampal volumes [7, 8]. The results of a recent
tion of (1.) genetic polymorphisms predominantly affecting the serotonin meta-analysis suggest that hippocampal volumes are
system and the HPA (stress) axis, (2.) deficits in brain development, (3.) early diminished in patients with BPD relative to controls especially
adverse (traumatising) childhood experiences and (4.) later (adolescent) in cases with a co-morbid PTSD [9]. In addition, left hippo-
adverse experiences. Neurobiological studies have revealed structural and campal volume was inversely correlated with a lifetime his-
functional deficits especially in limbic and paralimbic brain areas, as well as tory of aggressive behaviour [10]. The reduction was more
their interaction between each other and interactions with cognitive-execu- pronounced in patients with multiple hospitalisations [10].
tive brain regions. On the basis of this general assumption, the following This finding seems to be important because the hippocampus
review is about experimental-empirical studies concerning the possible has demonstrated to be one important brain region for the
neurobiological background of personality disorders, particularly borderline control of aggression and impulsive behaviour. The authors
personality disorder (BPD) and antisocial personality disorder (APD)/psy- concluded that their findings suggest that structural changes
chopathy (PP). might facilitate aggressive behaviour [10].
Key words: personality disorders; neuroscience; fMRT; EEG; early traumata; Apart from structural abnormalities in the amygdala and
emotion regulation; impulse control the hippocampus, reduced volumes have been found in
frontal regions [11], for example in the orbitofrontal and
ventromedial prefrontal cortex (OFC, VMPFC), the dorso-
lateral prefrontal cortex (DLPFC) and the anterior cingulate
Borderline personality disorders cortex (ACC; [12]), in the superior parietal cortex and
the precuneus [13]. In BPD subjects with the co-morbid
diagnosis of dissociative amnesia or dissociative identity dis-
Structural imaging
order, the left post-central gyrus was significantly increased
Meta-analysis have revealed reduced hippocampal and compared to controls and to BPD subjects without these
amygdalar volumes in borderline personality disorder (BPD) symptoms [13]. In a study examining teenagers with a first
patients compared to healthy controls [1, 2]. Both brain presentation of BDP compared to controls, deficits in the
areas are associated with affect regulation and emotion. For OFC, but not in the hippocampus or amygdala were identi-
that reason, the volume reduction may be a biological sub- fied [14]. The orbitofrontal cortex is involved in the con-
strate of BPD symptomatology [3]. However, hippocampal scious perception of emotions, the emotional preparation
anomalies are not specific to BPD; for example, patients with and motivation of actions, the assessment of consequences of
post-traumatic stress disorder (PTSD) have also shown re- one’s own behaviour and of individual and social risks, the
duced volumes [4, 5]. The influence of traumatic experi- identification of the emotional expression and of the mean-
ences on neurobiological anomalies in BPD is not yet clear: ing of the actions of other people (empathy), as well as learn-
Driessen et al. [6] found reduced hippocampal volumes as ing and control of socially adequate behaviour. Hippocampal
well as a non-significant trend for reduced amygdala volumes and amygdala volume reductions observed in adult BPD
in a sample of BPD patients with a history of physical or samples may develop during the course of the disorder, al-
sexual abuse in childhood [6]. The comparison of BPD though longitudinal studies are needed to examine this.
Minzberg and colleagues [15] demonstrated an increased
Correspondence: grey mater concentration in the amygdala and a decreased
Professor Günter Schiepek, PhD concentration in the rostral/subgenual ACC compared to
Institut für Synergetik und Psychotherapieforschung healthy subjects. Others suggested a potential association
Paracelsus Medizinische Privatuniversität between 5-HT1A receptor gene polymorphism and amygdala
Ignaz Harrer Strasse 79
AT-5020 Salzburg
volume. This finding might be disease-related and could
Austria contribute to the amygdala findings [16]. Soloff and col-
guenter.schiepek[at]ccsys.de leagues [17] demonstrated that BPD suicide attempters had

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 Review article

diminished grey matter in the insula compared to non-at- frontal cortex of patients with BPD compared to healthy con-
tempters. High-lethality attempters demonstrated decreases trols during resting conditions [22]. However, the results are
in the right OFC, the right mid-superior temporal gyrus, the inconsistent: Juengling et al. [23] demonstrated a hypo-
right insula and the right parahippocampal gyrus. The re- metabolism in the left hippocampus and an in-creased
sults indicated structural differences with respect to suicidal metabolism in the ACC, the superior frontal gyrus, the
behaviour. right inferior frontal gyrus, and the right precentral gyrus
The studies mentioned above suggest that BPD is asso- in inpatients with BPD. By contrast, a decreased metabolism
ciated with abnormalities in the limbic structures and that in the ACC, the DLPFC, and the basal ganglia was revealed
these abnormalities probably underlie emotional dysfunc- in patients compared to controls [24]. De la Fuente and
tion in BPD symptomatology. Decreased volumes of these colleagues demonstrated a relative hypometabolism in pre-
limbic structures are suggested to hold promise as candidate frontal areas, the anterior part of the cingulate cortex as well
endophenotypes in BPD [2]. as thalamic, caudate, and lenticular nuclei [25].
Proton magnetic resonance spectroscopy ([1H]MRS)
studies also provide an insight into baseline neuronal
Functional neuroimaging
function by measuring levels of metabolite concentration.
Pain Van Elst et al. [26] conducted a pilot study assessing the
One characteristic feature of BPD is self-injurious behaviour N-acetylaspartate (NAA) concentration (a marker of neu-
in conjunction with a reduced pain perception. Female inpa- ronal integrity) in patients with BPD and no co-morbid psy-
tients with BPD who do not report pain during self-injury chiatric illnesses versus normal controls. The results indi-
(BPD-nP) showed less pain intensity during the cold pressure cated a significant reduction in NAA concentration in the
test compared to BPD patients who report pain during self- DLPFC of BPD patients compared to normal controls, which
injury (BPD-P), female inpatients with major depression, would indicate deficits in executive function, working
and also compared to healthy subjects. In addition, the total memory, or the ability to integrate emotion and cognition.
absolute theta power was significantly higher in the BPD-nP Soloff et al. [27] used FDG-PET imaging procedures to assess
group compared to depressive patients and healthy subjects, serotonergic functioning. The results suggest that, compared
with a trend toward being significantly higher compared to to controls, BPD patients showed diminished glucose intake
the BPD-P group. It is suggested that increased theta activity in orbital and medial regions of the prefrontal cortex. This
is characteristic of this group of patients and may be indica- finding is noteworthy when considering that BPD partici-
tive of diffuse brain dysfunction [18]. pants were not depressed, which provides the preliminary
Schmahl et al. [19] examined nociceptive processes in pa- evidence that serotonergic dysfunction in BPD is not solely
tients with BPD using event-related potentials (ERPs): ERPs the result of co-morbid major depression.
of BPD patients differed only marginally when compared to
those of healthy controls. However, BPD patients showed Presentation of emotional stimuli
significantly higher heat pain thresholds and lower pain Neuroimaging studies showed that a network of regions is
ratings than control subjects despite similar electrophysio- involved in emotion regulation, including the amygdala,
logical responses. This probably indicates that the sensory- hippocampus, and the orbitofrontal-ventromedial frontal
discriminative pain processing does not differ between cortex. The crucial function of these brain regions in the
groups. Hypoalgesia in BPD may be influenced by altered expression, control, and modulation of emotion and impul-
intracortical processing or active suppression of pain. sivity in humans has led to the hypothesis that dysfunctions
Schmahl et al. demonstrated smaller overall volumes of in these regions could be the reason for some of the psycho-
activity in BPD patients than in controls in response to iden- pathological symptoms seen in BPD.
tical heat stimuli. When the temperature was adjusted In general, neuroimaging provides evidence for a height-
according to the pain threshold, BPD patients showed ened responsivity to emotional stimuli among individuals with
increased responses in the DLPFC and decreased activity in BPD. A greater activation of the amygdala in response to the
the perigenual ACC and the amygdala compared to healthy negative compared to the neutral stimuli was reported in
controls. The authors assumed that the interaction between BPD patients, who met the affective instability criterion for
DLPFC, ACC, and amygdala is associated with an anti-noci- BPD, had no current Axis I disorder, and were medication-
ceptive mechanism [20]. free compared to healthy controls. However, the two groups
did not differ in their self-reported emotional response to the
Vigilance and resting state stimuli suggesting that the BPD group did not experience the
An examination of EEG-vigilance (arousal, wakefulness) in pictures to be more arousing or more negative [28]. In addi-
patients with BPD showed significantly lower rates of EEG- tion, the frequency of negative stimuli seemed to have an
vigilance compared to obsessive compulsive disorder (OCD) important influence on neurobiological findings: BPD pa-
patients. The result may indicate an instable regulation of tients showed greater amygdala activation than healthy
EEG-vigilance in BPD patients and is in line with the as- controls and patients with schizotypal personality disorder,
sumption that sensation seeking and impulsivity in BPD and a prolonged return to baseline, particularly at repeated
have a compensatory and autoregulatory function to stabi- presentation of emotional pictures [29].
lise the activation of the brain [21]. Other research has demonstrated that BPD patients with
Studies using [18F]-fluorodesoxyglucose positron emis- co-occurring Axis I disorder showed higher levels of left
sion tomography (FDG-PET) found differences in the pre- amygdala activation at the presentation of sad, neutral, and

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 Review article

fearful faces [30]. Interestingly, the most striking difference bellum. The authors concluded that the activation of both
between the groups occurred in response to neutral items: amygdala and prefrontal areas could reflect an increased
the evaluation of these pictures was uniformly negative, effortful but insufficient attempt to control intense emotions
threatening, and untrustworthy. The findings from this during the recall of unresolved life events in patients with
study provide a foundation for elucidating the neuronal BPD.
substrates of behavioural and emotional facets of BPD, Buchheim and colleagues [37] examined the functional
contributing to disturbed interpersonal relationships [30]. neuroanatomy of attachment trauma while BPD patients were
Another study focusing on emotions like fear and anger telling individual stories to attachment relevant picture
in BPD showed a significantly larger deactivation in the stimuli (Adult Attachment Projective [38]). BPD patients
bilateral rostral/subgenual ACC to fear in patients compared and healthy controls told stories in response to the AAP
to controls. However, there were no significant differences pictures while being scanned. Group differences in narrative
between groups in these areas in response to anger. The and neural responses to “monadic” pictures (characters
authors concluded that BPD patients exhibit changes in facing attachment threats alone) and “dyadic” pictures
fronto-limbic activity in the processing of fear stimuli, (interaction between characters in an attachment context)
with an exaggerated amygdala response and an impaired were analysed. Behavioural narrative data showed that
emotion-modulation of ACC activity. The relative hypo- monadic pictures were significantly more traumatic for
responsivity to anger compared to fear could be related to BPD patients than for controls. In addition, BPD patients
an inability of BPD patients to manage socially undesirable exhibited significantly more anterior mid-cingulate cortex
behaviour in interpersonal settings [31]. Hypervigilance and activation in response to monadic pictures than controls.
emotional dysregulation may influence disturbed inter- In response to dyadic pictures patients showed more activa-
personal relationships [30]. In addition, the presentation of tion in the right superior temporal sulcus and less activa-
fear stimuli seemed to be related to a dysfunctional fronto- tion in the right parahippocampal gyrus compared to con-
limbic connectivity in BPD patients during fear processing trols. These results give evidence for potential neuronal
with reduced connections to the frontal areas to overt fear mechanisms of attachment trauma underlying interpersonal
processing and reduced connections to the thalamus for symptoms of BPD, such as fearful and painful intolerance
automatic fear processing [32]. In addition, prolonged amyg- of aloneness and reduced positive memories of dyadic inter-
dala responses and medial prefrontal dysfunctions have actions [37].
been demonstrated during instructed fear processing in In summary, emotion processes and their neurobiolo-
BPD patients: patients showed increased connectivity be- gical bases are deficient in BPD patients; for example, amyg-
tween the amygdala and the ventromedial prefrontal cortex dala responses are prolonged and enhanced especially dur-
(VMPFC) and decreased connectivity of the subgenual ACC ing repeated presentation of emotional stimuli. In addition,
with the dorsal ACC [33]. traumatic experiences play an important role in these pro-
The presentation of autobiographical memories led to cesses. These deficits may be part of the neural mechanisms
increased BOLD responses in the bilateral OFC and insular underlying emotional dysregulation in BPD patients [33].
cortex, left ACC, and medial prefrontal cortex as well as in Functional anomalies could also influence cognitive pro-
the parietal and parahippocampal areas; these results were cesses. A recent study by Enzi and colleagues [39] demon-
related with a more aversive and arousing experience as- strated that deficient emotion processing is likely to affect
sessed by self-reports [34]. In addition, hyperactivations the reward system in patients with BPD.
were seen during neutral and negative stimuli. The authors
concluded that the lack of selective activation of areas Executive functions
involved in autobiographical memory retrieval suggests a BPD patients often have deficits in executive processes, for
general tendency towards a self-referential mode of infor- example flexibility, inhibitory control, planning, and error
mation processing in BPD or a failure to switch between processing. Electrophysiologically, diminished error-related
emotionally salient and neutral stimuli [34]. responses and inhibition-associated potentials were demon-
Traumatic experiences or PTSD diagnosis seem to influence strated in patients compared to healthy subjects [40, 41].
the processing of emotions. The presentation of traumatic These responses were influenced by the impulsiveness of
memories and aversive, but non-traumatic memories in BPD patients. The assessment of decision-making and re-
patients with BPD led to the activation of different neural ward processes demonstrated that patients with BPD made
networks: BPD patients without PTSD revealed predomi- more risky choices which did not improve their performance
nantly increased BOLD responses in the OFC and the Broca during the Iowa Gambling Task [42]. Concerning electro-
area, whereas patients with PTSD showed increased re- physiological responses, feedback-related negativity was
sponses in the amygdala, anterior temporal lobes, and diminished and was correlated with enhanced impulsivity
mesio-temporal areas [35]. Beblo et al. [36] investigated and enhanced risk taking behaviour in patients. In contrast,
neural correlates of the recall of unresolved life events in P300 amplitudes following negative feedback were increased
patients with BPD and healthy controls. Individual cue in BPD patients. These findings suggest dysfunctional deci-
words were used in order to stimulate autobiographical sion-making processes in patients and especially problems
memories. When contrasting unresolved and resolved with learning to avoid disadvantageous choices [42]. Func-
life events, patients showed significant bilateral activation tional MRI studies focusing on the inhibition of behavioural
of fronto-temporal areas including the insula, amygdala, left responses demonstrated that patients with impulsive per-
posterior cingulate cortex, right occipital cortex, and cere- sonality disorders (BPD; antisocial personality disorder)

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exhibited more widespread activity with bilateral activation defines a conceptually similar disorder to antisocial per-
in the medial frontal gyrus, the superior frontal gyrus, and sonality disorder called (F60.2) dissocial personality disorder.
the inferior frontal gyrus as well as the ACC. The authors Psychopathy can be defined for example by “Hare’s Psycho-
suggested inefficient processing with activations in a wider pathy Check List-Revised” (PCL-R; [46]): (1.) Aggressive
cortical area compared to healthy subjects [43]. narcissism: for example glibness/superficial charm, grandiose
Other studies focused on the influence of emotions on sense of self-worth, pathological lying, lack of guilt, lack of
cognitive processes. The interaction of negative emotions empathy; (2.) Socially deviant lifestyle: for example need for
and behavioural inhibition led to decreased responses in stimulation, parasitic lifestyle, poor behavioural control, lack
the VMPFC (e.g., OFC, subgenual ACC) and extended amyg- of realistic, long-term goals, juvenile delinquency.
dalar-ventro-striatal activity [44]. The authors assumed that
their findings suggested specific fronto-limbic neuronal sub-
Functional neuroimaging
strates associated with core clinical features of emotional and
behavioural dyscontrol in BPD [44]. In addition, hyper-respon- Impulsive aggression
siveness to distracting emotional pictures negatively affected Reactive-impulsive aggression and violence are the domi-
the working memory performance of patients [45]. nant types of antisocial behaviour and are positively corre-
lated to increased levels of anger and impulsivity. They occur
as a reaction to perceived threats or provocation and are
Summary
often followed by remorse [47]. Signs of a relationship
The cause of borderline personality disorder is complex, with between impulsive aggression and a reduced volume of the
several factors interacting in various ways with each other. frontal lobe or other dysfunctions of the prefrontal cortex,
It is a complex dynamic system both psychologically and especially OFC and VMPFC, are found in patients with a
neurobiologically. Genetic factors and adverse childhood variety of psychiatric disorders such as BPD [48] and APD
experiences (e.g. attachment trauma, emotional neglect) [49, 50], in suicidal behaviour [51], and in murderers
may cause emotional dysregulation and heightened impul- pleading not guilty by reason of insanity [52, 53]. One major
sivity leading to dysfunctional behaviours and psycho- function ascribed to VMPFC and OFC is the regulation of
social deficits, which again could reinforce emotional emotional responses, especially in the context of threatening
dysregulation and impulsivity. Structural and functional and risky situations.
neuroimaging have revealed a dysfunctional frontolimbic OFC and VMPFC are closely interconnected with other
network of brain regions, which seem to mediate BPD symp- limbic brain areas such as the rostral ACC and the amygdala
tomatology. Taken together, these findings may suggest that [54]. Accordingly, the relative balance of activity between
BPD patients exhibit reduced hippocampal, orbitofrontal, the prefrontal cortex and limbic structures could be dis-
and amygdala volumes and an increased activation in the turbed, when it comes to impulsive aggression and violence
amygdala in response to negative emotional stimuli. How- [55]. Raine et al. [52] demonstrated reduced prefrontal and
ever, some neuroimaging studies also showed inconsistent increased subcortical activity, specifically in murderers who
results; the impact of various influencing factors on neuro- committed their violent acts in an unplanned and impulsive
biological correlates of BPD should be investigated in more manner. Patients with impulsive aggression showed an
detail. exaggerated amygdala activity and reduced OFC activation in
response to angry faces, providing evidence for an amyg-
dala-OFC dysfunction in response to social threat signals in
Neurobiological basis of antisocial personality individuals with impulsive aggression [47]. These data
disorder (APD) and psychopathy suggest a link between a disturbed frontal-limbic circuitry
and a state of sub-cortical hyper-arousal (primarily mediated
There is no universally accepted definition of personality by the amygdala) leading to impulsive aggression and emo-
disorders related to antisocial behaviour. A frequently used tional dysregulation. The amygdala and the OFC are key
definition is given in DSM-IV as “Personality disorders structures in the so-called ventral system of emotion percep-
cluster B” with the following diagnostic criteria: (1.) Failure tion [56]. According to this concept, the ventral system is
to conform to social norms with respect to lawful behaviours important, among others, for the rapid appraisal of emo-
as indicated by repeatedly performing acts leading to arrest; tional material and the automatic regulation of autonomic
(2.) deceitfulness, as indicated by repeatedly lying, use responses to emotional stimuli. It is assumed that activation
of aliases, or conning others for personal profit or pleasure; of the dorsal ACC and of the OFC/VMPFC in healthy impul-
(3.) impulsivity or failure to plan ahead; (4.) irritability and sive individuals operates as a compensatory mechanism,
aggressiveness, as indicated by repeated physical fights or which is absent in clinical populations [57]. Patients with
assaults; (5.) reckless disregard for safety of self or others; conduct disorder and APD, likewise characterised by height-
(6.) consistent irresponsibility, as indicated by repeated ened impulsivity, showed a marked decrease in the dorsal
failure to sustain consistent work behaviour or honour ACC when viewing negative pictures [57, 58]. In conclu-
financial obligations; (7.) lack of remorse, as indicated by sion, prefrontal hypofunction in combination with amygdalar
being indifferent to or rationalising following having hurt, hyperfunction consistently occur throughout anatomical and
mistreated, or stolen from another individual. The World functional studies with clinical and forensic populations,
Health Organisation’s International Statistical Classification of which are characterised by emotional dyscontrol and impul-
Diseases and Related Health Problems, tenth edition (ICD-10), sivity/aggression.

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Proactive-instrumental aggression and psychopathy neural system [75]. Others demonstrated a participation of
Persons satisfying the criteria of psychopathy are characterised the dorsomedial PFC in cognitive aspects of social inter-
by a dominance of instrumental, proactive, premeditated action, while the OFC/VMPFC is involved in affective pro-
or “predatory” aggression in terms of goal-directed activity. cesses associated with compassion for the suffering oppo-
Psychopaths often exhibit a high degree of self-control at nent [76]. Interestingly, stronger OFC/VMPFC activations
lying, deceiving and manipulating others, and simulating for more empathic participants and a positive correlation
empathy for example, while hiding their true motives. Psy- between amygdala activity and pain of the opponent were
chopathy is considered a reliable predictor for violence, high reported. These findings point towards a higher responsive-
rates of recidivism, and poor treatment responsivity [59]. ness of the OFC/VMPFC to distress cues signalled by the
A thinner cortex in a number of areas has been demon- amygdala in more empathic individuals and may relate to a
strated in psychopathic inmates compared to non-psycho- neuronal basis of empathy deficits as seen in psychopaths.
paths, for example in the left insula, the dorsal ACC, the The investigation of a possible link between affective and
precentral gyri, and the anterior temporal cortices [60]. In cognitive processes in psychopathy revealed that, unlike
addition, the connectivity between dorsal ACC and insula healthy subjects, persons with dissocial personality disorder
was decreased. A study comprising a large sample of incar- did not show any influence of negative conditions on behav-
cerated men demonstrated decreased grey matter in several ioural results; in psychopaths negative emotions did not
limbic and paralimbic areas, such as parahippocampal areas, disturb cognitive tasks [77]. In addition, psychopaths exhi-
amygdala and hippocampal regions, temporal pole, posterior bited a reduced activity in the superior temporal gyrus (STG)
cingulate, and OFC [61]. Actual studies focusing on brain as opposed to an increase in controls at presentation of
connectivity by means of diffusion tensor imaging extended negative emotional stimuli. This is in line with other studies
these findings by demonstrating that psychopathy is asso- showing increased temporo-parietal activity and decreased
ciated with a reduction of functional connectivity between prefrontal activity at the presentation of incompatible mate-
the ventromedial prefrontal cortex (VMPFC) and the amyg- rial in healthy subjects and reflecting a “load” of more chal-
dala as well as between VMPFC and the medial parietal lenging cognitive processes [78]. According to the authors,
cortex [62, 63]. this indicates that the interaction between STG and the
In adult psychopaths a combined amygdala-OFC dys- VMPFC is disturbed in psychopaths.
function can be found [62, 63]; they particularly show Fecteau et al. [79] tried to distinguish between the recog-
deficits in associative learning and emotionality [64–66]. nition of pain of others and caring for it in a sample of persons
Regrettably, neuroimaging data on amygdala and OFC acti- with psychopathic personality traits in a non-psychiatric
vation in psychopaths are somewhat inconsistent: some sample. The observation of painful stimuli led to a significant
studies reported reduced activation of limbic areas in psycho- reduction in the amplitude of TMS-induced motor evoked
paths compared to controls using aversive conditioning potentials. Individuals with the greatest MEP reduction were
[67, 68] or affective memory tasks [68], whereas others those scoring highest on the cold-heartedness measure. This
found enhanced activations in the amygdala, the OFC, and could indicate that psychopathic patients can have a better
the DLPFC during emotional learning [69, 70] and the pro- understanding of the suffering of others, but also that they
cessing of negative emotional pictures [71]. Using a facial have no concern for the pain of others. This coincides with
emotion processing task, Deeley et al. (2006) failed to detect findings of spared mental abilities in psychopaths [80].
any amygdala or OFC activity in criminal psychopaths [72]. In summary, the neurobiological findings on psycho-
Possible reasons for these discrepancies are different stimu- pathy suggest that the condition is due to dysfunctions of the
lation paradigms across studies, small sample sizes, and dif- ventral and ventromedial prefrontal regions, insular cortex,
ferences regarding the symptomatology. Another possibility temporo-parietal cortical areas, subcortical limbic regions,
is that these differences are due to differences in the seroton- and in particular the amygdala. According to Yang and
ergic control of the VMPFC via 5HT1A receptors: an increase Raine [81], core psychopathy deficits impair (1.) the evalu-
in density and affinity of these receptors leads to an in- ation of positive or negative reinforcers (OFC/VMPFC),
creased activity of the VMPFC and reduced levels of impul- (2.) the processing of affective stimuli including its context
sivity, while a decrease in density and affinity of 5-HT1A (amygdala, hippocampus), (3.) the assessment of emotional
receptors leads to a decreased VMPFC activity and higher salience and regulation of emotional responses (ACC), and
impulsivity [73, 74]. These findings point to the existence (4.) the pain and empathy system (insula, STG).
of subtypes of psychopathy, including impulsive and non-
impulsive ones depending on the strength and the moment
Subtypes of psychopathy
of psychotraumatization.
A lack of empathy has often been assumed in the context Successful versus unsuccessful psychopaths
of both reactive and proactive psychopathic aggression and The general assumption that psychopathy is characterised
violence. A study concerning empathic and violent behav- by a hyporesponsibility of the autonomic stress response has
iour in healthy subjects by varying the appropriateness of been questioned by studies on distinct subgroups of criminal
empathic/aggressive behaviour showed identical activations psychopaths, who have been either convicted for their
in a circuit including the VMPFC and the amygdala for the crimes (unsuccessful psychopaths) or have remained undis-
appropriate situations, irrespective of whether the behav- covered so far (successful psychopaths). Unsuccessful psy-
iour was violent or compassionate. This finding suggests chopaths showed reduced cardiovascular stress reactivity,
that context-appropriate behaviour is guided by a common which is in line with previous research. However, successful

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psychopaths demonstrated even greater autonomic reactivity 95]. In addition, a positive association between the allelic
and stronger executive functions than both the unsuccessful variant of the MAOA polymorphism coding for high MAOA
psychopaths and the controls [82]. Another study with the activity and self-reported aggression and impulsivity in men
same sample of psychopaths demonstrated a reduction in was also reported [89]. These findings may be indicative of a
prefrontal grey matter volumes specific to the unsuccessful higher genotypic risk for impulsivity/aggression in males
psychopaths compared with control subjects and successful conferred by serotonin-related polymorphisms.
psychopaths [83]. Decreased prefrontal volumes may render Meyer-Lindenberg et al. [96] found that carriers of
unsuccessful psychopaths particularly susceptible to poor MAOA-L had volume reductions relative to the volume
decision-making, impulsive aggression, and unregulated in MAOA-H subjects in the rostral and dorsal ACC, the
antisocial behaviour – thus raising the probability of ‘getting amygdala, the insula, and the hypothalamus. In addition,
caught’. By contrast, successful psychopaths showed a MAOA-L carriers showed increased amygdala activation
relative sparing of prefrontal grey matter that may provide and diminished reactivity of regulatory prefrontal areas com-
them with normal executive functioning and intact capaci- pared with MAOA-H in a face-matching task. The authors
ties for the control of affective states. This could allow suc- postulate that their data identify differences in limbic cir-
cessful psychopaths to react sensitively to environmental cuitry for emotion regulation and cognitive con-trol that
cues signalling danger and, therefore, to avoid conviction could be involved in the association of MAOA with impulsive
[82, 83]. A number of recent studies confirmed that success- aggression. However, their study was performed on healthy
ful psychopaths exhibit normal cognitive abilities related volunteers, who were not characterised by increased levels
to normal structure and functions of the dorsolateral PFC of aggressive or violent behaviour, so that they were not
and dorsal anterior cingulate cortex [84]. Accordingly, they studying the relationship of MAOA and violence per se.
reveal an intact P300 component of the event-related poten-
tial in cognitive tasks, while their ventral and ventromedial
Summary
frontal cortex mostly reveals a hyporesponsivity [85].
The neurobiological data regarding antisocial personality
Primary and secondary psychopaths disorder and psychopathy confirm the hypothesis that two
A related distinction between subtypes of psychopathy is major types of antisocial behaviour exist: reactive-impulsive
that between “primary” or “low-anxious” and non-impul- aggression and proactive-instrumental aggression. While the
sive psychopaths on the one hand, and “secondary” or former describes the majority of violent criminals, the latter
“high-anxious” and impulsive ones on the other. The study is characteristic of the small group of psychopaths. Both
by Motzkin et al. [63] on prefrontal connectivity in psycho- groups are characterised by dysfunctional autonomic re-
pathy revealed that low-anxious, primary psychopaths re- sponses, disturbances of the serotonin system, and deficits
veal a significantly higher connectivity between VMPFC and in the interaction of limbic cortical-frontal and sub-cortical
amygdala compared to secondary psychopaths with rela- centres in the context of impulse control, empathy, and the
tively low connectivity resulting in lower or higher levels of processing of affects and emotions, particularly fear and
impulsivity, respectively. While psychopaths are generally anger [97].
characterised by an inter-hemispheric imbalance, those be- With respect to antisocial individuals, there is strong
longing to the primary, impulse-controlled subtype revealed evidence that structural or functional impairments (i.e., vol-
a hypoactive right (mostly frontal) hemisphere, while those ume loss and decreased activity) of the frontal cortex, espe-
included in the secondary, impulse-driven subtype were cially of OFC and VMPFC, are associated with impulsive
characterised by a hyperactive left hemisphere (overview in aggression and violent behaviour. This goes along with
[86]). increased sub-cortical activity, for example in the amygdala.
In psychopaths which are characterised by proactive-
instrumental aggression and psychopathy, there are deficits
Neuropharmacological and genetic deficits in individuals
in the processing of negative emotional information and
with APD
generally emotional hypo-responsivity exists. The majority
Increased impulsivity and impulsive aggression have long been of studies report a reduced activation of limbic centres in psy-
associated with a central serotonin deficit both in healthy chopaths compared to controls using aversive conditioning.
subjects as well as in various clinical populations [87–90]. Kiehl’s paralimbic dysfunction model describes distributed
Furthermore, there are a number of studies describing a re- abnormalities in the amygdala, the OFC, the temporal pole,
duced serotonergic modulation of frontal brain areas in the the anterior and posterior cingulate cortex, the insula, and
context of impulsivity and aggression [48, 91]. These studies the parahippocampal regions [69, 98]. Others found en-
provide neuro-functional evidence for the suggested link hanced activations in the amygdala, OFC, and DLPFC during
between OFC/ACC activity, serotonin, and inhibitory con- emotional learning. Most remarkably, in most studies
trol. More specifically, they suggest that OFC and adjacent psychopathic individuals exhibit no impairment in intel-
regions exert an inhibitory effect on impulsive aggression lectual-cognitive abilities and theory of mind, they simply
through serotonergic mechanisms. appear to have no concern for the pain and emotions of
A genetic contribution to the relationship between sero- others. Successful psychopaths demonstrated even greater
tonin function and impulsive aggression is supported by autonomic reactivity and stronger executive function than both
many studies referring to the serotonin transporter (5-HT) the unsuccessful psychopaths and the controls. They appear
gene (e.g. [92, 93]) and the tryptophan hydroxylase gene [94, to be specifically competent at internalising anger and

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 Review article

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