Neurobiological Basis of Psychopathy


Psychopathy is often confused with Antisocial Personality Disorder (APD), yet it is a distinct personality construct characterized by unique emotional impairments such as lack of empathy, and instrumental antisocial behaviors such as manipulativeness. Currently, Hare’s Psychopathy Checklist – Revised (PCL-R) is the standard diagnostic tool for assessing psychopathy. While it was estimated that 80% of the incarcerated population meets the diagnostic criteria for APD, only a third could be considered psychopaths, and they tend to be the worst repeat offenders. However, it should be noted that not all psychopaths are criminals, and many of them are very capable of becoming successful and achieving high positions in society. Researchers have long been looking for neuronal basis for this destructive and chronic disorder, and indeed several regions of the brain involved in emotional processing have been implicated. In particular, the amygdala, critical for fear and emotional processing, has been found to be reduced in size in psychopaths. Another area of interest is the orbitofrontal cortex, which is involved in instrumental learning and response reversal. Both learning processes are impaired in psychopaths, which correlate to a cortical reduction in that region1. Other structural abnormalities in the hippocampus, anterior cingulate cortex, and the corpus callosum have also been found in psychopaths. In general, it is hypothesized that the temporal-amygdala-prefrontal circuitry is dysfunctional, thus generating the marked ssocial and emotional impairments that are characteristic of psychopathy.


Consider what these two individuals have in common.
The BTK Killer, Dennis Rader
The BTK killer operated in Wichita, Kansas, USA between 1974 and 1991. The acronym, his infamous signature, stands for “Bind, Torture, Kill”. He terrorized the Sedgwick County for more than a decade, during which he murdered ten people, including a 10 year old girl and her entire family. Most of his victims were women. As part of his modus operandi, he would first stalk his victims, break into their homes, tie them up, and strangle them repeatedly before finally killing them. During his active period, he arrogantly taunted the police with letters containing grisly details of the killings. Despite massive police efforts, the BTK killer remained uncaught for more than a decade after his last killing in 1991. In 2004, he remerged and the last letter he sent had ultimately led to his arrest in 2005. He was convicted and is serving 10 consecutive life sentences.
Bernie Madoff
The other man was equally sinister, although in a completely different way. He was a well known businessman, but he will mostly likely go down in history as the operator that pulled off the largest financial fraud in U.S. history. While he lived in a life of high class luxury, his Ponzi scheme striped thousands of people of their hard-earned pensions. The fraudulent operation ran for over three decades, and the billions of missing money are still not fully recovered. In 2009, he pleaded guilty to 11 federal felonies, and was sentenced to 150 years in prison.

The BTK killer is Dennis Rader, and the fraudulent businessman, well known due to all the media coverage, is Bernie Madoff. Although both of them have been convicted, the natures of their crimes are very different, and every other aspects of the two men’s lives are poles apart. Dennis Rader had worked as a security guard and city dog-catcher, while Bernie Madoff was former non-executive chairman of the NASDAQ stock market. But under closer scrutiny, the two men do have one thing in common: they are both psychopaths.
The word ‘psychopathy’ comes from combining the Ancient Greek words ‘psyche’ meaning “mind” and “soul”, and ‘path’ meaning “disease” and “suffering”. Indeed its manifestations do look like pathology of the soul. Psychopaths have a total lack of empathy and remorse, and their experience of emotions is often described as shallow and superficial. They have no regard for the rights of others and the rules of society, causing them to be more concentrated in the prison population. They are often described as selfish, arrogant, callous, impulsive, irresponsible, and manipulative. Treatment of psychopaths is notoriously difficult, and there is little evidence of a cure. In 1801, Philippe Pinel, a French physician, wrote about psychopathy asManie sans delire, meaning “insanity without confusion or delusion”. Since then a great deal of efforts have been spent investigating this destructive and chronic personality disorder. Currently, the advances in brain imaging techniques have really propelled the field forward. Researchers now have a chance to catch a glimpse into the neurological underpinnings of psychopathy.

Symptoms and diagnostic criteria

Psychopathy is rather difficult to diagnose. Psychopaths are often highly intelligent and manipulative, appearing charming and charismatic, making them difficult to identify. It is commonly confused with Anti-Personality Disorder (APD), but while it was estimated that 80% of the prison population meets the diagnostic criteria for APD, only a third could be considered as psychopaths. Psychopathy is estimated to have a prevalence of 1% in the general population. Although it has been a well established personality construct for a long time now, the current Diagnostic and Statistical Manual (DSM IV–R) still do not have psychopathy as an official diagnostic label. The current standard in diagnosing psychopaths is the Hare’s Psychopathy Checklist-Revised (PCL-R).

Hare’s Psychopathy Checklist (PCL-R)

Robert Hare, Professor Emeritus at the University of British Columbia, is a pioneer in the research of psychopathy. He and his colleagues first developed a clinical rating scale to assess psychopathy on two factors. The current PCL-R has been further expanded into three factors (1.a, 1.b, and 2.a). The checklist consists of 20 items, each scored on a 3-point scale, rated by a psychologist or other professional through a semi-structured interview. If an item does not apply, it would be assigned a value of 0, and if it fully applies 2 would be assigned. Normal people typically score between 0 and 5, while psychopaths often have scores between 30 and 40.
Hare’s Psychopathy Checklist (PCL-R)
PCL-R Factors 1a and 1b are correlated with the affective and interpersonal core of the disorder and reflect traits such as lack of remorse or guilt, callousness/lack of empathy, glibness/superficial charm, grandiose sense of self-worth, and pathological lying. This dimension is correlated with extraversion, positive affect, and predatory aggression, and is considered as core personality traits of psychopathy. It was suggested that this factor could even be beneficial to psychopaths, allowing them to be cunning and manipulative.
PCL-R Factor 2 reflects behavior, the aspects of psychopathy that involve an antisocial, impulsive, and socially deviant lifestyle such as the need for stimulation, poor behavior controls, irresponsibility, and parasitic lifestyle. It is strongly related with Antisocial Personality Disorder (ASPD) and criminality. This dimension also correlates with defensive aggression and impulsive violence.

Difference from Antisocial Personality Disorder (ASPD)

Non-professionals often assume that psychopathic individuals are all aggressive, violent criminals. But in reality most violent offenders tend to have Antisocial Personality Disorder (ASPD). ASPD is associated with a high score on Factor 2 of the PCL-R. But In order to receive a diagnosis as a psychopath, one has to have the characteristic emotional impairments outlined in Factor 1. The two disorders also have difference behavioral manifestations. Individuals with ASPD often exhibit high defensive aggression, reacting violently to slight provocations. On the other hand, psychopaths tend to have high predatory aggression, which is less likely to be reactive and more likely to be instrumental and goal-directed. So contrary to popular belief, psychopaths are quite capable of becoming very successful.

Dysfunctional Brain Regions and Implicated Impairments

Since psychopathy is characterized by unique emotional deficits such as the lack of empathy and remorse, researchers have hypothesized that brain structures critically involved in emotional processing, such as the limbic system, are dysfunctional in psychopaths. Learning impairments are involved as well since psychopaths are known to be impulsive and insensitive to punishments. Other behavioral studies also suggested that psychopaths have abnormal abstract and language processing, which could be related to dysfunctional hemispherical lateralization.

Amygdala and Hippocampus – fear and emotional processing

The amygdala has been known to be involved in aversive conditioning and instrumental learning. As part of the limbic system, it is also critical for emotional processing, specifically the response to fearful and sad facial expressions. One major trait of psychopathy is fearlessness, which corresponds to the consistent findings that psychopaths are impaired in fear conditioning. Many studies have reported that psychopaths are insensitive to cues that predict punishment, have abnormal or absent neurophysiological responses to aversive stimuli, and fail to experience fear in anticipation of shock (Arnett, 1997). More recently, Birbaumer et al. (2005) used functional magnetic resonance imaging (fMRI) to map the brain regions activated during fear conditioning in which psychopaths and matched controls were tested with a simple Pavlovian paradigm. Researchers then compared the patterns of activation, and found significant differences between the two groups. Specifically, the psychopaths only showed right amygdala activation, whereas healthy controls had bilateral activation. The authors concluded that the abnormal neuronal activation pattern in the amygdala is an indication of dissociation in emotional and cognitive processing, and is the neuronal basis for psychopath’s impairment in encoding expected outcomes during learning.
Amygdala structural abnormalities in psychopathic individuals (Boccardi et al., 2011)
These findings, along with the pronounced emotional processing deficits observed in psychopaths, have lead researchers to suspect the amygdala to be critically involved in psychopathy. Indeed, specific amygdala structural abnormalities were found in a study done using cortical pattern matching and radial distance mapping techniques (Boccardi et al., 2011). Compared with healthy controls, the basolateral nucleus of the amygdala was significantly reduced in tissue size in psychopaths, and the central and lateral nuclei were enlarged.

Abnormal hippocampal morphology in psychopathic individuals versus controls (Boccardi et al., 2010)
Another structure that has been closely examined in relation to psychopathy is the hippocampus. The hippocampus is critical for learning and memory processes such as long-term memory consolidation and contextual fear learning. Although the fMRI study done by Birbaumer et al. (2005) did not indicate abnormal activation of the hippocampus, nonetheless multiple studies have found hippocampal structural abnormalities in psychopathic individuals. In an earlier study, Laakso and colleagues (2001) used magnetic resonance imaging (MRI) to measure hippocampus volume in healthy controls and psychopaths. They reported a significant negative correlation between degree of psychopathy and volume of posterior half of the hippocampus. In another study, researchers also found that highly psychopathic individuals tended to exhibit a specific abnormal hippocampal morphology (Boccardi et al., 2010). Even more interestingly, Raine et al. (2004) assessed both successful and unsuccessful psychopaths, and found that unsuccessful criminalized psychopaths had much more exaggerated hippocampal structural asymmetry than their successful uncaught counterparts and healthy controls. Specifically, the right hippocampus was significantly larger than the left, and the abnormality was localized to the anterior region. Together, these results indicate that the hippocampus is critically involve in psychopathy, and its dysfunction could contribute to insensitivity to cues predicting punishment, impairment in fear conditioning, and deficit in retrieval of emotional memory and social learning.

Ventromedial Prefrontal Cortex and Orbitofrontal Cortex – instrumental learning and response reversal

Studies have found that some regions of the ventromedial prefrontal cortex (vmPFC) contribute to emotional regulation. Data also suggest that vmPFC has a role in encoding reinforcement outcome information, which is critical for appropriate decision making. In an earlier review, Blair (2008) compiled neuropsychological and neuroimaging data, and presented a strong case for amygdala and vmPFC abnormalities in psychopaths. As both regions are instrumental in formation and representation of stimulus-reinforcement associations, Blair argued that psychopathic individuals are compromised in functions of the amygdala and vmPFC, and the interaction between the two regions. This would explain psychopath’s inability with updating value of positive reinforcers with negative experiences, and impairment in reversal learning.
Ventral side of human brain.

The orbitofrontal cortx (OFC) is another prefrontal cortical region that is in close proximity to the vmPFC, and both send and project to extensively to the amygdala. This region is important for representing reinforcement-expectation information, and again is critical for successful decision making. The OFC is also involved in error prediction and facilitates in learning of reward or punishment correlations. Boccardi and colleagues (2011) were again able to show a reduction in the orbitofrontal cortex and other midline structures as well. Aside from reduced amygdala activation, Birbaumer et al. (2005) also found that psychopaths also lacked OFC activation, and demonstrated a general pattern of reduced activity in the limbic-prefrontal circuitry. Altogether, the data suggest that abnormal activation patters seen in both the mvPFC and the OFC are the underlying neurological cause for the impulsive, irresponsible, and callous behavioral manifestations of psychopathy.

Corpus Callosum – affective and language processing and interhemispheric transfer

Corpus callosum in a human brain.
The corpus callosum is not a cortical structure, but nonetheless it is very important for normal brain functioning. It is a large bundle of fibers carrying axons that travel between the two hemispheres. In 2003, Raine and colleagues (2003) looked the structural differences of the corpus callosum between psychopathic individuals and controls. Interestingly, they found that larger callosal volumes were correlated with affective and interpersonal deficits, and low autonomic stress reactivity. The data suggest that psychopathic antisocial individuals have distinctive corpus callosum structural abnormalities, and on the whole tend to have a larger volume. The researchers further hypothesized that these abnormalities contributes to the lack of emotional depth, poor social and emotional relations, and deficient autonomic reactivity to stress that are characteristic of psychopathy. In addition, although psychopathy does not typically involve impairments in other cognitive domains, researcher have found that psychopaths do tend to have memory and language impairments, specifically with abstract words. Such effects could be due to a disruption in information transfer across the two hemispheres.

Future Directions

As the behavioral characteristics of psychopaths tend to be highly destructive and detrimental to society, further research is needed to explore treatment and prevention methods. Although psychopaths are notoriously difficult to rehabilitate with behavioral means, neurological or pharmological interventions could be new alternatives. There still many limitations to the current research. For example, all of the studies exclusively used male psychopathic subject. Manifestations of psychopathy in females and younger population should also be examined in order to gain a more comprehensive view of the disorder. There is also evidence that suggest psychopathy is a developmental disorder. To further investigate this, researchers will need to conduct longitudinal studies looking at the change of these vulnerable brain structures across one’s life time. Investigation into tracking the progression of this disorder and mapping the neurological changes of at risk individuals could be very valuable in developing preventative measures. As psychopathic criminals tend to be the worst repeat offenders and pose a high cost on society, further research efforts could have valuable implications.


Arnett, P. A. (1997). Autonomic responsivity in psychopaths: A critical review and theoretical proposal. Clinical Psychology Review, 17(8), 903-936.
Birbaumer, N., Veit, R., Lotze, M., Erb, M., Hermann, C., Grodd, W. G., et al. (2005). Deficient fear conditioning in psychopathy: A functional magnetic resonance imaging study. Archives of General Psychiatry, 62(7), 799-850.
Blair, R. J. R. (2008). The amygdala and ventromedial prefrontal cortex: functional contributions and dysfunction in psychopathy. Philosophical Transactions of the Royal Society, 363, 2557-2565.
Boccardi, M., Frisoni, G. G., Hare, R. D., Cavedo, E., Najt, P., Pievani, M., et al. (2011). Cortex and amygdala morphology in psychopathy. Psychiatry Research: Neuroimaging, 193(2011), 85-89.
Boccardi, M., Ganzola, R., Rossi, R., Sabattoli, R., Laakso, M. P., Repo-Tiihonen, E., et al. (2010). Abnormal hippocampal shape in offenders with psychopathy. Human Brain Mapping, 31(2010), 438-447.
Laakso, M. P., Vaurio, O., Koivisto, E., Salvolainen, L., Eronen, M., Aronen H. J., et al. (2001). Psychopathy and the posterior hippocampus. Behavioural Brain Research, 118, 187-193.
Raine , A., Lencz, T., Taylor, K., Hellige, J., Bihrle, S., Lacasse L., et al. (2003). Corpus callosum abnormalities in psychopathic antisocial individuals. Archives of General Psychiatry, 60(11), 1134-1142.
Raine, A., Ishikawa, S. S., Arce, E., Lencz, T., Knuth, K. H., Bihrle, S., et al. (2004). Hippocampal structural asymmetry in unsuccessful psychopaths. Biological Psychiatry, 55(2), 185-191.