Available online at www.sciencedirect.com
ScienceDirect Psychopathic traits from an RDoC perspective§ RJR Blair In this review an RDoC approach is applied to psychopathic traits. Two core neuro-cognitive systems relevant to the emergence of psychopathic traits are considered. These are the response to other individuals’ emotional displays and reinforcement-based decision-making. Addresses Section of Affective Cognitive Neuroscience, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA Corresponding author: Blair, RJR ([email protected])
Current Opinion in Neurobiology 2015, 30:79–84 This review comes from a themed issue on Neuropsychiatry Edited by Steven Hyman and Raquel Gur
http://dx.doi.org/10.1016/j.conb.2014.09.011 0959-4388/# 2014 Published by Elsevier Ltd.
The recent proposal to apply a Research Domain Criteria (RDoC) framework to the consideration of psychiatric conditions means that this is an exciting time for researchers interested in taking a neuropsychiatric approach to studying clinical disorders. The goal of the RDoC project is to define basic dimensions of functioning (neuro-cognitive mechanisms such as those mediating fear) to be studied across multiple units of analysis, from genes to neural circuits to behaviors, cutting across disorders as traditionally defined [1]. As such, RDoC rests on work from neuropsychiatry and its underpinnings in basic work in molecular, systems and cognitive neuroscience. The aim of this brief review is to apply an RDoC approach to psychopathic traits. Psychopathic traits have a core callous–unemotional component (e.g., lack of guilt and empathy) and an impulsive– antisocial component [2]. They are detectable early in childhood and persist into adulthood [3]. Clinically, understanding psychopathic traits is important, as their presence can interfere with socialization [4] and currently available treatment for conduct disorder [5]. However, § This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health under grant number 1-ZIA-MH002860-08.
www.sciencedirect.com
only a fraction of those who receive the psychiatric diagnoses of oppositional defiant disorder, conduct disorder and antisocial personality disorder show significant psychopathic traits (e.g., possibly just over 45% of patients with CD [6]). This review will concentrate on the two main neuro-cognitive mechanisms found to be dysfunctional in psychopathic traits. There are genetic and environmental contributions to the development of psychopathic traits [7]. While the molecular genetics of the disorder remain effectively unknown, several environmental risk factors (enrichment, diet, paternal deprivation, maternal substance abuse during pregnancy) that compromise neural systems implicated in psychopathic traits (amygdala, caudate and ventromedial prefrontal cortex) have been identified [8,9,10]. In this review an RDoC approach will be applied to psychopathic traits. Two main neuro-cognitive systems relevant to the emergence of the disorder will be considered. These involve the response to other individuals’ emotional displays and reinforcement-based decisionmaking.
Response to other individuals’ emotional displays Within the RDoC social processes domain (http:// nimh.nih.gov/research-priorities/rdoc/social-processesworkshop-proceedings.shtml), there is a ‘‘reception of facial communication’’ construct that focuses on the neural systems responsive to emotional expressions. It should be noted though that the emotional displays of others are processed by at least partially distinct neuro-cognitive systems that reflect the specific communicatory roles of the expressions (e.g., fear for threatbased aversive conditioning, disgust for taste aversion learning and anger for initiating changes in current behavior) [2]. The main impairment in psychopathic traits relates to the processing of other individuals’ distress cues (emotional displays of fear, sadness and pain). The processing of angry and disgusted expressions is relatively preserved in this population [11]. Responsiveness to distress cues: stimulusreinforcement learning
It is suggested that distress cues serve as aversive social reinforcers [2]. Objects and representations of actions associated with these distress cues gain negative valence and are judged as ‘‘bad’’. An individual who finds actions that distress others less aversive than a typically developing individual will be more likely to use antisocial Current Opinion in Neurobiology 2015, 30:79–84
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behavior, including aggression, to achieve their goals [2] (Figure 1). Considerable data has demonstrated that the amygdala is critical for stimulus-reinforcement learning [12]. It is argued that the amygdala is critical for the socialization of care-based transgressions (transgressions that result in harm to other individuals) because of its role in stimulus-reinforcement learning [2]. The suggestion is that individual finds representations of care-based transgressions aversive because they have been associated with the ‘‘punishment’’ of other individuals’ distress [2]. Social referencing (a paradigm where the child learns the valence of an object by watching the parent’s reaction to it; e.g., avoiding objects associated with parent fear) is thought to rely on stimulus-reinforcement learning [13] and social referencing is disrupted by amygdala damage [14]. Indeed, considerable work shows that the amygdala responds to distress cues, particularly fearful expressions [15] but also sad expressions and the pain of others [16,17]. Moreover, the amygdala and ventromedial frontal cortex are critically involved in making care-based moral judgments (judging actions that harm other individuals to be wrong) [2].
to neutral expressions [18,19–22]. In work where the paradigm used identifies an amygdala response to fearful relative to neutral expressions in comparison individuals, adults with psychopathic traits also show a reduction in this differential response [23,24]. Moreover, both youth and adults with psychopathic traits show reduced amygdala and/or ventromedial frontal cortex responses to displays of pain in others [25,26]. In addition, it is the callous–unemotional component of psychopathic traits that appears to be particularly associated with the reduced amygdala response to distress cues [19,20,22,25]. Consistent with the idea that dysfunction in learning on the basis of distress cues should result in an individual who socializes poorly, parenting variables that influence level of antisocial behavior in individuals with low callous–unemotional traits do not have a significant impact on individuals with high callous–unemotional traits [4]. Moreover, youth and adults with psychopathic traits show reduced amygdala and/or ventromedial prefrontal cortex activity and reduced amygdala-ventromedial frontal prefrontal cortex activity when making care-based moral judgments [27,28].
Reinforcement-based decision-making Patients with psychopathic traits show reduced amygdala responses to distress cues. Adolescents with psychopathic traits show reduced amygdala responses to fearful relative
RDoC refers to a ‘‘positive valence systems’’ domain. Relating to this, reinforcement-based decision-making will be considered here.
Figure 1
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(A) Implementation of a fMRI social referencing paradigm (where participants learn the value of an object from observing other individual’s emotional reaction to it); (B) reduced amygdala responses in youth with disruptive behavior disorders and psychopathic traits to fearful expressions [18]; and (C) differential responses within the amygdala to fearful expressions by group [18]. Current Opinion in Neurobiology 2015, 30:79–84
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Psychopathic traits from an RDoC perspective Blair 81
Considerable, animal and human work has focused on reinforcement-based decision making. Regions considered importantly involved include the amygdala, striatum (particularly caudate), ventromedial frontal cortex, dorsal anterior cingulate cortex and anterior insula cortex. Deficits in reinforcement-based decision-making are found in patients with psychopathic traits [29,30]. However, the same deficits are also found in individuals with disruptive behavior disorders (oppositional defiant disorder, conduct disorder and antisocial personality disorder) without psychopathic traits [30,31,32]. In other words, they seem to be a risk factor for antisocial behavior generally rather than that seen in the context of psychopathic traits in particular. It should also be noted that patients with ADHD, substance abuse, depression and schizophrenia have all been reported to show deficits in reinforcementbased decision-making [33,34]. It will be important to determine whether these impairments are differentiable and thus potential associated with different symptoms or common across disorders (i.e., implying a risk for behavioral abnormalities beyond antisocial behavior). At least four forms of potential dysfunction can be considered: Stimulus-reinforcement learning
Stimulus-reinforcement learning (of which aversive conditioning is a subtype) involves the formation of an association between a stimulus and a reinforcement that occurs in temporal proximity to this stimulus. Considerable work attests to the important role of the amygdala in
stimulus-reinforcement learning [12]. Impairments in stimulus-reinforcement learning, and aversive conditioning particularly, continue to be documented in individuals with psychopathic traits [35] and are associated with reduced amygdala responding [36]. Moreover, such impairments predict the emergence of antisocial behavior in developmental, longitudinal studies [37]. Stimulusreinforcement learning, particularly when the reinforcement is social, is critical for appropriate socialization — it is critical to learn the value of social behaviors. Impairment in stimulus-reinforcement learning is thought to be a major factor leading to difficulty in the socialization of individuals with psychopathy [2] (Figure 2). Heightened reward sensitivity
Externalizing problems, including both drug addiction and psychopathy, have been linked to increased sensitivity to reward [38]. It has been argued that higher reward sensitivity should be associated with greater reward seeking behavior and reduced processing of potential costs [38]. However, the robustness of this phenomenon is unclear. Most studies examining individuals at heightened risk for substance abuse or patients with substance abuse report reduced, not increased, striatal activity to rewards [39–41]; see also below. There has been a report of increased striatal responsiveness to reward as a function of psychopathy level in healthy individuals [38]. However, a second paper showed decreased striatal responsiveness to reward as a function of psychopathy level in a
Figure 2
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(A) Illustration of a trial from the passive avoidance paradigm where the participant receives monetary feedback for responding to stimuli. Some stimuli when responded to on average engender reward. Others engender punishment and the participant learns to avoid them; (B) reduced modulation of striatal responses to reward as a function of prediction error in youth with disruptive behavior disorders; (C) reduced modulation of ventromedial frontal cortex responses when choosing objects as a function of expected value in youth with disruptive behavior disorders. www.sciencedirect.com
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healthy comparison group and no group differences between this group and patients with psychopathy in striatal responsiveness to reward [42].
because the costs and benefits of engaging in reactive aggression are not properly represented.
Conclusions Reduced reward sensitivity
A series of studies have reported reduced sensitivity to reward within caudate and/or ventromedial frontal cortex in youth with CD [29,32,43]. Moreover, there have been reports of reduced reward prediction errors in striatum in both youth with disruptive behavior disorders and substance abuse [32,41]; these populations fail to show the increase in striatal activity following unexpected reward that is related to dopaminergic activity [44]. There is also evidence of reduced modulation of ventromedial frontal cortex activity as a function of expected value in patients with disruptive behavior disorders [32]. Atypical response to punishment
Several studies have reported an atypically increased response to punishment within striatum and ventromedial frontal cortex in patients with disruptive behavior disorders [29,32,43]. Punishments that are worse than expected are typically associated with a reduction in striatal activity in healthy adults and youths [45]. In contrast, adolescents with disruptive behavior disorders showed a positive relationship between prediction errors to punishment and activity within striatum [32]; see also [29,43]. Our preliminary hypothesis is that the dysfunction interferes with valence-based modulation of dopaminergic prediction error signaling (there is less augmentation for a positive prediction error and less suppression for a negative prediction error) but that novelty-based modulation of dopaminergic activity remains intact. The increased response to punishment only reflects the novelty of the occurrence in patients with disruptive behavior disorders. However, this hypothesis requires formal testing. Disruption in prediction error and expected value signaling will likely interfere with socialization; the individual will be less likely to learn to avoid actions that harm other individuals. In addition, disrupted decision-making will result in increased frustration; the individual’s decisions will be less likely to achieve their goals. Increased frustration-based reactive aggression may be a consequence of this. Moreover, impairments in the representation of expected value when choosing actions will likely increase the risk for aggression more generally [32]. Aggression is often seen as a response to provocation by another (it is indexed in this way via tasks such as the Point Subtraction Aggression Paradigm [46]). However, the participant’s retaliatory responses are selected, not automatic. As such they involve instrumental behavioral choices and should, and do, recruit regions implicated in representing the value of behavioral choices [47,48]. In short, impairment in the role of ventromedial frontal cortex in the representation of reinforcement expectancies should increase the risk for reactive aggression Current Opinion in Neurobiology 2015, 30:79–84
The presence of psychopathic traits is associated with a particularly severe form of disruptive behavior disorder (whether receiving the psychiatric diagnosis of oppositional defiant disorder, conduct disorder or antisocial personality disorder). There are both genetic and environmental contributions to the emergence of these traits though molecular level details are in urgent need of being specified. The aim of this brief review was to apply an RDoC approach to psychopathic traits and consider two core neuro-cognitive systems relevant to the emergence of the disorder: the response to other individuals’ emotional displays and reinforcement-based decision-making. Given the identification of these functional processes and the implications of their dysfunction for specific aspects of disruptive behavior, the goal now becomes identifying how they can be modulated. We need to determine what aspects of which therapies, psychopharmacological and psychosocial, have an impact on these functional processes. Then we will be better able to help individuals with psychopathic traits in the future.
Conflict of interest statement Nothing declared.
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as: of special interest of outstanding interest 1.
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Lynam DR et al.: Longitudinal evidence that psychopathy scores in early adolescence predict adult psychopathy. J Abnorm Psychol 2007, 116(1):155-165.
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Waller R, Gardner F, Hyde LW: What are the associations between parenting, callous–unemotional traits, and antisocial behavior in youth? A systematic review of evidence. Clin Psychol Rev 2013, 33:593-608.
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Manders WA et al.: Psychopathy as predictor and moderator of multisystemic therapy outcomes among adolescents treated for antisocial behavior. J Abnorm Child Psychol 2013, 41:1121-1132.
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Rowe R et al.: The role of callous and unemotional traits in the diagnosis of conduct disorder. J Child Psychol Psychiatry 2010, 51(6):688-695.
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Barker ED et al.: The impact of prenatal maternal risk, fearless temperament and early parenting on adolescent callous– unemotional traits: a 14-year longitudinal investigation. J Child Psychol Psychiatry 2011, 52:878-888.
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Workman JL et al.: Post-weaning environmental enrichment alters affective responses and interacts with behavioral www.sciencedirect.com
Psychopathic traits from an RDoC perspective Blair 83
testing to alter nNOS immunoreactivity. Pharmacol Biochem Behav 2011, 100:25-32. 10. Seidel K et al.: Paternal deprivation affects the development of corticotrophin-releasing factor-expressing neurones in prefrontal cortex, amygdala and hippocampus of the biparental Octodon degus. J Neuroendocrinol 2011, 23:1166-1176. 11. Dawel A et al.: Not just fear and sadness: meta-analytic evidence of pervasive emotion recognition deficits for facial and vocal expressions in psychopathy. Neurosci Biobehav Rev 2012, 36:2288-2304. Important meta-analytic review of the expression recognition literature showing, in tables, the impairment in the recognition fearful and sad expressions and the relative sparing of the recognition of angry and disgusted expressions. 12. Sears RM, Schiff HC, LeDoux JE: Molecular mechanisms of threat learning in the lateral nucleus of the amygdala. Prog Mol Biol Transl Sci 2014, 122:263-304. 13. Mineka S, Zinbarg R: A contemporary learning theory perspective on the etiology of anxiety disorders: it’s not what you thought it was. Am Psychol 2006, 61:10-26. 14. Jeon D et al.: Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC. Nat Neurosci 2010, 13:482-488. 15. Murphy FC, Nimmo-Smith I, Lawrence AD: Functional neuroanatomy of emotions: a meta-analysis. Cogn Affect Behav Neurosci 2003, 3:207-233. 16. Blair RJR et al.: Dissociable neural responses to facial expressions of sadness and anger. Brain 1999, 122:883-893. 17. Lamm C, Decety J, Singer T: Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain. Neuroimage 2011, 54:2492-2502. 18. Marsh AA et al.: Reduced amygdala response to fearful expressions in children and adolescents with callous– unemotional traits and disruptive behavior disorders. Am J Psychiatry 2008, 165:712-720. First paper to demonstrate reduced amygdala responses in youth with psychopathic traits to the fearful expressions of others. 19. Jones AP et al.: Amygdala hypoactivity to fearful faces in boys with conduct problems and callous–unemotional traits. Am J Psychiatry 2009, 166:95-102. 20. White SF et al.: Reduced amygdala responding in youth with disruptive behavior disorder and psychopathic traits reflects a reduced emotional response not increased top–down attention to non-emotional features. Am J Psychiatry 2012, 169(7):750-758.
27. Marsh AA et al.: Reduced amygdala-orbitofrontal connectivity during moral judgments in youths with disruptive behavior disorders and psychopathic traits. Psychiatry Res 2011, 194:279-286. 28. Harenski CL et al.: Aberrant neural processing of moral violations in criminal psychopaths. J Abnorm Psychol 2010, 119:863-874. 29. Finger EC et al.: Disrupted reinforcement signaling in the orbital frontal cortex and caudate in youths with conduct disorder or oppositional defiant disorder and a high level of psychopathic traits. Am J Psychiatry 2011, 168:834-841. 30. Finger EC et al.: Abnormal ventromedial prefrontal cortex function in children with psychopathic traits during reversal learning. Arch Gen Psychiatry 2008, 65:586-594. 31. De Brito SA et al.: Cool and hot executive function impairments in violent offenders with antisocial personality disorder with and without psychopathy. PLOS ONE 2013, 8:e65566. First paper to demonstrate reduced modulation of ventromedial frontal cortex activity when choosing stimuli as a function of expected value and reduced striatal responses to reward as a function of prediction error in youth with disruptive behavior disorders. 32. White SF et al.: Disrupted expected value signaling in youth with disruptive behavior disorders to environmental reinforcers. J Am Acad Child Adolesc Psychiatry 2014, 53:579588.e9. 33. Gradin VB et al.: Expected value and prediction error abnormalities in depression and schizophrenia. Brain 2011, 134:1751-1764. 34. Parvaz MA et al.: Sensitivity to monetary reward is most severely compromised in recently abstaining cocaine addicted individuals: a cross-sectional ERP study. Psychiatry Res 2012, 203:75-82. 35. Rothemund Y et al.: Fear conditioning in psychopaths: eventrelated potentials and peripheral measures. Biol Psychol 2012, 90:50-59. 36. Birbaumer N et al.: Deficient fear conditioning in psychopathy: a functional magnetic resonance imaging study. Arch Gen Psychiatry 2005, 62:799-805. One of the few studies in this field where a biomarker, in this case ability to show aversive conditioning, has been used to predict future antisocial behavior. 37. Gao Y et al.: Association of poor childhood fear conditioning and adult crime. Am J Psychiatry 2010, 167:56-60. 38. Buckholtz JW et al.: Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nat Neurosci 2010, 13:419-421.
21. Viding E et al.: Amygdala response to preattentive masked fear in children with conduct problems: the role of callous– unemotional traits. Am J Psychiatry 2012, 169:1109-1116.
39. Yau WY et al.: Nucleus accumbens response to incentive stimuli anticipation in children of alcoholics: relationships with precursive behavioral risk and lifetime alcohol use. J Neurosci 2012, 32:2544-2551.
22. Lozier LM et al.: Mediation of the relationship between callous– unemotional traits and proactive aggression by amygdala response to fear among children with conduct problems. JAMA Psychiatry 2014, 71:627-636.
40. Schneider S et al.: Risk taking and the adolescent reward system: a potential common link to substance abuse. Am J Psychiatry 2012, 169:39-46.
23. Dolan MC, Fullam RS: Psychopathy and functional magnetic responance imaging blood oxygenation level-dependent respones to emotional faces in violence patients with schizophrenia. Biol Psychiatry 2009, 66:570-577. 24. Decety J et al.: Neural processing of dynamic emotional facial expressions in psychopaths. Soc Neurosci 2014, 9: 36-49. 25. Marsh AA et al.: Empathic responsiveness in amygdala and anterior cingulate cortex in youths with psychopathic traits. J Child Psychol Psychiatry 2013, 54:900-910. 26. Decety J, Skelly LR, Kiehl KA: Brain response to empathyeliciting scenarios involving pain in incarcerated individuals with psychopathy. JAMA Psychiatry 2013, 70:638-645. www.sciencedirect.com
41. Tanabe J et al.: Reduced neural tracking of prediction error in substance-dependent individuals. Am J Psychiatry 2013, 170:1356-1363. 42. Pujara M et al.: Neural correlates of reward and loss sensitivity in psychopathy. Soc Cogn Affect Neurosci 2013, 9:794-801. 43. Crowley TJ et al.: Risky decisions and their consequences: neural processing by boys with antisocial substance disorder. PLoS ONE 2010, 5:pe12835. 44. Schultz W: Multiple functions of dopamine neurons. F1000 Biol Rep. 2010, 2:2. 45. O’Doherty JP: Beyond simple reinforcement learning: the computational neurobiology of reward-learning and valuation. Eur J Neurosci 2012, 35:987-990. Current Opinion in Neurobiology 2015, 30:79–84
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46. Cherek DR et al.: Studies of violent and nonviolent male parolees: I. Laboratory and psychometric measurements of aggression. Biol Psychiatry 1997, 41:514-522. 47. White SF et al.: Callous–unemotional traits modulate the neural response associated with punishing another individual during
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social exchange: a preliminary investigation. J Personal Disord 2013, 27:99-112. 48. White SF et al.: Punishing unfairness: rewarding or the organization of a reactively aggressive response? Hum Brain Mapp 2014, 35:2137-2147.
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ScienceDirect Psychopathic traits from an RDoC perspective§ RJR Blair In this review an RDoC approach is applied to psychopathic traits. Two core neuro-cognitive systems relevant to the emergence of psychopathic traits are considered. These are the response to other individuals’ emotional displays and reinforcement-based decision-making. Addresses Section of Affective Cognitive Neuroscience, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA Corresponding author: Blair, RJR ([email protected])
Current Opinion in Neurobiology 2015, 30:79–84 This review comes from a themed issue on Neuropsychiatry Edited by Steven Hyman and Raquel Gur
http://dx.doi.org/10.1016/j.conb.2014.09.011 0959-4388/# 2014 Published by Elsevier Ltd.
The recent proposal to apply a Research Domain Criteria (RDoC) framework to the consideration of psychiatric conditions means that this is an exciting time for researchers interested in taking a neuropsychiatric approach to studying clinical disorders. The goal of the RDoC project is to define basic dimensions of functioning (neuro-cognitive mechanisms such as those mediating fear) to be studied across multiple units of analysis, from genes to neural circuits to behaviors, cutting across disorders as traditionally defined [1]. As such, RDoC rests on work from neuropsychiatry and its underpinnings in basic work in molecular, systems and cognitive neuroscience. The aim of this brief review is to apply an RDoC approach to psychopathic traits. Psychopathic traits have a core callous–unemotional component (e.g., lack of guilt and empathy) and an impulsive– antisocial component [2]. They are detectable early in childhood and persist into adulthood [3]. Clinically, understanding psychopathic traits is important, as their presence can interfere with socialization [4] and currently available treatment for conduct disorder [5]. However, § This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health under grant number 1-ZIA-MH002860-08.
www.sciencedirect.com
only a fraction of those who receive the psychiatric diagnoses of oppositional defiant disorder, conduct disorder and antisocial personality disorder show significant psychopathic traits (e.g., possibly just over 45% of patients with CD [6]). This review will concentrate on the two main neuro-cognitive mechanisms found to be dysfunctional in psychopathic traits. There are genetic and environmental contributions to the development of psychopathic traits [7]. While the molecular genetics of the disorder remain effectively unknown, several environmental risk factors (enrichment, diet, paternal deprivation, maternal substance abuse during pregnancy) that compromise neural systems implicated in psychopathic traits (amygdala, caudate and ventromedial prefrontal cortex) have been identified [8,9,10]. In this review an RDoC approach will be applied to psychopathic traits. Two main neuro-cognitive systems relevant to the emergence of the disorder will be considered. These involve the response to other individuals’ emotional displays and reinforcement-based decisionmaking.
Response to other individuals’ emotional displays Within the RDoC social processes domain (http:// nimh.nih.gov/research-priorities/rdoc/social-processesworkshop-proceedings.shtml), there is a ‘‘reception of facial communication’’ construct that focuses on the neural systems responsive to emotional expressions. It should be noted though that the emotional displays of others are processed by at least partially distinct neuro-cognitive systems that reflect the specific communicatory roles of the expressions (e.g., fear for threatbased aversive conditioning, disgust for taste aversion learning and anger for initiating changes in current behavior) [2]. The main impairment in psychopathic traits relates to the processing of other individuals’ distress cues (emotional displays of fear, sadness and pain). The processing of angry and disgusted expressions is relatively preserved in this population [11]. Responsiveness to distress cues: stimulusreinforcement learning
It is suggested that distress cues serve as aversive social reinforcers [2]. Objects and representations of actions associated with these distress cues gain negative valence and are judged as ‘‘bad’’. An individual who finds actions that distress others less aversive than a typically developing individual will be more likely to use antisocial Current Opinion in Neurobiology 2015, 30:79–84
80 Neuropsychiatry
behavior, including aggression, to achieve their goals [2] (Figure 1). Considerable data has demonstrated that the amygdala is critical for stimulus-reinforcement learning [12]. It is argued that the amygdala is critical for the socialization of care-based transgressions (transgressions that result in harm to other individuals) because of its role in stimulus-reinforcement learning [2]. The suggestion is that individual finds representations of care-based transgressions aversive because they have been associated with the ‘‘punishment’’ of other individuals’ distress [2]. Social referencing (a paradigm where the child learns the valence of an object by watching the parent’s reaction to it; e.g., avoiding objects associated with parent fear) is thought to rely on stimulus-reinforcement learning [13] and social referencing is disrupted by amygdala damage [14]. Indeed, considerable work shows that the amygdala responds to distress cues, particularly fearful expressions [15] but also sad expressions and the pain of others [16,17]. Moreover, the amygdala and ventromedial frontal cortex are critically involved in making care-based moral judgments (judging actions that harm other individuals to be wrong) [2].
to neutral expressions [18,19–22]. In work where the paradigm used identifies an amygdala response to fearful relative to neutral expressions in comparison individuals, adults with psychopathic traits also show a reduction in this differential response [23,24]. Moreover, both youth and adults with psychopathic traits show reduced amygdala and/or ventromedial frontal cortex responses to displays of pain in others [25,26]. In addition, it is the callous–unemotional component of psychopathic traits that appears to be particularly associated with the reduced amygdala response to distress cues [19,20,22,25]. Consistent with the idea that dysfunction in learning on the basis of distress cues should result in an individual who socializes poorly, parenting variables that influence level of antisocial behavior in individuals with low callous–unemotional traits do not have a significant impact on individuals with high callous–unemotional traits [4]. Moreover, youth and adults with psychopathic traits show reduced amygdala and/or ventromedial prefrontal cortex activity and reduced amygdala-ventromedial frontal prefrontal cortex activity when making care-based moral judgments [27,28].
Reinforcement-based decision-making Patients with psychopathic traits show reduced amygdala responses to distress cues. Adolescents with psychopathic traits show reduced amygdala responses to fearful relative
RDoC refers to a ‘‘positive valence systems’’ domain. Relating to this, reinforcement-based decision-making will be considered here.
Figure 1
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(A) Implementation of a fMRI social referencing paradigm (where participants learn the value of an object from observing other individual’s emotional reaction to it); (B) reduced amygdala responses in youth with disruptive behavior disorders and psychopathic traits to fearful expressions [18]; and (C) differential responses within the amygdala to fearful expressions by group [18]. Current Opinion in Neurobiology 2015, 30:79–84
www.sciencedirect.com
Psychopathic traits from an RDoC perspective Blair 81
Considerable, animal and human work has focused on reinforcement-based decision making. Regions considered importantly involved include the amygdala, striatum (particularly caudate), ventromedial frontal cortex, dorsal anterior cingulate cortex and anterior insula cortex. Deficits in reinforcement-based decision-making are found in patients with psychopathic traits [29,30]. However, the same deficits are also found in individuals with disruptive behavior disorders (oppositional defiant disorder, conduct disorder and antisocial personality disorder) without psychopathic traits [30,31,32]. In other words, they seem to be a risk factor for antisocial behavior generally rather than that seen in the context of psychopathic traits in particular. It should also be noted that patients with ADHD, substance abuse, depression and schizophrenia have all been reported to show deficits in reinforcementbased decision-making [33,34]. It will be important to determine whether these impairments are differentiable and thus potential associated with different symptoms or common across disorders (i.e., implying a risk for behavioral abnormalities beyond antisocial behavior). At least four forms of potential dysfunction can be considered: Stimulus-reinforcement learning
Stimulus-reinforcement learning (of which aversive conditioning is a subtype) involves the formation of an association between a stimulus and a reinforcement that occurs in temporal proximity to this stimulus. Considerable work attests to the important role of the amygdala in
stimulus-reinforcement learning [12]. Impairments in stimulus-reinforcement learning, and aversive conditioning particularly, continue to be documented in individuals with psychopathic traits [35] and are associated with reduced amygdala responding [36]. Moreover, such impairments predict the emergence of antisocial behavior in developmental, longitudinal studies [37]. Stimulusreinforcement learning, particularly when the reinforcement is social, is critical for appropriate socialization — it is critical to learn the value of social behaviors. Impairment in stimulus-reinforcement learning is thought to be a major factor leading to difficulty in the socialization of individuals with psychopathy [2] (Figure 2). Heightened reward sensitivity
Externalizing problems, including both drug addiction and psychopathy, have been linked to increased sensitivity to reward [38]. It has been argued that higher reward sensitivity should be associated with greater reward seeking behavior and reduced processing of potential costs [38]. However, the robustness of this phenomenon is unclear. Most studies examining individuals at heightened risk for substance abuse or patients with substance abuse report reduced, not increased, striatal activity to rewards [39–41]; see also below. There has been a report of increased striatal responsiveness to reward as a function of psychopathy level in healthy individuals [38]. However, a second paper showed decreased striatal responsiveness to reward as a function of psychopathy level in a
Figure 2
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(A) Illustration of a trial from the passive avoidance paradigm where the participant receives monetary feedback for responding to stimuli. Some stimuli when responded to on average engender reward. Others engender punishment and the participant learns to avoid them; (B) reduced modulation of striatal responses to reward as a function of prediction error in youth with disruptive behavior disorders; (C) reduced modulation of ventromedial frontal cortex responses when choosing objects as a function of expected value in youth with disruptive behavior disorders. www.sciencedirect.com
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healthy comparison group and no group differences between this group and patients with psychopathy in striatal responsiveness to reward [42].
because the costs and benefits of engaging in reactive aggression are not properly represented.
Conclusions Reduced reward sensitivity
A series of studies have reported reduced sensitivity to reward within caudate and/or ventromedial frontal cortex in youth with CD [29,32,43]. Moreover, there have been reports of reduced reward prediction errors in striatum in both youth with disruptive behavior disorders and substance abuse [32,41]; these populations fail to show the increase in striatal activity following unexpected reward that is related to dopaminergic activity [44]. There is also evidence of reduced modulation of ventromedial frontal cortex activity as a function of expected value in patients with disruptive behavior disorders [32]. Atypical response to punishment
Several studies have reported an atypically increased response to punishment within striatum and ventromedial frontal cortex in patients with disruptive behavior disorders [29,32,43]. Punishments that are worse than expected are typically associated with a reduction in striatal activity in healthy adults and youths [45]. In contrast, adolescents with disruptive behavior disorders showed a positive relationship between prediction errors to punishment and activity within striatum [32]; see also [29,43]. Our preliminary hypothesis is that the dysfunction interferes with valence-based modulation of dopaminergic prediction error signaling (there is less augmentation for a positive prediction error and less suppression for a negative prediction error) but that novelty-based modulation of dopaminergic activity remains intact. The increased response to punishment only reflects the novelty of the occurrence in patients with disruptive behavior disorders. However, this hypothesis requires formal testing. Disruption in prediction error and expected value signaling will likely interfere with socialization; the individual will be less likely to learn to avoid actions that harm other individuals. In addition, disrupted decision-making will result in increased frustration; the individual’s decisions will be less likely to achieve their goals. Increased frustration-based reactive aggression may be a consequence of this. Moreover, impairments in the representation of expected value when choosing actions will likely increase the risk for aggression more generally [32]. Aggression is often seen as a response to provocation by another (it is indexed in this way via tasks such as the Point Subtraction Aggression Paradigm [46]). However, the participant’s retaliatory responses are selected, not automatic. As such they involve instrumental behavioral choices and should, and do, recruit regions implicated in representing the value of behavioral choices [47,48]. In short, impairment in the role of ventromedial frontal cortex in the representation of reinforcement expectancies should increase the risk for reactive aggression Current Opinion in Neurobiology 2015, 30:79–84
The presence of psychopathic traits is associated with a particularly severe form of disruptive behavior disorder (whether receiving the psychiatric diagnosis of oppositional defiant disorder, conduct disorder or antisocial personality disorder). There are both genetic and environmental contributions to the emergence of these traits though molecular level details are in urgent need of being specified. The aim of this brief review was to apply an RDoC approach to psychopathic traits and consider two core neuro-cognitive systems relevant to the emergence of the disorder: the response to other individuals’ emotional displays and reinforcement-based decision-making. Given the identification of these functional processes and the implications of their dysfunction for specific aspects of disruptive behavior, the goal now becomes identifying how they can be modulated. We need to determine what aspects of which therapies, psychopharmacological and psychosocial, have an impact on these functional processes. Then we will be better able to help individuals with psychopathic traits in the future.
Conflict of interest statement Nothing declared.
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