Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The neurobiology of psychopathic traits in youths

Key Points

  • Youths with conduct disorder and psychopathic traits are particularly difficult to treat.

  • Psychopathic traits are associated with two main impairments: a reduced empathic response to distress in others and impairment in reinforcement-based decision making.

  • The reduced empathic response to distress principally reflects a reduced amygdala response to the distress of others (their fear, sadness or pain).

  • The impairment in reinforcement-based decision making reflects dysfunction in the roles of the ventromedial prefrontal cortex (vmPFC) and caudate in representing expected reward and punishment and in detecting inconsistencies between obtained and expected rewards or punishments.

  • These two main impairments interfere with socialization, leading to the development of an individual with reduced guilt and increased probability of using instrumental antisocial behaviour to achieve their goals.

  • Heritability studies implicate a genetic contribution to these impairments; however, molecular genetic information on this disorder remains in its infancy.

  • Environmental variables that affect the development of the amygdala, vmPFC and caudate have been identified, but their role in the development of psychopathic traits has not been clearly demonstrated.

  • Not all youths with conduct disorder show psychopathic traits — there are individuals with a notably different pathophysiology marked by anxiety and increased responsiveness to threat.

  • Effective treatment of conduct disorder may require differentiating patients into those with psychopathic traits versus those with anxiety and increased responsiveness to threat and developing distinct treatment approaches for each group.

Abstract

Conduct disorder is a childhood behaviour disorder that is characterized by persistent aggressive or antisocial behaviour that disrupts the child's environment and impairs his or her functioning. A proportion of children with conduct disorder have psychopathic traits. Psychopathic traits consist of a callous–unemotional component and an impulsive–antisocial component, which are associated with two core impairments. The first is a reduced empathic response to the distress of other individuals, which primarily reflects reduced amygdala responsiveness to distress cues; the second is deficits in decision making and in reinforcement learning, which reflects dysfunction in the ventromedial prefrontal cortex and striatum. Genetic and prenatal factors contribute to the abnormal development of these neural systems, and social–environmental variables that affect motivation influence the probability that antisocial behaviour will be subsequently displayed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Core regions implicated in, and functions disrupted by, psychopathic traits.
Figure 2: A framework for understanding conduct disorder.

Similar content being viewed by others

References

  1. Kazdin, A. E., Whitley, M. & Marciano, P. L. Child–therapist and parent–therapist alliance and therapeutic change in the treatment of children referred for oppositional, aggressive, and antisocial behavior. J. Child Psychol. Psychiatry 47, 436–445 (2006).

    Article  PubMed  Google Scholar 

  2. Barry, C. T. et al. The importance of callous-unemotional traits for extending the concept of psychopathy to children. J. Abnorm. Psychol. 109, 335–340 (2000).

    Article  PubMed  Google Scholar 

  3. Lynam, D. R., Caspi, A., Moffitt, T. E., Loeber, R. & Stouthamer-Loeber, M. Longitudinal evidence that psychopathy scores in early adolescence predict adult psychopathy. J. Abnorm. Psychol. 116, 155–165 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Burke, J. D., Loeber, R. & Lahey, B. B. Adolescent conduct disorder and interpersonal callousness as predictors of psychopathy in young adults. J. Clin. Child Adolesc. Psychol. 36, 334–346 (2007).

    Article  PubMed  Google Scholar 

  5. Wootton, J. M., Frick, P. J., Shelton, K. K. & Silverthorn, P. Ineffective parenting and childhood conduct problems: the moderating role of callous–unemotional traits. J. Consult. Clin. Psychol. 65, 301–308 (1997). The first study to report that the type of parenting has less of an impact on the behaviour of youths with high levels of callous–unemotional traits relative to youths with low levels of callous–unemotional traits; that is, the study shows that the pathophysiology of callous–unemotional traits interferes with socialization.

    Article  CAS  PubMed  Google Scholar 

  6. Hawes, D. J. & Dadds, M. R. The treatment of conduct problems in children with callous–unemotional traits. J. Consult. Clin. Psychol. 73, 737–741 (2005).

    Article  PubMed  Google Scholar 

  7. Waschbusch, D. A., Carrey, N. J., Willoughby, M. T., King, S. & Andrade, B. F. Effects of methylphenidate and behavior modification on the social and academic behavior of children with disruptive behavior disorders: the moderating role of callous/unemotional traits. J. Clin. Child Adolesc. Psychol. 36, 629–644 (2007). A good example of a paper showing that psychosocial techniques have less of an impact on the behaviour of youths with high levels of callous–unemotional traits than youths with low levels of callous–unemotional traits. This paper is of particular interest as it also suggests that methylphenidate administration may be helpful in youths with high callous–unemotional traits.

    Article  PubMed  Google Scholar 

  8. Marsh, A. A. et al. Reduced amygdala response to fearful expressions in children and adolescents with callous-unemotional traits and disruptive behavior disorders. Am. J. Psychiatry 165, 712–720 (2008). The first study to document that youths with psychopathic traits show reduced amygdala responses to the fearful expressions of other individuals.

    Article  PubMed  Google Scholar 

  9. Finger, E. C. et al. Abnormal ventromedial prefrontal cortex function in children with psychopathic traits during reversal learning. Arch. General Psychiatry 65, 586–594 (2008).

    Article  Google Scholar 

  10. Jones, A. P., Laurens, K. R., Herba, C. M., Barker, G. J. & Viding, E. Amygdala hypoactivity to fearful faces in boys with conduct problems and callous–unemotional traits. Am. J. Psychiatry 166, 95–102 (2009).

    Article  PubMed  Google Scholar 

  11. Pardini, D. A., Frick, P. J. & Moffitt, T. E. Building an evidence base for DSM-5 conceptualizations of oppositional defiant disorder and conduct disorder: introduction to the special section. J. Abnorm. Psychol. 119, 683–688 (2010).

    Article  PubMed  Google Scholar 

  12. Hare, R. D. A research scale for the assessment of psychopathy in criminal populations. Pers. Indiv. Differ. 1, 111–119 (1980).

    Article  Google Scholar 

  13. Frick, P. J. Callous–unemotional traits and conduct problems: a two-factor model of psychopathy in children. Issues Criminal. Legal Psychol. 24, 47–51 (1995).

    Google Scholar 

  14. Blair, R. J. R. Responding to the emotions of others: dissociating forms of empathy through the study of typical and psychiatric populations. Conscious. Cogn. 14, 698–718 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Frith, U. Autism: Explaining the Enigma (Blackwell, 1989).

    Google Scholar 

  16. Blair, R. J. R. et al. Theory of mind in the psychopath. J. Forens. Psychiatry 7, 15–25 (1996).

    Article  Google Scholar 

  17. Richell, R. A. et al. Theory of mind and psychopathy: can psychopathic individuals read the 'language of the eyes'? Neuropsychologia 41, 523–526 (2003).

    Article  CAS  PubMed  Google Scholar 

  18. Dolan, M. & Fullam, R. Theory of mind and mentalizing ability in antisocial personality disorders with and without psychopathy. Psychol. Med. 34, 1093–1102 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Jones, A. P., Happe, F. G., Gilbert, F., Burnett, S. & Viding, E. Feeling, caring, knowing: different types of empathy deficit in boys with psychopathic tendencies and autism spectrum disorder. J. Child Psychol. Psychiatry 51, 1188–1197 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Anastassiou-Hadjicharalambous, X. & Warden, D. Cognitive and affective perspective-taking in conduct-disordered children high and low on callous-unemotional traits. Child Adolesc. Psychiatry Ment. Health 2, 16 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sebastian, C. L. et al. Neural responses to affective and cognitive theory of mind in children with conduct problems and varying levels of callous-unemotional traits. Arch. Gen. Psychiatry 69, 814–822 (2012).

    Article  PubMed  Google Scholar 

  22. Lombardo, M. V. et al. Shared neural circuits for mentalizing about the self and others. J. Cogn. Neurosci. 22, 1623–1635 (2010).

    Article  PubMed  Google Scholar 

  23. Amodio, D. M. & Frith, C. D. Meeting of minds: the medial frontal cortex and social cognition. Nature Rev. Neurosci. 7, 268–277 (2006).

    Article  CAS  Google Scholar 

  24. Saxe, R. & Baron-Cohen, S. The neuroscience of theory of mind. Soc. Neurosci. 1, 1–9 (2006).

    Article  Google Scholar 

  25. Blair, R. J. R. Facial expressions, their communicatory functions and neuro-cognitive substrates. Phil. Trans. R. Soc. Lond. B 358, 561–572 (2003).

    Article  CAS  Google Scholar 

  26. Fridlund, A. in International Review of Studies on Emotion Vol. 2 (ed. Strongman, K. T.) 117–137 (Wiley-Blackwell;1992).

    Google Scholar 

  27. Marsh, A. A. & Blair, R. J. Deficits in facial affect recognition among antisocial populations: a meta-analysis. Neurosci. Biobehav. Rev. 32, 454–465 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Dawel, A., O'Kearney, R., McKone, E. & Palermo, R. Not just fear and sadness: meta-analytic evidence of pervasive emotion recognition deficits for facial and vocal expressions in psychopathy. Neurosci. Biobehav. Rev. 36, 2288–2304 (2012).

    Article  PubMed  Google Scholar 

  29. White, S. F. et al. Reduced activity within the dorsal endogenous orienting of attention network to fearful expressions in youth with disruptive behavior disorders and psychopathic traits. Dev. Psychopathol. 24, 1105–1116 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Carre, J. M., Hyde, L. W., Neumann, C. S., Viding, E. & Hariri, A. R. The neural signatures of distinct psychopathic traits. Soc. Neurosci. 8, 122–135 (2013).

    Article  PubMed  Google Scholar 

  31. Blair, R. J. R., Colledge, E., Murray, L. & Mitchell, D. G. A selective impairment in the processing of sad and fearful expressions in children with psychopathic tendencies. J. Abnorm. Child Psychol. 29, 491–498 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Blair, R. J. R. et al. Reduced sensitivity to other's fearful expressions in psychopathic individuals. Pers. Indiv. Differ. 37, 1111–1121 (2004).

    Article  Google Scholar 

  33. Dolan, M. & Fullam, R. Face affect recognition deficits in personality-disordered offenders: association with psychopathy. Psychol. Med. 36, 1563–1569 (2006).

    Article  PubMed  Google Scholar 

  34. Dadds, M. R. et al. Attention to the eyes and fear-recognition deficits in child psychopathy. Br. J. Psychiatry 189, 280–281 (2006). An important study documenting that the impairment in the recognition of fearful expressions seen in youths with callous–unemotional traits is significantly reduced when the participant's attention is directed to the eye region of the face. This improvement is also seen in patients with amygdala lesions.

    Article  PubMed  Google Scholar 

  35. Stevens, D., Charman, T. & Blair, R. J. R. Recognition of emotion in facial expressions and vocal tones in children with psychopathic tendencies. J. Genet. Psychol. 162, 201–211 (2001).

    Article  CAS  PubMed  Google Scholar 

  36. Woodworth, M. & Waschbusch, D. Emotional processing in children with conduct problems and callous/unemotional traits. Child Care Health Dev. 34, 234–244 (2008).

    Article  CAS  PubMed  Google Scholar 

  37. Blair, R. J. R., Budhani, S., Colledge, E. & Scott, S. Deafness to fear in boys with psychopathic tendencies. J. Child Psychol. Psychiatry 46, 327–336 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Munoz, L. Callous–unemotional traits are related to combined deficits in recognizing afraid faces and body poses. J. Am. Acad. Child Adolesc. Psychiatry 48, 554–562 (2009).

    Article  PubMed  Google Scholar 

  39. Blair, R. J. R. Responsiveness to distress cues in the child with psychopathic tendencies. Pers. Indiv. Differ. 27, 135–145 (1999).

    Article  Google Scholar 

  40. de Wied, M., van Boxtel, A., Matthys, W. & Meeus, W. Verbal, facial and autonomic responses to empathy-eliciting film clips by disruptive male adolescents with high versus low callous-unemotional traits. J. Abnorm. Child Psychol. 40, 211–223 (2012).

    Article  PubMed  Google Scholar 

  41. Anastassiou-Hadjicharalambous, X. & Warden, D. Physiologically-indexed and self-perceived affective empathy in conduct-disordered children high and low on callous–unemotional traits. Child Psychiatry Hum. Dev. 39, 503–517 (2008).

    Article  PubMed  Google Scholar 

  42. Aniskiewicz, A. S. Autonomic components of vicarious conditioning and psychopathy. J. Clin. Psychol. 35, 60–67 (1979).

    Article  CAS  PubMed  Google Scholar 

  43. Cheng, Y., Hung, A. Y. & Decety, J. Dissociation between affective sharing and emotion understanding in juvenile psychopaths. Dev. Psychopathol. 24, 623–636 (2012).

    Article  PubMed  Google Scholar 

  44. Pardini, D. A. & Byrd, A. L. Perceptions of aggressive conflicts and others' distress in children with callous-unemotional traits: 'I'll show you who's boss, even if you suffer and I get in trouble'. J. Child Psychol. Psychiatry 53, 283–291 (2012).

    Article  PubMed  Google Scholar 

  45. Dadds, M. R., El Masry, Y., Wimalaweera, S. & Guastella, A. J. Reduced eye gaze explains “fear blindness” in childhood psychopathic traits. J. Am. Acad. Child Adolesc. Psychiatry 47, 455–463 (2008).

    Article  PubMed  Google Scholar 

  46. Pessoa, L., Kastner, S. & Ungerleider, L. G. Attentional control of the processing of neutral and emotional stimuli. Cognitive Brain Res. 15, 31–45 (2002).

    Article  Google Scholar 

  47. Adolphs, R. et al. A mechanism for impaired fear recognition after amygdala damage. Nature 433, 68–72 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. White, S. F. et al. Reduced amygdala response in youths with disruptive behavior disorders and psychopathic traits: decreased emotional response versus increased top-down attention to nonemotional features. Am. J. Psychiatry 169, 750–758 (2012).

    Article  PubMed  Google Scholar 

  49. Viding, E. et al. Amygdala response to preattentive masked fear in children with conduct problems: the role of callous-unemotional traits. Am. J. Psychiatry 169, 1109–1116 (2012).

    Article  PubMed  Google Scholar 

  50. Marsh, A. A. et al. Empathic responsiveness in amygdala and anterior cingulate cortex in youths with psychopathic traits. J. Child Psychol. Psychiatry 54, 900–910 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Klinnert, M. D., Emde, R. N., Butterfield, P. & Campos, J. J. Social referencing: the infant's use of emotional signals from a friendly adult with mother present. Annu. Prog. Child Psychiatry Child Dev. 22, 427–432 (1987).

    Google Scholar 

  52. Mineka, S. & Cook, M. Mechanisms involved in the observational conditioning of fear. J. Exp. Psychol. Gen. 122, 23–38 (1993).

    Article  CAS  PubMed  Google Scholar 

  53. Blair, R. J. R. The amygdala and ventromedial prefrontal cortex in morality and psychopathy. Trends Cogn. Sci. 11, 387–392 (2007).

    Article  CAS  PubMed  Google Scholar 

  54. Jeon, D. et al. Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC. Nature Neurosci. 13, 482–488 (2010).

    Article  CAS  PubMed  Google Scholar 

  55. Cushman, F., Gray, K., Gaffrey, A. & Mendes, W. B. Simulating murder: the aversion to harmful action. Emotion 12, 2–7 (2012).

    Article  PubMed  Google Scholar 

  56. O'Doherty, J. P. Beyond simple reinforcement learning: the computational neurobiology of reward-learning and valuation. Eur. J. Neurosci. 35, 987–990 (2012).

    Article  PubMed  Google Scholar 

  57. Balleine, B. W. & O'Doherty, J. P. Human and rodent homologues in action control: corticostriatal determinants of goal-directed and habitual action. Neuropsychopharmacology 35, 48–69 (2010).

    Article  PubMed  Google Scholar 

  58. Budhani, S., Marsh, A. A., Pine, D. S. & Blair, R. J. R. Neural correlates of response reversal: considering acquisition. Neuroimage 34, 1754–1765 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. Kuhnen, C. M. & Knutson, B. The neural basis of financial risk-taking. Neuron 47, 763–770 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. Driscoll, D. M., Dal Monte, O., Solomon, J., Krueger, F. & Grafman, J. Empathic deficits in combat veterans with traumatic brain injury: a voxel-based lesion-symptom mapping study. Cogn. Behav. Neurol. 25, 160–166 (2012).

    Article  PubMed  Google Scholar 

  61. Engen, H. G. & Singer, T. Empathy circuits. Curr. Opin. Neurobiol 23, 275–282 (2012).

    Article  CAS  PubMed  Google Scholar 

  62. Janowski, V., Camerer, C. & Rangel, A. Empathic choice involves vmPFC value signals that are modulated by social processing implemented in IPL. Soc. Cogn. Affect. Neurosci. 8, 201–208 (2013).

    Article  PubMed  Google Scholar 

  63. Leopold, A. et al. Damage to the left ventromedial prefrontal cortex impacts affective theory of mind. Soc. Cogn. Affect. Neurosci. 7, 871–880 (2012).

    Article  PubMed  Google Scholar 

  64. Finger, E. C. 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 168, 834–841 (2011).

    Article  Google Scholar 

  65. Fisher, L. & Blair, R. J. R. Cognitive impairment and its relationship to psychopathic tendencies in children with emotional and behavioural difficulties. J. Abnorm. Child Psychol. 26, 511–519 (1998).

    Article  CAS  PubMed  Google Scholar 

  66. O'Brien, B. S. & Frick, P. J. Reward dominance: associations with anxiety, conduct problems, and psychopathy in children. J. Abnorm. Child Psychol. 24, 223–240 (1996).

    Article  CAS  PubMed  Google Scholar 

  67. Blair, R. J. R., Colledge, E. & Mitchell, D. G. Somatic markers and response reversal: is there orbitofrontal cortex dysfunction in boys with psychopathic tendencies? J. Abnorm. Child Psychol. 29, 499–511 (2001).

    Article  CAS  PubMed  Google Scholar 

  68. Budhani, S. & Blair, R. J. R. Response reversal and children with psychopathic tendencies: success is a function of salience of contingency change. J. Child Psychol. Psychiatry 46, 972–981 (2005).

    Article  CAS  PubMed  Google Scholar 

  69. Blair, R. J. R. Moral reasoning in the child with psychopathic tendencies. Pers. Indiv. Differ. 22, 731–739 (1997).

    Article  Google Scholar 

  70. Fairchild, G. et al. Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects. Biol. Psychiatry 66, 162–168 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Rothemund, Y. et al. Fear conditioning in psychopaths: event-related potentials and peripheral measures. Biol. Psychol. 90, 50–59 (2012).

    Article  PubMed  Google Scholar 

  72. Birbaumer, N. et al. Deficient fear conditioning in psychopathy: a functional magnetic resonance imaging study. Arch. Gen. Psychiatry 62, 799–805 (2005).

    Article  PubMed  Google Scholar 

  73. Fairchild, G., Van Goozen, S. H., Stollery, S. J. & Goodyer, I. M. Fear conditioning and affective modulation of the startle reflect in male adolescents with early-onset of adolescence-onset conduct disorder and healthy control subjects. Biol. Psychiatry 63, 279–285 (2008).

    Article  PubMed  Google Scholar 

  74. Gao, Y., Raine, A., Venables, P. H., Dawson, M. E. & Mednick, S. A. Association of poor childhood fear conditioning and adult crime. Am. J. Psychiatry 167, 56–60 (2010).

    Article  PubMed  Google Scholar 

  75. Blair, R. J. The amygdala and ventromedial prefrontal cortex: functional contributions and dysfunction in psychopathy. Phil. Trans. R. Soc. B 363, 2557–2565 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. White, S. F. et al. Disrupted expected value and prediction error signaling in youth with disruptive behavior disorders during a passive avoidance task. Am. J. Psychiatry 170, 315–323 (2013). The first model-based fMRI study of the reinforcement-based decision-making impairment in youths with disruptive behaviour disorders and its relationship with psychopathic traits. This was the first study to report specific computational impairments in this population in prediction error and expected value signalling within the caudate and vmPFC, respectively.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Dayan, P. & Balleine, B. W. Reward, motivation, and reinforcement learning. Neuron 36, 285–298 (2002).

    Article  CAS  PubMed  Google Scholar 

  78. Rescorla, R. A. & Wagner, A. R. in Classical Conditioning II (eds Black, A. H. & Prokasy, W. F.) 64–99 (Century-Crofts, 1972).

    Google Scholar 

  79. Rubia, K. et al. Disorder-specific dissociation of orbitofrontal dysfunction in boys with pure conduct disorder during reward and ventrolateral prefrontal dysfunction in boys with pure ADHD during sustained attention. Am. J. Psychiatry 166, 83–94 (2009).

    Article  PubMed  Google Scholar 

  80. Crowley, T. J. et al. Risky decisions and their consequences: neural processing by boys with antisocial substance disorder. PLoS ONE 5, e12835 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Bjork, J. M., Chen, G., Smith, A. R. & Hommer, D. W. Incentive-elicited mesolimbic activation and externalizing symptomatology in adolescents. J. Child Psychol. Psychiatry 51, 827–837 (2010).

    Article  PubMed  Google Scholar 

  82. Anderson, N. E. & Kiehl, K. A. The psychopath magnetized: insights from brain imaging. Trends Cogn. Sci. 16, 52–60 (2012).

    Article  PubMed  Google Scholar 

  83. Marsh, A. A. et al. Reduced amygdala–orbitofrontal connectivity during moral judgments in youths with disruptive behavior disorders and psychopathic traits. Psychiatry Res. 194, 279–286 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Strohle, A. et al. Reward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder. Neuroimage 39, 966–972 (2008).

    Article  PubMed  Google Scholar 

  85. Plichta, M. M. et al. Neural hyporesponsiveness and hyperresponsiveness during immediate and delayed reward processing in adult attention-deficit/hyperactivity disorder. Biol. Psychiatry 65, 7–14 (2009).

    Article  PubMed  Google Scholar 

  86. Scheres, A., Milham, M. P., Knutson, B. & Castellanos, F. X. Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder. Biol. Psychiatry 61, 720–724 (2007).

    Article  PubMed  Google Scholar 

  87. Chassin, L., Pitts, S. C., DeLucia, C. & Todd, M. A longitudinal study of children of alcoholics: predicting young adult substance use disorders, anxiety, and depression. J. Abnorm. Psychol. 108, 106–119 (1999).

    Article  CAS  PubMed  Google Scholar 

  88. Serec, M. et al. Health-related lifestyle, physical and mental health in children of alcoholic parents. Drug Alcohol Rev. 31, 861–870 (2012).

    Article  PubMed  Google Scholar 

  89. Heitzeg, M. M., Nigg, J. T., Yau, W. Y., Zubieta, J. K. & Zucker, R. A. Affective circuitry and risk for alcoholism in late adolescence: differences in frontostriatal responses between vulnerable and resilient children of alcoholic parents. Alcohol. Clin. Exp. Res. 32, 414–426 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Yau, W. Y. et al. Nucleus accumbens response to incentive stimuli anticipation in children of alcoholics: relationships with precursive behavioral risk and lifetime alcohol use. J. Neurosci. 32, 2544–2551 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Jensen, P. S. et al. ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J. Am. Acad. Child Adolesc. Psychiatry 40, 147–158 (2001).

    Article  CAS  PubMed  Google Scholar 

  92. Armstrong, T. D. & Costello, E. J. Community studies on adolescent substance use, abuse, or dependence and psychiatric comorbidity. J. Consult. Clin. Psychol. 70, 1224–1239 (2002).

    Article  PubMed  Google Scholar 

  93. Huebner, B. et al. Morphometric brain abnormalities in boys with conduct disorder. J. Am. Acad. Child Adolesc. Psychiatry 47, 540–547 (2008).

    Article  PubMed  Google Scholar 

  94. Sterzer, P., Stadler, C., Poustka, F. & Kleinschmidt, A. A structural neural deficit in adolescents with conduct disorder and its association with lack of empathy. Neuroimage 37, 335–342 (2007).

    Article  PubMed  Google Scholar 

  95. Fairchild, G. et al. Brain structure abnormalities in early-onset and adolescent-onset conduct disorder. Am. J. Psychiatry 168, 624–633 (2011).

    Article  PubMed  Google Scholar 

  96. Fairchild, G. et al. Brain structure abnormalities in adolescent girls with conduct disorder. J. Child Psychol. Psychiatry 54, 86–95 (2013).

    Article  PubMed  Google Scholar 

  97. Ermer, E., Cope, L. M., Nyalakanti, P. K., Calhoun, V. D. & Kiehl, K. A. Aberrant paralimbic gray matter in incarcerated male adolescents with psychopathic traits. J. Am. Acad. Child Adolesc. Psychiatry 52, 94–103 (2013). One of the few structural imaging studies of youths with psychopathic traits. It is particularly important because of the large number of participants assessed.

    Article  PubMed  PubMed Central  Google Scholar 

  98. De Brito, S. A. et al. Size matters: increased grey matter in boys with conduct problems and callous-unemotional traits. Brain 132, 843–852 (2009).

    Article  PubMed  Google Scholar 

  99. Dalwani, M. et al. Reduced cortical gray matter volume in male adolescents with substance and conduct problems. Drug Alcohol Depend. 118, 295–305 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Krusei, M. J. P., Casanova, M. F., Mannheim, G. & Johnson-Bilder, A. Reduced temporal lobe volume in early onset conduct disorder. Psychiatry Res. 132, 1–11 (2004).

    Article  Google Scholar 

  101. Hyatt, C. J., Haney-Caron, E. & Stevens, M. C. Cortical thickness and folding deficits in conduct-disordered adolescents. Biol. Psychiatry 72, 207–214 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Fahim, C. et al. Neuroanatomy of childhood disruptive behavior disorders. Aggress. Behav. 37, 326–337 (2011).

    Article  PubMed  Google Scholar 

  103. Craig, M. C. et al. Altered connections on the road to psychopathy. Mol. Psychiatry 14, 946–953 (2009).

    Article  CAS  PubMed  Google Scholar 

  104. Motzkin, J. C., Newman, J. P., Kiehl, K. A. & Koenigs, M. Reduced prefrontal connectivity in psychopathy. J. Neurosci. 31, 17348–17357 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Sundram, F. et al. White matter microstructural abnormalities in the frontal lobe of adults with antisocial personality disorder. Cortex 48, 216–229 (2012).

    Article  PubMed  Google Scholar 

  106. Finger, E. C. et al. Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits. Psychiatry Res. 202, 239–244 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Sarkar, S. et al. Frontotemporal white-matter microstructural abnormalities in adolescents with conduct disorder: a diffusion tensor imaging study. Psychol. Med. 43, 401–411 (2013).

    Article  CAS  PubMed  Google Scholar 

  108. Passamonti, L. et al. Abnormal anatomical connectivity between the amygdala and orbitofrontal cortex in conduct disorder. PLoS ONE 7, e48789 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Upadhyay, J. et al. Alterations in brain structure and functional connectivity in prescription opioid-dependent patients. Brain 133, 2098–2114 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Bodensteiner, J. B. & Schaefer, G. B. Wide cavum septum pellucidum: a marker of disturbed brain development. Pediatr. Neurol. 6, 391–394 (1990).

    Article  CAS  PubMed  Google Scholar 

  111. Sarwar, M. The septum pellucidum: normal and abnormal. Am. J. Neuroradiol. 10, 989–1005 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. White, S. F. et al. The relationship between large cavum septum pellucidum and antisocial behavior, callous–unemotional traits and psychopathy in adolescents. J. Child Psychol. Psychiatry 54, 575–581 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Raine, A., Lee, L., Yang, Y. & Colletti, P. Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy. Br. J. Psychiatry 197, 186–192 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  114. May, F. S., Chen, Q. C., Gilbertson, M. W., Shenton, M. E. & Pitman, R. K. Cavum septum pellucidum in monozygotic twins discordant for combat exposure: relationship to posttraumatic stress disorder. Biol. Psychiatry 55, 656–658 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  115. Nopoulos, P., Krie, A. & Andreasen, N. C. Enlarged cavum septi pellucidi in patients with schizophrenia: clinical and cognitive correlates. J. Neuropsychiatry Clin. Neurosci. 12, 344–349 (2000).

    Article  CAS  PubMed  Google Scholar 

  116. Kim, M. J. et al. The occurrence of cavum septi pellucidi enlargement is increased in bipolar disorder patients. Bipolar Disord. 9, 274–280 (2007).

    Article  PubMed  Google Scholar 

  117. Swayze, V. et al. Magnestic resonance imaging of brain anomalies in fetal alcohol syndrome. Pediatrics 99, 232–240 (1997).

    Article  PubMed  Google Scholar 

  118. Streissguth, A. P. et al. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J. Dev. Behav. Pediatr. 25, 228–238 (2004).

    Article  PubMed  Google Scholar 

  119. Wakschlag, L. S. et al. Interaction of prenatal exposure to cigarettes and MAOA genotype in pathyways to youth antisocial behavior. Mol. Psychiatry 15, 928–937 (2013).

    Article  CAS  Google Scholar 

  120. Schlotz, W. & Phillips, D. I. Fetal origins of mental health: evidence and mechanisms. Brain Behav. Immunol. 23, 905–916 (2009).

    Article  Google Scholar 

  121. Ermer, E., Cope, L. M., Nyalakanti, P. K., Calhoun, V. D. & Kiehl, K. A. Aberrant paralimbic gray matter in criminal psychopathy. J. Abnorm. Psychol. 121, 649–658 (2012).

    Article  PubMed  Google Scholar 

  122. van Goozen, S. H., Matthys, W., Cohen-Kettenis, P. T., Thijssen, J. H. & van Engeland, H. Adrenal androgens and aggression in conduct disorder prepubertal boys and normal controls. Biol. Psychiatry 43, 156–158 (1998).

    Article  CAS  PubMed  Google Scholar 

  123. Fairchild, G. et al. Cortisol diurnal rhythm and stress reactivity in male adolescents with early-onset or adolescence-onset conduct disorder. Biol. Psychiatry 64, 599–606 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Lopez-Duran, N. L., Olson, S. L., Hajal, N. J., Felt, B. T. & Vazquez, D. M. Hypothalamic pituitary adrenal axis functioning in reactive and proactive aggression in children. J. Abnorm. Child Psychol. 37, 169–182 (2009).

    Article  PubMed  Google Scholar 

  125. LeDoux, J. E. The amygdala. Curr. Biol. 17, R868–R874 (2007).

    Article  CAS  PubMed  Google Scholar 

  126. Hawes, D. J., Brennan, J. & Dadds, M. R. Cortisol, callous-unemotional traits, and pathways to antisocial behavior. Curr. Opin. Psychiatry 22, 357–362 (2009).

    Article  PubMed  Google Scholar 

  127. Blair, R. J. R., Peschardt, K. S., Budhani, S., Mitchell, D. G. & Pine, D. S. The development of psychopathy. J. Child Psychol. Psychiatry 47, 262–276 (2006).

    Article  CAS  PubMed  Google Scholar 

  128. Rhee, S. H. & Waldman, I. D. Genetic and environmental influences on antisocial behavior: a meta-analysis of twin and adoption studies. Psychol. Bull. 128, 490–529 (2002).

    Article  PubMed  Google Scholar 

  129. Viding, E., Blair, R. J. R., Moffitt, T. E. & Plomin, R. Evidence for substantial genetic risk for psychopathy in 7-year-olds. J. Child Psychol. Psychiatry 46, 592–597 (2005). One of the first studies to document the high heritability of callous–unemotional traits in youths.

    Article  PubMed  Google Scholar 

  130. Viding, E. et al. In search of genes associated with risk for psychopathic tendencies in children: a two-stage genome-wide association study of pooled DNA. J. Child Psychol. Psychiatry 51, 780–788 (2010).

    Article  PubMed  Google Scholar 

  131. Smolka, M. N. et al. Catechol-O-methyltransferase Val158Met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. J. Neurosci. 25, 836–842 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Heinz, A. J., Beck, A., Meyer-Lindenberg, A., Sterzer, P. & Heinz, A. Cognitive and neurobiological mechanisms of alcohol-related aggression. Nature Rev. Neurosci. 12, 400–413 (2011).

    Article  CAS  Google Scholar 

  133. Meyer-Lindenberg, A. et al. Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc. Natl Acad. Sci. USA 103, 6269–6274 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Rujescu, D., Giegling, I., Gietl, A., Hartmann, A. M. & Moller, H. J. A functional single nucleotide polymorphism (V158M) in the COMT gene is associated with aggressive personality traits. Biol. Psychiatry 54, 34–39 (2003).

    Article  CAS  PubMed  Google Scholar 

  135. Caspi, A. et al. Role of genotype in the cycle of violence in maltreated children. Science 297, 851–854 (2002).

    Article  CAS  PubMed  Google Scholar 

  136. Beitchman, J. H. et al. Serotonin transporter polymorphisms and persistent, pervasive childhood aggression. Am. J. Psychiatry 164, 1103–1105 (2006).

    Article  Google Scholar 

  137. Zai, C. et al. Dopaminergic system genes in childhood aggression: possible role for DRD2. World J. Biol. Psychiatry 13, 65–74 (2012).

    Article  PubMed  Google Scholar 

  138. Sadeh, N. et al. Serotonin transporter gene associations with psychopathic traits in youth vary as a function of socioeconomic resources. J. Abnorm. Psychol. 119, 604–609 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Hirata, Y., Zai, C. C., Nowrouzi, B., Beitchman, J. H. & Kennedy, J. L. Study of the catechol-O-methyltransferase (COMT) gene with high aggression in children. Aggress. Behav 39, 45–51 (2013).

    Article  PubMed  Google Scholar 

  140. Hariri, A. R. et al. A susceptibility gene for affective disorders and the response of the human amygdala. Arch. Gen. Psychiatry 62, 146–152 (2005).

    Article  CAS  PubMed  Google Scholar 

  141. Moul, C., Dobson-Stone, C., Brennan, J., Hawes, D. & Dadds, M. An exploration of the serotonin system in antisocial boys with high levels of callous-unemotional traits. PLoS ONE 8, e56619 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Beitchman, J. H. et al. Childhood aggression, callous-unemotional traits and oxytocin genes. Eur. Child Adolesc. Psychiatry 21, 125–132 (2012).

    Article  PubMed  Google Scholar 

  143. McCrory, E. J. et al. Heightened neural reactivity to threat in child victims of family violence. Curr. Biol. 21, R947–R948 (2011).

    Article  CAS  PubMed  Google Scholar 

  144. Tottenham, N. et al. Elevated amygdala response to faces following early deprivation. Dev. Sci. 14, 190–204 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Bogdan, R., Williamson, D. E. & Hariri, A. R. Mineralocorticoid receptor Iso/Val (rs5522) genotype moderates the association between previous childhood emotional neglect and amygdala reactivity. Am. J. Psychiatry 169, 515–522 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  146. Dodge, K. A., Pettit, G. S., Bates, J. E. & Valente, E. Social information-processing patterns partially mediate the effect of early physical abuse on later conduct problems. J. Abnorm. Psychol. 104, 632–643 (1995). A classic study demonstrating the impact that physical abuse has on the development of hostile attribution biases and the implications of this for the development of reactive aggression.

    Article  CAS  PubMed  Google Scholar 

  147. Fontaine, N. M., Rijsdijk, F. V., McCrory, E. J. & Viding, E. Etiology of different developmental trajectories of callous-unemotional traits. J. Am. Acad. Child Adolesc. Psychiatry 49, 656–664 (2010).

    PubMed  Google Scholar 

  148. Barker, E. D., Oliver, B. R., Viding, E., Salekin, R. T. & Maughan, B. 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 52, 878–888 (2011).

    Article  PubMed  Google Scholar 

  149. Durlak, J. A., Weissberg, R. P., Dymnicki, A. B., Taylor, R. D. & Schellinger, K. B. The impact of enhancing students' social and emotional learning: a meta-analysis of school-based universal interventions. Child Dev. 82, 405–432 (2011).

    Article  PubMed  Google Scholar 

  150. Chamberlain, P. & Smith, D. K. in Evidence-Based Psychotherapies for Children and Adolescents (eds Kazdin, A. E. & Weisz, J. R.) 282–300 (Guilford Press, 2003).

    Google Scholar 

  151. Henggeler, S. W. & Lee, T. in Evidence-Based Psychotherapies for Children and Adolescents (eds Kazdin, A. E. & Weisz, J. R.) 301–322 (Guilford Press, 2003).

    Google Scholar 

  152. Eyberg, S. M., Nelson, M. M. & Boggs, S. R. Evidence-based psychosocial treatments for children and adolescents with disruptive behavior. J. Clin. Child Adolesc. Psychol. 37, 215–237 (2008).

    Article  PubMed  Google Scholar 

  153. Oxford, M., Cavell, T. A. & Hughes, J. N. Callous/unemotional traits moderate the relation between ineffective parenting and child externalizing problems: a partial replication and extension. J. Clin. Child Adolesc. Psychol. 32, 577–585 (2003).

    Article  PubMed  Google Scholar 

  154. Pasalich, D. S., Dadds, M. R., Hawes, D. J. & Brennan, J. Do callous-unemotional traits moderate the relative importance of parental coercion versus warmth in child conduct problems? An observational study. J. Child Psychol. Psychiatry 52, 1308–1315 (2011).

    Article  PubMed  Google Scholar 

  155. Haas, S. M. et al. Treatment response in CP/ADHD children with callous/unemotional traits. J. Abnorm. Child Psychol. 39, 541–552 (2011).

    Article  PubMed  Google Scholar 

  156. Masi, G. et al. Predictors of nonresponse to psychosocial treatment in children and adolescents with disruptive behavior disorders. J. Child Adolesc. Psychopharmacol. 21, 51–55 (2011).

    Article  PubMed  Google Scholar 

  157. Manders, W. A., Dekovic, M., Asscher, J. J., van der Laan, P. H. & Prins, P. J. Psychopathy as predictor and moderator of multisystemic therapy outcomes among adolescents treated for antisocial behavior. J. Abnorm. Child Psychol. 41, 1121–1132 (2013).

    Article  PubMed  Google Scholar 

  158. Felmingham, K. et al. Changes in anterior cingulate and amygdala after cognitive behavior therapy of post traumatic stress disorder. Psychol. Sci. 18, 127–129 (2007).

    Article  PubMed  Google Scholar 

  159. Afifi, T. O., McMillan, K. A., Asmundson, G. J., Pietrzak, R. H. & Sareen, J. An examination of the relation between conduct disorder, childhood and adulthood traumatic events, and posttraumatic stress disorder in a nationally representative sample. J. Psychiatr. Res. 45, 1564–1572 (2011).

    Article  PubMed  Google Scholar 

  160. Hawes, D. J. & Dadds, M. R. Stability and malleability of callous-unemotional traits during treatment for childhood conduct problems. J. Clin. Child Adolesc. Psychol. 36, 347–355 (2007).

    Article  PubMed  Google Scholar 

  161. Pardini, D. A., Lochman, J. E. & Powell, N. The development of callous-unemotional traits and antisocial behavior in children: are there shared and/or unique predictors? J. Clin. Child Adolesc. Psychol. 36, 319–333 (2007).

    Article  PubMed  Google Scholar 

  162. Greenaway, M. & Elbe, D. Focus on aripiprazole: a review of its use in child and adolescent psychiatry. J. Can. Acad. Child Adolesc. Psychiatry 18, 250–260 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  163. Findling, R. L. Atypical antipsychotic treatment of disruptive behavior disorders in children and adolescents. J. Clin. Psychiatry 69 (Suppl. 4), 9–14 (2008).

    CAS  PubMed  Google Scholar 

  164. Zito, J. M. et al. Psychotropic medication patterns among youth in foster care. Pediatrics 121, e157–163 (2008).

    Article  PubMed  Google Scholar 

  165. Burris, K. D. et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J. Pharmacol. Exp. Ther. 302, 381–389 (2002).

    Article  CAS  PubMed  Google Scholar 

  166. Taylor, D. M. Aripiprazole: a review of its pharmacology and clinical use. Int. J. Clin. Pract. 57, 49–54 (2003).

    CAS  PubMed  Google Scholar 

  167. Huang, M., Ichiwaka, J., Li, Z., Dai, J. & Meltzer, H. Y. Augmentation by citalopram of risperidone-induced monoamine release in rat prefrontal cortex. Psychopharmacol. (Berl.) 185, 274–281 (2006).

    Article  CAS  Google Scholar 

  168. Blair, K. S. et al. The role of 5-HTTLPR in choosing the lesser of two evils, the better of two goods: examining the impact of 5-HTTLPR genotype and tryptophan depletion in object choice. Psychopharmacology 196, 29–38 (2008).

    Article  CAS  PubMed  Google Scholar 

  169. Finger, E. C. et al. The impact of tryptophan depletion and 5-HTTLPR genotype on passive avoidance and response reversal instrumental learning tasks. Neuropsychopharmacology 32, 206–215 (2007).

    Article  CAS  PubMed  Google Scholar 

  170. Marsh, A. A. et al. Impaired recognition of fear facial expressions in 5-HTTLPR S-polymorphism carriers following tryptophan depletion. Psychopharmacology (Berl.) 189, 387–394 (2006).

    Article  CAS  Google Scholar 

  171. Schultz, W. Multiple functions of dopamine neurons. F1000 Biol. Rep. 2, 2 (2010).

    PubMed  PubMed Central  Google Scholar 

  172. Dayan, P. Instrumental vigour in punishment and reward. Eur. J. Neurosci. 35, 1152–1168 (2012).

    Article  PubMed  Google Scholar 

  173. Hasler, G., Mondillo, K., Drevets, W. C. & Blair, R. J. R. Impairments of probabilistic response reversal and passive avoidance following catecholamine depletion. Neuropsychopharmacology 34, 2691–2698 (2009).

    Article  PubMed  CAS  Google Scholar 

  174. Takahashi, H. et al. Effects of dopaminergic and serotonergic manipulation on emotional processing: a pharmacological fMRI study. Neuroimage 27, 991–1001 (2005).

    Article  PubMed  Google Scholar 

  175. Hariri, A. R. et al. Dexroamphetamine modulates the response of the human amygdala. Neuropsychopharmacology 27, 1036–1040 (2002).

    Article  CAS  PubMed  Google Scholar 

  176. Rugino, T. A. & Janvier, Y. M. Aripiprazole in children and adolescents: clinical experience. J. Child Neurol. 20, 603–610 (2005).

    Article  PubMed  Google Scholar 

  177. Allison, D. B. & Casey, D. E. Antipsychotic-induced weight gain: a review of the literature. J. Clin. Psychiatry 62, 22–31 (2001).

    CAS  PubMed  Google Scholar 

  178. Lambert, M. T., Copeland, L. A., Sampson, N. & Duffy, S. A. New-onset type-2 diabetes associated with atypical antipsychotic medications. Biol. Psychiatry 30, 919–923 (2006).

    CAS  Google Scholar 

  179. Schoenbaum, G. & Roesch, M. Orbitofrontal cortex, associative learning, and expectancies. Neuron 47, 633–636 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Schoenbaum, G., Chiba, A. A. & Gallagher, M. Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning. Nature Neurosci. 1, 155–159 (1998).

    Article  CAS  PubMed  Google Scholar 

  181. Insel, T. et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167, 748–751 (2010).

    Article  PubMed  Google Scholar 

  182. Aharoni, E. et al. Neuroprediction of future rearrest. Proc. Natl Acad. Sci. USA 110, 6223–6228 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Pardini, D. A., Erickson, K., Loeber, R. & Raine, A. Lower amygdala volume in men is associated with childhood aggression, early psychopathic traits, and future violence. Biol. Psychiatry http://dx.doi.org/10.1016/j.biopsych.2013.04.003 (2013).

  184. Blanchard, R. J., Blanchard, D. C. & Takahashi, L. K. Attack and defensive behaviour in the albino rat. Animal Behav. 25, 197–224 (1977).

    Article  Google Scholar 

  185. Panksepp, J. Affective Neuroscience: The Foundations of Human and Animal Emotions (Oxford Univ. Press, 1998).

    Google Scholar 

  186. Gregg, T. R. & Siegel, A. Brain structures and neurotransmitters regulating aggression in cats: implications for human aggression. Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 91–140 (2001).

    Article  CAS  PubMed  Google Scholar 

  187. Lin, D. et al. Functional identification of an aggression locus in the mouse hypothalamus. Nature 470, 221–226 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  188. Nelson, R. J. & Trainor, B. C. Neural mechanisms of aggression. Nature Rev. Neurosci. 8, 536–546 (2007).

    Article  CAS  Google Scholar 

  189. Blair, R. J. R. Neuro-cognitive models of aggression, the antisocial personality disorders and psychopathy. J. Neurol. Neurosurg. Psychiatry 71, 727–731 (2001).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  190. Mobbs, D. et al. When fear is near: threat imminence elicits prefrontal-periacqueductal gray shifts in humans. Science 317, 1079–1083 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  191. Mobbs, D. et al. Neural activity associated with monitoring the oscillating threat value of a tarantula. Proc. Natl Acad. Sci. USA 107, 20582–20586 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  192. Mobbs, D. et al. From threat to fear: the neural organization of defensive fear systems in humans. J. Neurosci. 29, 12236–12243 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  193. Dodge, K. A., Lochman, J. E., Harnish, J. D., Bates, J. E. & Pettit, G. S. Reactive and proactive aggression in school children and psychiatrically impaired chronically assaultive youth. J. Abnorm. Psychol. 106, 37–51 (1997).

    Article  CAS  PubMed  Google Scholar 

  194. Lahey, B. B., Loeber, R., Burke, J., Rathouz, P. J. & McBurnett, K. Waxing and waning in concert: dynamic comorbidity of conduct disorder with other disruptive and emotional problems over 7 years among clinic-referred boys. J. Abnorm. Psychol. 111, 556–567 (2002).

    Article  PubMed  Google Scholar 

  195. Frick, P. J., Ray, J. V., Thornton, L. C. & Kahn, R. E. Can callous-unemotional traits enhance the understanding, diagnosis, and treatment of serious conduct problems in children and adolescents? A comprehensive review. Psychol. Bull. http://dx.doi.org/10.1037/a0033076 (2013). An important recent review on diagnostic considerations with respect to conduct disorder and callous–unemotional traits.

  196. Patrick, C. J. Emotion and psychopathy: startling new insights. Psychophysiology 31, 319–330 (1994).

    Article  CAS  PubMed  Google Scholar 

  197. Verona, E., Patrick, C. J. & Joiner, T. E. Psychopathy, antisocial personality, and suicide risk. J. Abnorm. Psychol. 110, 462–470 (2001).

    Article  CAS  PubMed  Google Scholar 

  198. Feder, A., Nestler, E. J. & Charney, D. S. Psychobiology and molecular genetics of resilience. Nature Rev. Neurosci. 10, 446–457 (2009).

    Article  CAS  Google Scholar 

  199. Blair, R. J. R. A cognitive developmental approach to morality: investigating the psychopath. Cognition 57, 1–29 (1995).

    Article  CAS  PubMed  Google Scholar 

  200. Haidt, J. The emotional dog and its rational tail: a social intuitionist approach to moral judgment. Psychol. Rev. 108, 814–834 (2001).

    Article  CAS  PubMed  Google Scholar 

  201. Greene, J. D., Sommerville, R. B., Nystrom, L. E., Darley, J. M. & Cohen, J. D. An fMRI investigation of emotional engagement in moral judgment. Science 293, 1971–1972 (2001).

    Article  Google Scholar 

  202. Moll, J., Zahn, R., de Oliveira-Souza, R., Krueger, F. & Grafman, J. Opinion: the neural basis of human moral cognition. Nature Rev. Neurosci. 6, 799–809 (2005).

    Article  CAS  Google Scholar 

  203. Glenn, A. L., Raine, A. & Schug, R. A. The neural correlates of moral decision-making in psychopathy. Mol. Psychiatry 14, 5–6 (2008).

    Article  Google Scholar 

  204. Harenski, C. L., Harenski, K. A., Shane, M. S. & Kiehl, K. A. Aberrant neural processing of moral violations in criminal psychopaths. J. Abnorm. Psychol. 119, 863–874 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  205. Sakai, J. T., Dalwani, M. S., Gelhorn, H. L., Mikulich-Gilbertson, S. K. & Crowley, T. J. A. Behavioral test of accepting benefits that cost others: associations with conduct problems and callous-unemotionality. PLoS ONE 7, e36158 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  206. Smetana, J. G. Preschool children's conceptions of moral and social rules. Child Dev. 52, 1333–1336 (1981).

    Article  Google Scholar 

  207. Smetana, J. G. in The Child as Psychologist: An Introduction to the Development of Social Cognition (ed. Bennett, M.) 111–141 (Harvester Wheatsheaf, 1993).

    Google Scholar 

  208. Haidt, J. The new synthesis in moral psychology. Science 316, 998–1002 (2007).

    Article  CAS  PubMed  Google Scholar 

  209. Glenn, A. L., Iyer, R., Graham, J., Koleva, S. & Haidt, J. Are all types of morality compromised in psychopathy. J. Personal. Disord. 23, 384–398 (2009).

    Article  Google Scholar 

  210. Aharoni, E., Antonenko, O. & Kiehl, K. A. Disparities in the moral intuitions of criminal offenders: the role of psychopathy. J. Res. Pers. 45, 322–327 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  211. Blair, R. J. R. & Cipolotti, L. Impaired social response reversal: a case of “acquired sociopathy”. Brain 123, 1122–1141 (2000).

    Article  PubMed  Google Scholar 

  212. Murphy, F. C., Nimmo-Smith, I. & Lawrence, A. D. Functional neuroanatomy of emotions: a meta-analysis. Cogn. Affect. Behav. Neurosci. 3, 207–233 (2003).

    Article  PubMed  Google Scholar 

  213. Martel, G. et al. Murine GRPR and stathmin control in opposite directions both cued fear extinction and neural activities of the amygdala and prefrontal cortex. PLoS ONE 7, e30942 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  214. Klucken, T. et al. The 5-HTTLPR polymorphism is associated with altered hemodynamic responses during appetitive conditioning. Hum. Brain Mapp. 34, 2549–2560 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  215. Stein, J. L. et al. Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N = 1198) using genome-wide search. Mol. Psychiatry 16, 927–937 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  216. Workman, J. L., Fonken, L. K., Gusfa, J., Kassouf, K. M. & Nelson, R. J. Post-weaning environmental enrichment alters affective responses and interacts with behavioral testing to alter nNOS immunoreactivity. Pharmacol. Biochem. Behav. 100, 25–32 (2011).

    Article  CAS  PubMed  Google Scholar 

  217. Isaacs, E. B. et al. The effect of early human diet on caudate volumes and IQ. Pediatr. Res. 63, 308–314 (2008).

    Article  PubMed  Google Scholar 

  218. Seidel, K., Poeggel, G., Holetschka, R., Helmeke, C. & Braun, K. Paternal deprivation affects the development of corticotrophin-releasing factor-expressing neurones in prefrontal cortex, amygdala and hippocampus of the biparental octodon degus. J. Neuroendocrinol. 23, 1166–1176 (2011).

    Article  CAS  PubMed  Google Scholar 

  219. D'Addario, C. et al. Ethanol induces epigenetic modulation of prodynorphin and pronociceptin gene expression in the rat amygdala complex. J. Mol. Neurosci. 49, 312–319 (2013).

    Article  CAS  PubMed  Google Scholar 

  220. Kochanska, G., Gross, J. N., Lin, M. H. & Nichols, K. E. Guilt in young children: development, determinants, and relations with a broader system of standards. Child Dev. 73, 461–482 (2002).

    Article  PubMed  Google Scholar 

  221. Kochanska, G. Multiple pathways to conscience for children with different temperaments: from toddlerhood to age 5. Dev Psychol. 33, 228–240 (1997).

    Article  CAS  PubMed  Google Scholar 

  222. Ernst, M. et al. Amygdala and nucleus accumbens in responses to receipt and omission of gains in adults and adolescents. Neuroimage 25, 1279–1291 (2005).

    Article  PubMed  Google Scholar 

  223. Hare, T. A. et al. Biological substrates of emotional reactivity and regulation in adolescence during an emotional go-nogo task. Biol. Psychiatry 63, 927–934 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  224. Galvan, A. et al. Earlier development of the accumbens relative to orbitofrontal cortex might underlie risk-taking behavior in adolescents. J. Neurosci. 26, 6885–6892 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  225. Quevedo, K. M., Benning, S. D., Gunnar, M. R. & Dahl, R. E. The onset of puberty: effects on the psychophysiology of defensive and appetitive motivation. Dev. Psychopathol. 21, 27–45 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  226. Wendelken, C., Baym, C. L., Gazzaley, A. & Bunge, S. A. Neural indices of improved attentional modulation over middle childhood. Dev. Cogn. Neurosci. 1, 175–186 (2011).

    Article  PubMed  CAS  Google Scholar 

  227. Velanova, K., Wheeler, M. E. & Luna, B. The maturation of task set-related activation supports late developmental improvements in inhibitory control. J. Neurosci. 29, 12558–12567 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  228. Wymbs, B. T. et al. Callous–unemotional traits as unique prospective risk factors for substance use in early adolescent boys and girls. J. Abnorm. Child Psychol. 40, 1099–1110 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  229. Alia-Klein, N. et al. Gene × disease interaction on orbitofrontal gray matter in cocaine addiction. Arch. Gen. Psychiatry 68, 283–294 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  230. Kasanetz, F. et al. Prefrontal synaptic markers of cocaine addiction-like behavior in rats. Mol. Psychiatry 18, 729–737 (2013).

    Article  CAS  PubMed  Google Scholar 

  231. Yucel, M. et al. Regional brain abnormalities associated with long-term heavy cannabis use. Arch. Gen. Psychiatry 65, 694–701 (2008).

    Article  PubMed  Google Scholar 

  232. Koenigs, M., Baskin-Sommers, A., Zeier, J. & Newman, J. P. Investigating the neural correlates of psychopathy: a critical review. Mol. Psychiatry 16, 792–799 (2011).

    Article  CAS  PubMed  Google Scholar 

  233. Pardini, D. A. & Phillips, M. Neural responses to emotional and neutral facial expressions in chronically violent men. J. Psychiatry Neurosci. 35, 390–398 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  234. Deeley, Q. et al. Facial emotion processing in criminal psychopathy. Preliminary functional magnetic resonance imaging study. Br. J. Psychiatry 189, 533–539 (2006).

    Article  PubMed  Google Scholar 

  235. Contreras-Rodriguez, O. et al. Disrupted neural processing of emotional faces in psychopathy. Soc. Cogn. Affect. Neurosci. http://dx.doi.org/10.1093/scan/nst014 (2013).

  236. Dolan, M. C. & Fullam, R. S. Psychopathy and functional magnetic responance imaging blood oxygenation level-dependent respones to emotional faces in violence patients with schizophrenia. Biol. Psychiatry 66, 570–577 (2009).

    Article  PubMed  Google Scholar 

  237. Sommer, M. et al. In psychopathic patients emotion attribution modulates activity in outcome-related brain areas. Psychiatry Res. 182, 88–95 (2010).

    Article  PubMed  Google Scholar 

  238. Blair, R. J. R., Jones, L., Clark, F. & Smith, M. The psychopathic individual: a lack of responsiveness to distress cues? Psychophysiology 34, 192–198 (1997).

    Article  CAS  PubMed  Google Scholar 

  239. House, T. H. & Milligan, W. L. Autonomic responses to modeled distress in prison psychopaths. J. Personal. Social Psychol. 34, 556–560 (1976).

    Article  CAS  Google Scholar 

  240. Newman, J. P., Patterson, C. M. & Kosson, D. S. Response perseveration in psychopaths. J. Abnorm. Psychol. 96, 145–148 (1987).

    Article  CAS  PubMed  Google Scholar 

  241. Budhani, S., Richell, R. A. & Blair, R. J. Impaired reversal but intact acquisition: probabilistic response reversal deficits in adult individuals with psychopathy. J. Abnorm. Psychol. 115, 552–558 (2006).

    Article  PubMed  Google Scholar 

  242. Young, L., Koenigs, M., Kruepke, M. & Newman, J. P. Psychopathy increases perceived moral permissibility of accidents. J. Abnorm. Psychol. 121, 659–667 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  243. Koenigs, M., Kruepke, M., Zeier, J. & Newman, J. P. Utilitarian moral judgment in psychopathy. Soc. Cogn. Affect. Neurosci. 7, 708–714 (2011). An interesting paper documenting the impairment in moral judgements seen in individuals with psychopathy.

    Article  PubMed  PubMed Central  Google Scholar 

  244. Yang, Y., Raine, A., Colletti, P., Toga, A. W. & Narr, K. L. Morphological alterations in the prefrontal cortex and the amygdala in unsuccessful psychopaths. J. Abnorm. Psychol. 119, 546–554 (2010).

    Article  PubMed  Google Scholar 

  245. Yang, Y., Raine, A., Colletti, P., Toga, A. W. & Narr, K. L. Abnormal temporal and prefrontal cortical gray matter thinning in psychopaths. Mol. Psychiatry 14, 561–562 (2009).

    Article  CAS  PubMed  Google Scholar 

  246. Ly, M. et al. Cortical thinning in psychopathy. Am. J. Psychiatry 169, 743–749 (2012).

    Article  PubMed  Google Scholar 

  247. Kiehl, K. A. et al. Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging. Biol. Psychiatry 50, 677–684 (2001).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, USA, under grant number 1-ZIA-MH002860-08.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. James R. Blair.

Ethics declarations

Competing interests

The author declares no competing financial interests.

PowerPoint slides

Glossary

Observational fear

The phenomenon that an infant's avoidance responses to a previously novel object are modified by the mother's apparent emotional reaction to this object. Typically, infants avoid objects associated with maternal fear.

Transgressions

Actions that violate norms.

Passive avoidance learning

An experimental paradigm in which the individual learns to approach or passively avoid (by not responding to) objects that elicit either reward or punishment (for example, money gain or loss).

Operant extinction

An experimental paradigm in which the individual learns that responding to an object is rewarding but then, after a change of reinforcement contingency, should extinguish this response as responding comes to be associated with punishment.

Reversal learning

An experimental paradigm in which the individual initially learns to make a response towards one of a paired set of stimuli to gain reward but then, after a change of reinforcement contingency, should reverse their behaviour towards the second object as the first object comes to be associated with punishment.

Prediction error

The difference between the amount of reward or punishment received and the amount expected.

Expected value

The expected reward or punishment following the commission of a specific response.

Functional anisotropy

A parameter in diffusion tensor imaging, which images brain structures by measuring the diffusion properties of water molecules. It provides information about the microstructural integrity of white-matter tracts.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blair, R. The neurobiology of psychopathic traits in youths. Nat Rev Neurosci 14, 786–799 (2013). https://doi.org/10.1038/nrn3577

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn3577

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing