Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits

nature neuroscience VOLUME 13 | NUMBER 4 | APRIL 2010 4 1 9 B r i e f c o m m u n i c at i o n s The net annual burden of crime in the US has been estimated to exceed $1 trillion 1 , making criminal behavior a costly large-scale social problem and a critical target for scientific investigation. Although the risk architecture underlying criminality is complex, psychopathy has emerged as a particularly robust predictor of criminal behavior and recidivism. Psychopathy is a personality disorder characterized by a combination of superficial charm, persistent instrumental antisocial behavior, marked sensation-seeking and poor reflection, blunted empathy and punishment sensitivity, and shallow emotional experiences 2 . Recent research on the neural substrates of psychopathy has focused on the profound emotional deficits seen in psychopaths and has emphasized the possible contributions of amygdala and ventromedial prefrontal cortex dysfunction to deficient fear processing and empathy 3 . However, although emotional and interpersonal deficits are often considered to be core features of the disorder, the empirical linkage of such deficits to criminality (particularly, to risk for committing violent crimes) is mixed Prior research has also shown that psychopathic individuals have a markedly increased risk of developing substance use problems 8 . Such associations mirror preclinical work demonstrating that impulsive traits predict enhanced susceptibility to drug-seeking and relapse 9 . Given the strong link between psychopathy and substance abuse, previous studies indicating that the mesolimbic dopamine (DA) system is important in the pathophysiology of substance use disorders and evidence that individual differences in the mesolimbic DA system predispose the development of substance abuse 9 , we hypothesized that psychopathic traits would be associated with dysfunction in mesolimbic DA reward circuitry. To test the prediction that individuals with psychopathic traits are characterized by alterations in mesolimbic DA neurochemistry and neurophysiology, we used positron emission tomography (PET) imaging of psychostimulantinduced DA release, in concert with a functional magnetic resonance imaging (fMRI) probe of the reward system. Psychopathic traits were measured with the psychopathic personality inventory (PPI), a wellvalidated trait measure of psychopathy, in a sample of community volunteers with no prior history of substance abuse (see Supplementary Data and Supplementary Discussion). Prior studies have shown that the PPI is composed of two underlying latent factors: a 'fearless dominance' (PPI-FD) factor indexing emotional-interpersonal facets of psychopathy and an 'impulsive antisociality' (PPI-IA) factor linked to socially deviant behavior To examine the relationship between psychopathic traits and DA release, we performed voxel-wise correlation analyses between PPI factor scores and maps of the percentage change in [ 18 F]fallypride binding potential between placebo and amphetamine (0.43 mg per kg of body weight; two-day, single-blind protocol, n = 30; Supplementary Methods an