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Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy

  • Adrian Raine (a1), Lydia Lee (a2), Yaling Yang (a3) and Patrick Colletti (a4)



Antisocial personality disorder and psychopathy have been hypothesised to have a neurodevelopmental basis, but this proposition has not been formally tested.


This study tests the hypothesis that individuals with cavum septum pellucidum (CSP), a marker of limbic neural maldevelopment, will show higher levels of psychopathy and antisocial personality.


Cavum septum pellucidum was assessed using anatomical magnetic resonance imaging in a community sample. Those with CSP (n = 19) were compared with those lacking CSP (n = 68) on antisocial personality, psychopathy and criminal offending.


Those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. The pervasiveness of this association was indicated by the fact that those lacking a diagnosis of antisocial personality disorder, but who were charged or convicted for an offence, had a more extensive CSP than non-antisocial controls. Results could not be attributed to prior trauma exposure, head injury, demographic factors or comorbid psychiatric conditions.


Our findings appear to be the first to provide evidence for a neurodevelopmental brain abnormality in those with antisocial personality disorder and psychopathy, and support the hypothesis that early maldevelopment of limbic and septal structures predisposes to the spectrum of antisocial behaviours.

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Corresponding author

Adrian Raine, Departments of Criminology, Psychiatry, and Psychology, Jerry Lee Center of Criminology, 3809 Walnut Street, University of Pennsylvania, Philadelphia, PA 19104, USA. Email:


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1 Shepherd, J. Combined approach is needed – violence as a public health problem. BMJ 2003; 326: 104.
2 Department of Health and Human Services. Youth Violence: A Report of the Surgeon General. Department of Health and Human Services, 2001.
3 Moffitt, TE. Adolescence-limited and life-course-persistent antisocial behavior: a developmental taxonomy. Psychol Rev 1993; 100: 674701.
4 Raine, A, Lencz, T, Scerbo, A. Antisocial personality: neuroimaging, neuropsychology, neurochemistry, and psychophysiology. In Neuropsychiatry of Behavior Disorders (ed Ratey, JH): 5078. Blackwell, 1995.
5 Davidson, RJ, Putnam, KM, Larson, CL. Dysfunction in the neural circuitry of emotion regulation – a possible prelude to violence. Science 2000; 289: 591–4.
6 Blair, RJR. The amygdala and ventromedial prefrontal cortex: functional contributions and dysfunction in psychopathy. Philos Trans R Soc B Bio Sci 2008; 363: 2557–65.
7 Kiehl, KA. A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction. Psychiatry Res 2006; 142: 107–28.
8 Raine, A, Buchsbaum, M, LaCasse, L. Brain abnormalities in murderers indicated by positron emission tomography. Biol Psychiatry 1997; 42: 495508.
9 Laakso, MP, Vaurio, O, Savolainen, L, Repo, E, Soininen, H, Aronen, HJ, et al. A volumetric MRI study of the hippocampus in type 1 and 2 alcoholism. Behav Brain Res 2000; 109: 177–86.
10 Raine, A, Ishikawa, SS, Arce, E, Lencz, T, Knuth, KH, Bihrle, S, et al. Hippocampal structural asymmetry in unsuccessful psychopaths. Biol Psychiatry 2004; 55: 185–91.
11 George, DT, Rawlings, RR, Williams, WA, Phillips, MJ, Fong, G, Kerich, M, et al. A select group of perpetrators of domestic violence: evidence of decreased metabolism in the right hypothalamus and reduced relationships between cortical/subcortical brain structures in position emission tomography. Psychiatry Res Neuroimaging 2004; 130: 1125.
12 Raine, A, Yang, Y. Neural foundations to moral reasoning and antisocial behavior. Soc Cogn Affect Neurosci 2006; 1: 203–13.
13 Oliveira-Souza, R, Hare, RD, Bramati, IE, Garrido, GJ, Ignacio, FA, Tovar-Moll, F, et al. Psychopathy as a disorder of the moral brain: fronto-temporo-limbic grey matter reductions demonstrated by voxel-based morphometry. Neuroimage 2008; 40: 1202–13.
14 Raine, A, Stoddard, J, Bihrle, S, Buchsbaum, M. Prefrontal glucose deficits in murderers lacking psychosocial deprivation. Neuropsychiatry Neuropsychol Behav Neurol 1998; 11: 17.
15 Bechara, A, Damasio, H, Tranel, D, Damasio, AR. Deciding advantageously before knowing the advantageous strategy. Science 1997; 275: 1293–4.
16 Damasio, AR. A neural basis for sociopathy. Arch Gen Psychiatry 2000; 57: 128–9.
17 Damasio, A. Descartes' Error: Emotion, Reason, and the Human Brain. GP Putnam's Sons, 1994.
18 Viding, E, Jones, AP. Cognition to genes via the brain in the study of conduct disorder. Q J Exp Psychol 2008; 61: 171–81.
19 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 2007; 37: 335–42.
20 Marsh, AA, Finger, EC, Mitchell, DGV, Reid, ME, Sims, C, Kosson, DS, 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: 712–20
21 Mechelli, A, Tognin, S, McGuire, PK, Prata, D, Sartori, G, Fusar-Poli, P, et al. Genetic vulnerability to affective psychopathology in childhood: a combined voxel-based morphometry and functional magnetic resonance imaging study. Biol Psychiatry 2009; 66: 231–7.
22 De Brito, SA, Mechelli, A, Wilke, M, Laurens, KR, Jones, AP, Barker, GJ, et al. Size matters: increased grey matter in boys with conduct problems and callous-unemotional traits. Brain 2009; 132: 843–52.
23 Jones, AP, Laurens, KR, Herba, CM, Barker, GJ, Viding, E. Amygdala hypoactivity to fearful faces in boys with conduct problems and callous-unemotional traits. Am J Psychiatry 2009; 166: 95102.
24 Pansky, B, Allen, DJ, Budd, GC. Review of Neuroscience (2nd edn). Macmillan Publishing Company, 1988.
25 Sarwar, M. The septum pellucidum – normal and abnormal. Am J Neuroradiol 1989; 10: 9891005.
26 Kim, MJ, Lyoo, IK, Dager, SR, Friedman, SD, Chey, J, Hwang, J, et al. The occurrence of cavum septi pellucidi enlargement is increased in bipolar disorder patients. Bipolar Disord 2007; 9: 274–80.
27 Nopoulos, P, Krie, A, Andreasen, NC. Enlarged cavum septi pellucidi in patients with schizophrenia: clinical and cognitive correlates. J Neuropsychiatry Clin Neurosci 2000; 12: 344–9.
28 Swayze, VW, Johnson, VP, Hanson, JW, Piven, J, Sato, Y, Giedd, JN, et al. Magnetic resonance imaging of brain anomalies in fetal alcohol syndrome. Pediatrics 2006; 99: 232–40.
29 Raine, A, Lencz, T, Bihrle, S, LaCasse, L, Colletti, P. Reduced prefrontal gray matter volume and reduced autonomic activity in antisocial personality disorder. Arch Gen Psychiatry 2000; 57: 119–27.
30 Ventura, J, Liberman, RP, Green, MF, Shaner, A, Mintz, J. Training and quality assurance with Structured Clinical Interview for DSM-IV (SCID-I/P). Psychiatr Res 1998; 79: 163–73.
31 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorder (4th edn) (DSM–IV). APA, 1994.
32 First, MB, Spitzer, RL, Gibbon, M, Williams, JBW, Benjamin, L. Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II, Version 2.0). New York State Psychiatric Institute, 1994.
33 Hare, RD. The Hare Psychopathy Checklist–Revised (PCL–R) (2nd edn). Multi-Health Systems, 2003.
34 Raine, A, Lencz, T, Taylor, K, Hellige, JB, Bihrle, S, LaCasse, L, et al. Corpus callosum abnormalities in psychopathic antisocial individuals. Arch Gen Psychiatry 2003; 60: 1142.
35 Yang, YL, Raine, A, Lencz, T, Bihrle, S, LaCasse, L, Colletti, P. Volume reduction in prefrontal gray matter in unsuccessful criminal psychopaths. Biol Psychiatry 2005; 57: 1103–8.
36 Wechsler, D. Wechsler Adult Intelligence Scale – Revised. Psychological Corporation, 1981.
37 Hollingshead, AB. Four Factor Index of Social Status. Yale University, 1975.
38 Rex, DE, Ma, JQ, Toga, AW. The loni pipeline processing environment. Neuroimage 2003; 19: 1033–48.
39 Kwon, JS, Shenton, ME, Hirayasu, Y, Salisbury, DF, Fischer, IA, Dickey, CC, et al. MRI study of cavum septi pellucidi in schizophrenia, affective disorder, and schizotypal personality disorder. Am J Psychiatry 1998; 155: 509–15.
40 May, FS, Chen, QC, Gilbertson, MW, Shenton, ME, Pitman, RK. Cavum septum pellucidum in monozygotic twins discordant for combat exposure: relationship to posttraumatic stress disorder. Biol Psychiatry 2004; 55: 656–8.
41 Gorenstein, EE, Newman, JP. Disinhibitory psychopathy – a new perspective and a model for research. Psychol Rev 1980; 87: 301–15.
42 Potegal, M, Blau, A, Glusman, M. Effects of anteroventral septal lesions on intraspecific aggression in male hamsters. Physiol Behav 1981; 26: 407–12.
43 Siegel, A, Bhatt, S, Bhatt, R, Zalcman, SS. The neurobiological bases for development of pharmacological treatments of aggressive disorders. Curr Neuropharmacol 2007; 5: 135–47.
44 Clemete, CD, Chase, MH. Neurobiological substrates of aggressive behavior. Annu Rev Physiol 1973; 35: 329–56.
45 Veenema, AH, Neumann, ID. Neurobiological mechanisms of aggression and stress coping: a comparative study in mouse and rat selection lines. Brain Behav Evol 2007; 70: 274–85.
46 Insel, TR, Young, LJ. The neurobiology of attachment. Nat Rev Neurosci 2001; 2: 129–36.
47 Bowlby, J. Attachment and Loss: I. Attachment. Hogarth Press, 1969.
48 Rutter, M. Maternal Deprivation Reassessed (2nd edn). Penguin, 1982.
49 Moll, J, Krueger, F, Zahn, R, Pardini, M, Oliveira-Souzat, R, Grafman, J. Human fronto-mesolimbic networks guide decisions about charitable donation. Proc Natl Acad Sci USA 2006; 103: 15623–8.
50 Gao, Y, Raine, A, Chan, F, Venables, PH, Mednick, SA. Early maternal and paternal bonding, childhood physical abuse, and adult psychopathic personality. Psychol Med 2010; 40: 1007–16.
51 Brennan, PA, Grekin, ER, Mednick, SA. Maternal smoking during pregnancy and adult male criminal outcomes. Arch Gen Psychiatry 1999; 56: 215–9.
52 Streissguth, AP, Bookstein, FL, Barr, HM, Sampson, PD, O'Malley, K, Young, JK. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J Dev Behav Pediatr 2004; 25: 228–38.
53 Neugebauer, R, Hoek, HW, Susser, E. Prenatal exposure to wartime famine and development of antisocial personality disorder in early adulthood. JAMA 1999; 282: 455–62.
54 Liu, JH, Raine, A, Venables, PH, Dalais, C, Mednick, SA. Malnutrition at age 3 years and externalizing behavior problems at ages 8, 11 and 17 years. Am J Psychiatry 2004; 161: 2005–13.
55 Gao, Y, Raine, A, Venables, PH, Mednick, SA. Poor fear conditioning at age 3 years predisposes to adult crime at age 23. Am J Psychiatry 2010; 167: 156–60.
56 Olds, D, Henderson, CRJ, Cole, R, Eckenrode, J, Kitzman, H, Luckey, D, et al. Long-term effects of nurse home visitation on children's criminal and antisocial behavior: 15-year follow-up of a randomized controlled trial. JAMA 1998; 280: 1238–44.
57 Raine, A, Venables, PH, Dalais, C, Mellingen, K, Reynolds, C, Mednick, SA. Early educational and health enrichment at age 3–5 years is associated with increased autonomic and central nervous system arousal and orienting at age 11 years: evidence from the Mauritius Child Health Project. Psychophysiol 2001; 38: 254–66.
58 Raine, A, Mellingen, K, Liu, JH, Venables, PH, Mednick, SA. Effects of environmental enrichment at 3–5 years on schizotypal personality and antisocial behavior at ages 17 and 23 years. Am J Psychiatry 2003; 160: 1627–35.
59 van Praag, H, Kempermann, G, Gage, FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999; 2: 266–70.
60 Moffitt, TE. The new look of behavioral genetics in developmental psychopathology: gene–environment interplay in antisocial behaviors. Psychol Bull 2005; 131: 533–54.
61 Viding, E, Jones, AP, Frick, PJ, Moffitt, TE, Plomin, R. Heritability of antisocial behaviour at 9: do callous-unemotional traits matter? Dev Sci 2008; 11: 1722.


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Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy

  • Adrian Raine (a1), Lydia Lee (a2), Yaling Yang (a3) and Patrick Colletti (a4)
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