A Neural Basis for Sociopathy

THE IDEA that the structures of the frontal lobe play a critical role in normal social behavior is now well established. The association was first gleaned more than a century ago thanks to the case of Phineas Gage, in whom focal damage to unspecified frontal regions (Gage died without an autopsy and only his skull was recovered) resulted in a sudden and profound change of personality marked by inappropriate social behavior. More recently, it has become clear that several sectors of the prefrontal cortex contribute to the acquisition and manipulation of the type of knowledge on which adaptive social behaviors depend. Some prefrontal sectors (in particular, those that are located in the orbital and medial surfaces of the frontal lobes) seem to play an indispensable role in the achievement and maintenance of a normal social personality. Lesions that compromise these frontal sectors or their subjacent white matter that are located either bilaterally or only in the right hemisphere impair the ability to make appropriate decisions in the personal and social realms.^{1 - 4}

Curiously, the contemporary reconstruction of Phineas Gage's brain using modern neuroimaging techniques suggests that his brain lesion encompassed medial and orbital territories.⁵ In short, there is now abundant evidence that adult-onset lesions in the human prefrontal cortices lead to maladaptive social behavior characterized by systematic violations of social conventions and even moral rules. Prior and proper acquisition of social knowledge, as well as normal exercise of such knowledge up to the time when lesions occur, does not preclude the onset of abnormal social behavior, provided the requisite prefrontal regions are rendered dysfunctional.^{6 - 9}

The evidence from brain lesions has contributed to the fundamental elucidation of the functions of the prefrontal cortex and has had an important practical consequence: the development of a workable hypothesis concerning one possible origin of sociopathic behavior, and more specifically, the neural basis of antisocial personality disorders. While it is true that the social inappropriateness of patients with adult-onset prefrontal damage tends not to include violent and criminal behavior, it is apparent that the altered social profile seen in the neurological patients resembles, in many respects, the features noted in lifelong developmental sociopathic individuals. It is thus reasonable to hypothesize that the symptoms of developmental sociopathic individuals are related to the malfunction of neural systems, which include critical components in the prefrontal cortex.

Uncovering support for this intriguing hypothesis is not easy, given the paucity of any obvious neuropathologic signature in developmental sociopathy. Yet that is precisely what Raine et al¹⁰ offer in a persuasive article in this issue of the ARCHIVES. Based on systematic measurements of gray and white matter volumes obtained from magnetic resonance studies, Raine et al demonstrate that men with a diagnosis of antisocial personality disorder have a significantly reduced amount of prefrontal gray matter when compared with normal men or with drug- or alcohol-dependent men without antisocial personality disorder. Although the authors do not trace the significant reduction to a specific prefrontal sector, the mere fact that the reduction is related to the prefrontal region is valuable and suggestive. It may be possible to inquire in follow-up studies if the reduction is in fact due to a disproportionate diminution of prefrontal sectors, such as the orbital and medial territories. Be that as it may, the current result does identify a potential neuropathologic signature consonant with the neurological results. Should other authors replicate the presence of this anatomical trait in comparable subject groups, the finding will indeed be remarkable.

The authors were careful to assess psychiatric comorbidity (eg, schizophrenia spectrum or affective and nonantisocial personality disorders), and they show that their developmental sociopathy group had, if anything, a lower rate of such comorbidity. This is noteworthy, because should the replications indicate that the finding is not present in other psychiatric populations, then we would be dealing with a notable advance in the understanding of mental diseases.

Raine et al report another finding that adds weight to their effort to tie antisocial personality disorder to the current neurological evidence. Relative to the control groups, their antisocial group exhibited reduced skin-conductance responses and heart rates during the performance of a task that required them to read to the examiner a self-prepared recitation of their flaws and failures. The fact that this aptly chosen social stressor did not cause the autonomic responses commonly seen in a normal population establishes the selective emotional disturbance of these individuals, a disturbance that sets in at the level of secondary emotions, such as embarrassment and guilt. This disturbance is comparable with the one we have studied in neurological patients with selective prefrontal damage; even the psychophysiologic defects are similar.

It would not be prudent to conclude from this study and from previous neurobiological studies that inappropriate social behavior is solely a consequence of prefrontal dysfunction caused by acquired lesions or a consequence of structural and functional defects caused by genetic factors, development factors, or both. But the evidence presented in the study by Raine et al, along with the neurological evidence from adult-onset lesions and, quite recently, the demonstration that early-onset prefrontal damage leads to a condition nearly indistinguishable from developmental antisocial personality,¹¹ indicates that malfunctioning circuitry in certain prefrontal sectors can cause these behavioral manifestations. One must be careful, however, not to fall in the phrenological trap set behind every new identification of a brain area with some putative role: the normal or pathologic effects associated with that certain area can be properly understood only in the context of multicomponent neural systems. As a consequence, the normal or pathologic effects related to a given area are quite often the result of actions elsewhere in the brain. In the case of antisocial personality disorder, the malfunction of prefrontal circuits is probably accompanied by malfunction in varied subcortical territories (eg, in amygdala, in brainstem nuclei, in certain sectors of basal ganglia and basal forebrain), and in higher-order association cortices outside of the frontal region. Whatever comprehensive explanation we may formulate for such disorders will have to not only take into account the operation of these large-scale systems but also consider the many factors likely to shape the assembly and eventual operation of these systems. Those factors range from the level of molecules and neurons to the level of social and cultural phenomena that impinge on the life of whole individuals.