Subtle deficits in the prefrontal cortex of antisocial, violent men who were not institutionalized were found in a study reported in the February Archives of General Psychiatry.

The study showed that the volume of prefrontal gray matter was significantly smaller in men with antisocial personality disorder (APD) than in two groups of controls—one made up of men with a history of drug and alcohol abuse, the other men with no such history. The men with APD also exhibited lower autonomic activity while performing a stressful exercise than did the controls.

The study was believed to be the first to use magnetic resonance imaging to assess brain structure in antisocial personality disorder, the researchers noted. Its findings extend previous studies that correlated damage to prefrontal gray and white matter with violent, antisocial behavior. Unlike most previous research, however, the new study does not focus on subjects who had suffered gross brain damage. It is also unusual in its use of community volunteers who admitted to committing violent acts rather than institutionalized offenders.

Most previous studies did not control for comorbid psychiatric conditions associated with structural brain abnormalities, such as affective and schizophrenia-spectrum disorders. Adrian Raine, D.Phil., and his colleagues at the University of Southern California in Los Angeles attempted to control for this confounding factor by forming a psychiatric control group. They matched the comorbid clinical conditions of the 21 subjects in the APD group with 21 subjects from the other two groups. Again, the APD group was found to have lower mean volumes of prefrontal gray matter than the psychiatric control group.

Raines and his colleagues evaluated autonomic arousal because research has shown that patients with antisocial personality disorder respond to socially meaningful events with low levels of arousal and attention. These responses are consistent with the role of the prefrontal cortex in modulating emotion, arousal, and attention, they note.

To test autonomic activity, the California investigators asked subjects to prepare a speech describing their own faults. Heart rate and skin conductance were measured while the subjects read their speeches to the experimenter in a videotaped session. The research team found that among subjects with antisocial personality disorder, those who had deficits in prefrontal gray matter volume had reduced skin conductance activity but not reduced heart rate.

Raines and his colleagues offer several hypotheses for how prefrontal and autonomic deficits could predispose an individual to antisocial behavior.

First, the prefrontal cortex is part of a neural circuit that is central to fear conditioning and response to stress. Poor conditioning is theoretically associated with poor development of conscience. When subjected to social criticism and other aversive stimuli, a person with low arousal could be less susceptible to socialization.

Second, deficits in autonomic and central nervous system arousal may make a person seek stimulation and engage in antisocial behavior to compensate for the underarousal.

Third, patients with prefrontal damage are prone to making bad choices because they fail to give anticipatory autonomic responses when presented with risky options.

Raines and his colleagues acknowledge that they did not delineate which part of the prefrontal cortex is reduced in ADP, nor did they measure other brain areas. The study demonstrates a correlation, not causality, they warn. They also emphasized that psychological and social factors interact with the multiple brain systems to produce behavior.

In a commentary that accompanies the article, Antonio R. Damasio, M.D., of the University of Iowa College of Medicine noted the difficulty of establishing the existence of neuropathology in the development of sociopathy. He cautioned against ascribing antisocial behavior solely to prefrontal dysfunction.

"One must be careful," he wrote, "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."