Impulsive behavior in the mentally ill carries tremendous costs including increased violence risk lengthened hospital stays, increased ward turmoil, and complicated treatment planning. Impulsivity is associated with high risk behaviors including violent behavior, sexual promiscuity, and substance abuse. Because dysfunctions associated with impulsivity have been found in the frontal lobes and regions with which they share rich connections, it has long been hypothesized that impulsive behavior is related to impaired connectivity between frontal and other regions. White matter (WM) brain regions contain the main connections between brain regions. Thus, WM integrity in frontal regions might be disrupted in impulsive individuals. Diffusion tensor imaging (DTI) is a technique that can provide quantitative assessment of the structural integrity of white matter. Water diffusion in neurons tends to follow the long axis of the axon. This diffusion is referred to as anisotropic. DTI-derived measures include fractional anisotropy (FA), which is a quantitative measure diffusion anisotropy. Lower FA in WM is thought to reflect compromised fiber integrity. In our initial studies on 35 men with schizophrenia, we found a significant negative correlation between inferior frontal WM FA and clinical measures of impulsivity. Moreover, when patients were grouped according to high and low levels of impulsivity, the high impulsivity group had lower FA in inferior frontal WM. The decrease in FA in high impulsive patients suggests a disruption in WM integrity in these regions. Decreased inferior frontal WM FA also was negatively correlated with measures of aggression. We propose to examine the relationship between impulsivity and inferior frontal WM integrity in 60 patients with schizophrenia and 60 age- and gender-matched healthy controls. Impulsivity will be assessed with self rating scales and neurocognitive tests of response inhibition. Participants will be divided into high and low impulsivity groups. We predict that inferior frontal WM FA will be lower in the high than low impulsivity group: Experimental measures of response inhibition will be used to further our understanding of the impulsivity/WM relationship. A secondary aim will examine the relationship between FA and violence. Understanding the neural basis of impulsivity in schizophrenia would help identify at-risk patients and inform new treatment approaches.
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