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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH064783-04
Application #
7151120
Study Section
Special Emphasis Panel (ZRG1-BDCN-5 (01))
Program Officer
Meinecke, Douglas L
Project Start
2003-12-01
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2008-11-30
Support Year
4
Fiscal Year
2007
Total Cost
$234,967
Indirect Cost
Name
Nathan Kline Institute for Psychiatric Research
Department
Type
DUNS #
167204762
City
Orangeburg
State
NY
Country
United States
Zip Code
10962
Lee, M; Sehatpour, P; Hoptman, M J et al. (2017) Neural mechanisms of mismatch negativity dysfunction in schizophrenia. Mol Psychiatry 22:1585-1593
Li, Hui-Jie; Xu, Yong; Zhang, Ke-Rang et al. (2015) Homotopic connectivity in drug-naïve, first-episode, early-onset schizophrenia. J Child Psychol Psychiatry 56:432-43
Kantrowitz, Joshua T; Hoptman, Matthew J; Leitman, David I et al. (2015) Neural Substrates of Auditory Emotion Recognition Deficits in Schizophrenia. J Neurosci 35:14909-21
Hoptman, Matthew J (2015) Impulsivity and aggression in schizophrenia: a neural circuitry perspective with implications for treatment. CNS Spectr 20:280-6
Kantrowitz, J T; Hoptman, M J; Leitman, D I et al. (2014) The 5% difference: early sensory processing predicts sarcasm perception in schizophrenia and schizo-affective disorder. Psychol Med 44:25-36
Hoptman, Matthew J; Zuo, Xi-Nian; D'Angelo, Debra et al. (2012) Decreased interhemispheric coordination in schizophrenia: a resting state fMRI study. Schizophr Res 141:1-7
Antonius, Daniel; Prudent, Vasthie; Rebani, Yasmina et al. (2011) White matter integrity and lack of insight in schizophrenia and schizoaffective disorder. Schizophr Res 128:76-82
Nolan, Karen A; D'Angelo, Debra; Hoptman, Matthew J (2011) Self-report and laboratory measures of impulsivity in patients with schizophrenia or schizoaffective disorder and healthy controls. Psychiatry Res 187:301-3
Bell, Ryan P; Foxe, John J; Nierenberg, Jay et al. (2011) Assessing white matter integrity as a function of abstinence duration in former cocaine-dependent individuals. Drug Alcohol Depend 114:159-68
Hoptman, Matthew J; Antonius, Daniel (2011) Neuroimaging correlates of aggression in schizophrenia: an update. Curr Opin Psychiatry 24:100-6

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