This is a proposal to study mechanisms of state-dependent change in impulsivity. Understanding of the mechanisms of short term changes in impulsivity will be important in designing means for diagnosis, monitoring, and treatment of the potentially destructive disorders where impulsivity is prominent or where even small changes in impulsivity may have dire consequences. Most existing knowledge concerns impulsivity as a stable trait rather than the near term likelihood of impulsive behavior. The overall hypothesis of this proposal is that state-dependent flucutations in impulsivity are related to changes in noradrenergic function and occur against the backgrand of stable trait-related impulsivity that may depend on serotonergic function. Bipolar disorder provides a model for state-dependent change since increased impulsivity is closely linked to the manic state. Antisocial personality provides a comparison group where impulsivity is less related to affective state. Norepinephrine and its neurophysiological effects are also increased in mania. Effects on event-related potentials provide an objective and readily available measure that is directly related to the CNS. Based on this model, we will investigate whether short term changes in impulsivity are related to changes in noradrenergic activity and its neurophpysiological consequences. State-related changes in impulsivity will be measured using behavioral laboratory methods that our group has developed.
The Specific Aims are 1) to compare state and trait measures of impulsivity, noradrenergic function, and event-related potentials (sensory gating) in euthymic and manic subjects with bipolar disorder, subjects with antisocial personality disorder, and healthy control subjects, 2) to investigate effects of pharmacologically decreasing noradrenergic function with clonidine in manic subjects with bipolar disorder and in subjects with antisocial personality disorder, with the hypothesis that there will be parallel reductions in plasma MHPG, state-related impulsivity, and sensory gating impairment, 3) to investigate effects of pharmacologically increased noradrenergic activity by yohimbine in subjects with antisocial personality disorder and healthy controls, with the hypothesis that there will be parallel increases in the same parameters reduced in manic subjects by clonidine in AIM 2, and 4) in AIMS 2 and 3 we will investigate the relationship between baseline trait-like impulsivity and the sensitivity of impulsivity to changes in noradrenergic function. The results of these experiments may suggest means for monitoring risk for impulsive behavior and for a rational treatment schema for impulsivity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH069944-05
Application #
7588818
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Meinecke, Douglas L
Project Start
2005-04-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2011-03-31
Support Year
5
Fiscal Year
2009
Total Cost
$299,210
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Psychiatry
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Lijffijt, Marijn; Lane, Scott D; Moeller, F Gerard et al. (2015) Trait impulsivity and increased pre-attentional sensitivity to intense stimuli in bipolar disorder and controls. J Psychiatr Res 60:73-80
Henna, Elaine; Hatch, John P; Nicoletti, Mark et al. (2013) Is impulsivity a common trait in bipolar and unipolar disorders? Bipolar Disord 15:223-7
Swann, Alan C; Lijffijt, Marijn; Lane, Scott D et al. (2013) Pre-attentive information processing and impulsivity in bipolar disorder. J Psychiatr Res 47:1917-24
Swann, Alan C; Lijffijt, Marijn; Lane, Scott D et al. (2013) Norepinephrine and impulsivity: effects of acute yohimbine. Psychopharmacology (Berl) 229:83-94
Swann, Alan C; Lijffijt, Marijn; Lane, Scott D et al. (2013) Antisocial personality disorder and borderline symptoms are differentially related to impulsivity and course of illness in bipolar disorder. J Affect Disord 148:384-90
Lijffijt, Marijn; Cox, Blake; Acas, Michelle D et al. (2012) Differential relationships of impulsivity or antisocial symptoms on P50, N100, or P200 auditory sensory gating in controls and antisocial personality disorder. J Psychiatr Res 46:743-50
Swann, Alan C; Lijffijt, Marijn; Lane, Scott D et al. (2011) Criminal conviction, impulsivity, and course of illness in bipolar disorder. Bipolar Disord 13:173-81
Swann, Alan C; Lijffijt, Marijn; Lane, Scott D et al. (2011) Interacting mechanisms of impulsivity in bipolar disorder and antisocial personality disorder. J Psychiatr Res 45:1477-82
Swann, Alan C (2011) Antisocial personality and bipolar disorder: interactions in impulsivity and course of illness. Neuropsychiatry (London) 1:599-610
Swann, A C; Lijffijt, M; Lane, S D et al. (2010) Interactions between bipolar disorder and antisocial personality disorder in trait impulsivity and severity of illness. Acta Psychiatr Scand 121:453-61

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