Over the last 4 years since the funding of this project, the UT Houston SAR-MDC has shown that cocaine dependence is associated with behavioral deficits including decision-making, behavioral inhibition, and the broader clinical construct of impulsivity. Likewise, we found differences between cocaine dependent subjects and non-drug using controls on Magnetic Resonance Imaging (MRI) measures of brain structure and function. In addition, we have acquired data showing that within cocaine users there is an association between these behavioral deficits and alterations in brain structure, brain function, and poor treatment response. For the renewal of this project, the focus will advance to determining the specific role of these brain MRI findings in treatment outcome by means of a carefully chosen battery of functional and structural MRI techniques in order to predict treatment response to specific classes of medication based on mechanism of action. Our previous blood oxygen level dependent (BOLD) fMRI data showed that cocaine dependent subjects (relative to controls) have (1) less dorsolateral prefrontal cortical, striatal, and thalamic activation during a working memory task, possibly reflecting impaired dopamine function;(2) greater activation in medial orbitofrontal cortex during impulsive responding on a Go-Nogo task, possibly reflecting impaired serotonin function;and (3) greater activation in medial orbitofrontal cortex and medial frontal cortex after negative feedback on a reversal learning task, also possibly reflecting impairment of serotonin function. In order to follow-up the treatment implications of this data, this project will examine (a) pretreatment brain activation on these tasks as predictors of neurotransmitter-specific treatment response, and (b) eariy changes (after three weeks of pharmacotherapy) in task-related fMRI activation as predictors of subsequent longer-term neurotransmitter-specific treatment response. In addition, the relationship between treatment response and measures of white-matter structural integrity as measured by diffusion tensor MRI (DTI) and magnetization transfer ratio MRI (MTR) will be examined.

Public Health Relevance

In spite of the significant public health concerns regarding cocaine dependence, there is as yet no FDA approved medication for the disorder. If a greater understanding of the basic neurobiology of the effects of chronic cocaine use on the human brain can be gained from this study it would be significant and could lead to the development of new medications for cocaine dependence.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Specialized Center (P50)
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Special Emphasis Panel (ZDA1-EXL-T)
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University of Texas Health Science Center Houston
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D'Souza MA, Johann M; Wardle PhD, Margaret; Green PhD, Charles E et al. (2018) Resting Heart Rate Variability: Exploring Associations With Symptom Severity in Adults With Substance Use Disorders and Posttraumatic Stress. J Dual Diagn :1-6
Vujanovic, Anka A; Wardle, Margaret C; Bakhshaie, Jafar et al. (2018) Distress tolerance: Associations with trauma and substance cue reactivity in low-income, inner-city adults with substance use disorders and posttraumatic stress. Psychol Addict Behav 32:264-276
Miller, William R; Fox, Robert G; Stutz, Sonja J et al. (2018) PPAR? agonism attenuates cocaine cue reactivity. Addict Biol 23:55-68
Vujanovic, Anka A; Smith, Lia J; Green, Charles E et al. (2018) Development of a novel, integrated cognitive-behavioral therapy for co-occurring posttraumatic stress and substance use disorders: A pilot randomized clinical trial. Contemp Clin Trials 65:123-129
Ma, Liangsuo; Steinberg, Joel L; Wang, Qin et al. (2017) A preliminary longitudinal study of white matter alteration in cocaine use disorder subjects. Drug Alcohol Depend 173:39-46
Schmitz, Joy M; Green, Charles E; Hasan, Khader M et al. (2017) PPAR-gamma agonist pioglitazone modifies craving intensity and brain white matter integrity in patients with primary cocaine use disorder: a double-blind randomized controlled pilot trial. Addiction 112:1861-1868
Wardle, Margaret C; Vincent, Jessica N; Suchting, Robert et al. (2017) Anhedonia Is Associated with Poorer Outcomes in Contingency Management for Cocaine Use Disorder. J Subst Abuse Treat 72:32-39
Vujanovic, Anka A; Rathnayaka, Nuvan; Amador, Christina D et al. (2016) Distress Tolerance: Associations With Posttraumatic Stress Disorder Symptoms Among Trauma-Exposed, Cocaine-Dependent Adults. Behav Modif 40:120-43
Vujanovic, Anka A; Wardle, Margaret C; Liu, Shijing et al. (2016) Attentional bias in adults with cannabis use disorders. J Addict Dis 35:144-53
Ahn, Woo-Young; Ramesh, Divya; Moeller, Frederick Gerard et al. (2016) Utility of Machine-Learning Approaches to Identify Behavioral Markers for Substance Use Disorders: Impulsivity Dimensions as Predictors of Current Cocaine Dependence. Front Psychiatry 7:34

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