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.
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.
|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|
|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|
|Azadeh, Shabnam; Hobbs, Brian P; Ma, Liangsuo et al. (2016) Integrative Bayesian analysis of neuroimaging-genetic data with application to cocaine dependence. Neuroimage 125:813-824|
|Sharma, Jyoti; Rathnayaka, Nuvan; Green, Charles et al. (2016) Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding. Behav Med 42:1-8|
Showing the most recent 10 out of 88 publications