Browsing by Subject "Cocaine-Related Disorders"
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Item Examining the Relationship between Impulsive Personalities and Neural Functioning in Cocaine-Addicted Participants(2013-05-17) Jester, Bryan Elliott; Adinoff, BryonBACKGROUND: Those who suffer from addiction are unable to discontinue use despite serious consequences affecting their social, professional, and family lives. Individuals who suffer from the disorder often alienate themselves from loved ones and lose their jobs. Addiction involves continuing a behavior despite severe negative consequences. Numerous studies have identified a relationship between impulsivity and the development of substance abuse. This study examines the relationship of impulsive personality facets and neural functioning associated with inhibition. SUBJECTS: The study sample included 24 healthy control participants and 56 cocaine-addicted participants. Participants ranged in age from 25 to 54 years old with a mean age of 43.27 (±SD 7.84). The group was comprised of 68 male and 12 female participants, 28.7% self identified as Caucasian, 66.3% African American, 3.8% Hispanic, and 1.3% Asian/Other. Healthy controls and cocaine-addicted participants were similar in age and race but differed in gender (p= .02). The control group had 17 males and 7 females while the cocaine-addicted group had 51 males and 5 females. METHODS: Demographic information was gathered for all participants. Each participant also completed a Neuroticism Extroversion and Openness (NEO) personality measure and Temperament and Character Inventory (TCI), Structured Clinical Interview for DSM-IV (SCID), Wechsler Test of Adult Reading (WTAR). They then performed the stop signal task (SST) during functional magnetic resonance imaging (fMRI) to gather data on neural activation during Stop-Success (SS) and Stop-Failure (SF). fMRI data was analyzed using FSL imaging software. All statistics were run with SPSS software. Functional ROIs were identified and analyzed in fMRI Expert Analysis Tool query (FEATqueary) to gather data on each participantÕs change in blood oxygen level dependent (BOLD) activation during Stop-Success (SS) and Stop-Failure (SF). Impulsive personality facets were then used to identify relationships between BOLD activations of the ROIs. RESULTS: Between group comparisons found significant differences in mean scores on all of the impulsive personality facets except for Exploratory Excitability and Persistence from the TCI, and Excitement Seeking from the NEO. Neuroimaging results are similar to other studies utilizing the SST finding changes in activation of the middle frontal gyrus, superior frontal gyrus, cingulate gyrus, medial frontal gyrus, insula, caudate and supramarginal gyrus during Stop-Failure; and superior parietal lobule, middle frontal gyrus, precuneus, supramarginal gyrus, inferior temporal gyrus, and middle occipital gyrus during Stop-Success. However, no differences in BOLD activation between groups were observed. Numerous relationships were identified between the personality facets and BOLD activation of the regions of interest (ROIs). To further elucidate this relationship between neural functioning and personality a principal component analysis (PCA) was conducted on all eleven personality facets. The PCA allowed for the identification of an impulse control personality component and an impulse drive personality component. A significant interaction with the impulse drive and the left posterior hippocampus was identified. DISCUSSION: This study allowed for the examination of how impulsive personality facets relate to, or interact with, neural functioning during a task designed to measure inhibition. Despite failing to find a difference in activation of the ROIs between cocaine-addicted participants and healthy controls, the study successfully identified the cocaine-addicted group to have a significantly more impulsive personality than healthy controls. It also identified numerous relationships between the personality facets and neural functioning. This gives credence to the idea that neural functioning and personalities are associated in some way. Reverse relationships were observed between the groups in the relationships between the Impulse Drive personality component and SF activation of the hippocampus; and the TCI facet of Purposefulness and SS activation of the right thalmus. These reverse relationships may signify a difference between the groups that may either predispose the cocaine-addicted participants to developing substance abuse, or it may be a neuro-functional change that has resulted due to prolonged exposure to cocaine.Item The Impact of Cognition on Treatment Adherence in Comorbid Bipolar Disorder and Cocaine Dependence(2013-01-17) Fagan, Colleen Susan; Brown, E., Sherwood, M.D., Ph.D.Although bipolar disorder and substance dependence are associated with treatment nonadherence and cognitive impairment, few studies have investigated the relationship between treatment adherence and cognitive functioning. Participants in this study were 120 outpatients with bipolar disorder and cocaine dependence enrolled in a 10 week randomized, double-blind, placebo controlled trial of lamotrigine. Baseline performance on the Stroop Color and Word Test and the Rey Auditory Verbal Learning Test were examined for their effect on retention, appointment attendance, medication adherence, and return of medication bottles. Participants with decreased scores on Word condition of the Stroop Color and Word Test were more likely and those with decreased Interference scores were as likely to attend appointments. Participants with better Rey Auditory Verbal Learning Test Total Recall scores returned more medication bottles. Cognitive functioning did not impact medication adherence or study retention. The findings suggest a relationship between cognitive functioning and treatment attendance. Assessment and treatment of cognitive dysfunction may identify and help patients at-risk for treatment nonadherence. Future studies with a more comprehensive neuropsychological test battery and advanced medication adherence measures are warranted.Item Mu-Opioid Receptors involvment in Cocaine addiction(2009-06-19) Simmons, Diana Lynn; Self, David W.The nucleus accumbens (NAc) receives dopaminergic input from the ventral tegmental area (VTA) and is intricately involved in the reinforcing properties of cocaine. Mu-opioid receptors (MOR) are highly expressed in the NAc and act to modulate glutamatergic and dopaminergic input in response to various stimuli. Chronic cocaine self-administration may modulate MOR expression and mediate increased craving and relapse that characterizes cocaine addiction. Chapter 3 determined MOR regulation by cocaine administration. Both contingent and non-contingent cocaine administration decrease MOR specifically in the core while delta opioid receptors (DOR) were not altered by chronic cocaine. Cocaine self-administration mediated down-regulation of MOR was ?-endorphin dependent since blockade of ?-endorphin prevented MOR phosphorylation, down-regulation, and endocytosis. Chapter 4 determined whether opioid receptor stimulation was sufficient to reinstate drug-seeking behaviors in extinguished animals. Both MOR and DOR specific agonists (DAMGO and DPDPE, respectively) induced cocaine seeking as did the endogenous opioids, ?-endorphin and endogenously released enkephalins. Blockade of MOR decreased cocaine-primed reinstatement, indicating MOR involvement in drug-primed reinstatement. Chapter 5 identified long-term neuroadaptations possibly involved in high craving and relapse rates typically seen in humans and modeled in animals. MOR expression increased with withdrawal time indicating a potential correlate of time-dependent increases in cocaine seeking in withdrawal. To determine whether the up-regulation of MOR translated into enhanced cocaine-seeking behavior, MOR stimulated locomotor activity and cocaine-seeking/reinstatement was assessed. Locomotor behavior in response to intra-NAc DAMGO infusions did not change after long-term withdrawal, however there were age variables that may have contributed to the negative data. When drug-seeking was assessed at 6 w withdrawal, animals had increased drug-seeking behavior compared to 1 w withdrawal animals, an effect that was potentiated by intra-NAc ?-endorphin. DAMGO increased relapse to cocaine-seeking at 6 w withdrawal with no effect at 1 w withdrawal. ?-endorphin primed reinstatement was similar in both groups however the effect was only significant in the 6 w withdrawal group. These findings indicate NAc MOR is regulated by cocaine self-administration and withdrawal and stimulation of MOR results in drug craving and relapse behaviors. Results further indicate a potential target in the treatment of cocaine addiction.Item Neural Activity during the Stop Signal Task, a Disinhibition Task, Predicts Relapse in Cocaine-Dependent Patients(2013-08-01) Vo, Lan Chi Le; Adinoff, BryonKeywords: neuroimaging, addiction, cocaine, relapse, impulsivity, disinhibition, stop signal task, SST, fMRI Background: Relapse is a prevalent phenomenon in addiction. Impaired inhibitory control is associated with relapse and is a significant predictor of cocaine use and treatment retention. Objective: Functional magnetic resonance imaging (fMRI) was used to examine the association between BOLD response during the Stop Signal Task (SST, a measure of inhibitory control), and time to relapse in cocaine-dependent patients. Methods: Forty-nine 2-4 weeks abstinent cocaine-dependent participants were assessed and then followed weekly for up to 26 weeks as outpatients. Relapse was defined as any use of cocaine during the follow up period. The patients were categorized into 27 individuals in the relapse group (relapsed within 30 days) and 22 in the non-relapse group (did not relapse at 30 days). BOLD response during successful inhibition (“StopSuccess”) during SST was compared between groups (z>2.3, p=0.05). Regions of interest (ROIs) were also identified using mean percent BOLD signal change in the combined patient group. Percent BOLD change values were calculated within the significantly activated voxels during StopSuccess (voxel-based analysis, P = 0.15). Identified clusters were used in discriminant analysis through the Statistical Product and Service Solutions software to predict group membership. Results: Consistent with our hypothesis, the study found BOLD changes during the SST that were able to predict those who relapse from those who did not. Specifically, the left lateral occipital cortex exhibited greater BOLD activation in the relapse group than the non-relapse group. On the other hand, the relapse group had lower BOLD activation in the left lateral orbitofrontal cortex and left anterior insula. Using discriminant analysis, these two regions of interest were able to classify 76.9% of individuals into their respective groups correctly with cross-validation. Conclusion: The left lateral occipital cortex, left lateral orbitofrontal cortex and left anterior insula can be used to identify those at risk of relapse and offer insights into mechanisms of relapse.Item Neural Dysfunction during Decision-Making as a Predictor of Cocaine Relapse(2013-01-17) Braud, Jacquelyn Ashley; Adinoff, Bryon, M.D.Cocaine dependence is a costly disorder characterized by recurrent relapse events. The current investigation used functional magnetic resonance imaging (fMRI) during a decision-making task to predict relapse to drug use in a cocaine-dependent sample. Forty-five treatment-seeking cocaine-dependent subjects, two to four weeks abstinent, and 23 healthy control subjects underwent 3T fMRI. The Response Reversal Task was administered in the scanner to elicit decision-making processes. Individuals were followed for up to six months post-discharge from inpatient substance use treatment to determine time-to-relapse. Seventy-eight percent of the patient sample relapsed an average of 35 days after treatment; ten individuals did not relapse during the follow-up period. No group differences were found between healthy control and cocaine-addicted groups in activation patterns or behavioral measures of decision-making performance. Mean percent BOLD signal change in the patient group was used to identify regions of interest (ROIs) for discriminant analyses to classify patients by short- and long-term relapse. The fMRI activation patterns in the precuneus, bilateral orbitofrontal cortex, left insula, right dorsolateral prefrontal cortex, paracingulate, left hippocampus, and bilateral amygdala correctly classified 71% of patients by short-term and long-term relapse. This investigation suggests that neuroimaging may be a valid predictor of cocaine relapse, which could allow for better individual tailoring of treatment options for improving long-term abstinence.Item The Role of Adult Neurogenesis in Cocaine Addiction(2009-01-14) Noonan, Michele Ann; Eisch, AmeliaNew neurons are born in the adult hippocampus in a region known as the subgranular zone (SGZ). This process is dynamically regulated and new neurons are thought to be important for certain types of spatial learning and memory. Proliferation of SGZ neural progenitors is decreased by drugs of abuse, yet it is not clear how the type and amount of drug as well as the pattern of administration changes long-term effects on neurogenesis. In addition, it is unclear what role if any SGZ neurogenesis plays in initiating drug-taking or relapse behaviors, or whether changes in neurogenesis are merely side effects of drug-taking. I first examined effects of chronic cocaine self-administration and withdrawal on the different stages of neurogenesis. I found an early deficit in proliferation of neural progenitors, as well as a 4 week delayed increase in doublecortin-positive (DCX+) immature neurons which were common to both rats in withdrawal or those continuing to self-administer cocaine. I next asked the question of the functional consequence of changes in adult hippocampal neurogenesis to the acquisition and maintenance of drug-taking, as well as relapse to drug-taking. I found that reduced adult neurogenesis via cranial irradiation prior to cocaine-taking was associated with increased acquisition of drug-taking and increased motivation for cocaine, but not sucrose, while reduced adult neurogenesis after rats have acquired cocaine self-administration was associated with increased resistance to extinction of drug-seeking behavior. Finally, I asked if formation of drug-context associations would be altered in rodents with reduced neurogenesis in a passive drug exposure paradigm. I found that a transgenic mouse with reduced adult neurogenesis has impaired long-term drug-context memory in the cocaine conditioned place preference paradigm (CPP). Together these findings suggest that reduced adult hippocampal neurogenesis is a risk factor for drug addiction, that decreased proliferation after chronic drug intake likely contributes to drug-taking and drug-seeking behaviors, and that the delayed increase in immature neurons after drug-taking is likely protective against relapse. In sum, increases in adult hippocampal neurogenesis are beneficial both to the naïve and addicted brain, and therapeutics specifically increasing adult neurogenesis could aid in preventing initial addiction as well preventing future relapse.