Biomedical subjects

Rajita Sinha

Publications and source records attributed to Rajita Sinha.

At least 19 recordsLinked to original sources

PubMed2006

Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings.

OBJECTIVE: A preliminary study examined whether lofexidine decreases stress-induced and cue-induced opioid craving and improves opioid abstinence in naltrexone-treated opioid-dependent individuals. MATERIALS AND METHODS: Eighteen opioid-dependent patients were stabilized for 4 weeks with naltrexone (50 mg daily) and lofexidine (2.4 mg bid) before entering a 4-week randomized, double-blind placebo-controlled discontinuation study where one group continued on lofexidine for an additional 4 weeks, while the second was tapered to placebo (Lofexidine-naltrexone vs Placebo-naltrexone). Ten patients also participated in guided imagery exposure to stress, drug cue, and neutral scenarios in a single laboratory session. RESULTS: Lofexidine-naltrexone patients had higher opioid abstinence rates and improved relapse outcomes as compared to the Placebo-naltrexone group. Furthermore, Lofexidine-naltrexone patients had significantly lower heart rates and an attenuated stress and drug cue-induced opioid craving response in the laboratory as compared to the Placebo-naltrexone group. CONCLUSIONS: Although preliminary, these findings are the first to document lofexidine's potential in addressing stress-related opioid craving and relapse outcomes in humans. The results also suggest that combination therapies that target both drug-related reinforcement (naltrexone) and stress- and cue-related aspects of drug seeking could be beneficial in addiction relapse prevention. Further development of lofexidine to address stress-related opioid craving and relapse is warranted.

Adult↗

PubMed2006

Gender differences in the neural correlates of response inhibition during a stop signal task.

We used functional magnetic resonance imaging to examine gender differences in the neural correlates of response inhibition during a stop signal task. The task has a frequent "go" signal to set up a pre-potent response tendency and a less frequent "stop" signal for subjects to withhold their response. A contrast in brain activation was made between successful and failed inhibitions for individual subjects. We compared 20 men and 20 women matched in age and years of education and in stop signal performance, with stop success rate, post-error slowing and task-related frustration ratings as covariates. The results showed greater activation in men, compared to women, in a wide array of cortical and subcortical areas, including the globus pallidus and motor thalamus during stop signal inhibition. In contrast, no brain regions demonstrated greater activation in women, even at a lower statistical threshold. Moreover, while men activated the medial superior frontal and anterior cingulate cortices, women activated the caudate tail to mediate response inhibition. These results extended gender differences in regional brain activation to response inhibition during a cognitive motor task. Men activated the motor circuitry while women appeared to involve visual association or habit learning during stop signal performance.

Adult↗

PubMed2006

Performance monitoring and stop signal inhibition in abstinent patients with cocaine dependence.

Impulsivity has been associated with drug abuse and relapse. As a measure of impulsivity, response inhibition in a stop signal task is impaired in substance abusers compared to healthy control subjects. However, cognitive processes besides response inhibition can affect performance in the stop signal task. Greater response readiness to the go signal increases stop signal reaction time (SSRT) and greater performance monitoring elicited by the stop signal decreases SSRT. Prolonged SSRT, therefore, may reflect differences in these other task-related cognitive processes rather than impaired response inhibition. Using a tracking stop-signal task, we compared 18 abstinent cocaine dependent patients with 41 age- and education-matched healthy controls. We computed SSRT for each individual subject on the basis of the horse race model. We also computed the fore-period (FP) effect to measure response readiness to the go signal and the post-signal slowing (PSS) effect to measure performance monitoring to the stop signal. Cocaine subjects showed increased SSRT and decreased PSS effect, compared to healthy controls. Covariance adjustment for the PSS effect eliminated the SSRT difference from healthy controls. These results suggest that diminished performance monitoring can be a critical cognitive mechanism underlying impaired response inhibition in cocaine dependent patients.

Adult↗

PubMed2006

Gender differences in cardiovascular and corticoadrenal response to stress and drug cues in cocaine dependent individuals.

RATIONALE: Extensive research suggests that gender may affect neuroendocrine and cardiovascular arousal mechanisms underlying biological responses to stress. OBJECTIVE: To examine the impact of gender on response to stress and to drug-cue exposure in treatment-seeking cocaine abusers. METHODS: Fifty recently abstinent cocaine dependent individuals (25F/25M), who were matched on cocaine use history, were exposed to a brief guided-imagery procedure that involved imagining a recent personal stressful situation, a personal drug-related situation and neutral-relaxing situation, one imagery per session, presented in random order. Subjective craving and anxiety, cardiovascular measures and plasma adrenocorticotrophic hormone (ACTH), cortisol and prolactin were assessed. RESULTS: Males showed significantly higher levels of ACTH, cortisol, and SBP, both at baseline and following all three imagery conditions. Females showed significantly higher basal heart rate and prolactin, although no gender differences were observed following imagery. No gender differences were seen in subjective anxiety or cocaine craving. CONCLUSIONS: Results indicate significant gender differences in baseline sensitivity and subsequent variations in hypothalamus-pituitary-adrenal (HPA) and cardiovascular response to imagery challenge. Such gender-specific responses could have implications for the development of pharmacological treatments that address stress and drug-cue-related relapse in cocaine-abusing individuals.

Adrenocorticotropic Hormone↗

PubMed2006

Antisocial personality and stress-induced brain activation in cocaine-dependent patients.

We explore the neural correlates underlying distress processing in antisocial personality in cocaine-dependent individuals. Twenty-seven abstinent cocaine-dependent individuals took part in script-guided stress imagery in a functional magnetic resonance imaging study. Regional brain activation during stress imagery was compared with a baseline period, for male and female participants separately. Their California Psychological Inventory socialization scores were then correlated in region of interest analysis with corticolimbic brain regions that showed significant activation during stress. The effect size of activity change in the medial prefrontal cortex is associated with lower socialization score (i.e. greater sociopathy) and with the change in heart rate, but only among female participants. These results highlight important sex differences in the association between antisocial personality and distress processing in cocaine-dependent individuals.

Adult↗

PubMed2006

Imaging response inhibition in a stop-signal task: neural correlates independent of signal monitoring and post-response processing.

Execution of higher cortical functions requires inhibitory control to restrain habitual responses and meet changing task demands. We used functional magnetic resonance imaging to show the neural correlates of response inhibition during a stop-signal task. The task has a frequent "go" stimulus to set up a pre-potent response tendency and a less frequent "stop" signal for subjects to withhold their response. We contrasted brain activation between successful and failed inhibition for individual subjects and compared groups of subjects with short and long stop-signal reaction times. The two groups of subjects did not differ in their inhibition failure rates or the extent of signal monitoring, error monitoring, or task-associated frustration ratings. The results showed that short stop-signal reaction time or more efficient response inhibition was associated with greater activation in the superior medial and precentral frontal cortices. Moreover, activation of these inhibitory motor areas correlated negatively with stop-signal reaction time. These brain regions may represent the neural substrata of response inhibition independent of other cognitive and affective functions.

Adult↗

PubMed2006

Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes.

BACKGROUND: Cocaine dependence is associated with high rates of relapse. Stress and drug cue exposure are known to increase cocaine craving and stress arousal, but the association between these responses and cocaine relapse has not been previously studied. OBJECTIVE: To examine whether stress-induced and drug cue-induced cocaine craving and hypothalamic-pituitary-adrenal axis responses evoked in the laboratory are associated with subsequent cocaine relapse. DESIGN: Prospective study design assessing cocaine relapse and drug use during a 90-day follow-up period after discharge from inpatient treatment and research. Data were analyzed by Cox proportional hazards regression and multiple regression. SETTING: Inpatient treatment and research unit in a community mental health center. PATIENTS: Forty-nine treatment-seeking cocaine-dependent individuals. MAIN OUTCOME MEASURES: Time to cocaine relapse, number of days of cocaine use, and amount of cocaine used per occasion in the follow-up phase. RESULTS: Greater stress-induced, but not drug cue-induced, cocaine craving was associated with a shorter time to cocaine relapse. Stress-induced corticotropin and cortisol responses predicted higher amounts of cocaine use per occasion in the 90-day follow-up. CONCLUSIONS: These results demonstrate that stress-related increases in cocaine craving and hypothalamic-pituitary-adrenal axis responses are each associated with specific cocaine relapse outcomes. The findings support the use of stress-induced drug craving and associated hypothalamic-pituitary-adrenal axis responses to evaluate cocaine relapse propensity. Furthermore, treatments that address stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses could be of benefit in improving relapse outcomes in cocaine dependence.

Adrenocorticotropic Hormone↗

PubMed2006

The use of contingency management and motivational/skills-building therapy to treat young adults with marijuana dependence.

Marijuana-dependent young adults (N = 136), all referred by the criminal justice system, were randomized to 1 of 4 treatment conditions: a motivational/skills-building intervention (motivational enhancement therapy/cognitive-behavioral therapy; MET/CBT) plus incentives contingent on session attendance or submission of marijuana-free urine specimens (contingency management; CM), MET/CBT without CM, individual drug counseling (DC) plus CM, and DC without CM. There was a significant main effect of CM on treatment retention and marijuana-free urine specimens. Moreover, the combination of MET/CBT plus CM was significantly more effective than MET/CBT without CM or DC plus CM, which were in turn more effective than DC without CM for treatment attendance and percentage of marijuana-free urine specimens. Participants assigned to MET/CBT continued to reduce the frequency of their marijuana use through a 6-month follow-up.

Adolescent↗

PubMed2006

Cue-induced brain activity changes and relapse in cocaine-dependent patients.

This study used functional magnetic resonance imaging (fMRI) to examine the association between brain activation during exposure to cocaine-related cues and relapse to drug use in cocaine-dependent (CD) patients. We imaged 17 CD subjects during a 2-week in-patient stay. The subjects then entered a 10-week outpatient placebo-controlled, double-blind randomized clinical trial where urine toxicologies were assessed three times weekly to calculate the treatment effectiveness score (TES). Worse TES correlated with BOLD activation in the left precentral, superior temporal, and posterior cingulate cortices (PCC), and right middle temporal and lingual cortices (R>0.65; P<0.005). The left PCC activation also distinguished eight nonrelapsers (TES above mean and completed treatment) from nine relapsers. Cocaine-free urines were significantly greater in the nonrelapsers (92%) than in the relapsers (66%), who also remained in treatment for an average of only 3.2 weeks. Self-reports of craving during fMRI did not differ between nonrelapsers and relapsers and did not correlate with TES. Relapse to cocaine abuse was associated with increased activation in the sensory association cortex, the motor cortex, and PCC while viewing images of cocaine-related cues. These results suggest that relapse to cocaine abuse is associated with increased brain activation to cocaine cues in sensory, motor, and cognitive-emotional processing areas. This physiological activation was a better predictor of relapse than subjective reports of craving, and may be a useful target for treatment development.

Adult↗

PubMed2006

Gender specific associations between types of childhood maltreatment and the onset, escalation and severity of substance use in cocaine dependent adults.

We examined associations between types of childhood maltreatment and the onset, escalation, and severity of substance use in cocaine dependent adults. In men (n = 55), emotional abuse was associated with a younger age of first alcohol use and a greater severity of substance abuse. In women (n = 32), sexual abuse, emotional abuse, and overall maltreatment was associated with a younger age of first alcohol use, and emotional abuse, emotional neglect, and overall maltreatment was associated with a greater severity of substance abuse. There was no association between childhood maltreatment and age of nicotine or cocaine use. However, age of first alcohol use predicted age of first cocaine use in both genders. All associations were stronger in women. Findings suggest that early intervention for childhood victims, especially females, may delay or prevent the early onset of alcohol use and reduce the risk for a more severe course of addiction.

Adult↗

PubMed2006

Alexithymia and stress-induced brain activation in cocaine-dependent men and women.

OBJECTIVE: Alexithymia means a reduced capacity to identify and describe one's own feelings. Both stress and an alexithymic response to stress can contribute to relapse into drug abuse, but to our knowledge the neural processing of an alexithymic response to stress in cocaine-dependent individuals has not been examined. METHODS: In a functional magnetic resonance imaging session,17 male and 10 female abstinent cocaine-dependent subjects participated in script-guided imagery of neutral or stressful situations. Spatial preprocessing and statistical analysis of brain images were performed using Statistical Parametric Mapping Software (SPM2). Blood oxygen level-dependent contrasts between stress and neutral imagery were correlated voxelwise with scores on the 26-item Toronto Alexithymia Scale (TAS). RESULTS: Male cocaine users demonstrated a positive correlation between TAS scores and activation in the right putamen and middle frontal cortex during stressful, compared with neutral, imagery. In contrast, no brain regions showed a negative correlation with TAS scores. Female subjects demonstrated a negative correlation between TAS scores and activation in the right amygdala, thalamus, putamen, and left frontal and bilateral temporal cortices, and no positive correlations with TAS scores during stressful, compared with neutral, imagery. CONCLUSIONS: Women with greater alexithymic features showed reduced left-hemispheric cortical and right-hemispheric subcortical activation during processing of stress. However, men showed an opposite correlation in the right frontal cortex and putamen, suggesting that responses to stress in the putamen (activation v. deactivation) and frontal cortex (activation v. deactivation, as well as right v. left correlations) are critically different in association with alexithymia between male and female cocaine-dependent patients.

Adult↗

PubMed2005

Recent cannabis abuse decreased stress-induced BOLD signals in the frontal and cingulate cortices of cocaine dependent individuals.

Previous neuroimaging studies showed that use of marijuana can alter patterns of cortical activation during rest or a task challenge. We used functional magnetic resonance imaging to examine whether recent cannabis abuse contributed to stress-induced blood-oxygen-level-dependent (BOLD) contrast in a group of cocaine-dependent individuals. Emotional stress was induced using the script-guided imagery paradigm, in which subjects imagined being in a real-life stressful situation and, as a control, in a neutral situation, while BOLD signals of their brain were acquired with a 1.5 T scanner. Abstinent cocaine-dependent subjects with recent marijuana abuse (n=8) were compared with abstinent cocaine-dependent subjects who had not abused marijuana recently (n=18). The two groups were otherwise matched in their demographic characteristics and drug use history. All subjects were abstinent for at least 15 days and drug free as confirmed by urine drug screening before the imaging session. Recent cannabis abusers demonstrated hypo-activation in frontal cortical areas including the perigenual anterior cingulate during increased emotional stress. In contrast, at the same statistical threshold, no brain regions showed increased activation in recent cannabis abusers compared with non-abusers. The group difference in the perigenual anterior cingulate remained even when lifetime cocaine and alcohol consumption was accounted for in covariance analysis. These results provide evidence that recent cannabis abuse is associated with decreased activation in the frontal cortex during an emotional stress task. The results suggest an abnormal cognitive control mechanism during affective processing in association with heavy cannabis use.

Adult↗

PubMed2005

Neural activity associated with stress-induced cocaine craving: a functional magnetic resonance imaging study.

OBJECTIVE: Stress is known to increase cocaine craving and relapse risk in cocaine dependence. Identifying neural activity associated with stress and stress-induced cocaine craving is important in understanding the neurobiology of cocaine craving and relapse. METHOD: Blood oxygenation level dependent (BOLD) signal changes were assessed in a functional magnetic resonance imaging (fMRI) session with healthy controls and treatment-engaged, abstinent, cocaine-dependent individuals (patients) as they participated in brief guided imagery and recall of three personal stress and three personal neutral situations. RESULTS: During stress, patients showed significantly less BOLD activation than controls in specific frontal and para-limbic regions, such as the anterior cingulate (AC) region, left hippocampal/parahippocampal region, right fusiform gyrus, and the right postcentral gyrus. On the other hand, patients had increased activity in the caudate and dorsal striatum region during stress, activation that was significantly associated with stress-induced cocaine craving ratings. CONCLUSIONS: Patients failed to activate AC and related circuits during stress, regions associated with control, and regulation of emotion and distress states. Instead, they exhibited greater craving-related activation in the dorsal striatum, a region related to reward pathways and part of the obsessive-compulsive circuitry. Such functional alterations in stress processing may underlie the stress-related vulnerability to cocaine relapse often observed in cocaine-dependent individuals in early recovery.

Adult↗

PubMed2005

Sex differences in brain activation during stress imagery in abstinent cocaine users: a functional magnetic resonance imaging study.

BACKGROUND: Because stress mediates drug seeking and relapse, and sex differences have been observed in stress and in the development of cocaine addiction, in this study we used functional neuroimaging to examine the effect of sex on stress responses in abstinent cocaine users. METHODS: In a functional magnetic resonance imaging session, 17 male and 10 female cocaine-dependent subjects participated in script-guided imagery of neutral or stress situations. Subjects rated imagery vividness, anxiety, and cocaine craving for each trial. Brain activation during the stress and neutral imagery periods relative to their own baseline was examined in individual subjects. Sex contrast was obtained in second-level group analysis. RESULTS: Female subjects demonstrated more activation, compared with male subjects, in left middle frontal, anterior cingulate, and inferior frontal cortices and insula, and right cingulate cortex during stress imagery. Region of interest analysis showed that the change of activity in left anterior cingulate and right posterior cingulate cortices both correlated inversely with the change of craving rating during stress imagery. CONCLUSIONS: The greater left frontolimbic activity in women suggests that women might use more verbal coping strategies than do men while experiencing stress. The results also suggest a distinct role of the cingulate cortices in modulating stress-induced cocaine craving.

Adult↗

PubMed2005

A gender specific psychometric analysis of the early trauma inventory short form in cocaine dependent adults.

This study evaluated the gender specific psychometric properties of the Early Trauma Inventory-Short Form (ETI-SF) in a clinical sample of cocaine dependent men (N=58) and women (N=34). Participants were administered the ETI-SF, the Childhood Trauma Questionnaire Short Form (CTQ-SF), and the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Tests of internal consistency, convergent validity, and predictive validity were conducted separately by gender. Findings indicated that the ETI-SF demonstrated good internal consistency; Cronbach's alpha ranged from 0.73 to 0.80 for men and from 0.70 to 0.77 for women. The measure also demonstrated good convergence with the CTQ-SF in both sexes, indicating that reports of child maltreatment are consistent across interview and self-report measures. Further, predictive validity was demonstrated by the ability of various ETI-SF scales to predict the co-occurrence of psychiatric disorders commonly associated with early trauma. These included lifetime diagnosis of PTSD in men and women, the lifetime diagnosis of major depressive disorder in men, and the lifetime diagnoses of alcohol use disorders in women. The findings support the utility of the ETI-SF as a clinical research tool to obtain data on specific types of early trauma in drug abusing samples.

Adult↗

PubMed2005

The role of depression symptoms in predicting drug abstinence in outpatient substance abuse treatment.

OBJECTIVE: This study examined the role of depressive symptoms in the context of specific demographic and individual treatment characteristics in predicting drug abstinence at discharge from outpatient substance abuse treatment. METHODS: Data from 827 clients entering a large public funded outpatient substance abuse treatment program were analyzed using logistic regression to assess the effects of depressive symptoms on drug abstinence status at discharge. Analyses on the effects of gender, race, age, education level, frequency of drug use, insurance status, referral source, and length of stay in treatment on drug abstinence status at discharge were also conducted. RESULTS: Higher depressive symptom scores significantly predicted a decreased likelihood of clients' abstinence at discharge even after accounting for other significant demographic and treatment variables such as insurance status, race, age, primary drug of choice, frequency of drug use at admission and length of stay in treatment. CONCLUSION: The findings suggest that depression symptoms are an important factor affecting successful substance abuse treatment outcomes. Treatment approaches that address depressive symptoms are likely to enhance substance abuse treatment outcomes in real world clinical settings.

Adult↗

PubMed2005

Frequency of recent cocaine and alcohol use affects drug craving and associated responses to stress and drug-related cues.

RATIONALE: Stress is known to increase drug craving, associated physiological arousal and risk of relapse in drug dependent individuals. However, it is unclear whether these responses are altered by recent frequency of drug use. The current study examined whether frequency of cocaine and alcohol abuse alters drug craving and associated arousal with laboratory exposure to stress and to drug related cues. METHODS: Fifty-four recently abstinent treatment-seeking cocaine abusers who were part of a study on stress and drug craving were categorized into high- and low-frequency users on the basis of their recent cocaine use. The high use cocaine group also consumed significantly more alcohol than the low use cocaine group. Participants were exposed to a brief 5-min guided imagery procedure that involved imagining a recent personal stressful situation, a personal drug-related situation and a neutral-relaxing situation, one imagery session on separate days presented in random order. Subjective (craving and anxiety), cardiovascular (heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP)) and biochemical (adrenocorticotropic hormone (ACTH), cortisol, prolactin) measures were assessed. RESULTS: High-frequency abusers demonstrated a significantly greater drug craving, anxiety and associated cardiovascular and hypothalamic-pituitary-adrenal (HPA) response to both stress and drug-cue exposure as compared to low-frequency abusers. CONCLUSIONS: Increased frequency of recent cocaine and alcohol use is associated with an enhanced stress and cue-induced drug craving and arousal response that appears to be similar to the effects of cocaine, and one that may increase the vulnerability to drug-seeking behavior and relapse in drug dependent individuals.

Adult↗

PubMed2005

Neuroimaging study of sex differences in the neuropathology of cocaine abuse.

BACKGROUND: Female and male substance abusers differ in their disease patterns and clinical outcomes. An important question in addiction neuroscience thus concerns the neural substrates underlying these sex differences. OBJECTIVE: This article aims to examine what is known of the neural mechanisms involved in the sex differences between substance abusers. METHODS: We reviewed neuroimaging studies that addressed sex differences in cerebral perfusion deficits after chronic cocaine use and in regional brain activation during pharmacologic challenge and cue-induced craving. We also present results from a preliminary study in which cocaine-dependent men and women participated in script-guided imagery of stress- and drug cue-related situations while blood oxygenation level-dependent signals of their brain were acquired in a 1.5T scanner. Spatial pre-processing and statistical analysis of brain images were performed. Regional brain activation was compared between stress and drug cue trials in men versus women. RESULTS: The results of our study showed greater activation in the left uncus and right claustrum (both, statistical threshold of P = 0.01, uncorrected; extent = 10 voxels) in men (n = 5) during drug cue trials compared with stress trials. No brain regions showed greater activation during stress trials compared with drug cue trials. In contrast, women (n = 6) showed greater activation in the right medial and superior frontal gyri during stress trials compared with drug cue trials at the same statistical threshold. No brain regions showed more activation during drug cue trials than during stress trials. CONCLUSIONS: The studies reviewed underscore the need to consider sex-related factors in examining the neuropathology of cocaine addiction. Our preliminary results also suggest important sex differences in the effect of stress- and drug cue-associated brain activation in individuals with cocaine use disorder.

Adult↗