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Biomedical subjects

Vladimir Coric

Publications and source records attributed to Vladimir Coric.

15 recordsLinked to original sources
PubMed2006

Dopamine beta-hydroxylase gene (DbetaH) -1021C-->T influences self-reported paranoia during cocaine self-administration.

BACKGROUND: Variation in the gene for dopamine beta-hydroxylase (DbetaH) has been reported to associate with cocaine-induced paranoia as assessed by retrospective self-report. This association has yet to be tested prospectively. METHODS: Visual analog scale (VAS) ratings of paranoia were obtained in 31 cocaine users during three cocaine self-administration sessions (8, 16, and 32 mg/70 kg). Pharmacogenetic interactions between cocaine and a putative functional polymorphism in DbetaH (-1021C-->T) were assessed. RESULTS: VAS self-ratings showed significant or trend-level interactions of genotype and time during each session (p = .004, .09 and .003, respectively) with TT homozygotes endorsing greater paranoia over time than either CT or CC individuals. Interactions were significant at all doses in African Americans (n = 19; p = .02, .04 and .05). No other demographic or experimental variable distinguished genotypic groups. CONCLUSIONS: Results indicate that individuals homozygous for the 'very low-activity' T allele at DbetaH -1021C-->T show an increased propensity to paranoia over time during cocaine self-administration.

Adult↗
PubMed2006

Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms.

BACKGROUND: Excessive glutamatergic neurotransmission may contribute to the pathophysiology of major depressive disorder (MDD). Recent evidence suggests that riluzole and other agents that target glutamate neurotransmission may show antidepressant activity. METHODS: Ten patients with treatment-resistant depression had riluzole added to their ongoing medication regimen for 6 weeks, followed by an optional 6-week continuation phase. Depression and anxiety severity were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Linear mixed models were used to test for a linear trend in HDRS and HARS scores across time with treatment. RESULTS: Subjects' HDRS and HARS scores declined significantly following the initiation of riluzole augmentation therapy. The effect of riluzole was significant at the end of the first week of treatment and persisted for the 12-week duration of the study. CONCLUSIONS: These data suggest that riluzole augmentation produces antidepressant and anxiolytic effects in patients with treatment-resistant depression.

Adult↗
PubMed2006

Self-reported paranoia during laboratory "binge" cocaine self-administration in humans.

Cocaine-induced paranoia (CIP) has been extensively studied by retrospective interviews; however, only limited efforts have been made to further characterize CIP by human laboratory methods. We examined CIP in 28 healthy cocaine-dependent volunteers, who participated in 2-h, intravenous cocaine self-administration sessions at 8, 16, and 32 mg/70 kg doses, including 18 in a placebo-controlled design. Self-reports of paranoia showed significant main effects of cocaine dose (p=0.0002) and time (p=0.0003), and were statistically distinguishable from placebo at the two highest doses (16 and 32 mg). These effects were accounted for by a subgroup of vulnerable subjects in whom self-reports were consistent across dose and test-retest sessions. Subjects with CIP did not differ from those without CIP with respect to demographic, cocaine use, or cocaine self-administration variables. In conclusion, self-reports of CIP in the human lab are frequently endorsed, dose-dependent, and though variable between subjects, reproducible within subjects. Such methods may facilitate our understanding of the vulnerability to CIP in humans.

Adolescent↗
PubMed2006

Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder.

SUMMARY: Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that produces significant morbidity. The introduction of serotonin reuptake inhibitors in the 1980s represented an important advance in the treatment of OCD. However, few patients show complete remission of their symptoms, and some patients show minimal improvement with existing treatments. We review current treatment strategies and initial data supporting the efficacy of glutamate modulating agents as a novel class of pharmaceuticals for the treatment of OCD. Functional neuroimaging studies repeatedly reported metabolic hyperactivity in the cortico-striato-thalamo-cortical circuitry in patients with OCD. Recent magnetic resonance spectroscopy studies provide evidence of elevated glutamate levels in several brain regions in patients suffering from OCD. These findings raised the possibility that agents that reduce glutamate hyperactivity or its consequences in the CNS might be efficacious as novel therapeutic interventions. Indeed, initial evidence from our group suggests that the antiglutamatergic agent riluzole (Rilutek), which was developed for the treatment of amyotrophic lateral sclerosis, is effective in treatment-resistant OCD. Case reports suggest that other agents that modulate glutamatergic activity may likewise be effective. This new application of glutamate modulating agents holds promise for the treatment of this disabling and often inadequately treated disease.

Antidepressive Agents, Tricyclic↗
PubMed2005

N-acetylcysteine augmentation in serotonin reuptake inhibitor refractory obsessive-compulsive disorder.

RATIONALE: Dysfunction of glutamatergic neurotransmission has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD) and recent clinical reports suggest that some glutamate modulating agents are efficacious in the treatment of this disorder. N-acetylcysteine (NAC) is a readily available amino acid compound that is thought to attenuate glutamatergic neurotransmission. NAC may be useful in treating psychiatric disorders involving glutamatergic dysfunction such as OCD. OBJECTIVES: To examine the efficacy of augmentation with NAC in a patient with serotonin reuptake inhibitor (SRI)-refractory OCD. METHODS: A patient with SRI-refractory OCD was treated with an off-label use of NAC augmentation of fluvoxamine over several weeks. RESULTS: NAC augmentation of fluvoxamine resulted in a marked decrease in Yale-Brown Obsessive Compulsive Scale (Y-BBOCS) score and a clinically significant improvement in OCD symptoms. CONCLUSIONS: NAC augmentation was effective in treating SRI-refractory OCD in this single case. Further research is warranted to investigate the use of NAC and other glutamate modulating agents in the treatment of OCD.

Acetylcysteine↗
PubMed2005

Cortical gamma-aminobutyric acid levels and the recovery from ethanol dependence: preliminary evidence of modification by cigarette smoking.

BACKGROUND: Gamma-aminobutyric acid (GABA)ergic adaptations contribute to the neurobiology of ethanol dependence and withdrawal. Clinical data suggest that tobacco smoking attenuates alcohol withdrawal symptoms. This study's objective was to measure time-dependent cortical GABA levels with sobriety in ethanol-dependent patients with mild to moderate withdrawal severity, controlling for alcoholism-related neurotoxicity and smoking. METHODS: Proton magnetic resonance spectroscopy (MRS) was used to measure occipital cortical N-acetylaspartate (NAA), glutamate plus glutamine, and GABA in 12 ethanol-dependent men at approximately 1 week and 1 month of medication-free sobriety on an inpatient unit. Eight healthy men were studied once. The tissue composition of the MRS volume was determined. RESULTS: Adjusting for less white matter in patients, GABA differed insignificantly between ethanol-dependent patients (smokers plus nonsmokers) and healthy subjects. In early sobriety, nonsmoking patients had more GABA than did smoking patients, but by 1 month, GABA decreased in nonsmokers without changing in smokers. Smoking was associated with increased glutamate plus glutamine in patients and healthy subjects, adjusting for NAA levels. CONCLUSIONS: These data do not show that deficits in cortical GABA contribute directly to acute ethanol withdrawal. If smoking prevents withdrawal-related changes in cortical GABA systems, it may contribute to comorbidity of alcoholism and tobacco smoking.

Adult↗
PubMed2005

Sleep, sleep-dependent procedural learning and vigilance in chronic cocaine users: Evidence for occult insomnia.

Sleep disturbance has been implicated in cocaine use; however, the nature of the disturbance and its potential effects on cognition and learning are largely unknown. Twelve chronic cocaine users completed a 23-day inpatient study that included randomized, placebo-controlled, cocaine self-administration sessions. Six subjects received cocaine on each of days 4-6 and placebo on days 18-20, the other six received cocaine on each of days 18-20 and placebo on days 4-6. Sleep was measured by polysomnography, the Nightcap sleep monitor, and self-reported measures. Simple and vigilance reaction times were measured daily; a motor-sequence test of procedural learning was administered four times. Electrophysiological measures of sleep showed a different pattern than self-reported sleep across cocaine administration and abstinence: total sleep time and sleep latency were at their worst by 14-17 days of abstinence while self-reported sleep was at its best. Vigilance correlated positively with electrophysiologically measured sleep and negatively with self-reported measures. Similarly, sleep-dependent procedural learning correlated with total sleep time and was impaired at 17 days abstinence relative to 2- and 3-days abstinence. Slow-wave activity was lowest at days 4-9 of abstinence and highest during use and days 10-17 of abstinence. With sustained abstinence, chronic cocaine users exhibit decreased sleep, impaired vigilance and sleep-dependent procedural learning, and spectral activity suggestive of chronic insomnia. However, they report subjectively improving sleep, indicating they are unaware of this "occult" insomnia. These results suggest the possibility of homeostatic sleep drive dysregulation in chronic cocaine users.

Adult↗
PubMed2005

Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial.

BACKGROUND: Most patients with obsessive-compulsive disorder (OCD) show only partial reduction of symptoms with standard therapy. Recent imaging data suggests glutamatergic dysfunction in the corticostriatal pathway in OCD. We investigated the efficacy of augmentation therapy with riluzole, a glutamate-modulating agent, in treatment-resistant OCD. METHODS: Thirteen patients aged between 18 and 65 years with a primary diagnosis of OCD that had proven resistant to standard treatment were treated with the addition of riluzole to their existing pharmacotherapy. Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression Inventory (HAM-D), and Hamilton Anxiety Inventory (HAM-A) scores were obtained weekly. RESULTS: Thirteen treatment-resistant OCD patients received riluzole 50 mg twice a day. Y-BOCS scores improved significantly over time. Of 13 patients, 7 (54%) demonstrated a >35% reduction in Y-BOCS scores, and 5 (39%) were categorized as treatment responders. HAM-D and HAM-A scores for the group also significantly improved over time. Riluzole was well tolerated with no serious adverse effects noted. CONCLUSIONS: Riluzole appears to have significant antiobsessional, antidepressant, and antianxiety properties. The addition of this agent may be of practical clinical benefit in patients with OCD.

Adult↗
PubMed2005

A paradigm to investigate the self-regulation of cocaine administration in humans.

INTRODUCTION: Current laboratory paradigms of human cocaine administration generally dictate the timing of drug access in ways that may limit assessing aspects of cocaine-taking behavior. Patient-controlled analgesia (PCA) methods, which allow individuals less restricted access to narcotic (i.e., opiate) analgesics, have proven safe and clinically effective for self-regulated treatment of pain. The current study assessed the feasibility, safety, and validity of a model of ad libitum cocaine self-administration, in which participants self-selected the timing of cocaine infusions, using PCA techniques. METHODS: Eight nontreatment seeking, otherwise medically healthy, experienced cocaine users participated in a double-blind, placebo-controlled, escalating-dose regimen of intravenous cocaine (0, 8, 16, and 32 mg per 70 kg) on 4 test days, during which time participants had 2 h of access to cocaine via manual presses of a corded PCA pump button under a fixed ratio 1: time-out 5-min schedule. RESULTS: Procedures were well-tolerated by participants, and no significant adverse events were noted. Measures of cocaine self-administration (e.g., number of responses and interinfusion intervals) indicated a significant main effect of cocaine dose, consistent with predicted dose-response relationships (i.e., decreasing responses and increasing interinfusion intervals with increasing injection dose). Participants appeared to regulate their cocaine intake in a carefully controlled manner, using considerably less cocaine (about half) that permitted by pump loading, PCA parameters, and session duration. CONCLUSIONS: Data from this study support the validity of our PCA paradigm. Moreover, results suggest the apparent feasibility and safety of allowing experienced users to self-select the timing of cocaine infusions to intervals as short as 5 min. Such procedures may enhance our ability to identify effective pharmacological treatments for cocaine addiction.

Adult↗