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Lorenzo Leggio - One of the best experts on this subject based on the ideXlab platform.
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comparing and combining topiramate and aripiprazole on Alcohol related outcomes in a human laboratory study
Alcohol and Alcoholism, 2018Co-Authors: Carolina L Haasskoffler, Kimberly Goodyear, William H Zywiak, Lorenzo Leggio, George A Kenna, Robert M SwiftAbstract:Aims The goal of this study was to evaluate the efficacy of topiramate up to 200 mg/day and of aripiprazole up to 15 mg/day, alone and combined, in reducing Alcohol-related outcomes in a human laboratory study. Method This was a 5 week, between-subject, double-blind, placebo-controlled human laboratory study with topiramate [0 mg/day (placebo), 100 mg/day, 200 mg/day] and aripiprazole [0 mg/day (placebo), 7.5 mg/day, 15 mg/day] in 90 non-treatment seeking, heavy drinking, Alcohol-dependent individuals. Main outcomes were the efficacy of 200 mg/day topiramate and 15 mg/day aripiprazole, alone and combined, in reducing drinks consumed during an Alcohol self-administration procedure (human laboratory phase) and while receiving the study medications prior to the laboratory session (naturalistic drinking phase). Other outcomes in the laboratory phase included Alcohol Craving, and Alcohol biphasic effects. Results In the human laboratory phase, topiramate 200 mg/day reduced Alcohol Craving [**P < 0.01] and amplified Alcohol-induced stimulation [*P < 0.05], but did not reduce the number of drinks consumed. Topiramate 200 mg/day was also effective in reducing drinking days [*P < 0.05], and Alcohol Craving [*P < 0.05], in the naturalistic drinking phase. No significant findings were found for aripiprazole for any of the outcomes analyzed. Conclusion Participants receiving 200 mg/day topiramate reported reduced Alcohol drinking and Craving, and increased Alcohol-related stimulation. These findings provide further support for the role of topiramate as a pharmacological treatment for AUD. ClinicalTrial.gov Identifier NCT00884884. Short Summary This study tested topiramate and aripiprazole alone and in combination. The results replicate past findings and suggest that topiramate may be an effective treatment for Alcohol use disorder. The present results suggest that the combination of topiramate and aripiprazole do not warrant further evaluation.
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serum insulin levels are reduced by intravenous ghrelin administration but do not correlate with Alcohol Craving in Alcohol dependent individuals
The International Journal of Neuropsychopharmacology, 2016Co-Authors: Carolina L Haasskoffler, William H Zywiak, George A Kenna, Robert M Swift, Suzanne M De La Monte, Mary R Lee, Danielle Giovenco, Lorenzo LeggioAbstract:Background: Increasing evidence supports a role for appetite-regulating pathways like ghrelin, insulin and leptin in Alcoholism. We previously reported that intravenous (IV) exogenous ghrelin increases Alcohol Craving. We also reported, IV ghrelin reduces endogenous serum leptin, whose levels, in turn, negatively correlated with Alcohol Craving. Exogenous ghrelin administration decreases insulin secretion both in vitro and in vivo experiments. This study tested the hypothesis that IV ghrelin may also decrease endogenous serum insulin levels in Alcoholic individuals. Additionally, we explored possible correlations between serum insulin and Alcohol Craving since a correlation between insulin and Alcohol Craving was previously reported. Methods: This was a double-blind, placebo-controlled human laboratory study ( n =43). Non-treatment-seeking, Alcohol-dependent, heavy-drinkers were randomized to receive IV ghrelin or placebo, followed by an Alcohol cue-reactivity procedure. Results: There was a main effect for IV ghrelin, compared to placebo in reducing serum insulin [ P .05]. We did not find a correlation between the reduction of serum insulin and Alcohol Craving [ P >.05]. The change in serum insulin was consistent with a parallel reduction in serum connective-peptide (C-peptide) in the ghrelin group compared to placebo, although this difference did not reach statistical significance [P=.076]. No similar effects were found for other glucose-regulating hormones analyzed, i.e.: glucagon, glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP) [ P ’s>.05]. Conclusions: These findings indicate IV ghrelin administration has an effect on reducing serum insulin in Alcohol-dependent individuals, however the reduction of insulin did not correlate with changes in Alcohol cue-elicited Craving. We speculate that, unlike for leptin, the interactions between ghrelin and insulin relationship are limited at the peripheral level. However, mechanistic studies are needed to investigate this hypothesis.
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the crf1 antagonist verucerfont in anxious Alcohol dependent women translation of neuroendocrine but not of anti Craving effects
Neuropsychopharmacology, 2016Co-Authors: Melanie L Schwandt, David T George, Rajita Sinha, Laura E Kwako, Reza Momenan, Carlos R Cortes, Dimitri E Grigoriadis, Emilio Merlo Pich, Lorenzo LeggioAbstract:Blockade of corticotropin-releasing factor receptor 1 (CRF1) suppresses stress-induced Alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRF1 antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced Alcohol Craving in Alcohol-dependent patients. Anxious, Alcohol-dependent women (age 21-65 years, n=39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test. Craving was evaluated using two established protocols, one that combines a social stressor with physical Alcohol cue exposure, and one that uses guided imagery to present personalized stress, Alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and Alcohol cues. In contrast to our recent observations with another CRF1 antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left Alcohol Craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to Alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRF1 antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRF1 blockade in stress-induced Alcohol Craving and relapse.
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leptin levels are reduced by intravenous ghrelin administration and correlated with cue induced Alcohol Craving
Translational Psychiatry, 2015Co-Authors: Carolina L Haasskoffler, Lorenzo Leggio, George A Kenna, Robert M Swift, Suzanne M De La Monte, Elie AounAbstract:Increasing evidence supports the role of appetite-regulating pathways, including ghrelin and leptin, in Alcoholism. This study tested the hypothesis that intravenous exogenous ghrelin administration acutely decreases endogenous serum leptin levels, and that changes in leptin levels negatively correlate with Alcohol Craving. This was a double-blind, placebo-controlled human laboratory study. Non-treatment-seeking, Alcohol-dependent, heavy drinkers (n=45) were randomized to receive intravenous ghrelin or placebo, followed by a cue-reactivity procedure, during which participants were exposed to neutral (juice) and Alcohol trial cues. There was a main effect for intravenous ghrelin administration, compared with placebo, in reducing serum leptin levels (P<0.01). Post hoc analysis showed significant differences in serum leptin levels at the Alcohol trial (P<0.05) that persisted at the end of the experiment (P<0.05). By contrast, there were no significant differences in serum leptin levels at the juice trial (P=not significant (NS)). The change of serum leptin level at the Alcohol trial correlated with the increase in Alcohol urge (P<0.05), whereas urge to drink juice was not correlated with the leptin change at the juice trial (P=NS). These findings provide preliminary evidence of ghrelin-leptin cross-talk in Alcoholic individuals and suggest that their relationship may have a role in Alcohol Craving.
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relationship between the thyroid axis and Alcohol Craving
Alcohol and Alcoholism, 2015Co-Authors: Elie Aoun, Carolina L Haasskoffler, George A Kenna, Robert M Swift, Giovanni Addolorato, Mary R Lee, Lorenzo LeggioAbstract:Aims: A few studies have suggested a relationship between thyroid hormones and Alcohol dependence (AD) such as a blunted increase of thyroid stimulating hormone (TSH) in response to thyrotropin-releasing hormone (TRH), lower levels of circulating free triiodothyronine (fT3) and free thyroxine (fT4) levels and down regulation of the TRH receptors. The current study aimed to explore the relationship between the hormones of the thyroid axis and Alcohol-seeking behaviors in a sample of Alcohol-dependent patients. Methods: Forty-two treatment-seeking Alcohol-dependent individuals enrolled in a 12-week treatment study were considered. The Timeline Follow Back (TLFB) was used to assess the number of drinks consumed during the 12-week period. Blood levels of thyroid hormones (TSH, fT3 and fT4) were measured prior to and at the end of treatment. Questionnaires were administered to evaluate Craving for Alcohol (Penn Alcohol Craving Scale (PACS) and the Obsessive Compulsive Drinking Scale (OCDS) and its two subscales ODS for obsessions and CDS for compulsions) as well as anxiety (State and Trait Inventory (STAI)), depression (the Zung Self-Rating Depression Scale (Zung)) and aggression (the Aggressive Questionnaire (AQ)). Results: At baseline, we found significant positive cor- relations between fT3 and OCDS (r= 0.358, P= 0.029) and CDS (r= 0.405, P= 0.013) and negative correlations between TSH levels and STAI (r=�0.342, P= 0.031), and AQ (r=�0.35, P= 0.027). At the end of the 12-week study period, abstinent patients had a greater change in TSH than those who relapsed (�0.4 vs. �0.25, F(1,24) = 5.4, P= 0.029). Conclusion: If confirmed in larger samples, these findings could suggest that the thyroid axis might represent a biomarker of Alcohol Craving and drinking.
Rajita Sinha - One of the best experts on this subject based on the ideXlab platform.
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effects of prazosin on provoked Alcohol Craving and autonomic and neuroendocrine response to stress in Alcohol use disorder
Alcoholism: Clinical and Experimental Research, 2020Co-Authors: Verica Milivojevic, Gustavo A Angarita, Gretchen Hermes, Rajita Sinha, Helen C FoxAbstract:BACKGROUND Chronic Alcohol use results in changes to stress biology and autonomic arousal contributing to acute Alcohol withdrawal symptoms, neuroendocrine tolerance of the hypothalamic-pituitary-adrenal axis responses, high stress-induced Craving, and risk of Alcohol relapse. Thus, stress coping and recovery from Alcohol during early abstinence may be jeopardized by such stress system dysfunction. Significant preclinical evidence suggests that noradrenergic disruption may contribute to these Alcohol-related stress arousal changes and that alpha-1 adrenergic antagonists, such as prazosin, may normalize these stress system adaptations and reduce Alcohol intake. Thus, we hypothesized that prazosin would reduce stress-induced Craving and improve neuroendocrine and autonomic response to stress and Alcohol cue exposure during early abstinence. We secondarily also assessed the role of lifetime anxiety disorders on these prazosin effects. METHODS Forty inpatient treatment-seeking Alcohol-dependent individuals were randomly assigned to receive placebo (n = 18) or 16 mg/d, T.I.D., prazosin (n = 22) in a double-blind manner, titrated over 2 weeks. In weeks 3 to 4 after achieving full dose, patients were exposed to 3 5-minute personalized guided imagery conditions (stress cue, Alcohol cue, neutral/relaxing cue), on 3 consecutive days in a random, counterbalanced order. Alcohol Craving, anxiety, heart rate, cortisol, and adrenocorticotropic hormone (ACTH) levels were assessed at baseline, following imagery and at repeated recovery timepoints. RESULTS Prazosin reduced stress cue-induced Alcohol Craving (p < 0.05) and stress- and Alcohol cue-induced anxiety (p < 0.05) and increased heart rate responses in all imagery conditions (p < 0.05). Prazosin lowered basal cortisol and ACTH (p's < 0.05) and attenuated stress cue-induced rises in cortisol (p < 0.05) versus placebo. Finally, in those without lifetime anxiety disorder, the placebo group showed stress- and Alcohol cue-induced increases in cortisol (p's < 0.05), while the prazosin group did not. CONCLUSIONS Prazosin may attenuate stress cue-induced Alcohol Craving and anxiety during early abstinence while improving adrenergic and stress system function, effects which are independent of a history of lifetime anxiety disorders.
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the crf1 antagonist verucerfont in anxious Alcohol dependent women translation of neuroendocrine but not of anti Craving effects
Neuropsychopharmacology, 2016Co-Authors: Melanie L Schwandt, David T George, Rajita Sinha, Laura E Kwako, Reza Momenan, Carlos R Cortes, Dimitri E Grigoriadis, Emilio Merlo Pich, Lorenzo LeggioAbstract:Blockade of corticotropin-releasing factor receptor 1 (CRF1) suppresses stress-induced Alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRF1 antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced Alcohol Craving in Alcohol-dependent patients. Anxious, Alcohol-dependent women (age 21-65 years, n=39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test. Craving was evaluated using two established protocols, one that combines a social stressor with physical Alcohol cue exposure, and one that uses guided imagery to present personalized stress, Alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and Alcohol cues. In contrast to our recent observations with another CRF1 antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left Alcohol Craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to Alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRF1 antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRF1 blockade in stress-induced Alcohol Craving and relapse.
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the neurobiology of Alcohol Craving and relapse
Handbook of Clinical Neurology, 2014Co-Authors: Dongju Seo, Rajita SinhaAbstract:A major block to recovery from Alcoholism is substantial Alcohol Craving and the chronic relapsing nature of the illness. This chapter reviews relevant structural and functional neuroimaging studies and discusses neural mechanisms underlying Alcohol Craving and relapse in the context of influential risk factors (i.e., Alcohol, Alcohol cue, and stress). Review of neuroimaging studies suggests that neuroadaptations in the cortico-striatal-limbic circuit encompassing the medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, striatum, and amygdala significantly contribute to overwhelming Alcohol Craving and early relapse after a period of abstinence. The cortico-striatal-limbic circuit plays an important role in the modulation of emotion, reward, and decision making. As functional and structural chronic Alcohol-related neuroadaptations are consistently reported in this circuit, it is likely that sensitization of this circuit from continued Alcohol abuse may contribute to high Alcohol Craving and early relapse via impairments in the prefrontal executive function related to emotion regulation and decision making. This vulnerable neurobiologic state may be manifested as compulsive Craving and intense urge to resume Alcohol drinking in the face of environmental risk factors, including Alcohol, Alcohol cue, or stressful live events.
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disrupted ventromedial prefrontal function Alcohol Craving and subsequent relapse risk
JAMA Psychiatry, 2013Co-Authors: Cheryl Lacadie, Kwangik Hong, Keri Tuit, Todd R Constable, Rajita SinhaAbstract:Alcohol dependence is a chronic, relapsing illness, which contributes to significant global disease burden.1 The risk for relapse further perpetuates this disease burden and is increased in stress-related and Alcohol-related contexts that promote anxiety and Alcohol Craving.2-6 Neuroendocrine studies have demonstrated that upregulated hypothalamic-pituitary-adrenal axis response during a neutral-relaxing condition and blunted cortisol responses to stress significantly contribute to chronic Alcoholism and relapse.6-8 Evidence from electrophysiological studies also indicates disrupted electroencephalographic responses at rest during early recovery from Alcoholism. For example, excessive Alcohol use leads to neuroadaptations akin to a kindling-like process,9 resulting in a hyper-excitable neuronal state, particularly in frontal regions.10,11 Furthermore, Alcohol-related neuroadaptations increase stress sensitivity2,12 and stress-related anxiety response.13 These studies suggest the importance of examining neural mechanisms of stress and nonemotional, neutral-relaxing states in assessing their contribution to Alcohol relapse risk. Although recent advances in neuroimaging techniques have provided insights into neuronal abnormalities in brain structure and function associated with chronic Alcoholism, research on functional mechanisms associated with Alcohol relapse has been rare and primarily focused on Alcohol cue–related neural processes in the mesocortical-limbic pathways,14 with little attention to neural mechanisms involved in stress and neutral-relaxing states and their associations with Alcohol Craving and relapse. Because chronic Alcohol-related neuroadaptations target prefrontal networks that include the corticostriatal motivation pathways,15 such neuroadaptations could promote increased Craving and relapse risk.2,6,12,16 Alcohol-related dysfunction in frontal networks might particularly affect higher order executive function including response inhibition and decision-making functions.17-19 Furthermore, chronic Alcohol-related hyperactivity of the mesolimbic dopamine-related impulsive pathways may further compromise the prefrontal self-control regions involved in the regulation of Cravings and the will to resist relapse.17,19,20 However, the specific role of the prefrontal regions and their interconnected networks in Alcohol Craving and relapse risk in the context of stress and neutral-relaxing states is not known. Integrating the previously mentioned theoretical and empirical perspectives, the current study aimed to identify neural correlates of Alcohol Craving and future relapse risk in the context of stress, Alcohol cue, and neutral-relaxing situations in recovering Alcohol-dependent (AD) patients using a combined functional magnetic resonance imaging (fMRI) and prospective clinical design study. We examined all 3 conditions known to influence Alcoholism in previous studies to investigate patterns of differential neural responses during these conditions. The neutral-relaxing condition was included as an active comparison state because it does not increase Alcohol Craving,6 but it provides a context to assess changes in a resting-relaxed state while controlling for the non-specific effects of the experimental manipulation. In previous work, we identified disrupted neuroendocrine responses in the relaxed states in AD patients with a strong association with Alcohol relapse.6 A second aim was to identify whether the same neural responses that are predictive of Alcohol relapse show differences in brain responses when comparing recovering AD patients and demographically matched healthy control (HC) subjects. For the relapse aim, 45 inpatient treatment–engaged, 4- to 8-week–abstinent, recovering AD individuals participated in an fMRI session. Participants were discharged from inpatient treatment following the fMRI session and prospectively followed up with repeated face-to-face assessments at days 14, 30, and 90 to assess relapse risk (Figure 1A). Relapse risk was assessed with the frequently used clinical outcome measures of time to first drink (relapse), time to heavy drinking relapse (5 or more drinks/occasion in men; 4 or more drinks/occasion in women), and Alcohol relapse severity as measured by frequency of drinking days after first relapse. For group comparisons, we compared brain responses of age-matched, sex-matched, and intelligence-matched, right-handed, abstinent AD patients (a subgroup of the relapse sample) vs healthy, socially drinking individuals (30 in each group; eTable 1, http:www.jamapsych.com). Figure 1 Study design. A, For relapse sample, all 45 Alcohol-dependent (AD) patients resided in an inpatient treatment research facility for 6 weeks with functional magnetic resonance image (fMRI) testing in week 5, and patients were assessed with follow-up interviews ... A block design approach that used a well-validated, individually calibrated, script-driven guided-imagery procedure (see Sinha article21 for review) was implemented to experimentally induce challenging stress and Alcohol cue states and an active neutral-relaxing control state via exposure to 6 brief trials of 2 stress, 2 Alcohol cue, and 2 neutral-relaxing scenarios (different scripts presented in randomized order). The same fMRI procedures were used with both the AD patients and HC subjects in the study.
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prazosin effects on stress and cue induced Craving and stress response in Alcohol dependent individuals preliminary findings
Alcoholism: Clinical and Experimental Research, 2012Co-Authors: Helen C Fox, Kristen M Siedlarz, Keri Tuit, George M Anderson, Julie Hansen, Anne Kimmerling, Peter T Morgan, Rajita SinhaAbstract:Background: Stress, Alcohol cues, and dysregulated stress responses increase Alcohol Craving and relapse susceptibility, but few pharmacologic agents are known to decrease stress- and cue-induced Alcohol Craving and associated stress dysregulation in humans. Here we report findings from a preliminary efficacy study of the alpha-1 receptor antagonist, prazosin, in modulating these relapse-relevant factors in Alcohol-dependent individuals. Methods: Seventeen early abstinent, treatment-seeking Alcohol-dependent individuals (12 men and 5 women) were randomly assigned to receive either placebo or 16 mg daily prazosin in a double-blind, placebo-controlled manner over 4 weeks. During week 4, all patients participated in a 3-day laboratory experiment involving 5-minute guided imagery exposure to stress, Alcohol cue, and neutral-relaxing/control conditions, 1 exposure per day, on consecutive days in a random, counterbalanced order. Alcohol Craving, anxiety, negative emotion, cardiovascular measures, and plasma hypothalamic–pituitary–adrenal (HPA; cortisol, adenocorticotropic hormone) were assessed repeatedly in each session. Results: The prazosin group (n = 9) versus the placebo group (n = 8) showed significantly lower Alcohol Craving, anxiety, and negative emotion following stress exposure. The placebo group also showed significantly increased stress- and cue-induced Alcohol Craving, anxiety, negative emotion, and blood pressure (BP), as well as a blunted HPA response relative to the neutral condition, while the prazosin group showed no such increases in Craving, anxiety, negative emotion, and BP, and no blunted HPA response to stress and Alcohol cue exposure. Conclusions: Prazosin appears efficacious in decreasing stress- and cue-induced Alcohol Craving and may normalize the stress dysregulation associated with early recovery from Alcoholism. Further research to assess the efficacy of prazosin in reducing Alcohol Craving and stress-related relapse risk is warranted.
Arthur L Brody - One of the best experts on this subject based on the ideXlab platform.
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effects of citalopram on cue induced Alcohol Craving and thalamic d2 3 dopamine receptor availability
The International Journal of Neuropsychopharmacology, 2019Co-Authors: Todd Zorick, Kyoji Okita, M Mandelkern, Edythe D London, Arthur L BrodyAbstract:Author(s): Zorick, Todd; Okita, Kyoji; Mandelkern, Mark A; London, Edythe D; Brody, Arthur L | Abstract: BACKGROUND:Selective serotonin reuptake inhibitors are often used in Alcohol use disorders. Clinical trials with selective serotonin reuptake inhibitors for Alcohol use disorders, however, have yielded mixed results. The goal of this project was to assess whether a single i.v. dose of a selective serotonin reuptake inhibitor reduces Craving for Alcohol and/or simultaneously increases striatal dopamine concentration in individuals with Alcohol dependence. METHODS:Alcohol-dependent (DSM-IV-TR criteria) volunteers and matched controls (n = 10/group) underwent a double-blind, placebo-controlled, within-subjects study. Participants received i.v. citalopram (40 mg) or saline (counter-balanced) followed by a cue-induced Craving assessment and [18F]-fallypride positron emission tomography scanning. RESULTS:In the Alcohol-dependent individuals, the citalopram (compared with saline) resulted in decreased cue-induced Craving for Alcohol. For the whole study group, cue-induced Alcohol Craving was inversely correlated with thalamic (but not striatal) dopamine D2/3 receptor availability. CONCLUSIONS:Acute serotonin reuptake inhibition reduces cue-induced Alcohol Craving. Furthermore, thalamic dopamine abnormalities and the striatal hyperdopaminergic hypothesis of Alcohol use disorder are supported.
Jana Wrase - One of the best experts on this subject based on the ideXlab platform.
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identifying the neural circuitry of Alcohol Craving and relapse vulnerability
Addiction Biology, 2009Co-Authors: Andreas Heinz, Anne Beck, Sabine M Grusser, Anthony A Grace, Jana WraseAbstract:With no further intervention, relapse rates in detoxified Alcoholics are high and usually exceed 80% of all detoxified patients. It has been suggested that stress and exposure to priming doses of Alcohol and to Alcohol-associated stimuli (cues) contribute to the relapse risk after detoxification. This article focuses on neuronal correlates of cue responses in detoxified Alcoholics. Current brain imaging studies indicate that dysfunction of dopaminergic, glutamatergic and opioidergic neurotransmission in the brain reward system (ventral striatum including the nucleus accumbens) can be associated with Alcohol Craving and functional brain activation in neuronal systems that process attentional relevant stimuli, reward expectancy and experience. Increased functional brain activation elicited by such Alcohol-associated cues predicted an increased relapse risk, whereas high brain activity elicited by affectively positive stimuli may represent a protective factor and was correlated with a decreased prospective relapse risk. These findings are discussed with respect to psychotherapeutic and pharmacological treatment options.
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amygdala volume associated with Alcohol abuse relapse and Craving
American Journal of Psychiatry, 2008Co-Authors: Jana Wrase, Michael N Smolka, Nicos Makris, Dieter F Braus, Karl Mann, David N Kennedy, Verne S Caviness, Steven M Hodge, Lena Tang, Matthew D AlbaughAbstract:Objective: Amygdala volume has been associated with drug Craving in cocaine addicts, and amygdala volume reduction is observed in some Alcohol-dependent subjects. This study sought an association in Alcohol-dependent subjects between volumes of reward-related brain regions, Alcohol Craving, and the risk of relapse. Method: Besides Alcohol Craving, the authors assessed amygdala, hippocampus, and ventral striatum volumes in 51 Alcohol-dependent subjects and 52 age- and education-matched healthy comparison subjects after detoxification. After imaging and clinical assessment, patients were followed for 6 months and Alcohol intake was recorded. Results: Alcohol-dependent subjects showed reduced amygdala, hippocampus, and ventral striatum volumes and reported stronger Craving in relation to healthy comparison subjects. However, only amygdala volume and Craving differentiated between subsequent relapsers and abstainers. A significant decrease of amygdala volume in Alcohol-dependent subjects was associated with i...
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dysfunction of reward processing correlates with Alcohol Craving in detoxified Alcoholics
NeuroImage, 2007Co-Authors: Jana Wrase, Florian Schlagenhauf, Thorsten Kienast, Torsten Wustenberg, Felix Bermpohl, Thorsten Kahnt, Anne Beck, Andreas Strohle, Georg Juckel, Brian KnutsonAbstract:Abstract Objective Alcohol dependence may be associated with dysfunction of mesolimbic circuitry, such that anticipation of nonAlcoholic reward fails to activate the ventral striatum, while Alcohol-associated cues continue to activate this region. This may lead Alcoholics to crave the pharmacological effects of Alcohol to a greater extent than other conventional rewards. The present study investigated neural mechanisms underlying these phenomena. Methods 16 detoxified male Alcoholics and 16 age-matched healthy volunteers participated in two fMRI paradigms. In the first paradigm, Alcohol-associated and affectively neutral pictures were presented, whereas in the second paradigm, a monetary incentive delay task (MID) was performed, in which brain activation during anticipation of monetary gain and loss was examined. For both paradigms, we assessed the association of Alcohol Craving with neural activation to incentive cues. Results Detoxified Alcoholics showed reduced activation of the ventral striatum during anticipation of monetary gain relative to healthy controls, despite similar performance. However, Alcoholics showed increased ventral striatal activation in response to Alcohol-associated cues. Reduced activation in the ventral striatum during expectation of monetary reward, and increased activation during presentation of Alcohol cues were correlated with Alcohol Craving in Alcoholics, but not healthy controls. Conclusions These results suggest that mesolimbic activation in Alcoholics is biased towards processing of Alcohol cues. This might explain why Alcoholics find it particularly difficult to focus on conventional reward cues and engage in alternative rewarding activities.
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correlation of Alcohol Craving with striatal dopamine synthesis capacity and d2 3 receptor availability a combined 18f dopa and 18f dmfp pet study in detoxified Alcoholic patients
American Journal of Psychiatry, 2005Co-Authors: Andreas Heinz, Jana Wrase, Thomas Siessmeier, Hans Georg Buchholz, Gerhard Grunder, Yoshitaka Kumakura, Paul Cumming, Mathias Schreckenberger, Michael N Smolka, Frank RoschAbstract:OBJECTIVE: In abstinent Alcoholic patients, a low availability of dopamine D2/3 receptors in the ventral striatum and adjacent putamen was associated with a high level of Craving for Alcohol. Alcohol Craving may also depend on presynaptic dysfunction of striatal dopamine production, which may contribute to the risk of relapse. In this study, positron emission tomography (PET) was used to compare dopamine synthesis capacity in the striatum in Alcoholic patients and healthy comparison subjects. METHOD: Positron emission tomography (PET) was used to map the net blood-brain clearance of the dopa decarboxylase substrate 6-[18F]fluoro-l-dopa, an index of dopamine synthesis capacity, in the striatum of 12 detoxified male Alcoholic patients and 13 age-matched healthy men. The parametric maps were correlated with results of an earlier [18F]desmethoxyfallypride PET study of dopamine D2/3 receptor availability in the same 12 Alcoholic patients and in 12 of the healthy volunteers. Alcohol Craving was measured with th...
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correlation of stable elevations in striatal μ opioid receptor availability in detoxified Alcoholic patients with Alcohol Craving a positron emission tomography study using carbon 11 labeled carfentanil
Archives of General Psychiatry, 2005Co-Authors: Andreas Heinz, Jana Wrase, Matthias Reimold, Derik Hermann, B Croissant, Gotz Mundle, B M Dohmen, Dieter H Braus, Gunter Schumann, H J MachullaAbstract:BACKGROUND: The pleasant effects of food and Alcohol intake are partially mediated by mu-opiate receptors in the ventral striatum, a central area of the brain reward system. Blockade of mu-opiate receptors with naltrexone reduces the relapse risk among some but not all Alcoholic individuals. OBJECTIVE: To test the hypothesis that Alcohol Craving is pronounced among Alcoholic individuals with a high availability of mu-opiate receptors in the brain reward system. DESIGN: Patients and comparison sample. The availability of central mu-opiate receptors was measured in vivo with positron emission tomography (PET) and the radioligand carbon 11-labeled carfentanil in the ventral striatum and compared with the severity of Alcohol Craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS). SETTING: Hospitalized care. PARTICIPANTS: Volunteer sample of 25 male Alcohol-dependent inpatients assessed after detoxification of whom 12 underwent PET again 5 weeks later. Control group of 10 healthy men. MAIN OUTCOME MEASURES: After 1 to 3 weeks of abstinence, the availability of mu-opiate receptors in the ventral striatum, including the nucleus accumbens, was significantly elevated in Alcoholic patients compared with healthy controls and remained elevated when 12 Alcoholic patients had these levels measured 5 weeks later (P<.05 corrected for multiple testing). Higher availability of mu-opiate receptors in this brain area correlated significantly with the intensity of Alcohol Craving as assessed by the OCDS. CONCLUSIONS: Abstinent Alcoholic patients displayed an increase in mu-opiate receptors in the ventral striatum, including the nucleus accumbens, which correlated with the severity of Alcohol Craving. These findings point to a neuronal correlate of Alcohol urges.
Andreas Heinz - One of the best experts on this subject based on the ideXlab platform.
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identifying the neural circuitry of Alcohol Craving and relapse vulnerability
Addiction Biology, 2009Co-Authors: Andreas Heinz, Anne Beck, Sabine M Grusser, Anthony A Grace, Jana WraseAbstract:With no further intervention, relapse rates in detoxified Alcoholics are high and usually exceed 80% of all detoxified patients. It has been suggested that stress and exposure to priming doses of Alcohol and to Alcohol-associated stimuli (cues) contribute to the relapse risk after detoxification. This article focuses on neuronal correlates of cue responses in detoxified Alcoholics. Current brain imaging studies indicate that dysfunction of dopaminergic, glutamatergic and opioidergic neurotransmission in the brain reward system (ventral striatum including the nucleus accumbens) can be associated with Alcohol Craving and functional brain activation in neuronal systems that process attentional relevant stimuli, reward expectancy and experience. Increased functional brain activation elicited by such Alcohol-associated cues predicted an increased relapse risk, whereas high brain activity elicited by affectively positive stimuli may represent a protective factor and was correlated with a decreased prospective relapse risk. These findings are discussed with respect to psychotherapeutic and pharmacological treatment options.
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correlation of Alcohol Craving with striatal dopamine synthesis capacity and d2 3 receptor availability a combined 18f dopa and 18f dmfp pet study in detoxified Alcoholic patients
American Journal of Psychiatry, 2005Co-Authors: Andreas Heinz, Jana Wrase, Thomas Siessmeier, Hans Georg Buchholz, Gerhard Grunder, Yoshitaka Kumakura, Paul Cumming, Mathias Schreckenberger, Michael N Smolka, Frank RoschAbstract:OBJECTIVE: In abstinent Alcoholic patients, a low availability of dopamine D2/3 receptors in the ventral striatum and adjacent putamen was associated with a high level of Craving for Alcohol. Alcohol Craving may also depend on presynaptic dysfunction of striatal dopamine production, which may contribute to the risk of relapse. In this study, positron emission tomography (PET) was used to compare dopamine synthesis capacity in the striatum in Alcoholic patients and healthy comparison subjects. METHOD: Positron emission tomography (PET) was used to map the net blood-brain clearance of the dopa decarboxylase substrate 6-[18F]fluoro-l-dopa, an index of dopamine synthesis capacity, in the striatum of 12 detoxified male Alcoholic patients and 13 age-matched healthy men. The parametric maps were correlated with results of an earlier [18F]desmethoxyfallypride PET study of dopamine D2/3 receptor availability in the same 12 Alcoholic patients and in 12 of the healthy volunteers. Alcohol Craving was measured with th...
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correlation of stable elevations in striatal μ opioid receptor availability in detoxified Alcoholic patients with Alcohol Craving a positron emission tomography study using carbon 11 labeled carfentanil
Archives of General Psychiatry, 2005Co-Authors: Andreas Heinz, Jana Wrase, Matthias Reimold, Derik Hermann, B Croissant, Gotz Mundle, B M Dohmen, Dieter H Braus, Gunter Schumann, H J MachullaAbstract:BACKGROUND: The pleasant effects of food and Alcohol intake are partially mediated by mu-opiate receptors in the ventral striatum, a central area of the brain reward system. Blockade of mu-opiate receptors with naltrexone reduces the relapse risk among some but not all Alcoholic individuals. OBJECTIVE: To test the hypothesis that Alcohol Craving is pronounced among Alcoholic individuals with a high availability of mu-opiate receptors in the brain reward system. DESIGN: Patients and comparison sample. The availability of central mu-opiate receptors was measured in vivo with positron emission tomography (PET) and the radioligand carbon 11-labeled carfentanil in the ventral striatum and compared with the severity of Alcohol Craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS). SETTING: Hospitalized care. PARTICIPANTS: Volunteer sample of 25 male Alcohol-dependent inpatients assessed after detoxification of whom 12 underwent PET again 5 weeks later. Control group of 10 healthy men. MAIN OUTCOME MEASURES: After 1 to 3 weeks of abstinence, the availability of mu-opiate receptors in the ventral striatum, including the nucleus accumbens, was significantly elevated in Alcoholic patients compared with healthy controls and remained elevated when 12 Alcoholic patients had these levels measured 5 weeks later (P<.05 corrected for multiple testing). Higher availability of mu-opiate receptors in this brain area correlated significantly with the intensity of Alcohol Craving as assessed by the OCDS. CONCLUSIONS: Abstinent Alcoholic patients displayed an increase in mu-opiate receptors in the ventral striatum, including the nucleus accumbens, which correlated with the severity of Alcohol Craving. These findings point to a neuronal correlate of Alcohol urges.
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correlation of stable elevations in striatal μ opioid receptor availability in detoxified Alcoholic patients with Alcohol Craving a positron emission tomography study using carbon 11 labeled carfentanil
Archives of General Psychiatry, 2005Co-Authors: Andreas Heinz, Jana Wrase, Matthias Reimold, Derik Hermann, B Croissant, Gotz Mundle, B M Dohmen, Dieter H Braus, Gunter Schumann, H J MachullaAbstract:Background: The pleasant effects of food and Alcohol intake are partially mediated by µ-opiate receptors in the ventral striatum, a central area of the brain reward system. Blockade of µ-opiate receptors with naltrexone reduces the relapse risk among some but not all Alcoholic individuals. Objective: To test the hypothesis that Alcohol Craving is pronounced among Alcoholic individuals with a high availability of µ-opiate receptors in the brain reward system. Design: Patients and comparison sample. The availability of central µ-opiate receptors was measured in vivo with positron emission tomography (PET) and the radioligand carbon 11–labeled carfentanil in the ventral striatum and compared with the severity of Alcohol Craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS).