Leptin is associated with craving in females with alcoholism
ABSTRACT The appetite and weight regulating peptide leptin was associated recently with alcohol craving during withdrawal. Nevertheless, correlations were only significant with craving displayed on the visual analogue scale for maximum craving during the previous week (VAS), and not if assessed with the highly validated Obsessive Compulsive Drinking Scale (OCDS). The objective of the following study, therefore, is to elucidate further the associations between the leptin system and craving concepts during alcohol withdrawal. A sufficiently large sample size should allow multiple statistical subgroup and confounder analyses. We prospectively investigated 102 chronic alcoholic inpatients (23 females, 79 males) during withdrawal on days 0 (admission), 1, 2 and days 7-10. In addition to the statistical analysis of the total sample, females and males were to be analysed separately. For detecting associations between leptin levels and craving scores multiple regression analysis was performed. Plasma leptin levels were determined, and craving for ethanol was assessed by both the OCDS and the VAS. Leptin plasma levels significantly increased during alcohol withdrawal compared to day 0, while all craving scores decreased. Body mass corrected leptin plasma levels predicted craving on day 0 in the OCDS total score (R=0.55, F=7.91, df=1.19, p<0.05) and in the OCDS obsessive subscore (R=0.57, F>=8.48, df=1.19, p<0.05) in females. Neither in males nor in the total population did multiple regression analysis reveal any significant results. Leptin levels seem to change during inpatient alcohol withdrawal. In a multivariate model, correlations between leptin levels and the highly validated craving scores of the OCDS can only be assumed in females. Hence, gender differences have to be taken into account when searching for neurobiological models of alcohol craving.
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ABSTRACT: N-acetylcysteine (NAC), a glutamate-modulating agent with antioxidant and anti-inflammatory properties, has been considered as a potential anti-addictive drug. Beneficial effects were reported for cocaine, cannabis, and tobacco addicts, but the effect of NAC in alcoholics or in alcohol animal models is unknown. The aggravation of alcohol withdrawal symptoms, such as anxiety, has been associated with increased levels of serum corticosterone and leptin. Thus, the aim of this study was to assess the effects of NAC on anxiety, as well as corticosterone and leptin serum levels, after cessation of chronic alcohol treatment in rats. Male Wistar rats were treated with 2 g/kg ethanol, twice daily, by gavage for 30 days; control animals received an appropriate dose of glucose to balance caloric intake. Rats were treated for 4 days with NAC (60 and 90 mg/kg, intra-peritoneally [i.p.]) or saline after alcohol cessation. Twenty-four hours after the last treatment, rats were exposed to a 5-min session in the open-field test (OF). Corticosterone and leptin serum levels were determined by ELISA in samples collected within 30 min after the OF. Results showed that rats were hypoactive (decreased rearing, peripheral, and total crossings), and that corticosterone and leptin levels were increased 5 days after alcohol cessation. Four days of NAC prevented the behavioral and biochemical changes brought about by alcohol cessation. We suggest that, in addition to the anti-addictive properties reported for other drugs of abuse, NAC is potentially useful in the management of alcohol withdrawal. Copyright © 2015 Elsevier Inc. All rights reserved.Alcohol (Fayetteville, N.Y.) 02/2015; 49(3). DOI:10.1016/j.alcohol.2015.01.009 · 2.04 Impact Factor
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ABSTRACT: Childhood maltreatment has been associated with addiction and immune dysregulation, although neurobiological substrates underlying this association remain largely unknown. The aim of the study was to compare plasma levels of adipokines during early abstinence in crack cocaine dependent women with (CM+) and without history of childhood maltreatment (CM-). One hundred four crack cocaine female users were followed for 20 days in a detoxification inpatient treatment unit. Plasma levels of adiponectin, resistin and leptin were assessed every 7 days during 3 weeks of follow-up. The Childhood Trauma Questionnaire (CTQ) retrospectively assessed childhood maltreatment history. A healthy control group was included to provide adipokines reference values (HC). All crack users increased leptin plasma levels during early abstinence despite concentrations remained lower in comparison with non-users group. Crack users reporting childhood maltreatment exhibited a significant reduction in plasma levels of adiponectin and resistin when compared to CM- group. In addition, only CM- participants increased plasma levels of adiponectin during detoxification. This is the first study evaluating adipokines during crack cocaine abstinence. Our results suggest a modulator effect of childhood maltreatment on inflammatory status in treatment-seeking crack cocaine dependents during early abstinence.Psychiatry Research 07/2013; DOI:10.1016/j.psychres.2013.07.007 · 2.68 Impact Factor
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ABSTRACT: Stress and alcohol context cues are each associated with alcohol-related behaviors, yet neural responses underlying these processes remain unclear. This study investigated the neural correlates of stress and alcohol context cue experiences and examined sex differences in these responses. Using functional magnetic resonance imaging, brain responses were examined while 43 right-handed, socially drinking, healthy individuals (23 females) engaged in brief guided imagery of personalized stress, alcohol-cue, and neutral-relaxing scenarios. Stress and alcohol-cue exposure increased activity in the cortico-limbic-striatal circuit (P < 0.01, corrected), encompassing the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), left anterior insula, striatum, and visuomotor regions (parietal and occipital lobe, and cerebellum). Activity in the left dorsal striatum increased during stress, while bilateral ventral striatum activity was evident during alcohol-cue exposure. Men displayed greater stress-related activations in the mPFC, rostral ACC, posterior insula, amygdala, and hippocampus than women, whereas women showed greater alcohol-cue-related activity in the superior and middle frontal gyrus (SFG/MFG) than men. Stress-induced anxiety was positively associated with activity in emotion-modulation regions, including the medial OFC, ventromedial PFC, left superior-mPFC, and rostral ACC in men, but in women with activation in the SFG/MFG, regions involved in cognitive processing. Alcohol craving was significantly associated with the striatum (encompassing dorsal, and ventral) in men, supporting its involvement in alcohol "urge" in healthy men. These results indicate sex differences in neural processing of stress and alcohol-cue experiences and have implications for sex-specific vulnerabilities to stress- and alcohol-related psychiatric disorders.Human Brain Mapping 11/2011; 32(11):1998-2013. DOI:10.1002/hbm.21165 · 6.92 Impact Factor