There is robust evidence indicating an overlap between neurobiological circuitry and pathways that regulate addictions and those that regulate appetite and food intake. Rodent work suggests a role of the appetitive peptide leptin in cocaine-seeking behaviours. The goal of this study was to investigate the possible relationship between plasma leptin concentrations and cocaine craving and use in patients seeking treatment for cocaine dependence.Patients (N = 43) with a DSM-IV diagnosis of cocaine dependence were studied before starting detoxification (baseline; T0) and then again 14 days after (T1; only those patients who abstained from cocaine during the study). Blood samples for plasma leptin concentrations were collected and cocaine craving was assessed using the Brief Cocaine Craving Questionnaire (Brief-CCQ). Food craving was also assessed using a food Visual Analogue Scale (f-VAS). Barratt Impulsiveness Scale (BIS) was used to evaluate impulsivity.Plasma leptin concentrations at T0 significantly correlated with baseline Brief-CCQ scores (r = 0.34, p < 0.05). Furthermore, plasma leptin concentrations at T1 significantly correlated with the baseline amount of cocaine used (r = 0.5, p < 0.05). There were no significant correlations between plasma leptin concentrations and f-VAS scores either at T0 or T1 (p’s > 0.05).The present study suggests a potential relationship between plasma leptin concentrations and cocaine craving and use. Future mechanistic studies are needed to determine whether manipulations of leptin signalling may lead to novel pharmacological approaches to treat cocaine addiction.

Objectives This study aims to evaluate different kinds of temperament and attachment in a sample of alcohol-dependent patients, divided in Cloninger typology 1 and 2, compared to an healthy group. Materials and procedure A group of 40 patients was recruited, in a 3 months period, from Alcohology Unit of “Villa Rosa” in Viterbo. This sample was selected by a clinical diagnosis of Alcohol Dependence and compared to a control group of 40 healthy subjects. Each participant was screened by: SCID-I for Axis I Diagnosis, SCID-II for Axis II Diagnosis, TEMPS-A for Temperament, ECR for Attachment Styles. Results Statistical analysis showed significative differences between the two groups ( p < 0.05). The mean of the scores ( t Student) and the Mann-Whitney U test results higher in the experimental group. Regarding the ECR, we found differences in the “avoidance” between Cloninger's typology 1 and 2. Control group: 92.5% of the subjects showed a “secure” attachment, 7.5% a “dismissing” attachment. Experimental group: 40% of the sample showed a “secure” attachment, 35% a “dismissing” attachment, 17.5% a “preoccupied” attachment and 7.5% a “fearful/avoidant” attachment. Discussion Our sample showed that the “preoccupied” and the “dismissing” attachment styles were the most prevalent among alcoholists, while the “secure” style was typical of control subjects. Concerning the TEMPS-A we found high prevalence of the hyperthymic and cyclothymic temperaments.

Energy balance and food intake are regulated by a complex set of peptides that originate from multiple tissues. The discovery of leptin, a pleiotropic adipocyte-derived cytokine, has attracted increasing interest because it represents a link between metabolism, nutritional status and immune response. By binding to its receptors, leptin influences the activity of various hypothalamic neurones and the expression of several orexigenic and anorexigenic neuropetides. Orexigenic peptides include neuropeptide Y (NPY), melanin-concentrating hormone, agouti-related protein (AgRP), galanin, orexin and galanin-like peptide (GALP). Anorexigenic peptides include pro-opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), neurotensin, corticotropin-releasing hormone (CRH) and brain-derived neurotrophic factors. Furthermore, regulation of the effects of ghrelin on the hypothalamic neurones has been suggested to be one of the important mechanisms by which leptin may control food intake and body weight. Feeding behaviour is greatly influenced by the rewarding properties of food, and a wide range of evidence points to potential parallels between overeating and recognized addictive behaviours such as abuse of alcohol, nicotine, cocaine and heroin. Leptin, in addition to reducing food intake, decreases the reward value of brain self-stimulation in the lateral hypothalamus. Some studies have investigated the functional significance of leptin action in ventral tegmental area dopamine neurons not only to regulate food intake but also to modulate the actions of drugs of abuse. In particular, it has been suggested that the CART system, regulated by leptin, may be an important connection between food- and drug-related rewards.There are common underlying neuronal processes involved in drug abuse and obesity. Progress in these circuits has the promise to help develop treatment strategies to lower the enormous burden of both of these diseases.

Pregabalin (PRE) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the α2-δ subunit of voltage-gated calcium channels. In this randomised, double-blind comparison trial with naltrexone (NAL), we aimed to investigate the efficacy of PRE on alcohol drinking indices. Craving reduction and improvement of psychiatric symptoms were the secondary endpoints. Seventy-one alcohol-dependent subjects were detoxified and subsequently randomised into two groups, receiving 50 mg of NAL or 150—450 mg of PRE. Craving (VAS; OCDS), withdrawal (CIWA-Ar) and psychiatric symptoms (SCL-90-R) rating scales were applied. Alcohol drinking indices and craving scores were not significantly different between groups. Compared with NAL, PRE resulted in greater improvement of specific symptoms in the areas of anxiety, hostility and psychoticism, and survival function (duration of abstinence from alcohol). PRE also resulted in better outcome in patients reporting a comorbid psychiatric disorder. Results from this study globally place PRE within the same range of efficacy as that of NAL. The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomatology.

age are also examined. Patterns of infant sleep within these groups are also explored. Methods: In the study, pregnant women were screened for depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS), and their symptom severity was assessed longitudinally with the Beck Depression Inventory. Women were divided into 6 risk groups: low/stable, intermediate, and high/increasing depression based upon longitudinal symptom severity and medication use. The infant neuroendocrine system was examined using cord blood ACTH and cortisol. These infants were examined at 2 weeks of age using Neonatal Intensive Care Unit Neurobehavioral Scale (NNNS). Results: Infants born to women of the high/increasing depression group had significant elevations in cord blood ACTH at birth. On NNNS examination at two weeks, these infants were more hypotonic and less attentive. They habituated to stimuli more quickly and had fewer visual signs and higher skin reactivity. Infants born to women using antidepressants had further elevations in cord blood ACTH, and were found to be more tremulous and excitable during NNNS examination. Infants born to women with higher depression severity demonstrating aberrations in their early sleep patterns and sleep entrainment. Conclusions: Maternal depression risk and antidepressant use may construe a different developmental pathway for development of the infant neuroendocrine axis which may impact early neonatal neurologic development.

Introduction: Leptin is a 16-kDa protein secreted from white adipocytes; it acts by binding to specific hypothalamic receptors to alter the expression of several neuropeptides regulating neuroendocrine function, food intake and the body's entire energy balance. Leptin receptors have been found in several brain areas, including the cerebellum, cortex, hippocampus, thalamus and in peripheral tissues including the liver, pancreas, adrenals, ovaries, and hematopoietic stein cells. Leptin regulates and is regulated by several neuropeptides and hormones, such as neuropeptide Y, melanocyte-stimulating-hormone, Agouti-related-hormone, pro-opiomelanocortin, orexin, cocaine- and amphetamine-regulated transcript, melanin-concentrating-hormone, insulin, IGF-system, sympathetic/parasympathetic tone, Immune function and hemopoiesis (cytokines), the hypothalamic-pituitary-gonadal axis and the thyroid and adrenal axes (CRH, TSH). Actually, leptin is considered a modulator of withdrawal-induced craving in alcoholic subjects. During detoxification, craving call shift towards other kinds of craving (e.g., food or smoking), but if plasma leptin increases during withdrawal this shift can be attenuated, and consequentially appetite decreases and alcohol craving call be enhanced, determining possible relapses in alcohol consumption. Leptin is involved in the brain reward Circuitry together with the CART-system, regulated by leptin itself, CART may be all important connection between food- and drug-related rewards. We studied the hypothesis that leptin might modulate cocaine craving in cocaine-detoxified addicts, evaluating any possible correlation with metabolic, hormonal and psychometric parameters.Methods: A sample of 12 cocaine-dependent Subjects, according to DSM-IV-TR, was evaluated as follows: height, weight (BMI), blood pressure, heart rate, substance and drug consumption, triglicerides, cholesterol, plasma leptin value, cortisol, insulin, ACTH, FT3, FT4, and TSH; and SHAPS, VASc/f/s (Visual-Analogue-Scale for cocaine/food/sex), CCQ (Cocaine-Craving-Questionnaire), Barratt Impulsiveness Scale, HAM-D, and HAM-A at baseline and after 15 days of abstinence.Results: Leptin results positively correlated with VASc, CCQ and HAM-A; VASc was positively correlated with CCQ and HAM-D. VASf was negatively correlated with cholesterol (as attended) and positively with VASs and TSH. CCQ was positively related with HAM-D and the plasma leptin mean levels in the male subsample were higher with respect to controls. Data is expressed as mean, standard deviation and Pearson correlation coefficiency.Conclusions: In our sample, leptin correlates with cocaine craving measured by VASc and CCQ independently from BMI or the hypothalamic-pituitary-adrenal axis. At baseline, VASc (mean) was less than VASf and s mean score, confirming the shifting craving phenomenon. Cocaine craving is correlated with depressive symptoms and leptin correlates with anxious symptoms. Although our data confirm the correlation between leptin and cocaine craving, further Studies are requested.

Aims Patients with dual diagnosis are often excluded from clinical trials although more than half of all individuals with Bipolar Disorder have a substance abuse problem at some point in their lifetime, representing a high-risk clinical population. The purpose of this study was to investigate the safety and efficacy of quetiapine in the treatment of alcohol dependence comorbid with disorders characterized by high levels of mood and behavioral instability.Methods Twenty-eight subjects, after a detoxification period, were orally treated with flexible doses of quetiapine for 16 weeks. At each assessment patients were evaluated through the Obsessive Compulsive Drinking Scale (OCDS), the Visual Analogue Scale (VAS) for craving, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI) scale.Results Forty-three percent of patients remained totally alcohol free, 32% patients relapsed, with an average of 15.4 drinking days in the period of the study (112 days) and 25% dropped-out. Significant reductions from baseline to exit were observed in the OCDS, VAS, BPRS, HDRS, and number of drinking days per week. Changes in alcohol craving correlated with psychiatric symptoms as to BPRS and HDRS, with the highest level of correlation evidenced for the HDRS items of insomnia.Discussion In this open-label study, quetiapine decreased alcohol consumption, craving for alcohol, and psychiatric symptoms intensity, maintaining a good level of tolerance. A strength of this study is that the use of quetiapine was not adjunctive with other pharmacological and non-pharmacological treatment. Double-blind placebo-controlled studies are required with a larger study population to confirm these data. In the meantime, for a select group of psychiatric patients, quetiapine may offer some advantages in preventing relapse. Copyright (c) 2008 John Wiley & Sons, Ltd.

Aims: The aim of the present study is to characterize the relevance of withdrawal symptoms during the first 12 months of abstinence and their relation to anhedonia and craving. Methods: 102 detoxified subjects meeting clinical criteria for Alcohol Dependence in Remission were recruited at various time since the detoxification and subdivided into four groups according to the length of abstinence (group 1: 15-30 days; group 2: 30-90 days; group 3: 90-180 days; group 4: 180-360). Withdrawal symptomatology was assessed through the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The Visual Analogue Scale (VAS) for craving, the Snaith-Hamilton Pleasure Scale (SHAPS) and the Subscale for Anhedonia in the Scale for the Assessment of Negative Symptoms (SANSanh) where the other instruments employed. Results: Both anhedonia and withdrawal symptoms were identified in all the groups considered. SHAPS score and VAS for craving showed a significant difference between group 1 and groups 2, 3, and 4. As to CIWA-Ar items, apart from "orientation/clouding of sensorium" that was higher in groups 3 and 4 with respect to both groups 1 and 2, withdrawal symptoms were not significantly different between the periods considered. SHAPS and SANSanh were positively correlated to CIWA-Ar total score, "nausea and vomiting," and "headache/fullness in head." Discussion: The results of this study suggest the relevance of protracted withdrawal well beyond the limited period following the abrupt cessation of alcohol intake. The clinical dimension of anhedonia cannot be separated from the other behavioral symptoms of withdrawal and should be considered as part of the same process.

INTRODUCTION:Oxcarbazepine (OXC) reduces high-voltage-activated calcium currents, thus reducing glutamatergic transmission at corticostriatal synapses. This effect on NMDA glutamatergic transmission may play a role against the increased glutamatergic transmission determined by alcohol withdrawal. To investigate the efficacy and safety of OXC in relapse prevention we compared OXC at different dosages with Naltrexone (NAL) in a 90 days randomised open-label trial. Craving and psychiatric symptoms improvements were the secondary endpoints. METHODS:Eighty-four detoxified alcohol dependent subjects currently meeting clinical criteria for alcohol dependence were randomised into three groups: 27 patients received 50 mg of naltrexone, 29 received 1500-1800 mg of oxcarbazepine (OXC high), 28 patients 600-900 mg of oxcarbazepine (OXC low). Craving (VAS; OCDS) and withdrawal (AWRS) rating scales were applied; psychiatric symptoms were evaluated through the SCL-90-R. RESULTS:A significantly larger number of subjects remained alcohol free in the OXC high group (58.6%) with respect to both the OXC low (42.8%) and the NAL groups (40.7%). Comparing the OCDS total scores at the end of the treatment, the improvement was significantly greater for the NAL group with respect to the OXC low group. The reduction of the Hostility-Aggression subscore of the SCL-90-R was significantly greater in the OXC high group than that of the other groups. Dual diagnosis patients had a better outcome when treated with OXC high. DISCUSSION:OXC at a dosage of 1500-1800 mg/day might be beneficial in terms of alcohol relapse prevention. The low dosage formulation did not show the same trend, but it still remain in the same range as NAL. The mechanism involved in the efficacy of oxcarbazepine in relapse prevention could be less related to craving and more connected to the treatment of the comorbid psychiatric symptomatology and the alcohol protracted withdrawal syndrome.