Use of pharmacological treatments by a sample of Italian patients affected by alcohol use disorders

Title: USE OF PHARMACOLOGICAL TREATMENTS BY A SAMPLE OF ITALIAN PATIENTS AFFECTED BY ALCOHOL USE DISORDERS Author name(s): R. Agabio; E.M. Diana; D. Grazzini; R. Pirastu; G.L. Gessa Institution: Department of Biochemical Sciences, Section of Neuroscience, Preclinical and Clinical Pharmacology, University of Cagliari, Italy Text Background: It has often been reported that the majority of patients affected by Alcohol Use Disorders (AUDs) do not receive any pharmacological treatment. This study was aimed at investigating the use of the medications available in Italy (disulfiram, naltrexone, acamprosate, and γ-hydroxybutyric acid) by a sample of outpatients affected by AUDs. Methods: Four trained psychologists interviewed outpatients affected by AUDs in an area of Sardinia, Italy, of approximately 550.000 adult inhabitants. Results: A total sample of 208 outpatients affected by AUDs was interviewed (~1/3 of total outpatients affected by AUDs of that area). Their main features were: 166 males (79.5%); mean age=48.6±0.6 year; duration of AUDs=15.8±0.7 years; number of drinks per drinking days=19.4±1.3; number of criteria of DSM-IV-Tr=5.8±0.1. Before the admission into specific services, 13 patients (6.2%) had already received medication for AUDs; 7 patients (3.4%) had received disulfiram and 6 patients (2.9%) γ-hydroxybutyric acid. Over the same period, 22 patients (10.6%) had already attended self-help groups and 4 patients (1.9%) had received thiamine (Vitamine B1). After the admission into specific medical settings for the treatment of AUDs, 113 patients (54.3%) received medication for AUDs: 58 patients (27.9%) received disulfiram, 65 patients (31.2%) γ-hydroxybutyric acid, 2 patients (1.0%) naltrexone, and 6 patients (2.9%) acamprosate. In the same period, 54 patients (26.0%) frequented self-help associations, and 21 patients (10.1%) received thiamine. Conclusions: The results of this study confirm that the number of patients who receive a treatment for AUDs continues to be surprisingly low. Despite the long duration and the high level of severity of the AUDs, the majority of patients affected by AUDs did not receive any treatment before their admission in specific medical settings for the treatment of AUDs (10% of patients frequented self-help groups, 6% received a medication for AUDs, and 2% thiamine). After the admission into specific medical settings, the number of patients who received a treatment increased: 26% frequented self-help associations, 54% received a specific medication, and 10% received thiamine. However, approximately half of the patients did not receive any pharmacological treatment even if they frequented medical settings for the treatment of AUDs. Additional work is needed to understand the reasons of such a scarce use of treatments. Acknowledgements: This study was supported by a grant from Regione Autonoma della Sardegna

Unawareness of Alcoholic Content of Alcopops among 13-Year Old Italian Teenagers.

Aims: Alcopops are ready-mixed drinks containing approximately the same amount of alcohol as beer, usually sweet, and flavoured, particularly appealing to young people. The present study was aimed to investigate whether young adolescents aged 12-14 years, corresponding to the average age of the first drink, are capable of identifying the presence of alcohol in these beverages. Methods: Administration of a questionnaire comprising 8 questions investigating knowledge and consumption of different alcoholic and non-alcoholic beverages to a sample of 13-year old Italian students. Results: More than 20% of a sample of 224 students reported that they were unaware of the alcoholic content of alcopops at the age of the first drink. The number of students unable to distinguish alcopops from non-alcoholic beverages was significantly higher than students who were not able to distinguish beer from alcohol-free beverages. Conclusions: At the age of the first drink, the identification of alcopops as alcoholic beverages is more difficult than that of other beverages containing the same amount of alcohol. Information aimed at increasing the ability of adolescents to distinguish between alcoholic and non-alcoholic beverages should be provided to young adolescent students before they start drinking

Gender Differences among Sardinians with Alcohol Use Disorder

Sardinia is an Italian island in the Mediterranean characterized by secular isolation and the singular genetic characteristics of its inhabitants. Findings obtained in populations with diverse genetic make-up and cultural background indicate gender differences and/or similarities in drinking characteristics of patients with alcohol use disorder (AUD). Knowledge of these characteristics in AUD patients is useful to improve access to treatments. This paper investigated the drinking characteristics of 66 female and 282 male outpatients with AUD, born from 1937 to 1991, living in Sardinia, and compared their characteristics with those of AUD patients living in other countries. Most Sardinian patients were men, approximately 3 years younger than women; women consumed lower amounts of alcohol than men but did not differ from men in the severity of AUD. Men were more often single than women, while a higher proportion of women reported that their mother or spouse was affected by AUD. Anxiety and depression were more prevalent among women while a higher proportion of men were affected by substance use disorders. Women were older than men at the age of first drink, regular drinking, and onset of AUD, and progressed faster than men from regular use to AUD onset. Women did not differ from men in age at first request for care, and in the lapse from AUD onset to first request for care. Women and men waited for more than 8 and 9 years, respectively, before receiving medical treatment. Gender differences progressively decreased among younger patients. Although the scarce number of women in some cohorts limits the strength of these findings, drinking characteristics of Sardinian patients did not vary significantly from those of AUD patients living in other countries. These results suggest that the number of Sardinian women with AUD is increasing and services for treatment of AUD should (a) consider women’s specific needs, and (b) realize effective policies to reduce latency prior to accessing medical treatment for both men and women with AUD

Tryptophan depletion disinhibits punishment but not reward prediction: implications for resilience

Item does not contain fulltextRATIONALE: We have previously shown that tryptophan depletion enhances punishment but not reward prediction (Cools et al. in Neuropsychopharmacology 33:2291-2299, 2008b). This provided evidence for a valence-specific role of serotonin (which declines under depleted tryptophan) in aversive processing. Recent theoretical (Dayan and Huys in PLoS Comput Biol 4:e4, 2008) and experimental (Crockett et al. in J Neurosci 29:11993-11999, 2009) approaches have, however, further specified this role by showing that serotonin is critical for punishment-induced inhibition. OBJECTIVES: We sought to examine the role of serotonin in punishment-induced inhibition. We also examined the impact of induced mood on this effect to assess whether effects of tryptophan depletion on affective inhibition are moderated by mood. METHODS: Healthy females consumed a balanced amino acid mixture with (N = 20) or without (N = 21) the serotonin precursor tryptophan. Each subject completed either negative or neutral mood induction. All subjects completed the reward and punishment reversal learning task adopted in the previous study. RESULTS: We demonstrate a punishment prediction impairment in individuals who consumed tryptophan which was absent in individuals who were depleted of tryptophan. This effect was impervious to mood state. CONCLUSIONS: Our results suggest that serotonin promotes the inhibition of responses to punishing outcomes. This may lead to reduced punishment prediction accuracy in the presence of tryptophan and may contribute to resilience to affective disorders. Reduction of serotonin via tryptophan depletion then removes this inhibition. As such, we highlight a mechanism by which reduced serotonin can contribute to disorders of impulsivity and compulsivity as well as disorders of emotion.1 januari 201

The Effects of Acute Tryptophan Depletion on Reactive Aggression in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and Healthy Controls

Background: The neurotransmitter serotonin (5-HT) has been linked to the underlying neurobiology of aggressive behavior, particularly with evidence from studies in animals and humans. However, the underlying neurobiology of aggression remains unclear in the context of attention-deficit/hyperactivity disorder (ADHD), a disorder known to be associated with aggression and impulsivity. We investigated the effects of acute tryptophan depletion (ATD), and the resulting diminished central nervous serotonergic neurotransmission, on reactive aggression in healthy controls and adults with ADHD. Methodology/Principal Findings: Twenty male patients with ADHD and twenty healthy male controls were subjected to ATD with an amino acid (AA) beverage that lacked tryptophan (TRP, the physiological precursor of 5-HT) and a TRPbalanced AA beverage (BAL) in a double-blind, within-subject crossover-study over two study days. We assessed reactive aggression 3.25 hours after ATD/BAL intake using a point-subtraction aggression game (PSAG) in which participants played for points against a fictitious opponent. Point subtraction was taken as a measure for reactive aggression. Lowered rates of reactive aggression were found in the ADHD group under ATD after low provocation (LP), with controls showing the opposite effect. In patients with ADHD, trait-impulsivity was negatively correlated with the ATD effect on reactive aggression after LP. Statistical power was limited due to large standard deviations observed in the data on point subtraction, which may limit the use of this particular paradigm in adults with ADHD

The effects of acute tryptophan depletion on costly information sampling: impulsivity or aversive processing?

RATIONALE: The neurotransmitter serotonin (5-HT) has been implicated in both aversive processing and impulsivity. Reconciling these accounts, recent studies have demonstrated that 5-HT is important for punishment-induced behavioural inhibition. These studies focused on situations where actions lead directly to punishments. However, decision-making often involves making tradeoffs between small 'local' costs and larger 'global' losses. OBJECTIVE: We aimed to distinguish whether 5-HT promotes avoidance of local losses, global losses, or both, in contrast to an overall effect on reflection impulsivity. We further examined the influence of individual differences in sub-clinical depression, anxiety and impulsivity on global and local loss avoidance. METHODS: Healthy volunteers (N = 21) underwent an acute tryptophan depletion procedure in a double-blind, placebo-controlled crossover design. We measured global and local loss avoidance in a decision-making task where subjects could sample information at a small cost to avoid making incorrect decisions, which resulted in large losses. RESULTS: Tryptophan depletion removed the suppressive effects of small local costs on information sampling behaviour. Sub-clinical depressive symptoms produced effects on information sampling similar to (but independent from) those of tryptophan depletion. Dispositional anxiety was related to global loss avoidance. However, trait impulsivity was unrelated to information sampling. CONCLUSIONS: The current findings are consistent with recent theoretical work that characterises 5-HT as pruning a tree of potential decisions, eliminating options expected to lead to aversive outcomes. Our results extend this account by proposing that 5-HT promotes reflexive avoidance of relatively immediate aversive outcomes, potentially at the expense of more globally construed future losses

Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers

It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. Using a high-dose carbon dioxide (CO2) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO2-induced panic response in healthy volunteers. Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO2 inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO2. CO2-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p <0.05). In the separate-group analysis, Delta VAAS scores were positively correlated to the ratio Trp:I LNAA pound after treatment (r = 0.39; p <0.05). The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects

The Serotonin 5-HT7Dro Receptor Is Expressed in the Brain of Drosophila, and Is Essential for Normal Courtship and Mating

The 5-HT7 receptor remains one of the less well characterized serotonin receptors. Although it has been demonstrated to be involved in the regulation of mood, sleep, and circadian rhythms, as well as relaxation of vascular smooth muscles in mammals, the precise mechanisms underlying these functions remain largely unknown. The fruit fly, Drosophila melanogaster, is an attractive model organism to study neuropharmacological, molecular, and behavioral processes that are largely conserved with mammals. Drosophila express a homolog of the mammalian 5-HT7 receptor, as well as homologs for the mammalian 5-HT1A, and 5-HT2, receptors. Each fly receptor couples to the same effector pathway as their mammalian counterpart and have been demonstrated to mediate similar behavioral responses. Here, we report on the expression and function of the 5-HT7Dro receptor in Drosophila. In the larval central nervous system, expression is detected postsynaptically in discreet cells and neuronal circuits. In the adult brain there is strong expression in all large-field R neurons that innervate the ellipsoid body, as well as in a small group of cells that cluster with the PDF-positive LNvs neurons that mediate circadian activity. Following both pharmacological and genetic approaches, we have found that 5-HT7Dro activity is essential for normal courtship and mating behaviors in the fly, where it appears to mediate levels of interest in both males and females. This is the first reported evidence of direct involvement of a particular serotonin receptor subtype in courtship and mating in the fly