Jakob Hein

Ventral Striatal Activation During Reward Anticipation Correlates with Impulsivity in Alcoholics

BACKGROUND Alcohol dependence is often associated with impulsivity, which may be correlated with dysfunction of the brain reward system. We explored whether functional brain activation during anticipation of incentive stimuli is associated with impulsiveness in detoxified alcoholics and healthy control subjects. METHODS Nineteen detoxified male alcoholics and 19 age-matched healthy men participated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay (MID) task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain, avoidance of monetary loss, or no consequence. Impulsivity was assessed with the Barratt Impulsiveness Scale-Version 10 (BIS-10). RESULTS Detoxified alcoholics showed reduced activation of the ventral striatum during anticipation of monetary gain relative to healthy control subjects. Low activation of the ventral striatum and anterior cingulate during gain anticipation was correlated with high impulsivity only in alcoholics, not in control subjects. CONCLUSIONS This study suggests that reduced ventral striatal recruitment during anticipation of conventional rewards in alcoholics may be related to their increased impulsivity and indicate possibilities for enhanced treatment approaches in alcohol dependence.

Reward anticipation and outcomes in adult males with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) has been suggested to involve deficits in reward processing. We used functional magnetic resonance imaging (fMRI) to compare the neural responses to reward anticipation and outcomes in 10 adults with ADHD and 10 controls as they played a monetary incentive delay task. Adults with ADHD were unmedicated, and groups were matched for age, verbal IQ and smoking habits. Adults with ADHD showed decreased activation in the ventral striatum during the anticipation of gain, but increased activation of the orbitofrontal cortex in response to gain outcomes. Ventral striatal activation in adults with ADHD during gain anticipation was negatively correlated with self-rated symptoms of hyperactivity and impulsivity. These findings suggest that male adults with ADHD show neural signs of abnormal reward processing. Future studies will have to investigate whether these dysfunctional patterns might be normalized by treatment.

Leptin and its associations with measures of psychopathology in patients with anorexia nervosa.

Apart from energy homeostasis leptin has been shown to be involved in a number of neuronal networks. The aim of this study was to investigate how the residual variance of leptin levels, after controlling for BMI, is linked to eating-disorder-specific psychopathology and sexual desire in patients with anorexia nervosa (AN) compared to healthy controls. The sample included 57 subjects with acute AN and 77 healthy controls. Psychopathology was determined by EDI-2 and SCL-90-R and sexual problems were rated according to the Structured Interview of Anorexia Nervosa and Bulimic Syndromes (SIAB-EX). Plasma leptin was assessed by ELISA. Patients with a high drive for thinness had lower leptin levels at a given BMI and low leptin levels were associated with sexual problems, i.e. the absence of sexual desire and intimate relationships. Our results are in accordance with recent animal experiments linking low leptin levels with decreased sexual interest irrespective of body weight.

Efficacy and safety of levetiracetam for outpatient alcohol detoxification.

INTRODUCTION Anticonvulsant drugs are increasingly being used for alcohol detoxification in in- and outpatient settings. The aim of this study was to examine the efficacy, medical safety and mid-term outcome of levetiracetam, a drug with no marked liver toxicity, for outpatient alcohol detoxification. METHODS This was an open-label observational study. After screening eligibility for outpatient alcohol detoxification, patients were seen daily for 5 days and received levetiracetam in a flexible dosage regime between 500 and 4 000 mg/d for a maximum of 7 days. Diazepam was used as a rescue medication. The severity of alcohol withdrawal was evaluated daily using the ALCOHOL WITHDRAWAL SYNDROME SCALE (AWSS). Mid-term treatment outcome was assessed at a 6-month follow-up. RESULTS A total number of 131 consecutively admitted alcohol-dependent patients received an outpatient detoxification treatment, 122 (93.1%) completed the programme successfully. The mean initial dose of levetiracetam was 1 850 mg/d. Alcohol withdrawal syndrome as indicated by the AWSS score decreased clearly over 5 days. Overall, the medication was well tolerated. There was no treatment discontinuations due to side effects of levetiracetam. No serious medical complications, especially seizures or deliria, were observed during the detoxification. At the 6-month follow-up, 57 patients (43.5%) were still abstinent. Patients with previous detoxifications had a significant higher risk for relapse (HR=1.88; p=0.016; CI 95%: 1.12-3.14) than patients without previous treatments. DISCUSSION The findings of this study provide some evidence that levetiracetam is an efficacious and safe treatment option for outpatient alcohol detoxification. Further randomised, controlled trials including mid- and long-term follow-ups are needed to confirm these findings.

Psychopathology in underweight and weight-recovered females with anorexia nervosa

AbstractObjective: To compare general and eating disorder-specific psychopathology in patients with acute anorexia nervosa (acAN), weight-recovered patients (recAN) and healthy control women (HCW). Methods: One hundred anorexia nervosa patients (66 acAN and 34 recAN) and 88 HCW were included in our study. Psychopathology was assessed by self-report questionnaires [Symptom Check List 90 Revised (SCL-90-R), Eating Disorder Inventory-2 (EDI- 2)] as well as by interview [Structured Interview of Anorexia Nervosa and Bulimic Syndromes (SIAB-EX)] and compared using multivariate analysis of variance. Plasma leptin levels were determined using enzyme linked immunosorbent assay. Results: Mean comparisons indicated highly significant differences between acAN and recAN subjects on all psychopatholgy variables, except for perfectionism. RecAN subjects did not differ from HCW. Partial weight recovery was associated with decreasing levels of psychopathology. Correlational analyses suggested strong negative associations between leptin levels and psychopathology. Conclusion: Prolonged malnutrition, as indicated by suppressed plasma leptin levels, is strongly related to eating disorder-specific as well as general psychopathological symptoms. Weight recovery is associated with the absence of psychopathology. These data emphasize the interaction between somatic and psychological variables.

A combination of levetiracetam and tiapride for outpatient alcohol detoxification: a case series.

Objectives:Optimal pharmacotherapy of the alcohol withdrawal syndrome (AWS) in outpatient settings is still a matter of discussion. The aim of this evaluation was to examine the efficacy and tolerability of a combination of levetiracetam and tiapride for outpatient alcohol detoxification. Methods:This was an open-label evaluation. After screening eligibility for outpatient detoxification, 9 alcohol-dependent patients received levetiracetam and tiapride in a flexible dosage regimen up to 2500 and 300 mg/d, respectively, for a maximum of 7 days. Severity of alcohol withdrawal was assessed daily using the Alcohol Withdrawal Syndrome Scale (AWSS). Results:All patients completed the treatment successfully. The mean initial doses of levetiracetam and tiapride were 2166.7 and 300 mg/d, respectively. AWS as indicated by the AWSS score decreased clearly over 5 days. The combination of levetiracetam and tiapride was well tolerated. Neither treatment discontinuations because of side effects of the medication nor serious medical complications were observed during the detoxification. Conclusions:The results of this evaluation provide first evidence that the combination of levetiracetam and tiapride might be an effective and safe treatment option for mild to moderate AWS in outpatient settings. Further randomized controlled trials are warranted to confirm these preliminary results.

Treatment of pathological gambling with disulfiram: a report of 2 cases.

Introduction ▼ Pathological gambling (PG) is a condition consisting of persistent and repetitive patterns of gambling, often associated with impaired functioning, reduced quality of life, bankruptcy and divorce [1, 2] . The prevalence of PG in the general population is estimated as 0.42 % in the U. S. [3] , the corresponding rates in Germany range from 0.19 to 0.56 % [4] . Although several lines of clinical evidence suggest common features of PG and substance dependence [5] , the disorder is currently categorized in the group of “ habit and impulse disorders ” in ICD-10 [6] and “ impulsive control disorders not elsewhere classifi ed ” in DSM-IV [7] . Shared characteristics of PG and substance dependence include genetic [8] , phenomenological and clinical [9] as well as common neural features, especially alterations of the mesolimbic reward system [10] . An fMRI study reported a reduced activation in the ventral striatum and the ventromedial and ventrolateral prefrontal cortex in patients with PG in the processing of monetary rewards during a gambling paradigm in comparison to healthy subjects [11] . Similar results have been shown in patients with alcohol dependence [12 – 14] and cocaine dependence [15] , suggesting a common pathophysiological mechanism in both PG and substance dependence and thereby substantiating the understanding of PG as a non-substance-related addiction. Current treatment approaches for PG include cognitive-behavioral therapy as well as pharmacotherapies using opiate antagonists like naltrexone [16] , lithium [17] , selective serotonin reuptake inhibitors [18] and the glutamatergic agent N -acetylcysteine [19] . However, the overall eff ect sizes of these treatment concepts are only modest and approved pharmacotherapies are lacking. Disulfi ram, an aldehyde dehydrogenase inhibitor, is being used for more than 50 years as an aversion therapeutic agent for the treatment of alcohol dependence [20] . Besides this well-known mechanism of action, disulfi ram is also able to inhibit the dopamine beta-hydroxylase which metabolizes dopamine to norepinephrine [21] . Via this eff ect, administration of disulfi ram leads to an increase of dopamine concentrations while decreasing the concentrations of norepinephrine in the brain [22, 23] . Based upon the observations that PG is associated with diminished activation of the dopaminergic reward system [11] and elevated levels of norepinephrine or its metabolites in cerebrospinal fl uid, plasma and urine [24] , disulfi ram has been hypothesized to be a new pharmacological treatment option for this disorder [25, 26] . In cocaine dependence, disulfi ram has already shown preliminary effi cacy in reducing relapse rates. However, there is only low evidence for its broad clinical use until now [27] . In this report, we present 2 cases of patients meeting the diagnostic criteria for PG according to ICD-10 and DSM-IV who received a pharmacotherapy with disulfi ram. To assess changes in severity of PG, both patients completed the pathological gambling adaption of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS), a reliable and validated 10-item questionnaire [28] , at every visit.

»Spice« et cetera - Zur Wirksamkeit von Verbotsregelungen im Kontext einer globalisierten Suchtrealität

Seit dem 22. Januar sind Herstellung, Handel und Besitz der Modedroge »Spice« nach dem § 1 des »Gesetz uber den Verkehr mit Betaubungsmitteln« verboten (Deutsches Arzteblatt, 2009). Das Bundesgesundheitsministerium setzte dieses Verbot in einem Eilverfahren durch, nachdem eine Arbeitsgruppe am Institut fur forensische Toxikologie der Universitat Freiburg in der Substanz die synthetischen Cannabinoide CP 47-497 sowie JWH-018 nachweisen konnte (Auwarter et al., 2009). Der Nachweis der synthetischen Cannabinoide war in gewisser Hinsicht eher ein »Glucksfall«, denn war so das Verbot der Substanz leicht zu begrunden, die offiziell als Mittel zur »Verbesserung der Raumluft« gehandelt wurde. Interessanterweise werden die Hersteller von »Spice« eben wegen dieser synthetischen Zusatze in der Cannabiskonsumenten-Szene auch wegen »mieser Geschaftspraktiken« und »Profitgier« kritisiert (Cassee, 2009). Langst werden Alternativpraparate in den selben Laden, beispielsweise unter dem Namen »Space« angeboten, die offiziell naturlich wieder zur Verbesserung der Raumluft eingesetzt werden, aber inoffiziell ebenso wirken sollen wie das eben verbotene »Spice« (Oberlander, 2009). In den letzten Jahren werden mit groser Regelmasigkeit immer wieder neue Modedrogen in der Offentlichkeit diskutiert. Genannt seien GHB, Ketamin, Tilidin, Lachgas und Absinth, die jeweils in grosen medialen Wellen diskutiert wurden (Hein, Juckel, Kienast, & Heinz, 2005). Einige dieser Substanzen wurden verboten und andere mit Einschrankungen versehen. Insbesondere aber bei den pflanzlichen Drogen wie Bilsenkraut, Stechapfel, Engels-trompete – um nur einige wenige zu nennen – ist ein Verbot nicht praktikabel. Uberhaupt ist in der Konsumenten-Szene absolute Gelassenheit gegenuber den Aktivitaten des Gesetzgebers zu bemerken. Die Substanzen, die heute in den Medien bekannt und morgen vielleicht verboten werden, sind in der Szene oft schon »von gestern«. Auch das Konsummuster der bekannten Suchtmittel hat sich bei den Jugendlichen verandert. Viel diskutiert worden ist das so genannte »KomaSaufen«. Zwar trinken Jugendliche durchschnittlich etwa genauso viel Alkohol wie in fruheren Jahren, dies aber auf weniger Anlasse verteilt. 2007 gaben 63 % der mannlichen Jugendlichen zwischen 16 und 17 Jahren an, in den letzten dreisig Tagen mindestens einmal funf Getranke oder mehr konsumiert zu haben (Bundeszentrale fur gesundheitliche Aufklarung, 2007). Auch beim Cannabiskonsum hat sich vieles geandert, statt des gemeinschaftlichen Konsums beliebiger Cannabisprodukte werden THC-optimierte Hybridsorten gewissermasen Rausch-optimiert konsumiert (Unglaub, 2004). Gerade durch die interaktiven Gestaltungsmoglichkeiten des Web 2.0 hat sich in den letzten Jahren ein groses Kollektivwissen zu Rauschmitteln angesammelt, das oft die Kenntnisse von Fachleuten ubersteigt. So ist der brasilianische Muira Puama – Baum sicherlich nur wenigen Suchtexperten bekannt, im Internet kann man aber jederzeit nachlesen, wie man mit dem Holz eine halluzinogene Rauschwirkung erzielen kann (Drogenwiki.de, 2009). Deutschland ist ein Suchtstoffe konsumierendes Land, eine flachendeckende Abstinenz ist insofern nicht das Ziel der Drogenpolitik. Ziel des Gesetzgebers ist es vielmehr, die Kontrolle uber Suchtund Betaubungsmittel zu behalten. Angesichts der Globalisierung und des internationalen Austausches von Drogenkonsumenten scheint dieses Ziel zunehmend weniger realistisch. Angesichts neuer Kommunikationsrealitaten werden Verbote einzelner Substanzen am Sachverhalt des Drogenkonsums in Deutschland immer weniger andern konnen. »Spice« et cetera: On the effectiveness of prohibitory measures in a globalized addiction reality

Was können Werbebilder im Gehirn alkoholabhängiger Patienten auslösen? FMRT Studien zur Verarbeitung alkoholassoziierter Reize

Aims: If no intervention follows the detoxification, relapse rates among detoxified alcohol-dependent patients are very high at about 85 %, even after the withdrawal symptoms have abated. A crucial process that can lead to relapse is exposure to stimuli that have been closely associated with alcohol consumption. Alcohol advertisements on television and on billboards, for example, are omnipresent and may attract the attention of alcohol-dependent patients. Method: In several studies, abstinent alcohol-dependent patients and healthy controls were examined using functional magnetic resonance tomography and cue-reactivity paradigms with alcohol-related stimuli, including advertisements. Results: The results suggest altered brain activation in the so-called reward and attentional systems of alcohol-dependent patients, which is associated with alcohol craving and prospective risk of relapse. Conclusions: The results imply that alcohol-dependent patients are especially susceptible to alcohol-related advertisements.

Umwelt oder Gene — wo liegt die Ursache?

ZusammenfassungEine drohende Glatze kann für manche Männer zu einem ernsthaften psychischen Problem werden. Hilfe verspricht die Haartransplantation. Wir fragten den Leiter der Haarsprechstunde an der Klinik für Dermatologie und Allergologie der LMU München, was in dieser Hinsicht heute möglich ist.