Publications by authors named "Helmut Nakovics"

17 Publications

  • Page 1 of 1

Validation of the German Version of the Mind Excessively Wandering Scale (MEWS-G).

Fortschr Neurol Psychiatr 2021 Feb 26. Epub 2021 Feb 26.

Klinik für Psychiatrie und Psychotherapie, Zentralinstitut für Seelische Gesundheit Klinische Fakultät Mannheim, Universität Heidelberg.

Increasing evidence shows that unintentional mind wandering is linked to Attention Deficit Hyperactivity Disorder (ADHD) and that its frequency contributes to symptom severity and functional impairment in ADHD. However, empirical data on mind wandering in adult ADHD are still scarce, and a validated scale to assess mind wandering in German adult ADHD patients is lacking. The primary aim of this study is to assess the psychometric properties of the German version of the recently published Mind Excessively Wandering Scale (MEWS-G) in terms of factorial structure and factor stability, internal consistency and construct validity. Analyses were performed in 128 adults with ADHD, clinical and healthy controls. As described for the original English 15-item version of the scale, we found lowest item-total-correlations for items 6, 10 and 14 with item-total correlation of all: 0.54/ADHD: 0.32 (item 6), all: 0.55/ADHD: 0.39 (item 10) and all: 0.11/ADHD: -0.04 (item 14). Item-total correlations for the remaining items were 0.65-0.86 and Cronbach Alpha was 0.96 indicating good internal consistency of the 12-item version of scale, on which we based all further analyses. Principal component analysis indicated a one- and two- factorial scale structure respectively explaining 71.7 % and 78.7 % of variance. Both factors showed good stability with lower stability of the factor-2 solution if sample size was reduced. The two-factorial solution also had many cross-loadings and a strong correlation of both factors in confirmatory factorial analysis (rf1f2 = 0.87). It probably describes related and interdependent, but not distinct facets of mind wandering, which strongly argues for the one factorial structure of the scale. Mean MEWS-G score in ADHD was 23.77 ± 7.85 compared to 7.64 ± 7.27 in controls (p < .0001). According to ROC, the optimal cut-off point to discriminate ADHD and controls is at MEWS-G score = 13. On the symptom level, MEWS-G score was correlated with ADHD, depressive and total psychiatric symptom scores, on the personality level with neuroticsm and negatively with conscientiousness and on the functional level with social interaction difficulties and impaired self-efficacy. In summary, our study shows that MEWS-G is a reliable, valid instrument to assess spontaneous mind wandering in adult ADHD and to discriminate between ADHD and controls.
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http://dx.doi.org/10.1055/a-1362-9743DOI Listing
February 2021

Precision Medicine in Alcohol Dependence: A Controlled Trial Testing Pharmacotherapy Response Among Reward and Relief Drinking Phenotypes.

Neuropsychopharmacology 2018 03 20;43(4):891-899. Epub 2017 Nov 20.

Department of Psychology, Center on Alcoholism, Substance Abuse, and Addictions, University of New Mexico, Albuquerque NM, USA.

Randomized trials of medications for alcohol dependence (AD) often report no differences between active medications. Few studies in AD have tested hypotheses regarding which medication will work best for which patients (ie, precision medicine). The PREDICT study tested acamprosate and naltrexone vs placebo in 426 randomly assigned AD patients in a 3-month treatment. PREDICT proposed individuals whose drinking was driven by positive reinforcement (ie, reward drinkers) would have a better treatment response to naltrexone, whereas individuals whose drinking was driven by negative reinforcement (ie, relief drinkers) would have a better treatment response to acamprosate. The goal of the current analysis was to test this precision medicine hypothesis of the PREDICT study via analyses of subgroups. Results indicated that four phenotypes could be derived using the Inventory of Drinking Situations, a 30-item self-report questionnaire. These were high reward/high relief, high reward/low relief, low reward/high relief, and low reward/low relief phenotypes. Construct validation analyses provided strong support for the validity of these phenotypes. The subgroup of individuals who were predominantly reward drinkers and received naltrexone vs placebo had an 83% reduction in the likelihood of any heavy drinking (large effect size). Cutoff analyses were done for clinical applicability: individuals are reward drinkers and respond to naltrexone if their reward score was higher than their relief score AND their reward score was between 12 and 31. Using naltrexone with individuals who are predominantly reward drinkers produces significantly higher effect sizes than prescribing the medication to a more heterogeneous sample.
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http://dx.doi.org/10.1038/npp.2017.282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809801PMC
March 2018

Development and validation of the craving automated scale for alcohol.

Alcohol Clin Exp Res 2015 Feb;39(2):333-42

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.

Background: Alcohol consumption has been suggested to be associated with a dysregulation in habit formation and execution in dependent patients. Although there are established craving questionnaires assessing various components of craving, to our knowledge, no questionnaire exists to assess habitual and automated substance intake. In this study, we present and validate the "Craving Automated Scale for Alcohol" (CAS-A), a newly developed questionnaire assessing craving and other components of automated addictive behavior.

Methods: Forty-three recently detoxified alcohol-dependent patients were examined in an inpatient setting using a cross-sectional design. The CAS-A, a self-report questionnaire, was applied. According to classical test theory, we conducted principal component analyses (PCAs) to identify the components of CAS-A, after which we validated it using established craving questionnaires. Thirty-two healthy participants served as a control group.

Results: Our first-order PCA identified a 5-factor solution. A second-order analysis then identified 2 general factors. These factors were partially associated with established craving measures and with the severity of dependence.

Conclusions: Our findings suggest that CAS-A assesses additional components of addictive behavior compared to established measures. We interpret the 5 CAS-A factors as "only aware in hindsight," "no deliberate decision," "contrary to intention," "no perception," and "no control." We suggest the 2 general factors be interpreted as "unaware" and "nonvolitional." Our results indicate that the CAS-A indeed assesses some components of automated craving and automated drinking behavior in a more sophisticated way than established questionnaires. The CAS-A as a retrospective questionnaire can be considered to be a trait rather than a state measure.
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http://dx.doi.org/10.1111/acer.12636DOI Listing
February 2015

Factors affecting cognitive function of opiate-dependent patients.

Drug Alcohol Depend 2012 Jan 28;120(1-3):81-7. Epub 2011 Jul 28.

Department of General Psychiatry, University of Heidelberg, Vossstrasse 2, 69115 Heidelberg, Germany.

Background: A wide range of studies found that opiate-dependent patients suffer from cognitive impairment due to a number of different factors. However, this issue has never been examined systematically. Thus, the aim of the present study is to provide a comprehensive analysis of factors that might contribute to cognitive impairment of opiate-dependent patients and specifically differentiates between various cognitive abilities as these might be impacted differently.

Methods: Based on a comprehensive review of the literature with regard to previous findings and suggestions about which factors might affect cognitive functioning, we assessed a wide variety of variables related to substance use and opiate-dependence as well as demographic and socioeconomic variables. Cognitive functioning was assessed through a neuropsychological test-battery.

Results: We found that the duration of opiate dependence and maintenance treatment, as well as additional substance consumption (alcohol, amphetamines, and cocaine) are the main variables contributing to cognitive impairment in the domains of attention and executive function. Comorbid depressive symptoms negatively affected reaction times. There was no evidence for the role of demographic variables like age and education on cognitive functioning.

Conclusions: Our findings suggest that it might be important in the treatment of opiate dependence to address the consumption of additional substances and to closely monitor the negative effects of maintenance treatment on cognitive functioning.
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http://dx.doi.org/10.1016/j.drugalcdep.2011.07.001DOI Listing
January 2012

The vicious circle of perceived stigmatization, depressiveness, anxiety, and low quality of life in substituted heroin addicts.

Eur Addict Res 2011 7;17(5):241-9. Epub 2011 Jun 7.

Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany.

Background: Perceived stigmatization of drug addicts may interact with negative mood states and thus may contribute to the maintenance of addictive behavior.

Methods: Opiate maintenance patients (n = 106) and an unselected comparison group (n = 144) rated self-report questionnaires about perceived stigmatization, quality of life (QoL), depressiveness, anxiety, self-esteem, addiction characteristics, and social support.

Results: 63% of opiate maintenance patients felt discriminated in contrast to 16% of the comparison group. Perceived stigmatization was rated higher by opiate maintenance patients, and all domains of QoL were rated lower, even when statistically controlling depressiveness, anxiety and social factors. Perceived stigmatization was correlated to depressiveness, anxiety, low self-esteem and low QoL, but not addiction characteristics and social support. Structural equation models revealed anxiety and the pathway depressiveness enhancing feelings of being stigmatized resulting in low self-esteem to explain 74% of variance in mental QoL, whereas anxiety and a pathway stigmatization inducing depressiveness leading to low self-esteem explained 49% of variance in physical QoL.

Conclusions: A vicious circle of stigmatization, negative affective states and low QoL was confirmed. In addition to societal antistigma campaigns, antidepressive and anxiolytic therapy might have the potential to diminish feelings of being stigmatized and to improve QoL.
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http://dx.doi.org/10.1159/000328637DOI Listing
December 2011

Effects of repeated withdrawal from alcohol on recovery of cognitive impairment under abstinence and rate of relapse.

Alcohol Alcohol 2010 Nov-Dec;45(6):541-7. Epub 2010 Sep 29.

Department of Addictive Behaviour and Addiction Medicine/Department of Clinical and Cognitive Neuroscience, Central Institute of Mental Health,University of Heidelberg, Mannheim, Germany.

Aims: Several authors suggest that withdrawal from alcohol could cause neurotoxic lesions in the frontal lobe and thereby affect cognitive function. In line with this, previous studies have demonstrated greater cognitive impairment of alcohol-dependent patients with two or more previous detoxifications (Hi-detox) compared with patients with less than two detoxifications (Lo-detox). The aim of the present study was to investigate whether repeated withdrawal from alcohol affects recovery of cognitive function and is related to relapse.

Methods: Forty-eight alcohol-dependent patients (Hi-detox: n = 31, Lo-detox: n = 17) and 36 healthy controls underwent a comprehensive neuropsychological test-battery. Patients were tested after completion of detoxification (T1) and 3 (T2, n = 35) and 6 (T3, n = 28) months after discharge. Healthy controls were tested at T1 (n = 36) and T2 (n = 16). Drinking behaviour was assessed at all times.

Results: Patients performed significantly worse than controls at T1 as well as T2 with regard to attention/executive function. Recovery of attention/executive function was observed within the second 3 months after discharge, but the Hi-detox group performed worse than the Lo-detox group. No association with relapse was observed.

Conclusion: This study provides first evidence, that repeated withdrawal from alcohol might be associated with reduced brain plasticity as indicated by a delay of recovery from impairment of attention/executive function. However, little evidence was found for a direct influence of cognitive impairment on treatment success.
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http://dx.doi.org/10.1093/alcalc/agq065DOI Listing
June 2011

Consultation-liaison psychiatry in general hospitals: improvement in physicians' detection rates of alcohol use disorders.

Psychosomatics 2009 Nov-Dec;50(6):599-604

Department of Addictive Behavior and Addiction Medicine, Division of Biostatistics, Central Institute of Mental Health, Mannheim, University of Heidelberg, Mannheim, Germany.

Background: In the general hospital setting, alcohol-use disorders very commonly remain undetected.

Objective: The authors hypothesized that including a consultation-liaison (C-L) psychiatrist in primary-care rounds would improve detection rates of alcohol-use-disorders.

Method: Patients (N=165) on two medical wards were screened by means of the Alcohol Use Disorders Identification Test. Diagnoses were confirmed with the International Diagnostic Checklists and compared with physicians' detection rates. C-L intervention included demonstrations of standardized diagnostic procedures in order to change primary-care physicians' behavior.

Results: Primary-care-physicians' detection rates of alcohol-use disorders increased significantly after implementation of the C-L service, whereas no significant differences were observed on the control ward.

Conclusion: Tentative data thus underscore the efficacy of C-L psychiatry for detection and intervention in alcohol-use disorders.
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http://dx.doi.org/10.1176/appi.psy.50.6.599DOI Listing
March 2010

Orexin and leptin are associated with nicotine craving: a link between smoking, appetite and reward.

Psychoneuroendocrinology 2010 May 13;35(4):570-7. Epub 2009 Oct 13.

Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health (CIMH), Square J5, 68159 Mannheim, Germany.

Objective: Preclinical data suggest modulating effects of both orexin/hypocretin and leptin on dopaminergic transmission in mesolimbic reward pathways. This indicates a possible role of both peptides in reward function and motivation, and thus in addictive diseases. The aim of this study was to examine the possible association between orexin and leptin, and nicotine craving in smokers in a clinical case-control study under standardized conditions.

Methods: We compared orexin and leptin, ACTH and cortisol plasma concentrations (RIA) between tobacco smokers (n=60) during early nicotine withdrawal and healthy controls (n=64). Motivational aspects of nicotine craving were additionally assessed in the smoking participants using the Questionnaire of Smoking Urges (QSU).

Results: As main results we detected a significant negative correlation between orexin plasma concentration and nicotine craving (r=-0.28; p<.05), and a positive association between craving and leptin plasma concentration (r=0.29; p<.05).

Conclusions: Our results show an association between craving for nicotine and plasma concentrations of orexin and leptin suggesting that both peptides interfere with the dopaminergic transmission during nicotine withdrawal in a bidirectional manner and, thus, modulate craving for nicotine.
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http://dx.doi.org/10.1016/j.psyneuen.2009.09.005DOI Listing
May 2010

Impairment of cognitive abilities and decision making after chronic use of alcohol: the impact of multiple detoxifications.

Alcohol Alcohol 2009 Jul-Aug;44(4):372-81. Epub 2009 Jun 1.

Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, 68159 Mannheim, Germany.

Aims: In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function.

Methods: Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence.

Results: Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time.

Conclusions: Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.
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http://dx.doi.org/10.1093/alcalc/agp030DOI Listing
September 2009

[Development and validation of an overall instrument to measure craving across multiple substances: the Mannheimer Craving Scale (MaCS)].

Psychiatr Prax 2009 Mar 15;36(2):72-8. Epub 2008 Oct 15.

Zentralinstitut für Seelische Gesundheit Mannheim, Klinik für Abhängiges Verhalten und Suchtmedizin.

Objective: Based on the Obsessive Compulsive Drinking Scale (OCDS) we developed and validated the Mannheimer Craving Scale (MaCS) for quantitative measurements of craving across different substances and suitable for multiple substance abuse.

Methods: The MaCS questionnaire measures obsessive-compulsive symptoms in the context of substance abuse and dependence similar to the OCDS. The MaCS consists of 12 items and 4 additional items. Validation of the instrument was performed by means of 3 assessments of each subject within a project for the evaluation of a detox treatment on n = 292 alcohol and drug-dependent patients with multiple substance abuse.

Results: The MaCS showed a very high measurement reliability (0.87 < alpha < 0.93). The MaCS total score correlated highly significant with the mean intensity of craving (0.47 < r (tc ) < 0.64, p < 0.0001), with the maximum of craving (0.52 < r (tc) < 0.69, p < 0.0001), and with the frequency of craving (0.43 < r (tc) < 0.65, p < 0.0001) measured by means of analogue scales.

Conclusions: The MaCS for overall measurements of craving across multiple substances showed very good reliability and validity. In combination with a simple and universal feasibility of the MaCS these results indicate the applicability in everyday clinical settings as well as scientific settings.
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http://dx.doi.org/10.1055/s-2008-1067546DOI Listing
March 2009

Modifications of the Obsessive Compulsive Drinking Scale (OCDS-G) for use in longitudinal studies.

Addict Behav 2008 Oct 8;33(10):1276-81. Epub 2008 Jun 8.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, University of Heidelberg, Germany.

Since the application of the Obsessive Compulsive Drinking Scale (OCDS) has been reported to be problematic when used to measure alcohol craving in longitudinal studies, we examined the following questions: (1) Is it possible to skip problematic quantity items? (2) Is the score calculation rule using the higher value of item pairs necessary? (3) Can the shortened version of the OCDS be applied alternatively? We examined two samples including a total of 355 alcohol-dependent patients: a multi center study sample (n=149) and a validation control sample (n=206). Neither an advantage of the score calculation rule nor the necessity of including items regarding alcohol consumption could be demonstrated. The exclusion of consumption items lead to a clear, stable 2-factor structure with a maximum stability (.81-.91). Retest-reliability ranged from r(tt)=.73 to r(tt)=.76 at an average time interval of 5 weeks. Concerning stability (.68-.81) and reliability (r(tt)=.76), the short version turned out to be equivalent. The short version of the OCDS seems to be sufficient. If different effects on cognitive and behavioral levels are expected, the 12-item version without the quantity items should be applied.
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http://dx.doi.org/10.1016/j.addbeh.2008.05.013DOI Listing
October 2008

The startle reflex in alcohol-dependent patients: changes after cognitive-behavioral therapy and predictive validity for drinking behavior. A pilot study.

Psychother Psychosom 2007 ;76(6):385-90

Department of Addictive Behavior and Addiction Medicine, University of Heidelberg, Central Institute of Mental Health, Mannheim, Germany.

Background: Previous studies demonstrated an attenuation of the affect-modulated startle reflex when alcohol-dependent patients were viewing alcohol-associated pictures. This indicates an appetitive valence of these stimuli. We used the affect-modulated startle reflex to assess the effects of behavioral treatment on the emotional processing of alcohol-associated stimuli. Further, we examined whether the affect-modulated startle reflex is a predictor of treatment success.

Methods: Forty-three alcohol-dependent patients (21 females, mean age 45.67 years, SD 9.45) were recruited consecutively from an inpatient alcohol detoxification facility where patients attended a 3-week detoxification program including cognitive-behavioral treatment to successfully handle high-risk situations. The eye blink component of the affect-modulated startle response, self-reported cue-induced craving and skin conductance responses to alcohol-associated and control slides were assessed before and after treatment. Changes were analyzed using repeated measures analysis of variance. Drinking behavior was assessed in the 6 months following treatment, and a regression analysis was performed to evaluate the predictive validity of the affect-modulated startle response for drinking behavior.

Results: Drinking behavior as well as craving and skin conductance responses decreased significantly over time. The pattern of the affective modulation of the startle reflex was not altered over time. However, startle modulation and relapse were related, and within the group of relapsers, startle modulation was a significant predictor of drinking behavior.

Conclusions: Our results suggest that the modulation of the startle reflex may reflect more enduring and permanent processes of emotional responding to alcohol-related cues than autonomic arousal and self-reported craving, and that startle modulation by alcohol-associated cues may be a better predictor of drinking behavior for relapsers than other measures. Further studies including a control condition are necessary to validate these findings.
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http://dx.doi.org/10.1159/000107567DOI Listing
December 2007

Alcoholism in women: is it different in onset and outcome compared to men?

Eur Arch Psychiatry Clin Neurosci 2007 Sep 14;257(6):344-51. Epub 2007 Jul 14.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.

Onset and course of alcohol dependence show gender related differences (telescoping effect) suggesting that women are more vulnerable to chronic alcohol consumption. This raises the question whether the differences are associated with a different treatment outcome as well. We hypothesized, that alcohol dependent women with a telescoping course show a less favourable treatment outcome compared to men. We investigated 212 alcohol dependent patients; matching 106 consecutively admitted women with 106 men drawn from a total sample of 343 male patients. The treatment program consisted of a 6 week inpatient treatment and 12 months of outpatient aftercare. We assessed milestone variables in development and course of alcoholism and carried out standardized diagnostic tests, physical and blood examinations to evaluate the course of the disease and treatment outcome. Overall, we confirm the telescoping effect, a faster progression in the course of alcoholism (developmental events and adverse consequences) in women compared to men ("telescoping effect"). However, despite the telescoping effect treatment outcome was similar in women and men. During the inpatient treatment program no alcohol relapse occurred. Throughout the 12 months outpatient treatment we found no significant differences in the survival analysis between women (283.29+/-11.26 days) and men (284.72+/-12.16 days). At the end of the 12 months both groups had an abstinence rate of approximately 50% and a drop-out rate of 33%.
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http://dx.doi.org/10.1007/s00406-007-0737-zDOI Listing
September 2007

Enhanced expression of interleukin-18 in serum and pancreas of patients with chronic pancreatitis.

World J Gastroenterol 2006 Oct;12(40):6507-14

Department of Medicine II (Gastroenterology, Hepatology and Infectious Diseases), University Hospital of Heidelberg at Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim D-68135, Germany.

Aim: To investigate interleukin-18 (IL-18) in patients with chronic panreatitis (CP).

Methods: We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide (LPS) (doses 25 g/L, 250 g/L, 2500 g/L) and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon (IFN)-gamma and soluble CD14 in the serum were analysed by ELISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription (RT)-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Western blot. Immunohistochemistry for pancreatic IL-18 expression was performed.

Results: In patients, IL-18 serum levels were significantly enhanced by 76% (mean: 289.9+/-167.7 ng/L) compared with controls (mean: 165.2+/-43.6 ng/L; P<0.0005). IL-12 levels were enhanced by 25% in patients (18.3+/-7.3 ng/L) compared with controls (14.7+/-6.8 ng/L, P=0.0576) although not reaching the statistical significance. IFN-gamma and soluble CD14 levels were not increased. In vitro, LPS stimulated significantly and dose-dependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas.

Conclusion: IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100639PMC
http://dx.doi.org/10.3748/wjg.v12.i40.6507DOI Listing
October 2006

Effects of treatment with acamprosate on beta-endorphin plasma concentration in humans with high alcohol preference.

Neurosci Lett 2006 Aug 19;404(1-2):103-6. Epub 2006 Jun 19.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH), University of Heidelberg, Mannheim, Germany.

Treatment with acamprosate, a compound used for relapse prevention treatment of alcoholism, was recently shown to be associated with increased plasma concentration of beta-endorphin in rats selectively bred for high alcohol preference. The aim of our study was to prove this result in a comparative clinical study with a corresponding design. We studied 51 alcohol dependent patients following alcohol withdrawal during treatment with acamprosate versus placebo for 4 weeks. Data were analyzed for patients with high alcohol preference (HP) and low alcohol preference (LP) by dichotomizing the sample according to median alcohol intake prior to detoxification. In line with pre-clinical data, beta-endorphin plasma concentration in HP patients was significantly lower compared with LP patients. Four weeks of treatment with acamprosate resulted in a significantly increased beta-endorphin plasma concentration compared with placebo and a significant difference in HP patients but not in LP patients. In conclusion, acamprosate seems to modulate the endogenous opioid system. Our data are in accordance with the assumption that the effect of acamprosate on endorphin plasma concentrations is mainly based on the effect in the high preferring subgroup. Since beta-endorphin deficiency was earlier associated with alcohol craving and anxiety during withdrawal, abstinence maintaining effects of acamprosate might at least be partially related with the ability to modulate opioidergic activity especially in the subsample of HP patients with an attenuated opioidergic activity during this state.
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http://dx.doi.org/10.1016/j.neulet.2006.05.015DOI Listing
August 2006

A pilot study of oxcarbazepine versus acamprosate in alcohol-dependent patients.

Alcohol Clin Exp Res 2006 Apr;30(4):630-5

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.

Objectives: This pilot study has been designed to collect preliminary data on the use of a new antiepileptic drug in the management of alcoholic patients. Oxcarbazepine (OXC) blocks voltage-sensitive sodium channels. Its metabolite reduces high-voltage-activated calcium currents in striatal and cortical neurons, thus reducing glutamatergic transmission at corticostriatal synapses. This reduction is of interest in the treatment of alcohol dependence, as acamprosate (ACP) modulates NMDA receptors, resulting in an inhibition of glutamatergic transmission. Furthermore, OXC has revealed a mood-stabilizing effect in bipolar affective disorders. We have compared OXC with ACP in relapse prevention in recently withdrawn alcohol-dependent patients.

Methods: We investigated the efficacy and safety of OXC (vs ACP) by conducting a 24-week randomized, parallel-group, open-label, clinical trial on 30 acutely detoxified alcoholic patients. Survival analyses (Kaplan-Meier) were performed to look for evidence of a longer "survival" of patients receiving OXC. We assessed time to first severe relapse and additional secondary endpoints.

Results: After withdrawal, time to severe relapse and time to first consumption of any ethanol by OXC patients were not longer than for ACP patients. Abstinent patients in both study groups showed a significantly lower obsessive compulsive drinking scale-German version (OCDS-G) than relapsed patients. No undesired effects occurred when OXC patients consumed alcohol.

Conclusion: Our findings indicate that it could be worthwhile to test relapse prevention using OXC in an adequate sample. While the current sample size clearly limits further conclusions from this pilot study, it is noteworthy that OXC is well tolerated, even when alcohol is on board. Thus, in medication-based relapse prevention, OXC could be a promising alternative for alcoholic patients unable to benefit from ACP or naltrexone or those who have affective liability. OXC certainly merits a larger placebo-controlled trial.
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http://dx.doi.org/10.1111/j.1530-0277.2006.00082.xDOI Listing
April 2006

Investigating the structure of craving using structural equation modeling in analysis of the obsessive-compulsive drinking scale: a multinational study.

Alcohol Clin Exp Res 2005 Apr;29(4):509-16

Jellinek Addiction Treatment Centre, Amsterdam, The Netherlands.

Background: Currently, there is no agreement among researchers on the definition of craving and its underlying theoretical model. The Obsessive-Compulsive Drinking Scale (OCDS) seems to measure certain aspects of craving, but its theoretical basis remains unclear. The aim of this study was to investigate the structure of alcohol craving, using OCDS data.

Methods: OCDS data from four studies were pooled to obtain a large and heterogeneous sample of 505 participants. All participants were treatment-seeking alcoholics meeting DSM-IV criteria for alcohol dependence. The factor structures of the OCDS previously found were evaluated using confirmatory factor analyses. The goodness of fit of these solutions was compared with those of alternative causal models: an obsessive-compulsive disorder model, an inhibition model, and a cognitive-behavioral model. These alternative models were based on modern theories about craving and were tested in the OCDS data, using structural equation modeling. In this way, the current study replaced simple correlational analysis by a more sophisticated causal way of analyzing the underlying structure of the OCDS items. The best fitting model was selected by comparing the mean discrepancy between the implied and observed matrices of the models.

Results: The data showed that the previously reported factor structures had to be rejected. Also, the inhibition model and obsessive-compulsive disorder model did not fit the data. The cognitive-behavioral model showed encouraging fit. Optimizing strategies were applied to further improve the fit of this model, which resulted in a model with close fit to the data.

Conclusions: The causal cognitive-behavioral model proved to be superior. It showed that the OCDS contains many items that do not represent the core concept of craving but instead are indicators for the consequences of craving. From this model, it seems that craving, in a narrow sense, can be reliably assessed with only five items of the OCDS.
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http://dx.doi.org/10.1097/01.alc.0000158844.35608.48DOI Listing
April 2005