Bernhard Croissant

Neuroimaging of Gender Differences in Alcohol Dependence: Are Women More Vulnerable?

BACKGROUND Alcoholic brain damage has been demonstrated in numerous studies using neuropathology and brain imaging techniques. However, gender differences were addressed only in a few studies. Recent research has shown that development, course, and consequences of alcohol dependence may differ between female and male patients. Our investigation was built upon earlier research where we hypothesized that women develop alcoholic brain damage more readily than men do. To further compare the impact of alcohol dependence between men and women, we examined brain atrophy in female and male alcoholics by means of computed tomography (CT). METHODS The study group consisted of a total of 158 subjects (76 women: 42 patients, 34 healthy controls; 82 age-matched men: 34 patients, 48 healthy controls). All patients had a DSM-IV and ICD-10 diagnosis of alcohol dependence. CT with digital volumetry was performed twice in patients (at the beginning and end of the 6-week inpatient treatment program) and once in controls. RESULTS Patients of both genders had consumed alcohol very heavily. Although the average alcohol consumption in the year before the study was significantly lower in female alcoholics, this gender difference disappeared when controlled for weight. However, women had a significantly shorter duration of alcohol dependence. Despite this fact, both genders developed brain atrophy to a comparable extent. Brain atrophy was reversible in part after 6 weeks of treatment; it did not reach the level in the control groups. CONCLUSIONS Gender-specific differences in the onset of alcohol dependence were confirmed. This is in line with the telescoping effect, where a later onset and a more rapid development of dependence in women were described. Under the assumption of a gradual development of consequential organ damage, brain atrophy seems to develop faster in women. As shown in other organs (i.e., heart, muscle, liver), this may confirm a higher vulnerability to alcohol among women.

Correlation of Stable Elevations in Striatal μ-Opioid Receptor Availability in Detoxified Alcoholic Patients With Alcohol Craving: A Positron Emission Tomography Study Using Carbon 11–Labeled Carfentanil

Main Outcome Measures: After 1 to 3 weeks of abstinence, the availability of μ-opiate receptors in the ventral striatum, including the nucleus accumbens, was significantly elevated in alcoholic patients compared with healthy controls and remained elevated when 12 alcoholic patients had these levels measured 5 weeks later (P .05 corrected for multiple testing). Higher availability of μ-opiate receptors in this brain area correlated significantly with the intensity of alcohol craving as assessed by the OCDS.

Cue exposure in the treatment of alcohol dependence: Effects on drinking outcome, craving and self-efficacy

OBJECTIVES The aim of the present study was to investigate beneficial effects of cue exposure treatment for alcohol dependence by contrasting it with a well-established treatment approach. We hypothesized that cue exposure treatment is associated with a stronger decline of craving, a stronger increase in self-efficacy and has beneficial effects on drinking behaviour after discharge. DESIGN AND METHODS Sixty-three patients with a diagnosis of alcohol dependence were recruited from an in-patient alcohol-detoxification facility. Patients were sequentially assigned to either cue exposure or a standard cognitive-behavioural treatment. We assessed self-reports of craving and self-efficacy prior to treatment participation and at the end of treatment. Drinking behaviour was assessed in the 6-month period following discharge. RESULTS Both treatments were associated with a reduction of self-reported craving and an increase in self-reported measures of self-efficacy. A significant time x treatment interaction indicated a greater increase in self-reported measures of self-efficacy after cue exposure treatment. Measures of drinking behaviour showed clearly that both treatments were efficacious. Relapse rates and drinking-related variables were not significantly different for the two treatments at the 6-month follow-up. There was preliminary evidence that suggests that cue exposure therapy may be more effective for patients with severe alcohol dependence. CONCLUSIONS With respect to drinking behaviour, cue exposure and standard cognitive-behavioural treatment seem to be equally effective for patients with a moderate severity of alcohol dependence. Further studies are necessary to specify criteria for differential treatment indication.

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

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.

Neuropsychological Functioning of Opiate-Dependent Patients: A Nonrandomized Comparison of Patients Preferring either Buprenorphine or Methadone Maintenance Treatment

Objectives: In the present study, we investigated whether buprenorphine as a partial μ -opioid receptor agonist is associated with less cognitive impairment than methadone. Methods: Neuropsychological functioning of opioid-dependent patients, previously assigned to methadone (MMP, n = 30) or buprenorphine (BMP, n = 26) maintenance treatment according to their own preference, was compared and dose effects were investigated. Results: MMP and BMP performed equally well on all measures of neuropsychological functioning including the trail making test, the continuous performance test, and a vigilance task. However, patients receiving a higher dose of methadone were impaired in a vigilance task. Conclusions: In a free-choice administration of methadone or buprenorphine, there seems to be no difference in cognitive functioning. Possible explanations are discussed.

Factors affecting cognitive function of opiate-dependent patients.

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.

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

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.

Gefühl ohne Sprache oder Sprache ohne Gefühl? Weitere Hinweise auf die Validität der Entkopplungshypothese der Alexithymie

ZusammenfassungTheoretischer Hintergrund dieser Untersuchung ist die sog. Entkopplungshypothese der Alexithymie. Diese postuliert für alexithyme Individuen eine Dissoziation psychophysiologischer Aktivierungsprozesse und des subjektiven Affekterlebens speziell unter affektinduktiven Belastungen. 12 hochalexithyme und 14 niedrigalexithyme Probanden aus einer Gesamtstichprobe von 54 Individuen wurden bezüglich der elektrodermaler Spontanfluktuationsrate unter affektneutraler (Reiz-Reaktions-Aufgabe) und affektinduktiver Stimulierung (Videofilme) untersucht. Ihr Affekterleben während der Filmbetrachtung schätzten die Probanden selbst ein. Unter kognitiver Belastung bestanden hinsichtlich der elektrodermalen Aktivierung keine Gruppenunterschiede. Es kam in jedem Falle zu einem signifikanten Anstieg der Spontanfluktuationsrate. Unter affektinduktiver Belastung kam es jedoch nur bei den Niedrigalexithymen nicht aber bei den hochalexithymen Probanden zu einem signifikanten Anstieg der Spontanfluktuationsrate als Ausdruck einer autonomen Aktivierung. In der Bewertung ihres reizbezogenen Affekterlebens unterschieden sich die Gruppen nicht. Diese Befunde sind in Übereinstimmung mit der Entkopplungshypothese, und werden im Hinblick auf neuropsychologische und psychodynamisch-interaktionsdynamische Modellvorstellungen diskutiert.SummaryThe theoretical background of the present investigation was the decoupling hypothesis of alexithymia, which presumes for alexithymic individuals a dissociation of psychophysiological indicators of emotion from verbal cognitive awareness of one’s emotional state. To study alterations in reactivity to emotionally distressing stimuli in alexithymic individuals, 12 high-alexithymic and 14 low-alexithymic subjects (separated by TAS) out of a general sample of 54 were investigated. All subjects were exposed to cognitive (CPT) and affect inductive (film sequences) distress. During stimulus exposition electrodermal activity (sponateous fluctuations) was recorded. After stimulus exposition the subjects assessed their emotional reaction towards the film sequences (DAS). Concerning electrodermal activity no differences were found between high and low alexithymics under cognitive distress. In any case a significant autonomous arousal was registered. However, only the low alexithymic subjects but not the high alexithymics showed a significant increase of spontaneous fluctuations as expression of autonomous arousal during presentation of affect inductive stimuli. The altered psychophysiological reactivity found in high alexithymics in contrast to low alexithymic subjects was revealed specifically for the processing of emotional qualified stimuli. However, there was no difference between the groups in cognitive self assessment of emotional response towards the film sequences. The findings are discussed with reference to neurophysiological and psychodynamic models and the decoupling hypothesis of alexithymia.

Exploring the link between gender, sensation seeking, and family history of alcoholism in cortisol stress-response dampening

Many studies have demonstrated an inverse association between cortisol and risk-taking behaviors, with high-sensation seekers (HSS) showing lower cortisol levels. We investigated the potential link between sensation seeking (SS) and stress-induced stress responses, as well as alcohol-induced stress-response-dampening (SRD) effects in cortisol. First, we hypothesized that HSS would show inverse SRD effects in cortisol. Second, we hypothesized that females would display similar SRD effects to males. Third, we hypothesized an independent relationship between SS and family history (FH) with regard to alcohol-induced SRD effects in cortisol. 86 healthy men and women participated in two laboratory sessions, receiving alcohol in one of the two. Experimental stress paradigms were administered and serum cortisol was measured. SRD effects in cortisol developed for both genders in low-sensation seekers (LSS), but not in HSS. This study contributes to current literature by (1) supporting the association between SS and cortisol, (2) demonstrating that SRD effects in cortisol of females is inversely related to SS, and (3) demonstrating an independent relationship between SS and FH with regard to alcohol-induced SRD effects in cortisol.

Oxcarbazepine in Combination with Tiaprid in Inpatient Alcohol-withdrawal - a RCT

INTRODUCTION Oxcarbazepine (OXC), a derivative of Carbamazepine (CBZ), may represent a solution to metabolic and side effects of CBZ treatment due to the fact that renal excretion is its major route of elimination. The goal of the study is to compare the efficacy and tolerability of OXC/Tiaprid (TIA) combination therapy to the well established Clomethiazole (CLO) therapy in an inpatient setting. METHODS To investigate the efficacy of OXC/TIA in terms of lower alcohol withdrawal symptoms and better tolerability, 56 alcohol-dependent patients participated in a randomized open-label trial, where OXC/TIA and CLO treatments were compared. RESULTS Following admission, we observed that severity of alcohol withdrawal syndrome was comparable between OXC/TIA and CLO-patients. Overall tolerability was good. However, significantly more patients in the OXC/TIA-group (48.1%) displayed no AE compared to the CLO-group (24.1%). We found no significant differences between groups regarding total number of recorded adverse events (AEs). DISCUSSION OXC/TIA inpatient therapy proved to be as effective and participants demonstrated the same tolerance as with CLO. In medication-based alcohol withdrawal, OXC/TIA could have the potential to become a promising alternative for alcohol dependent patients unable to undergo inpatient withdrawal therapy with CLO. Our findings further indicate that it could be worthwhile testing OXC/TIA in alcohol withdrawal in daily care units and outpatient settings. This is an important question for national health care services, since outpatient therapy is more and more asked for as alternative to inpatient settings.