Disulfiram, an Option for the Treatment of Pathological Gambling?

Aim: Pathological gambling and comorbid alcohol dependence often occur in combination. Disulfiram is one of the proven drugs for alcohol dependence. In addition to its inhibiting acetaldehyde dehydrogenase, disulfiram inhibits dopamine β-hydroxylase and may thereby increase dopamine and decrease norepinephrine cerebral concentrations. Because there may be common neurochemical substrates and neuronal circuits for pathological gambling and addiction, we wished to explore the effect of disulfiram in gambling. Method: We describe the outcome of a patient with alcohol dependence and pathological gambling treated with disulfiram D. Results: During treatment with disulfiram, the patient reported that his desire to gamble disappeared entirely. Follow-up indicated that he has not gambled for >12 months. Conclusions: Although uncontrolled case observations should be interpreted with caution, disulfiram deserves further investigation in pathological gamblin

Volumetric Prefrontal Cortex Alterations in Patients With Alcohol Dependence and the Involvement of Self‐Control

Background: Aspects of self-control such as sensation seeking and impaired impulse control have been implicated in alcohol dependence (ALC). Conversely, sensation seeking has been ascribed a possible protective role in stress-related psychopathologies. We therefore examined gray matter (GM) morphology in individuals with ALC, focusing on differences in prefrontal regions that have been associated with self-control. Additionally, we accounted for differences in lifetime alcohol intake regarding self-control measures and cortical structures in ALC patients. Methods: With voxel-based morphometry (VBM) focusing on prefrontal a priori defined regions of interest, we assessed a group of 62 detoxified ALC patients and 62 healthy controls (HC). ALC patients were subsequently divided into high (n = 9) and low consumers (n = 53). Self-control was assessed by use of the Barratt Impulsiveness Scale and the Sensation Seeking Scale. Results: Compared to HC, ALC had significantly less GM volume in bilateral middle frontal gyrus (MFG) and right medial prefrontal cortex as well as in the right anterior cingulate. High-consuming ALC showed smaller GM in right orbitofrontal cortex as well as lower sensation seeking scores than low consumers. In low-consuming ALC, right MFG-GM was positively associated with magnitude of sensation seeking; particularly, larger MFG-GM correlated with greater thrill and adventure seeking. Conclusion: Thus, our findings (i) indicate deficient GM volume in prefrontal areas related to self-control and (ii) might accentuate the phenotypic divergence of ALC patients and emphasize the importance of the development of individual treatment options

PREDICTING PARTICIPATION IN AND SUCCESS OF A CONCURRENT SMOKING CESSATION PROGRAM DURING INPATIENT TREATMENT FOR ALCOHOL DEPENDENCE

Background: Predicting participation in and success of smoking cessation programs in alcohol dependent patients has yielded heterogeneous results. Moreover, these findings have rarely been based on prospective studies from clinical routine settings. Identifying predictors in prospective studies could help to tailor interventions that increase participation and success rates of smoking cessation therapies for these patients at a high risk for alcohol- and smoking-related morbidities and mortalities. Subjects and methods: During inpatient alcohol dependence treatment, 99 nicotine dependent patients were recruited. 73 patients chose to participate in a voluntary smoking cessation program. Interviews and questionnaires were used at baseline and at discharge to assess a large set of variables covering smoking and alcohol related factors, general psychopathology, quality of life and personality traits. Multiple logistic regression models were calculated to predict participation in the smoking cessation program and smoking abstinence at follow-up three months after discharge. Results: Participation in the smoking cessation program was predicted by higher stage of change, higher confidence in abstaining from smoking and lower perceived stress. Successful smoking cessation at follow-up was predicted by higher expectations of negative physical feelings due to smoking and lower expectations of temptations to smoke at baseline, and by lower number of daily smoked cigarettes at discharge. Conclusion: Despite the small sample size, this prospective study gives a first indication of clinically relevant predictors of participation in and success of a smoking cessation program by exploring many previously reported predictors simultaneously. The findings and their implications for treatment allocation and optimization are discussed. Key words

Reliability of the fMRI-based assessment of self-evaluation in individuals with internet gaming disorder

The self-concept—defined as the cognitive representation of beliefs about oneself—determines how individuals view themselves, others, and their actions. A negative self-concept can drive gaming use and internet gaming disorder (IGD). The assessment of the neural correlates of self-evaluation gained popularity to assess the self-concept in individuals with IGD. This attempt, however, seems to critically depend on the reliability of the investigated task-fMRI brain activation. As first study to date, we assessed test–retest reliability of an fMRI self-evaluation task. Test–retest reliability of neural brain activation between two separate fMRI sessions (approximately 12 months apart) was investigated in N = 29 healthy participants and N = 11 individuals with pathological internet gaming. We computed reliability estimates for the different task contrasts (self, a familiar, and an unknown person) and the contrast (self > familiar and unknown person). Data indicated good test–retest reliability of brain activation, captured by the “self”, “familiar person”, and “unknown person” contrasts, in a large network of brain regions in the whole sample (N = 40) and when considering both experimental groups separately. In contrast to that, only a small set of brain regions showed moderate to good reliability, when investigating the contrasts (“self > familiar and unknown person”). The lower reliability of the contrast can be attributed to the fact that the constituting contrast conditions were highly correlated. Future research on self-evaluation should be cautioned by the findings of substantial local reliability differences across the brain and employ methods to overcome these limitations

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. Its enzymatic activity results in secretion of a neuroprotective APP cleavage product (sAPPalpha) and prevents formation of the amyloidogenic A-beta peptides, major hallmarks of Alzheimer’s disease (AD). Elevated ADAM10 levels appeared to contribute to attenuation of A-beta-Plaque formation and learning and memory deficits in AD mouse models. Therefore, it has been assumed that ADAM10 might represent a valuable target in AD therapy. Here we screened a FDA-approved drug library and identified disulfiram as a novel ADAM10 gene expression enhancer. Disulfiram increased ADAM10 production as well as sAPP-alpha in SH-SY5Y human neuronal cells and additionally prevented A-beta aggregation in an in vitro assay in a dose-dependent fashion. In addition, acute disulfiram treatment of Alzheimer model mice induced ADAM10 expression in peripheral blood cells, reduced plaque-burden in the dentate gyrus and ameliorated behavioral deficits. Alcohol-dependent patients are subjected to disulfiram-treatment to discourage alcohol-consumption. In such patients, enhancement of ADAM10 by disulfiram-treatment was demonstrated in peripheral blood cells. Our data suggest that disulfiram could be repurposed as an ADAM10 enhancer and AD therapeutic. However, efficacy and safety has to be analyzed in Alzheimer patients in the future

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. Its enzymatic activity results in secretion of a neuroprotective APP cleavage product (sAPPalpha) and prevents formation of the amyloidogenic A-beta peptides, major hallmarks of Alzheimer’s disease (AD). Elevated ADAM10 levels appeared to contribute to attenuation of A-beta-Plaque formation and learning and memory deficits in AD mouse models. Therefore, it has been assumed that ADAM10 might represent a valuable target in AD therapy. Here we screened a FDA-approved drug library and identified disulfiram as a novel ADAM10 gene expression enhancer. Disulfiram increased ADAM10 production as well as sAPP-alpha in SH-SY5Y human neuronal cells and additionally prevented A-beta aggregation in an in vitro assay in a dose-dependent fashion. In addition, acute disulfiram treatment of Alzheimer model mice induced ADAM10 expression in peripheral blood cells, reduced plaque-burden in the dentate gyrus and ameliorated behavioral deficits. Alcohol-dependent patients are subjected to disulfiram-treatment to discourage alcohol-consumption. In such patients, enhancement of ADAM10 by disulfiram-treatment was demonstrated in peripheral blood cells. Our data suggest that disulfiram could be repurposed as an ADAM10 enhancer and AD therapeutic. However, efficacy and safety has to be analyzed in Alzheimer patients in the future

Supervised Disulfiram in Relapse Prevention in Alcohol-Dependent Patients Suffering From Comorbid Borderline Personality Disorder—A Case Series

Aims: Disulfiram is widely used to prevent alcoholic relapse. However, due to the intended adverse reaction with ethanol, some believe that its use is dangerous for patients with personality disorders or psychiatric comorbidities because of their increased risk of impulsivity or suicidal behaviour. We examined the safety and efficacy in relapse prevention of a series of alcoholics with borderline personality disorder (BPD). Methods: Case history study of patients diagnosed with BPD, prescribed disulfiram in a dose of 1.5-2.5 g/week, supervised by a physician in up to three brief contacts per week. Results: Two out of eight patients remained completely abstinent during the supervised disulfiram therapy over a mean period of 9.25 months. Adherence to treatment was 18.44 ± 21.78 months. The first relapse occurred after 1.38 ± 1.41 months. The cumulated time of abstinence was 16.88 ± 20.48 months. The overall tolerability was considered to be high; dizziness and fatigue appeared in all patients at the beginning of the therapy but did not persist. No serious adverse events or ethanol-disulfiram interactions were observed. No suicidal behaviour was reported. Conclusions: Although case observations should be interpreted with caution, supervised disulfiram seems to deserve further investigation in patients with comorbid BPD, for whom it appears to help prevent alcoholic relaps

The impact of COVID-19 pandemic on mental burden and quality of life in physicians: Results of an online survey

BackgroundIn previous pan-/epidemics such as the SARS epidemic of 2002/2003, negative effects on the wellbeing and an increase in symptoms of depression and anxiety were observed in doctors due to social isolation and the threat they experienced. Therefore, it is feared that the COVID-19 pandemic will also have a negative impact on the mental health and quality of life of doctors.ObjectiveThe impact of the COVID-19 pandemic on the mental health of physicians. In particular, on the subjective anxiety and burden, depression and quality of life for the total sample and subsamples (work in COVID-19 units vs. no work in COVID-19 units).Materials and methodsIn an online survey, 107 physicians (23–42 years) were asked about their mental health during the COVID-19 pandemic. In addition to socio-demographic data, pandemic- and work-related data were also included. For example, infection control measures, deployment on COVID-19 wards and the subjective perceived threat posed by the pandemic. The physicians were asked to rate their perceived anxiety and stress, retrospectively, at 7 different points in time during the pandemic. The Hospital Anxiety and Depression Scale (HADS) was used to retrospectively assess symptoms of anxiety and depression before and after the onset of the pandemic. The quality of life of the participants after 2 years of the pandemic was assessed using the WHO Quality of Life (WHOQOL-BREF).ResultsBoth subjective anxiety and burden showed wave-like patterns with higher scores in autumn, winter and spring. We observed significant differences between the seven measurement time points for anxiety [Chi2(6) = 197.05, p < 0.001] as well as for burden [Chi2(6) = 106.33, p < 0.001]. Symptoms of depression and anxiety increased significantly during the COVID-19 pandemic (M = 14.16, SD = 7.83) compared to the pre-pandemic time [M = 7.31, SD = 5.14, t(106) = −10.67, p < 0.001]. Physicians who worked at COVID-19 units showed higher scores in quality of life related to social relationships (M = 70.39, SD = 17.69) than physicians not working at COVID-19 units [M = 61.44, SD = 24.55, t(90.14) = −2.145, p = 0.035]. The multi-factorial ANOVA showed that previous psychiatric illness (p < 0.001), greater difference in depression scores (p = 0.014), higher anxiety scores (p = 0.048) and less work experience (p = 0.032) led to lower quality of life.ConclusionHospitals should offer specific support, such as supervision, to prevent the development of longer-term psychiatric sequelae likely to lead to sick leave and high costs for the healthcare system.Trial registrationThe study has been registered at the German Clinical Trials Registry (DRKS-ID: DRKS00028984)

Prevalence Estimates of ADHD in a Sample of Inpatients With Alcohol Dependence

Objective: ADHD is common in patients with alcohol dependence, but prevalence results are inconsistent. We investigated ADHD prevalence in a complex design to avoid over- or underdiagnosing. Method: Patients with alcohol dependence starting long-term residential treatment were included. A structured interview (Diagnostic Interview for ADHD in Adults [DIVA]) was conducted on all patients. DIVA results indicating childhood or adulthood ADHD were assessed in successive diagnostic interviews by two expert clinicians. Results: 415 of 488 patients had completed the entire diagnostic assessment. ADHD prevalence was 20.5%. DIVA results correlated moderately with experts’ diagnoses. In patients with ADHD, a higher comorbid illicit substance use was prevalent and alcohol dependence started earlier and was more severe. Conclusion: This study provides the largest sample on ADHD prevalence in alcohol dependent inpatients. Despite great efforts to avoid overestimation, we found every fifth patient to have ADHD. ADHD diagnosis should not be based solely on a structured interview but should be clinically confirmed. (J. of Att. Dis. 2020; 24(14) 2072–2083