Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial.

BACKGROUND: A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study is set to evaluate the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy when incorporated as an auxiliary intervention during inpatient rehabilitation for severe alcohol use disorder. Moreover, it intends to pinpoint the modifications in the two core neurocognitive systems underscored by dual-process models of addiction. METHODS: In this double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial, 62 participants aged 21-64 years will be enrolled to undergo psilocybin-assisted therapy as part of a 4-week inpatient rehabilitation for severe alcohol use disorder. The experimental group will receive a high dose of psilocybin (30 mg), whereas the control group will receive an active placebo dose of psilocybin (5 mg), both within the context of a brief standardized psychotherapeutic intervention drawing from key elements of acceptance and commitment therapy. The primary clinical outcome is the between-group difference regarding the change in percentage of heavy drinking days from baseline to four weeks posthospital discharge, while safety and feasibility metrics will also be reported as primary outcomes. Key secondary assessments include between-group differences in terms of changes in (1) drinking behavior parameters up to six months posthospital discharge, (2) symptoms of depression, anxiety, trauma, and global functioning, (3) neuroplasticity and key neurocognitive mechanisms associated with addiction, and (4) psychological processes and alcohol-related parameters. DISCUSSION: The discussion outlines issues that might arise from our design. TRIAL REGISTRATION: EudraCT 2022-002369-14 and NCT06160232.

Narrating: from Evolutionary to Clinical Advantages.

Human beings constantly narrate reality. They narrate themselves, to themselves and to others. They narrate each other and narrate humanity. They narrate the world and nature. They narrate meaning, the meaning of life and things. This article aims to explore this phenomenon of "narrating". Through a narrative review, we will attempt to gather elements of reflection on narrative, considered here as the ability to narrate, it means to represent oneself, to put meaning. Firstly, we will focus on how cognition, interpretation, and culture allow Homo Sapiens to narrate reality to himself. Then, we will explore why they do it and discover the evolutionary advantages of language, of sharing experiences between individuals through the phenomenon of cumulative cultural evolution, and how narrative facilitates the species' access to these advantages. Finally, we will delve into the clinical implications of narrative, discussing therapeutic interviews, therapy, and psychopathology. Narratives and pre-linguistic mental representations appear to have driven the Homo genus to develop cognitive abilities that enable the development of language and the sophistication of narratives as a cultural medium. Through language, Homo sapiens share their narratives and develop a cumulative common culture. Each individual's culture seems to be constructed in dialectic with this shared culture through narratives. This dialectic gives rise to psychopathological processes while also producing therapeutic leverage. Understanding the mechanisms of co-construction of these narratives is essential in clinical research in mental health. Furthermore, placing narratives in the perspective of an essential evolutionary strategy in the Homo genus solidifies the significance of the narrative faculty in the biological functioning of Homo sapiens, and so the importance of narratives in mental health.

Association Between Bipolar Disorder and Parkinson's Disease.

Bipolar disorder and Parkinson's disease are two distinct neurological conditions that share common features related to dopaminergic dysfunction. This article presents a comprehensive review of the existing literature to investigate the association between bipolar disorder and Parkinson's disease, focusing on the dopaminergic hypothesis and potential therapeutic options. The dopaminergic hypothesis suggests that both bipolar disorder and Parkinson's disease involve impairments in the nigrostriatal or mesolimbic dopaminergic pathways. Studies have demonstrated alterations in dopamine regulation during manic and depressive phases of bipolar disorder. Similarly, Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms. Recent analyses have highlighted a predisposition to Parkinson's disease in individuals with bipolar disorder. Longitudinal studies and meta-analyses have demonstrated an increased risk of developing Parkinson's disease in patients with bipolar disorder. However, differentiating idiopathic Parkinson's disease from parkinsonism induced by medications used in bipolar disorder can be challenging. Dopamine transporter (DAT) scans can aid in making a differential diagnosis. Treatment options for patients with both bipolar disorder and Parkinson's disease are limited. Neuroleptics, commonly used to manage psychotic symptoms in Parkinson's disease, may worsen motor symptoms and have limitations in bipolar disorder patients. Clozapine has shown efficacy in treating psychosis without worsening motor symptoms. Pimavanserin, an inverse agonist of the 5-HT2A receptor can offer new opportunities. However, its efficacy in bipolar disorder patients with Parkinson's disease remains unexplored. In conclusion, the association between bipolar disorder and Parkinson's disease is supported by the involvement of the dopaminergic system in both conditions. The identification of shared mechanisms opens new avenues for potential therapeutic interventions. Further research is needed to investigate the efficacy of pimavanserin and explore other treatment options for individuals with both bipolar disorder and Parkinson's disease.

Dissociative Identity Disorder: Between History and Culture.

The Dissociative Identity Disorder has undergone significant transformations over the years. Once regarded as a rare condition, it gained popularity in the 1980s in the United States following the publication of a book on the subject, only to subsequently wane due to extensive controversies. Presently, we are witnessing a resurgence of adolescents who believe they may be afflicted by this disorder. This article delves into the changes that have occurred since the initial surge in 1980, with a particular focus on the role of social media in the dissemination of Dissociative Identity Disorder. The concepts of Mass Social Media-Induced Illness and Munchausen's by Internet are explored to elucidate this phenomenon. Additionally, we examine the criteria essential for distinguishing imitative Dissociative Identity Disorder from genuine cases, with the aim of aiding accurate diagnosis by psychiatrists. Mental health professionals may encounter new challenges when assessing young adults whose presentations are influenced by social media, necessitating awareness of the impact of social media on the dissemination of certain disorders.

A Comparative Event-Related Potentials Study between Alcohol Use Disorder, Gambling Disorder and Healthy Control Subjects through a Contextual Go/NoGo Task.

(1) Background: Inhibitory and rewarding processes that mediate attentional biases to addiction-related cues may slightly differ between patients suffering from alcohol use (AUD) or gambling (GD) disorder. (2) Methods: 23 AUD inpatients, 19 GD patients, and 22 healthy controls performed four separate Go/NoGo tasks, in, respectively, an alcohol, gambling, food, and neutral long-lasting cueing context during the recording of event-related potentials (ERPs). (3) Results: AUD patients showed a poorer inhibitory performance than controls (slower response latencies, lower N2d, and delayed P3d components). In addition, AUD patients showed a preserved inhibitory performance in the alcohol-related context (but a more disrupted one in the food-related context), while GD patients showed a specific inhibitory deficit in the game-related context, both indexed by N2d amplitude modulations. (4) Conclusions: Despite sharing common addiction-related mechanisms, AUD and GD patients showed different patterns of response to (non-)rewarding cues that should be taken into account in the therapeutic context.

Transcranial direct current stimulation combined with alcohol cue inhibitory control training reduces the risk of early alcohol relapse: A randomized placebo-controlled clinical trial.

BACKGROUND: Approximately half of all people with alcohol use disorder (AUD) relapse into alcohol reuse in the next few weeks after a withdrawal treatment. Brain stimulation and cognitive training represent recent forms of complementary interventions in the context of AUD. OBJECTIVE: To evaluate the clinical efficacy of five sessions of 2 mA bilateral transcranial direct current stimulation (tDCS) for 20 min over the dorsolateral prefrontal cortex (DLPFC) (left cathodal/right anodal) combined with alcohol cue inhibitory control training (ICT) as part of rehabilitation. The secondary outcomes were executive functioning (e.g. response inhibition) and craving intensity, two mechanisms strongly related to abstinence. METHODS: A randomized clinical trial with patients (n = 125) with severe AUD at a withdrawal treatment unit. Each patient was randomly assigned to one of four conditions, in a 2 [verum vs. sham tDCS] x 2 [alcohol cue vs. neutral ICT] factorial design. The main outcome of treatment was the abstinence rate after two weeks or more (up to one year). RESULTS: Verum tDCS improved the abstinence rate at the 2-week follow-up compared to the sham condition, independently of the training condition (79.7% [95% CI = 69.8-89.6] vs. 60.7% [95% CI = 48.3-73.1]; p = .02). A priori contrasts analyses revealed higher abstinence rates for the verum tDCS associated with alcohol cue ICT (86.1% [31/36; 95% CI = 74.6-97.6]) than for the other three conditions (64% [57/89; 95% CI = 54-74]). These positive clinical effects on abstinence did not persist beyond two weeks after the intervention. Neither the reduction of craving nor the improvement in executive control resulted specifically from prefrontal-tDCS and ICT. CONCLUSIONS: AUD patients who received tDCS applied to DLPFC showed a significantly higher abstinence rate during the weeks following rehabilitation. When combined with alcohol specific ICT, brain stimulation may provide better clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov number NCT03447054 https://clinicaltrials.gov/ct2/show/NCT03447054.

Tobacco Use Cessation in Three Patients Suffering from Psychotic Disorders: The Impact of the COVID-19 Pandemic.

BACKGROUND: Tobacco use is one of the major causes of morbidity and mortality amoung patients suffering from psychotic disorders. The association between severe COVID-19 and tobacco use is still debated. The aim of this paper is to enhance the importance of providing up to date informations about nicotine and tobacco use in connection with the SARS-CoV-2-related conditions. METHODS: We present 3 cases of sudden tobacco use cessation in 3 long-term heavy smokers receiving mental health care for chronic psychotic disorders. Fear of severe form of COVID-19 was their principal motivation. Nicotine replacement therapy and quitline counseling were provided and no major withdrawal symptoms were declared. RESULTS: As mass media later wrongly presented tobacco use as a protective factor regarding COVID-19, all three patients resumed smoking. Rigorous counseling took advantage of psychotic symptoms to correct false informations and finally promote tobacco use cessation. CONCLUSIONS: The COVID-19 pandemic might paradoxically represent a great motivational factor to quit smoking, espacially when considering patients suffering from severe mental health disorders. Beyond the terrible suffering it causes, we illustrate with a case serie that this opportunity must be exploited by mental health professionals to improve quality and life expectancy of their patients.

Gastric Bypass and Alcohol Use: A Literature Review.

BACKGROUND: Obesity is public health issue; bariatric surgery is considered as the most efficient treatment. However, the risk of developing an alcohol use disorder could increase after Roux-en-Y bypass. The purpose of this review is to emphasize the further research needed in this area. METHODS: Pubmed and Sciencedirect databases were searched. Articles written in another language than French or English as well as abstracts, conference presentations, editorials and expert opinions were excluded. RESULTS: Most of studies included in this review show an increased risk of developing an AUD (alcohol use disorder) after gastric bypass surgery. Male sex, younger age, smoking, regular alcohol consumption, AUD, recreational drug use, lower sense of belonging and undergoing a RYGB (Roux-en-Y gastric bypass) were identified as risk factors. There is an alteration of alcohol metabolism after gastric bypass. Gut hormones could also play a role in the development of AUD. The hypothesis of an addiction transfer is still controversial. CONCLUSIONS: The risk of developing an AUD seems to increase after surgery. Long term follow-up, after the second post-surgery year, is needed. Further researches are needed to understand the mechanisms that underlie the development of AUD.

The Relationship between Typus Melancholicus and Unipolar Depression: A Literature Review.

BACKGROUND: The Typus Melancholicus (TM) is the premorbid personality of endogenous depression defined by Tellenbach and Kraus and characterized by orderliness, conscientiousness, norm orientation and intolerance of ambiguity. Tellenbach's hypothesis was to find around 50% of TM in the sample of patients with an Unipolar Depression (UD). The present paper aims to make a literature review on the relationship between the Typus Melancholicus (TM) and Unipolar Depression (UD). METHODS: Nineteen references were selected through searches on PubMed, Google Scholar and Sciences-Direct with the following MeSH terms in the title: Typus Melancholicus AND Depressive or Depression or Dépression or Depressione. Nine of them were selected for our review. RESULTS: Eight of the nine reviewed articles confirm Tellenbach's hypothesis. The literature review also shows that, in a population of UD, TM is always constant regardless of age or sex, has no relationship to clinical characteristics and could contribute to the chronicity of depression. The TM with depression have increased levels of "lack of vital drive" and "feelings of guilt" and low scores in irritability and dysphoria compared to Non-Typus Melancholicus (NTM). Due to its characteristics, TM could also be involved in some pathologies such as burnout or postpartum depression. TM does not seem to be linked to a particular Personality Disorder or maladaptive personality, but the two may coexist in certain circumstances. It has been suggested that specific psychotherapeutic methods can be used to treat TM with UD. CONCLUSIONS: The TM could be very useful in our clinical practice. Better practical knowledge of TM could lead to more efficient psychiatric care as well as heightened capacity to predict new episodes.

Neurophysiological markers of cue reactivity and inhibition subtend a three-month period of complete alcohol abstinence.

OBJECTIVE: Finding new tools for conventional management of alcohol disorders is a challenge for psychiatrists. Brain indications related to cognitive functioning could represent such an add-on tool. METHODS: Forty alcohol-dependent inpatients undertook two cognitive event-related potential (ERP) tasks at the beginning and at the end of a 4-week detoxification program. These comprised a visual oddball task investigating cue reactivity and a Go/No-go task tagging inhibition using oddball P3d and No-go P3d ERP components. Three months after discharge, the patient group (N = 40) was split into two subgroups: patients who remained abstinent during this post-treatment period (90 days; n = 15), and patients who relapsed (mean time: 28.5 ± 26.2 days; n = 25). Pattern changes of both ERP markers (oddball P3d and No-go P3d) during the detoxification were compared to differentiate these populations. RESULTS: Abstinent patients exhibited similar P3d responses devoted to alcohol cues in Sessions 1 and 2, but an increased No-go P3d devoted to No-go trials in alcohol-related contexts in Session 2 compared to Session 1. CONCLUSIONS: Specific cue-reactivity and inhibitory neurophysiological markers subtend a further three-months of complete abstinence. SIGNIFICANCE: Monitoring these ERP changes during detoxification may provide important clues regarding patients' future abstinence vs. relapse.

Changes in Pro-Inflammatory Markers in Detoxifying Chronic Alcohol Abusers, Divided by Lesch Typology, Reflect Cognitive Dysfunction.

AIM: To investigate pro-inflammatory markers in the blood and associate with cognitive impairment. METHODS: Il-6 and ferritin were assayed in the blood of 27 patients, divided according to Lesch typology, at the commencement and after 21 days of detoxification, together with a battery of cognitive tests. RESULTS: A significantly higher mean level of IL-6 was present in the blood of patients with Lesch typology 1 compared to the other typologies 2 and 3 on admission to the Detoxification Ward which did not alter significantly after detoxification. The mean level of IL-6 was initially elevated in Lesch typology 2 alcohol abusers and declined to the reference range after detoxification. Lesch typology 3 alcohol abusers showed normal levels of IL-6 at both time points. Only in Lesch typology 1 were the levels of ferritin and IL-10 significantly elevated at the start of the detoxification process. Cognitive impairment, as ascertained by Stroop test and Brown-Peterson procedure was greater in Lesch typology 1 than the other 2 patient groups. CONCLUSION: Such data might indicate a greater degree of neuroinflammation in Lesch typology 1 alcoholic patients. SHORT SUMMARY: Dividing a heterogeneous group of alcoholic subjects into homogenous groups according to Lesch typology, identifies a greater pro-inflammatory profile in Lesch typology 1 patients who also showed greater cognitive impairment.

On the automaticity of response inhibition in individuals with alcoholism.

BACKGROUND AND OBJECTIVES: Response inhibition is usually considered a hallmark of executive control. However, recent work indicates that stop performance can become associatively mediated ('automatic') over practice. This study investigated automatic response inhibition in sober and recently detoxified individuals with alcoholism.. METHODS: We administered to forty recently detoxified alcoholics and forty healthy participants a modified stop-signal task that consisted of a training phase in which a subset of the stimuli was consistently associated with stopping or going, and a test phase in which this mapping was reversed. RESULTS: In the training phase, stop performance improved for the consistent stop stimuli, compared with control stimuli that were not associated with going or stopping. In the test phase, go performance tended to be impaired for old stop stimuli. Combined, these findings support the automatic inhibition hypothesis. Importantly, performance was similar in both groups, which indicates that automatic inhibitory control develops normally in individuals with alcoholism.. LIMITATIONS: This finding is specific to individuals with alcoholism without other psychiatric disorders, which is rather atypical and prevents generalization. Personalized stimuli with a stronger affective content should be used in future studies. CONCLUSIONS: These results advance our understanding of behavioral inhibition in individuals with alcoholism. Furthermore, intact automatic inhibitory control may be an important element of successful cognitive remediation of addictive behaviors..

Quantification of phosphatidylethanol 16:0/18:1, 18:1/18:1, and 16:0/16:0 in venous blood and venous and capillary dried blood spots from patients in alcohol withdrawal and control volunteers.

Phosphatidylethanol species (PEths) are promising biomarkers of alcohol consumption. Here, we report on the set-up, validation, and application of a novel UHPLC-ESI-MS/MS method for the quantification of PEth 16:0/18:1, PEth 18:1/18:1, and PEth 16:0/16:0 in whole blood (30 µL) and in venous (V, 30 µL) or capillary (C, 3 punches (3 mm)) dried blood spots (DBS). The methods were linear from 10 (LLOQ) to 2000 ng/mL for PEth 16:0/18:1, from 10 (LLOQ) to 1940 ng/mL for PEth 18:1/18:1, and from 19 (LLOQ) to 3872 ng/mL for PEth 16:0/16:0. Extraction efficiencies were higher than 55% (RSD < 18%) and matrix effects compensated for by IS were between 77 and 125% (RSD < 10%). Accuracy, repeatability, and intermediate precision fulfilled acceptance criteria (bias and RSD below 13%). Validity of the procedure for determination of PEth 16:0/18:1 in blood was demonstrated by the successful participation in a proficiency test. The quantification of PEths in C-DBS was not significantly influenced by the hematocrit, punch localization, or spot volume. The stability of PEths in V-DBS stored at room temperature was demonstrated up to 6 months. The method was applied to authentic samples (whole blood, V-DBS, and C-DBS) from 50 inpatients in alcohol withdrawal and 50 control volunteers. Applying a cut-off value to detect inpatients at 221 ng/mL for PEth 16:0/18:1 provided no false positive results and a good sensitivity (86%). Comparison of quantitative results (Bland-Altman plot, Passing-Bablok regression, and Wilcoxon signed rank test) revealed that V-DBS and C-DBS were valid alternatives to venous blood for the detection of alcohol consumption.

On the relationship between emotional state and abnormal unfairness sensitivity in alcohol dependence.

Recent empirical findings suggest that alcohol dependence is characterized by heightened sensitivity to unfairness during social transactions. The present study went a step further and aimed to ascertain whether this abnormal level of sensitivity to unfairness is underlined by an increased emotional reactivity. Twenty-six recently abstinent alcohol-dependent (AD) individuals and 32 controls performed an ultimatum game (UG), in which participants had to respond to take-it-or-leave-it offers, ranging from fair to unfair and made by a fictive proposer. Emotional state was recorded during UG offers presentation and was indexed by the amplitude of skin conductance response (SCR). Results showed that AD decided to reject unfair offers more frequently than their controls, confirming previous data. The proportion of rejected unfair UG offers was correlated with SCR, in the AD but not in the control group. This finding suggests that deciding to accept or reject unfair UG offers is influenced by arousal-affective activity in AD, but not in controls. Heightened emotional reactivity may have driven AD to punish the proposer rather than acting as a rational economic agent. An implication of present findings is that AD might have difficult to cope with unfair situations triggered by social interactions. Future studies are needed in order to examine whether-emotional and behavioral-reactivity to unfairness during the UG could impact alcohol consumption and relapse in AD.

Reduced processing of alcohol cues predicts abstinence in recently detoxified alcoholic patients in a three-month follow up period: an ERP study.

One of the major challenges in alcohol dependence is relapse prevention, as rates of relapse following detoxification are high. Drug-related motivational processes may represent key mechanisms in alcoholic relapse. In the present study, event-related potentials (ERPs) were recorded during a visual oddball task administered to 29 controls (11 females) and 39 patients (9 females). Deviant stimuli were related or unrelated to alcohol. For patients, the task was administered following a 3-week detoxification course. Of these, 19 relapsed during the three months follow-up period. The P3, an ERP component associated with activation of arousal systems in the brain and motivational engagement, was examined with the aim to link the fluctuation of its amplitude in response to alcohol versus non-alcohol cues to the observed relapse rate. Results showed that compared to relapsers, abstainers presented with a decreased P3 amplitude for alcohol related compared to non-alcohol related pictures (p=.009). Microstate analysis and sLORETA topography showed that activation for both types of deviant cues in abstainers originated from the inferior and medial temporal gyrus and the uncus, regions implicated in detection of target stimuli in oddball tasks and of biologically relevant stimuli. Through hierarchical regression, it was found that the P3 amplitude difference between alcohol and non-alcohol related cues was the best predictor of relapse vulnerability (p=.013). Therefore, it seems that a devaluation of the motivational significance of stimuli related to alcohol, measurable through electrophysiology, could protect from a relapse within three months following detoxification in alcohol-dependent patients.

Neurophysiological correlates of response inhibition predict relapse in detoxified alcoholic patients: some preliminary evidence from event-related potentials.

BACKGROUND: Alcohol dependence is a chronic relapsing disease. The impairment of response inhibition and alcohol-cue reactivity are the main cognitive mechanisms that trigger relapse. Despite the interaction suggested between the two processes, they have long been investigated as two different lines of research. The present study aimed to investigate the interaction between response inhibition and alcohol-cue reactivity and their potential link with relapse. MATERIALS AND METHODS: Event-related potentials were recorded during a variant of a "go/no-go" task. Frequent and rare stimuli (to be inhibited) were superimposed on neutral, nonalcohol-related, and alcohol-related contexts. The task was administered following a 3-week detoxification course. Relapse outcome was measured after 3 months, using self-reported abstinence. There were 27 controls (seven females) and 27 patients (seven females), among whom 13 relapsed during the 3-month follow-up period. The no-go N2, no-go P3, and the "difference" wave (P3d) were examined with the aim of linking neural correlates of response inhibition on alcohol-related contexts to the observed relapse rate. RESULTS: Results showed that 1) at the behavioral level, alcohol-dependent patients made significantly more commission errors than controls (P<0.001), independently of context; 2) through the subtraction no-go P3 minus go P3, this inhibition deficit was neurophysiologically indexed in patients with greater P3d amplitudes (P=0.034); and 3) within the patient group, increased P3d amplitude enabled us to differentiate between future relapsers and nonrelapsers (P=0.026). CONCLUSION: Our findings suggest that recently detoxified alcoholics are characterized by poorer response-inhibition skills that demand greater neural resources. We propose that event-related potentials can be used in conjunction with behavioral data to predict relapse; this would identify patients that need a higher level of neural resources when suppressing a response is requested.

Polysubstance dependent patients display a more utilitarian profile in moral decision-making than alcohol-dependent patients, depressive patients and controls.

BACKGROUND: Addiction has been shown to be associated with the endorsement of utilitarian moral judgments. Ventro-medial prefrontal cortex (VMPFC) dysfunction may explain these findings. METHODS: 100 subjects were recruited: 25 polysubstance dependent patients, 25 alcohol dependent patients, 25 patients with major depressive disorders, and 25 normal controls. Subjects were assessed with a battery of 24 moral dilemmas: 8 impersonal dilemmas (no physical contact involved); 8 personal pareto (direct action that does not make the harmed individual worse off) and 8 personal non-pareto (direct action that does make the harmed individual worse off). The Iowa Gambling Task was used to document a possible connection between VMPFC dysfunction and responses to the moral dilemmas. RESULTS: Polysubstance dependent patients endorsed more utilitarian choices than controls on all types of dilemmas and more than depressed patients on impersonal and personal pareto dilemmas. Alcohol dependent patients had intermediate results between polysubstance dependent patients and controls but these differences were not significant. All patients showed significantly poorer performance compared to controls on the Iowa Gambling Task, but there was no significant association between Iowa Gambling Tasks scores and moral dilemma choices. CONCLUSION: Polysubstance dependent patients made more utilitarian choices when responding to moral dilemmas than depressed patients and normal controls, while alcoholic patients showed intermediate results. The absence of correlation between performance on the Iowa Gambling Task and the number of more utilitarian choices indicates that moral dilemma and decision making under uncertainty tap into separate mechanisms.

Separating intentional inhibition of prepotent responses and resistance to proactive interference in alcohol-dependent individuals.

BACKGROUND: Impulsivity is a hallmark of addictive behaviors. Addicts' weakened inhibition of irrelevant prepotent responses is commonly thought to explain this association. However, inhibition is not a unitary mechanism. This study investigated the efficiency of overcoming competition due to irrelevant responses (i.e., inhibition of a prepotent response) and overcoming competition in memory (i.e., resistance to proactive interference) in sober and recently detoxified alcohol-dependent individuals. METHODS: Three cognitive tasks assessing the inhibition of a prepotent response (Hayling task, anti-saccade task and Stroop task) and two tasks tapping into the capacity to resist proactive interference (cued recall, Brown-Peterson variant) were administered to 30 non-amnesic recently detoxified alcohol-dependent individuals and 30 matched healthy participants without alcohol dependency. In addition, possible confounds such as verbal updating in working memory was assessed. RESULTS: Alcohol-dependent subjects performed worse than healthy participants on the three cognitive tasks assessing the inhibition of irrelevant prepotent responses but group performance was similar in the tasks assessing overcoming proactive interference in memory, updating of working memory and abstract reasoning. CONCLUSIONS: These findings suggest that alcohol-dependence is mainly associated with impaired capacity to intentionally suppress irrelevant prepotent response information. Control of proactive interference from memory is preserved. Theoretical and clinical implications are discussed.

On the predictive validity of automatically activated approach/avoidance tendencies in abstaining alcohol-dependent patients.

BACKGROUND: Prominent addiction models posit that automatically activated approach/avoidance tendencies play a critical role in addiction. Nevertheless, only a limited number of studies have actually documented the relationship between relapse and automatically activated approach/avoidance tendencies. We compared automatically activated approach/avoidance tendencies towards alcohol in 40 abstaining alcohol-dependent patients and 40 controls. We also examined whether individual differences in automatically activated approach/avoidance tendencies towards alcohol are predictive of relapse in patients. METHODS: A Relevant Stimulus Response Compatibility task was used to measure relative approach/avoidance tendencies. In one block of trials, participants were asked to approach alcohol-related pictures and to avoid alcohol-unrelated pictures (i.e., compatible block). In a second block of trials, participants were asked to approach alcohol-unrelated pictures and to move away from alcohol-related pictures (i.e., incompatible block). Patients were tested between 18 and 21 days after they quit drinking. Relapse was assessed 3 months after patients were discharged from the hospital. RESULTS: Whereas abstaining alcohol-dependent patients were faster to respond to incompatible trials as compared to compatible trials, participants in the control group showed the exact opposite pattern. Within the patient group, the likelihood of relapse increased as participants were faster to respond to incompatible trials relative to compatible trials. CONCLUSIONS: Unlike controls, abstaining alcohol-dependent patients revealed a relative avoidance bias rather than relative approach bias. Moreover, relapse rates were found to increase as the relative tendency to avoid alcohol increased. This finding suggests that an avoidance orientation towards alcohol can potentially be harmful in clinical samples.