An epigenetic candidate-gene association study of parental styles in suicide attempters with substance use disorders.

Suicide attempts (SA) are prevalent in substance use disorders (SUD). Epigenetic mechanisms may play a pivotal role in the molecular mechanisms of environmental effects eliciting suicidal behaviour in this population. Hypothalamic-pituitary-adrenal axis (HPA), oxytocin and neurotrophin pathways have been consistently involved in SA, yet , their interplay with childhood adversity remains unclear, particularly in SUD. In 24 outpatients with SUDs, we examined the relation between three parental dysfunctional styles and history of SA with methylation of 32 genes from these pathways, eventually analysing 823 methylation sites. Extensive phenotypic characterization was obtained using a semi-structured interview. Parental style was patient-reported using the Measure of Parental Style (MOPS) questionnaire, analysed with and without imputation of missing items. Linear regressions were performed to adjust for possible confounders, followed by multiple testing correction. We describe both differentially methylated probes (DMPs) and regions (DMRs) for each set of analyses (with and without imputation of MOPS items). Without imputation, five DMRs in OXTR, CRH and NTF3 significantly interacted with MOPS father abuse to increase the risk for lifetime SA, thus covering the three pathways. After imputation of missing MOPS items, two other DMPs from FKBP5 and SOCS3 significantly interacted with each of the three father styles to increase the risk for SA. Although our findings must be interpreted with caution due to small sample size, they suggest implications of stress reactivity genes in the suicidal risk of SUD patients and highlight the significance of father dysfunction as a potential marker of childhood adversity in SUD patients.

Hospitalized cocaine detoxification patients in Paris, France: Increased patient levels and changing population characteristics since 2011.

AIM OF THE STUDY: The past twenty years have seen a rise in cocaine-related statistics in France, including cocaine use in the general population, emergency ward presentations of acute cocaine intoxication, cocaine use disorders related outpatient appointments and cocaine-related deaths. This study's objectives were to describe trends in patients' admission for specific cocaine detoxification as well as changes in patients' characteristics in the Assistance publique-Hôpitaux de Paris (AP-HP) hospitals group located in Paris region, France. METHODS: We reviewed the international classification of diseases 10th edition (ICD-10) discharge codes of the AP-HP hospitals group between 2011 and 2021. In addition, medical reports of the largest addiction medicine ward were also analysed for changes across the years 2009, 2014, 2019 and 2022. RESULTS: The regional database showed an almost 3-fold increase in cocaine-related disorders discharge codes between 2011 and 2019. This occurred due to a rise in hospital stays for cocaine dependence or cocaine acute intoxication prior to the fall in levels of inpatient stays associated with the coronavirus disease 2019 (COVID-19) pandemic. The in-depth analysis of inpatients' stays in the specialized addiction medicine ward also showed an increase in admissions for cocaine detoxification programs, with a prevalence of 1.19% in 2009 to 15.73% in 2022 (P=1.44×10-20). Inpatient characteristics showed significant changes, especially in 2022, namely: more daily users, less intravenous administration and less comorbid illicit substances use disorders, with heightened levels of cured hepatitis C patients (P<0.05). Inpatient prescriptions were primarily dopaminergic antagonists with sedatives properties (cyamemazine, loxapine and chlorpromazine), dopamine-receptors partial agonist (aripiprazole) and serotonin reuptake inhibitors. CONCLUSION: The referral to hospital care for cocaine detoxification has increased in Paris region since 2011, coupled with changes in inpatients' characteristics. This trend has significant implications for the management of inpatient hospital services.

USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder.

The risk of developing drug addiction is strongly influenced by the epigenetic landscape and chromatin remodeling. While histone modifications such as methylation and acetylation have been studied in the ventral tegmental area and nucleus accumbens (NAc), the role of H2A monoubiquitination remains unknown. Our investigations, initially focused on the scaffold protein melanoma-associated antigen D1 (Maged1), reveal that H2A monoubiquitination in the paraventricular thalamus (PVT) significantly contributes to cocaine-adaptive behaviors and transcriptional repression induced by cocaine. Chronic cocaine use increases H2A monoubiquitination, regulated by Maged1 and its partner USP7. Accordingly, Maged1 specific inactivation in thalamic Vglut2 neurons, or USP7 inhibition, blocks cocaine-evoked H2A monoubiquitination and cocaine locomotor sensitization. Additionally, genetic variations in MAGED1 and USP7 are linked to altered susceptibility to cocaine addiction and cocaine-associated symptoms in humans. These findings unveil an epigenetic modification in a non-canonical reward pathway of the brain and a potent marker of epigenetic risk factors for drug addiction in humans.

Behavioral sensitization to psychostimulants and opioids: What is known in rodents and what still needs to be explored in humans?

Repeated exposure to substances of abuse results in an increase in some behavioral responses. This phenomenon, called behavioral sensitization (BS), is well described in preclinical models. However, its existence in humans is still a matter of debate. After a review of preclinical evidence of BS and its mechanisms in animal models, we reviewed the evidence supporting the existence of BS in humans, despite the limited research available in this regard. We focused our review on opioids and psychostimulants, since they share the ability to promote addictive behaviors. Further, they induce BS despite their distinct sedative and stimulant properties. Moreover, we proposed future research perspectives in this review to address the remaining unsolved questions, especially regarding BS in humans using a harm reduction approach.

A single case report of STN-DBS for severe crack-cocaine dependence: double-blind ON vs. SHAM randomized controlled assessment.

Crack-cocaine dependence is a severe condition with a high mortality rate. This single case study report details the first deep brain stimulation (DBS) trial targeting the sub-thalamic nucleus (STN) for crack-cocaine dependence. The investigation aimed to assess the effects of STN-DBS on cocaine craving and cocaine use, as well as STN-DBS safety and tolerance in this indication. In this pilot study, we performed double blind cross-over trials, with "ON-DBS" vs. "SHAM-DBS" for 1-month periods. STN-DBS failed to reduce cocaine craving and use. An episode of DBS-induced hypomania occurred after several weeks of cocaine intake at stimulation parameters previously well tolerated. Future research on cocaine dependence should be conducted after a prolonged abstinence period and/or explore novel types of stimulation patterns.

Sex-related differences in the efficacy of Baclofen enantiomers on self-administered alcohol in a binge drinking pattern and dopamine release in the core of the nucleus accumbens.

Introduction: Clinical studies on the effectiveness of Baclofen in alcohol use disorder (AUD) yielded mixed results possibly because of differential effects of the enantiomers and sex-related differences. Here we examined the effect of the different Baclofen enantiomers on alcohol intake and on evoked dopamine release in the core of the nucleus accumbens (NAcc) in male and female Long Evans rats. Methods: Rats were trained to chronically self-administer 20% alcohol solution in daily binge drinking sessions and were treated with the different forms of Baclofen [RS(±), R(+) and S(-)]. The effects on the evoked dopamine release within the core of the nucleus accumbens were measured in brain slices from the same animals and the alcohol naïve animals using the fast scan cyclic voltammetry technique. Results: RS(±)-Baclofen reduced alcohol intake regardless of sex but more females were non-responders to the treatment. R(+)-Baclofen also reduced alcohol intake regardless of sex but females were less sensitive than males. S(-)-Baclofen did not have any effect on average but in some individuals, especially in the females, it did increase alcohol intake by at least 100%. There were no sex differences in Baclofen pharmacokinetic but a strong negative correlation was found in females with a paradoxical effect of increased alcohol intake with higher blood Baclofen concentration. Chronic alcohol intake reduced the sensitivity to the effect of Baclofen on evoked dopamine release and S(-)-Baclofen increased dopamine release specifically in females. Discussion: Our results demonstrate a sex-dependent effect of the different forms of Baclofen with no or negative effects (meaning an increase in alcohol self-administration) in subgroup of females that could be linked to a differential effect on dopamine release and should warrant future clinical studies on alcohol use disorder pharmacotherapy that will deeply analyze sex difference.

Prevalence of benzodiazepine use disorder during hospitalization for alcohol detoxification.

Benzodiazepines (BZDs) are the first-line treatment of alcohol withdrawal. Comorbidity between benzodiazepine use disorder (BUD) and alcohol use disorders (AUD) is common. However, the risk factors are poorly characterized due to the paucity of available BUD screening tools. The present study aimed to rectify this by conducting an observational screening investigation for BUD in patients hospitalized for alcohol detoxification in a specialized unit. During a face-to-face interview, a short BUD screening tool, Echelle Cognitive d'Attachement aux benzodiazépines (ECAB), was administered to record recent patterns of BZD use, thereby allowing categorization of AUD patients as follows: non-BZD users, BZD users without BUD, and BUD (ECAB ≥6). Clinical and sociodemographic risk factors were identified and recorded during clinical assessment and were analyzed using nonparametric bivariate tests and multinomial regression for association with BUD, with p < 0.05 for significance. Of the 150 AUD patients, 23 (15%) had comorbid BUD. Several variables were associated with ECAB score, with their independence being verified using multinomial regression, with lower risk of BUD versus BZD use, when the initial prescriber was an addiction specialist compared with a psychiatrist or a general practitioner [odds ratio (OR) = 0.12, 95% confidence interval (CI) = 0.14-0.75]. A higher risk of BZD use versus no use was evident when comorbid psychiatric disorders were present (OR = 9.2, 95%CI = 1.3-65). Our findings raise clinicians' awareness that in patients hospitalized for alcohol detoxification, BUD is highly prevalent but not specifically related to psychiatric disorders. BUD can be effectively screened by utilization of the ECAB.

A specific cognitive behavioral group therapy program for stimulant use disorder.

Introduction: Stimulant use is an important health issue. In the US in 2018, 2.8% of males and 1.5% of females older than 18 had used cocaine in the preceding 12 months. Objective: To intervene in a specific targeted group of Stimulant Use Disorder (SUD) patients according to CBT and relapse prevention theories, and to determine the program's feasibility and attendance. Method: Stimulant Use Disorder patients in addiction care were evaluated for addictive, psychological and psychiatric dimensions at baseline and conclusion in a 9-session CBT group program with several themes: define SUD, enhance motivation, involve close companions, cope with craving, decline a proposal, solve problems, invite expert patients, invest time and money, and review content. Results: In total, 41 patients attended at least one session. They were mainly poly dependent, primarily cocaine users. Sixty percent of the population also suffered from another psychiatric comorbidity. Median attendance for participants was 7/9 sessions. Conclusion: A specific targeted CBT group for stimulant dependent highly comorbid patients is feasible. These findings suggest that peers should be included in addiction care services.

Alcohol Withdrawal Is an Oxidative Stress Challenge for the Brain: Does It Pave the Way toward Severe Alcohol-Related Cognitive Impairment?

Alcohol use is a leading cause of mortality, brain morbidity, neurological complications and minor to major neurocognitive disorders. Alcohol-related neurocognitive disorders are consecutive to the direct effect of chronic and excessive alcohol use, but not only. Indeed, patients with severe alcohol use disorders (AUD) associated with pharmacological dependence suffer from repetitive events of alcohol withdrawal (AW). If those AW are not managed by adequate medical and pharmacological treatment, they may evolve into severe AW, or be complicated by epileptic seizure or delirium tremens (DT). In addition, we suggest that AW favors the occurrence of Wernicke's encephalopathy (WE) in patients with known or unknown thiamine depletion. We reviewed the literature on oxidative stress as a core mechanism in brain suffering linked with those conditions: AW, epileptic seizure, DT and WE. Thus, we propose perspectives to further develop research projects aiming at better identifying oxidative stress brain damage related to AW, assessing the effect of repetitive episodes of AW, and their long-term cognitive consequences. This research field should develop neuroprotective strategies during AW itself or during the periwithdrawal period. This could contribute to the prevention of severe alcohol-related brain damage and cognitive impairments.

Plasma tau, NfL, GFAP and UCHL1 as candidate biomarkers of alcohol withdrawal-associated brain damage: A pilot study.

In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal-associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.9%), aged 49.8 years [SD ±9.9]. Tau, NfL, GFAP and UCHL1 levels were measured using SIMOA and analysed with a quasipoisson regression model adjusted for age and sex. The NfL level was higher in the AC group (p = 0.013). In the AC group, the tau (p = 0.021) and UCHL1 (p = 0.021) levels were positively associated with the dose of diazepam per weight, and the tau (p = 0.045), NfL (p = 4.9 × 10-3 ) and UCHL1 (p = 0.036) levels were higher in the presence of signs of Wernicke's encephalopathy (n = 9). In the preclinical study, NfL and GFAP levels were assessed in the alcohol deprivation effect (ADE) procedure (N = 17) and control Wistar rats (N = 15). Furthermore, ADE rats were prospectively assessed: after 24 h (T1) and 3 weeks of AC (T2) (paired-samples Wilcoxon and Mann-Whitney tests). The NfL level was higher in the ADE model than in the control rats at both T1 and T2 (p = 0.033 and p = 1.3 × 10-3 ) and higher at T2 than at T1 (p = 0.040). Plasma tau, NfL and UCHL1 are potential biomarkers of brain suffering during alcohol withdrawal.

The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study.

BACKGROUND: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. AIMS: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. RESULTS: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. CONCLUSIONS: The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes. TRIAL REGISTRATION: ISRCTN15998989 20/12/2019.

Biomarkers of Relapse in Cocaine Use Disorder: A Narrative Review.

INTRODUCTION: Cocaine use disorder is a chronic disease with severe consequences and a high relapse rate. There is a critical need to explore the factors influencing relapse in order to achieve more efficient treatment outcomes. Furthermore, there is a great need for easy-to-measure, repeatable, and valid biomarkers that can predict treatment response or relapse. METHODS: We reviewed the available literature on the Pubmed database concerning the biomarkers associated with relapse in CUD, including central nervous system-derived, genetic, immune, oxidative stress, and "other" biomarkers. RESULTS: Fifty-one articles were included in our analysis. Twenty-five imaging brain anatomic and function assessment studies, mostly using fMRI, examined the role of several structures such as the striatum activity in abstinence prediction. There were fewer studies assessing the use of neuropsychological factors, neurotrophins, or genetic/genomic factors, immune system, or oxidative stress measures to predict abstinence. CONCLUSION: Several biomarkers have been shown to have predictive value. Prospective studies using combined multimodal assessments are now warranted.

Patients With Severe Alcohol-Related Cognitive Impairment Improve in Flexibility When Abstinence Is Maintained: A Comparative Study With Alzheimer's Disease.

The disease progression of severe alcohol-related cognitive impairment (ARCI) is debated. The aim of this study was to compare the cognitive change of patients with severe ARCI in inpatient setting to that of patients with Alzheimer's disease (AD). Fifteen consecutive patients with severe ARCI were recruited between 2013 and 2015. They received inpatient detoxification, neurological assessment, and inpatient cognitive rehabilitation in specialized facilities. Twelve patients, with documented AD matched on sex and initial cognitive impairment severity, were selected. All have benefited from two neuropsychological assessments. The neurocognitive change was tested in both groups with pair-wised Wilcoxon tests. ARCI and AD patients' time course was compared with Mann-Whitney-Wilcoxon test. In ARCI group, first assessment occurred at 2.9 (± 2.2) months of abstinence and follow-up 6.5 (± 2.9) months later, the mean age was 56.5 (± 7.4) years, and 12 were men. In AD group, follow-up occurred at 12.8 (± 2.9) months (p < 10-3), the mean age was 72.3 (± 8.4) years (p < 10-3), and 10 were men. ARCI patients significantly improved on one executive function test (TMT-B; p < 0.05), while AD patients have worsened memory subtests on Free-and-Cued-Selective-Reminding Test (p < 0.05). These tests showed a statistically different change between severe ARCI and AD group (p < 0.05). Severe ARCI patients have improved in executive functioning, discernible on the TMT-B test, in specific care setting, including abstinence maintenance and rehabilitation. The disease progression was different from that observed in AD patients.

Feasibility of an Extensive Strategy for Adult Diagnosis of Attention Deficit Hyperactivity Disorder Among Patients Suffering From Substance Use Disorders.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is found in up to 20% adults with Substance Use Disorder (SUD). ADHD + SUD is associated with a more complex clinical presentation and poorer outcomes than each disorder alone. In the presence of SUD, adult ADHD is particularly difficult to diagnose as both disorders can mimic or hide the symptoms of each other. Our university hospital in Paris recently started an extensive outpatient diagnostic procedure for adult patients with SUD to ascertain or refute ADHD diagnosis and to provide therapeutic guidance. Here, we report the acceptability of the assessment procedure for patients and the preliminary description of the current and lifetime clinical profiles as a function of the final diagnosis "ADHD vs. no ADHD." Method: Adult SUD patients with suspected ADHD were included in the current pilot study after stating they had no objection that their de-identified data were used for research purposes, according to French ethical procedures. Patients were evaluated for ADHD, comorbid mental disorders, cognitive state and dimensional psychological variables. They were assessed by trained psychologists and psychiatrists using standardized tools over a day. ADHD diagnosis was mainly based on the Diagnostisch Interview Voor ADHD for DSM-5 (DIVA-5). Results: Out of 18 eligible patients, 17 were included in the cohort (1 excluded) and none was opposed to using their data. Thirteen (76%) participants were diagnosed with ADHD. All patients appointed for the ADHD diagnostic procedure came, respected schedules and finished the evaluation. All patients were impaired on cognitive functioning and were highly comorbid, but ADHD patients seems to suffer even more from those conditions, especially for cannabis and stimulant use disorders. Discussion: Preliminary results show high acceptability of the procedure by ADHD-SUD patients. This result could be explained by all the organization adapted to the psychopathology. Patients' baseline motivation to participate also represents an uncontrolled variable that could promote the ability to follow the procedure. Acceptance results of the protocol are promising and represent a starting point to identify the best procedures to design patient-centered pharmacological and non-pharmacological therapies.

Occurrence and severity of cocaine-induced hallucinations: Two distinct phenotypes with shared clinical factors but specific genetic risk factors.

Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity. METHODS: Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and tested with CIH scores using a zero-inflated binomial model, which allows for the exploration of factors associated with occurrence and severity separately. RESULTS: Cocaine dependence (poccurrence= 6.18 × 10-5, pseverity= 9.25 × 10-8), number of cocaine dependence DSM IV-Tr criteria (poccurrence= 1.22 × 10-7, pseverity= 5.09 × 10-6), and frequency of intake during the worst period of misuse (poccurrence= 8.51 × 10-04, pseverity= 0.04) were associated with greater occurrence and higher severity of CIH. The genetic associations did not yield significant results after correction for multiple tests. However, some nominal associations of SNPs mapped to the VMAT2, DBH, DRD1, and DRD2 genes were significant. In the multivariate model, the significant variables were the number of cocaine dependence criteria, lifetime alcohol dependence, and the nominally associated SNPs. CONCLUSION: Our study shows that CIH occurrence and severity are two distinct phenotypes, with shared clinical risk factors; however, they likely do not share the same genetic background.

A pilot study of new approaches to exploring illness trajectories and patterns of comorbidity in major mental disorders.

AIMS: We explored lifetime comorbidities in clinical subsamples with a diagnosis of Psychosis (N = 143), bipolar (BD = 511), and unipolar disorders (UP = 861). METHODS: We analyzed trajectories and patterns of comorbidities using novel metrics, namely bubble plots and density of antecedent events per year of illness exposure per individual. RESULTS: Age at onset (AAO) of most comorbidities was similar to epidemiological studies, but cumulative rates were higher in clinical cases. There were some between group differences in patterns or burden of comorbidities, for example, Psychosis showed the earliest AAO of any mental disorder; UP showed the latest AAO of the index diagnosis. The relative risk of multimorbidity was lower in UP compared with other diagnoses, however, the goodness of fit for the illness trajectory path was lowest for BD. CONCLUSIONS: Bubble plots offer a useful representation of timing, sequence, cumulative probability and of comorbidities, the added value of reporting density measures was less obvious.

Childhood trauma and the severity of past suicide attempts in outpatients with cocaine use disorders.

Introduction: Suicide attempts have been associated with both cocaine use disorder (CocUD) and childhood trauma. We investigated how childhood trauma is an independent risk factor for serious and recurrent suicide attempts in CocUD. Method: 298 outpatients (23% women) with CocUD underwent standardized assessments of substance dependence (Diagnostic and Statistical Manual-mental disorders, fourth edition, text revised), impulsiveness, resilience, and childhood trauma, using validated tools. Suicide attempts history was categorized as single vs. recurrent or non-serious vs. serious depending on the lifetime number of suicide attempts and the potential or actual lethality of the worst attempt reported, respectively. Bivariate and multinomial regression analyses were used to characterize which childhood trauma patterns were associated with the suicide attempts groups. Results: 58% of CocUD patients reported childhood trauma. Recurrent and serious suicide attempts clustered together and were thus combined into "severe SA." Severe suicide attempt risk increased proportionally to the number of childhood traumas (test for trend, p = 9 × 10-7). Non-severe suicide attempt risk increased with impulsiveness and decreased with resilience. In multinomial regression models, a higher number of traumas and emotional abuse were independently and only associated with severe vs. non-severe suicide attempts (effect size = 0.82, AUC = 0.7). The study was limited by its cross-sectional design. Conclusion: These preferential associations between childhood trauma and severe suicide attempts warrant specific monitoring of suicide attempts risk in CocUD, regardless of the severity of addiction profiles.

Influence of Clinical Markers of Dopaminergic Behaviors on Depressive Symptoms During Withdrawal in Cocaine Users.

Background: During cocaine withdrawal, transient depressive symptoms that do not meet the criteria for depression, but promote relapse, are frequently observed. Their temporality could evoke a role of dopamine, especially since the underlying mechanism of these depressive symptoms is not well understood. We hypothesized that variation in the dopaminergic activity profile, modeled from clinical markers, could be implicated in the development of depressive symptoms during cocaine withdrawal. Methods: We compared patients reporting depressive symptoms (RDS+) or not (RDS-) during cocaine withdrawal. We evaluated dopaminergic activity through indirect clinical markers based on the known dopaminergic behaviors. A combined criterion was constructed for hyper and hypo dopaminergic models according to the O'Brien method and illustrated by the Hedges' effect-size and forest-plot graph. A multidimensional factorial analysis was carried out to determine which parameters discriminate RDS+/RDS- patients. Results: 313 patients were included, and 77% reported depressive symptoms during cocaine withdrawal. Hyperdopaminergic variables used to discriminate the two groups had a large overall effect size (-0.669) and included psychotic symptoms (-0.524), hallucinations (-0.548), and delusions (-0.528). The overall effect of the hypodopaminergic component was considerable (-0.604) with a large effect size for the severity of dependence (-0.616), withdrawal symptoms (-0.578), and anhedonia (-0.528). The combined model including hyperdopaminergic and hypodopaminergic components had the largest effect size (-0.785). Conclusion: The dopaminergic activities profile, assessed by indirect clinical markers, seems to characterize patients with depressive symptoms very well during cocaine withdrawal. RDS+ patients reported moreover higher levels of psychotic symptoms and more severe cocaine use disorder than RDS-.

Ascorbic Acid Deficiency Prevalence and Associated Cognitive Impairment in Alcohol Detoxification Inpatients: A Pilot Study.

Malnutrition has been reported in alcohol use disorder patients as having a possible influence on cognitive function. The aim of this study was to analyse the prevalence of ascorbic acid (AA) deficiency in inpatients admitted for alcohol detoxification and the associated factors, including cognitive impairment in the early period of abstinence. A retrospective chart review was conducted. The AA level was categorised into three groups: deficiency (AAD) (<2 mg/L), insufficiency (AAI) (2-5 mg/L) and normal level. The cognitive impairment was screened using the Montreal Cognitive Assessment (MoCA). Ninety-six patients were included (74 men; mean age 49.1 years (±11.5)). Twenty-seven AAD (28.1%) and twenty-two AAI (22.9%) were observed. In multivariate analysis, risk factors for AAD versus normal AA level were men (OR 17.8, 95%CI (1.63-194)), compensated cirrhosis (OR 9.35, 95%CI (1.60-54.6)) and street homelessness (OR 5.76, 95%CI (1.24-26.8) versus personal housing). The MoCA score was available for 53 patients (mean MoCA score: 25.7 (±3.3)). In multivariate analysis, the natural logarithm of AA (ß = 1.18, p = 0.037) and sedative use disorder (ß = -2.77, p = 0.046) were associated with the MoCA score. AAD and AAI are frequent in inpatients admitted for alcohol detoxification. A low level of AA was associated with cognitive impairment in the early period of abstinence.