Alcohol Withdrawal Research Articles

Improving Outcomes in Alcohol Withdrawal; an Alcohol and Drug Liaison Outreach Approach

Improving Outcomes in Alcohol Withdrawal; an Alcohol and Drug Liaison Outreach Approach

Improving Acute Treatment of Alcohol Withdrawal at an Inpatient De-addiction Ward (‘Vimukthi’) at Kerala State, India: Full Cycle of a Clinical Audit

Improving Acute Treatment of Alcohol Withdrawal at an Inpatient De-addiction Ward (‘Vimukthi’) at Kerala State, India: Full Cycle of a Clinical Audit

Sleep as an Important Target or Modifier in Alcohol Use Disorder Clinical Treatment: Example From a Recent Gabapentin Randomized Clinical Trial.

Alcohol consumption affects sleep both in healthy populations and in patients with alcohol use disorder (AUD). However, sleep has typically not been considered within AUD pharmacotherapy trials. We used data from a completed gabapentin clinical treatment trial to explore the medication's effect on patient-rated insomnia measured by a standard insomnia rating (Insomnia Severity Index [ISI]) and whether this influenced gabapentin's effects on alcohol consumption. This study included 90 individuals with current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition AUD criteria reporting current or past alcohol withdrawal. Participants were assigned to placebo or gabapentin (up to 1200 mg/day) for a 16-week randomized controlled trial with percent heavy drinking days (PHDD) and percent abstinent days (PDA) as outcomes. Utilizing mixed-effects models, this study assessed medication effects on ISI over the trial. We then examined the interaction of baseline ISI and medication on drinking. Finally, given our previous finding of alcohol withdrawal influencing gabapentin efficacy, we added change in ISI as a potential "moderator" of the interaction of medication effects and alcohol withdrawal on drinking. Sleep (ISI) improved more in those treated with gabapentin (60.6% reduction) compared with placebo (37.8% reduction; P = 0.013). Higher baseline ISI predicted drinking in gabapentin-treated individuals (lower PHDD [ P = 0.026] and higher (PDA [ P = 0.047]). ISI was an independent predictor of PHDD decrease and PDA increase ( P < 0.001; P = 0.002), but this did not significantly moderate gabapentin's effectiveness. Although gabapentin positively impacts both alcohol use and sleep, its effect on drinking is not fully dependent on sleep improvement, implying a direct biological mechanism on alcohol use.

Replacing the Clinical Institute Withdrawal Assessment-Alcohol revised with the modified Richmond Agitation and Sedation Scale for alcohol withdrawal to support management of alcohol withdrawal symptoms: potential impact on length of stay and complications.

We evaluated impact on length of stay and possible complications of replacing the Clinical Institute Withdrawal Assessment-Alcohol Revised (CIWA-Ar) scale with a slightly modified Richmond Agitation and Sedation Scale (mRASS-AW) to support managing patients admitted with alcohol withdrawal symptoms in a community hospital. Since mRASS-AW is viewed as easier and quicker to use than CIWA-Ar, provided use of mRASS-AW does not worsen outcomes, it could be a safe alternative in a busy ED environment and offer an opportunity to release nursing time to care. Retrospective time-series analysis of mean quarterly length of stay. All analyses exclusively used our hospital's administrative discharge diagnoses database. During April 1st 2012 to December 14th 2014, the CIWA-Ar was used in the ED and in-patient units to guide benzodiazepine dosing decisions for alcohol withdrawal symptoms. After this point, CIWA-Ar was replaced with mRASS-AW. Data was evaluated until December 31st 2020. mean quarterly length of stay. delirium, intensive care unit (ICU) admission, other post-admission complications, mortality. N = 1073 patients. No association between length of stay and scale switch (slope change 0.3 (95% CI - 0.03 to 0.6), intercept change, 0.06 (- 0.03 to 0.2). CIWA-Ar (n = 317) mean quarterly length of stay, 5.7 days (95% 4.2-7.1), mRASS-AW (n = 756) 5.0 days (95% CI 4.3-5.6). Incidence of delirium, ICU admission or mortality was not different. However, incidence of other post-admission complications was higher with CIWA-Ar (6.6%) than mRASS-AW (3.4%) (p = 0.020). This was the first study to compare patient outcomes associated with using mRASS-AW for alcohol withdrawal symptoms outside the ICU. Replacing CIWA-Ar with mRASS-AW did not worsen length of stay or complications. These findings provide some evidence that mRASS-AW could be considered an alternative to CIWA-Ar and potentially may provide an opportunity to release nursing time to care.

Assessment of Cognitive Function in Romanian Patients with Chronic Alcohol Consumption

Alcoholism presents a significant health concern with notable socioeconomic implications. Alcohol withdrawal syndrome (AWS) can manifest when individuals cease or drastically reduce their alcohol consumption after prolonged use. Non-alcoholic fatty liver disease (NAFLD) is characterized by substantial lipid accumulation in the liver cells of individuals with no history of alcohol consumption. There is evidence suggesting an association between cognitive impairment and both conditions. This study aimed to evaluate cognitive impairment in patients with NAFLD and AWS using the Mini-Mental State Examination (MMSE). This study involved 120 patients admitted to two hospitals in Craiova, Romania. Results indicated that patients with NAFLD did not exhibit cognitive impairment as measured by MMSE (Mean = 29.27, SD = 0.785). Conversely, patients with AWS showed more pronounced cognitive dysfunction, with a mean MMSE score at admission of 16.60 ± 4.097 and 24.60 ± 2.832 after 2 weeks under treatment with Vitamins B1 and B6 and Cerebrolysin. Additionally, our findings suggested that cognitive dysfunction among alcohol consumers was correlated with the severity of clinical symptoms, as demonstrated by the severity of tremors in our study. The two-week period under treatment and alcohol withdrawal was insufficient for cognitive function to return to normal levels. Observational studies on longer periods of time are advised.

Clinical and healthcare use outcomes after cessation of long term opioid treatment due to prescriber workforce exit: quasi-experimental difference-in-differences study

ABSTRACTObjectiveTo examine the association between prescriber workforce exit, long term opioid treatment discontinuation, and clinical outcomes.DesignQuasi-experimental difference-in-differences studySetting20% sample of US Medicare beneficiaries, 2011-18.ParticipantsPeople receiving long term opioid treatment whose...

Protein kinase C epsilon-mediated modulation of T-type calcium channels underlies alcohol withdrawal hyperexcitability in the midline thalamus.

Millions of people struggle with alcohol use disorder (AUD). Abrupt abstinence after a period of chronic alcohol use can precipitate the alcohol withdrawal syndrome (AWS), which includes hyperexcitability and, potentially, seizures. We have shown that T-type Ca2+ channels are novel, sensitive targets of alcohol, an effect that is dependent upon protein kinase C (PKC). The purpose of this study was to (1) understand midline thalamic neuronal hyperexcitability during alcohol withdrawal and its dependence on PKC; (2) characterize T channel functional changes using both current clamp and voltage clamp methods; and (3) determine which PKC isoform may be responsible for alcohol withdrawal (WD) effects. Whole-cell patch clamp recordings were performed in midline thalamic neurons in brain slices prepared from C57bl/6 mice that underwent chronic intermittent alcohol exposure in a standard vapor chamber model. The recordings were compared to those from air-exposed controls. T-channel inactivation curves and burst responses were acquired through voltage-clamp and current-clamp recordings, respectively. Whole-cell voltage clamp recordings of native T-type current exhibited a depolarizing shift in the voltage-dependency of inactivation during alcohol withdrawal compared to air-exposed controls. A PKCε translocation inhibitor peptide mitigated this change. Current clamp recordings demonstrated more spikes per burst during alcohol withdrawal. Consistent with voltage clamp findings, the PKCɛ translocation inhibitor peptide reduced the number of spikes per burst after WD. We found that alcohol WD produces T channel-mediated hyperexcitability in the midline thalamus, produced in part by a shift in the inactivation curve consistent with greater availability of T current. WD effects on T current inactivation were reduced to control levels by blocking PKCε translocation. Our results demonstrate that PKCε translocation plays an important role in the regulation of alcohol withdrawal-induced hyperexcitability in midline thalamic circuitry.

Over the Limit; Long-Term Seizure and Mortality Risk in Alcohol Withdrawal Seizures.

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A National Analysis of Alcohol Withdrawal Syndrome in Patients with Operative Trauma

BackgroundAlcohol withdrawal syndrome (AWS) presents with a complex spectrum of clinical manifestations that complicate postoperative management. In trauma setting, subjective screening for AWS remains challenging due to the criticality of injury in these patients. We thus identified several patient characteristics and perioperative outcomes associated AWS development. MethodsThe 2016–2020 National Inpatient Sample was queried to identify all non-elective adult (≥18 years) hospitalizations for blunt or penetrating trauma undergoing operative management with a diagnosis of AWS. Patients with traumatic brain injury or with a hospital duration of stay <2 days were excluded. Outcomes of interest included in-hospital mortality, perioperative complications, hospitalization costs, length of stay (LOS) and non-home discharge. ResultsOf an estimated 2,965,079 operative trauma hospitalizations included for analysis, 36,415 (1.23 %) developed AWS following admission. The AWS cohort demonstrated increased odds of mortality (Adjusted Odds Ratio [AOR] 1.46, 95 % Confidence Interval [95 % CI] 1.23–1.73), along with infectious (AOR 1.73, 95 % CI 1.58–1.88), cardiac (AOR 1.24, 95 % CI 1.06–1.46), and respiratory (AOR 1.96, 95 % CI 1.81–2.11) complications. AWS was associated with prolonged LOS, (β: 3.3 days, 95 % CI: 3.0 to 3.5), greater cost (β: +$8900, 95 % CI $7900–9800) and incremental odds of nonhome discharge (AOR 1.43, 95 % CI 1.34–1.53). Furthermore, male sex, Medicaid insurance status, head injury and thoracic operation were linked with greater odds of development of AWS. ConclusionIn the present study, AWS development was associated with increased odds of in-hospital mortality, perioperative complications, and resource burden. The identification of patient and operative characteristics linked with AWS may improve screening protocols in trauma care.

Assisted Versus Unassisted Domiciliary Alcohol Detoxification: A Randomized Controlled Trial

Background: Detoxification stands as a crucial phase in the treatment of alcohol use disorders (AUD), yet only limited data is available on the outcomes of home-based detoxification. Assisted domiciliary detoxification involves monitoring an individual’s withdrawal progress, while offering psychosocial support and detoxification services in the comfort of their home. Aim: To study outcomes of assisted over routine domiciliary alcohol detoxification in randomized controlled trials. Methodology: 100 consenting male patients who were advised of domiciliary detoxification were randomized into intervention ( n = 49) and control ( n = 51) groups. A predesigned semi-structured questionnaire was used to assess the socio-demographic and drinking-related variables. Both groups received routine care for alcohol withdrawal from respective treating doctors. Additionally, the intervention group received two sessions of brief intervention for alcohol and daily phone call assistance. Records were kept for adverse events. Phone calls were discontinued once detoxification was completed. Outcomes were measured for successful completion of detoxification and abstention from alcohol at the end of one month. Results: The intervention group had significantly higher successful detoxification rates (85.7% vs. 62.7%, p = .008) and significantly higher abstinence days at the end of one month compared to the control group (22 vs. 10 days, p &lt; .001) with an effect size of 1.2 (confidence interval (CI) 0.69–1.53). Conclusion: This study demonstrates that receiving assistance in the acute phase of domiciliary detoxification helps in a successful detoxification and achieving a significant level of abstinence at the end of one month compared to the control group.

An Evaluation of the Anxiolytic Potential of Amentoflavone in Adult Zebrafish Undergoing Alcohol Withdrawal: In Vivo and In Silico Studies

The constant use of alcoholic beverages can deregulate serotonin levels, affecting neurotransmitters and triggering symptoms of anxiety. In this context, the objective of this work was to evaluate the anxiolytic potential and possible action mechanisms of the natural compound amentoflavone against the deleterious effects caused by alcohol withdrawal on the behavior of adult zebrafish (aZF). The experiments showed that amentoflavone did not change locomotion and did not cause toxicity in aZF during up to 96 h of analysis, with a median lethal concentration (LC50) greater than 1.0 mg/mL. The reversal of anxiety by pretreatment with granisetron suggested that the anxiolytic effect of amentoflavone is dependent on serotonergic 5-HT3A/3B receptors. Furthermore, amentoflavone reversed anxiety due to flumazenil pretreatment, suggesting a dependence on the GABAA receptor. The three concentrations of amentoflavone tested were effective in treating anxiety resulting from alcohol withdrawal. In silico analysis validated the in vivo results, supporting the idea that the interaction of amentoflavone with the protein occurs in a more stable manner than reference compounds. Amid growing interest in natural alternatives to treat anxiety disorders, amentoflavone is a potential candidate for a new anxiolytic compound that acts specifically on the 5HT3A/3B and GABAergic serotonergic pathways.

Patient Factors Associated With Prolonged Length of Stay After Traumatic Brain Injury.

Background For traumatic brain injury (TBI) survivors, recovery can lead to significant time spent in the inpatient/rehabilitation settings. Hospital length of stay (LOS) after TBI is a crucial metric of resource utilization and treatment costs. Risk factors for prolonged LOS (PLOS) after TBI require further characterization. Methodology We conducted a retrospective analysis of patients with diagnosed TBI at an urban trauma center. PLOS was defined as the 95th percentile of the LOS of the cohort. Patients with and without PLOS were compared using clinical/injury factors. Analyses included descriptive statistics, non-parametric analyses, and multivariable logistic regression for PLOS status. Results The threshold for PLOS was >24 days. In the cohort of 1,343 patients, 77 had PLOS. PLOS was significantly associated with longer mean intensive care unit (ICU) stays (16.4 vs. 1.5 days), higher mean injury severity scores (18.6 vs. 13.8), lower mean Glasgow coma scale scores (11.3 vs. 13.7) and greater mean complication burden (0.7 vs. 0.1). PLOS patients were more likely to have moderate/severe TBI, Medicaid insurance, and were less likely to be discharged home.In the regression model, PLOS was associated with ICU stay, inpatient disposition, ventilator use, unplanned intubation, and inpatient alcohol withdrawal. Conclusions TBI patients with PLOS were more likely to have severe injuries, in-hospital complications, and Medicaid insurance. PLOS was predicted by ICU stay, intubation, alcohol withdrawal, and disposition to inpatient/post-acute care facilities. Efforts to reduce in-hospital complications and expedite discharge may reduce LOS and accompanying costs.Further validation of these results is needed from larger multicenter studies.

Biochemical, Hematological, Inflammatory, and Gut Permeability Biomarkers in Patients with Alcohol Withdrawal Syndrome with and without Delirium Tremens.

Background: Delirium Tremens (DT) is known to be a serious complication of alcohol withdrawal syndrome (AWS). Neurotransmitter abnormalities, inflammation, and increased permeability are associated with the pathogenesis of AWS and DT. However, the biomarkers of these conditions are still poorly understood. Methods: In this work, biochemical, hematologic, inflammatory, and gut permeability biomarkers were investigated in the following three groups: healthy controls (n = 75), severe AWS patients with DT (n = 28), and mild/moderate AWS without DT (n = 97). Blood sampling was performed after resolution of the acute condition (on 5 ± 1 day after admission) to collect clinical information from patients and to investigate associations with clinical scales. Biomarker analysis was performed using automated analyzers and ELISA. Inflammatory biomarkers included the erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), and platelet-to-lymphocyte ratio (PLR). Results: Among the biochemical biomarkers, only glucose, total cholesterol, and alanine aminotransferase (ALT) changed significantly in the analyzed groups. A multiple regression analysis showed that age and ALT were independent predictors of the CIWA-Ar score. Hematologic biomarker analysis showed an increased white blood cell count, and the elevated size and greater size variability of red blood cells and platelets (MCV, RDWc, and PDWc) in two groups of patients. Gut permeability biomarkers (FABP2, LBP, and zonulin) did not change, but were associated with comorbid pathologies (alcohol liver disease and pancreatitis). The increase in inflammatory biomarkers (ESR and PLR) was more evident in AWS patients with DT. Cluster analysis confirmed the existence of a subgroup of patients with evidence of high inflammation, and such a subgroup was more frequent in DT patients. Conclusions: These findings contribute to the understanding of biomarker variability in AWS patients with and without DT and support the heterogeneity of patients by the level of inflammation.

Is Phenobarbital an Effective Treatment for Alcohol Withdrawal Syndrome?

BackgroundAlcohol use disorder is associated with a variety of complications, including alcohol withdrawal syndrome (AWS), which may occur in those who decrease or stop alcohol consumption suddenly. AWS is associated with a range of signs and symptoms, which are most commonly treated with GABAergic medications. Clinical QuestionIs phenobarbital an effective treatment for AWS? Evidence ReviewStudies retrieved included two prospective, randomized, double-blind studies and three systematic reviews. These studies provided estimates of the effectiveness and safety of phenobarbital for treatment of AWS. ConclusionsBased on the available literature, phenobarbital is reasonable to consider for treatment of AWS. Clinicians must consider the individual patient, clinical situation, and comorbidities when selecting a medication for treatment of AWS.

Effectiveness assessment of sulfur-containing amino acids in rats with experimental “alcohol withdrawal syndrome” with modified zoosocial interaction methods

The aim of the work was to compare the effects of ademethionine, acetylcysteine and taurine on the zoosocial behavior of rats in a post-intoxicated state after an acute ethanol poisoning.Materials and methods. The study was conducted on male rats of the Wistar line. The post-intoxication state was modeled by a single injection of ethanol (3 g/kg, intraperitoneally). 30 min after awakening, the animals were injected with a physiological solution, acetylcysteine (1 g/kg), ademetionine (100 mg/kg) or taurine (40 mg/kg). A zoosocial interaction test was performed 30 min after the administration.Results. Among the behavioral indicators investigated, the following were validated: the number of acts of freezing, their duration, the number of acts of sniffing in front, the number of acts of avoidance and the number of vertical stances without support (p &lt;0.05 between the values of the negative and positive control groups in all cases). The administration of acetylcysteine, ademetionine and taurine reduced the number of freezing acts by 53.64, 7.27 and 24.51%, respectively (p &lt;0.05 when compared with the indicator index in the animals from the positive control group in all cases). The administration of acetylcysteine and taurine reduced the number of avoidance acts by 50 and 10%, respectively (p &lt;0.05 when compared to that of the animals from the positive control group in both cases). All amino acids normalized the communicative performance, although it did not differ from that of the animals from the positive control group (p &gt;0.05). Alcoholization reduced the number of vertical stances by 65% (p &lt;0.001 when compared with that in the animals from the negative control group), and when followed by the administration of ademetionine and taurine, the reduction was 38 and 36%, respectively (p &lt;0.05 when compared to that in the animals from the negative control group).Conclusion. According to the data obtained, sulfur-containing amino acids, primarily those that had central effects, normalized neuronal functions, positively influencing a complex behavior of rats. Taking into account the results of the previous studies, it was possible to conclude that the therapeutic effect of ademetionine and taurine in the context of a post-intoxication state is mediated by their central effects, which are not so pronounced in comparison with acetylcysteine.

Adolescent alcohol binge drinking and withdrawal: behavioural, brain GFAP-positive astrocytes and acute methamphetamine effects in adult female rats

RationaleAlcopop beverages are generally the first alcoholic beverage that young females drink which contain high levels of sugar and alcohol. The over-consumption of these drinks may encourage alcohol co-administration with methamphetamine (METH) impacting on drinking behaviour and glial function.AimsThe aims of this study were to evaluate the effect of adolescent binge alcohol exposure on consumption level, anxiety-like behaviour, cross-sensitization with METH and on astrocyte expression in reward related brain regions.MethodsAdolescent female Sprague-Dawley rats had daily 1-hour oral alcohol consumption of alcopop (ALCP; with sucrose) or ethanol-only (ETOH; without sucrose), transitioned from 5 to 15% (v/v) ethanol content for 34 days. Water and sucrose groups act as controls. During alcohol withdrawal, rats were tested for anxiety on the elevated plus maze (EPM) and locomotor activity following saline or METH (1 mg/kg i.p) treatment. Brains were then collected to assess astrocyte immunofluorescence for glial fibrillary acidic protein (GFAP) in reward-related brain regions.ResultsRats pretreated with 5% ALCP consumed significantly more volume and ethanol intake when compared to 5% EtOH rats. Both ALCP and EtOH groups had a higher preference ratio for 5% than 15% alcohol solutions and ALCP rats had greater ethanol intake at 15% than EtOH rats. Alcohol withdrawal showed no significant differences between groups on anxiety, METH cross-sensitization effects or GFAP intensity in the regions studied.ConclusionsOverall, the addition of sucrose to alcoholic solutions encouraged female rats to consume larger volumes and greater ethanol intake compared to ethanol-only solutions, yet did not have long lasting effects on behaviour and astrocytes.

Load and go: Assessing safety outcomes of patients discharged from the emergency department after receiving phenobarbital for alcohol withdrawal.

Phenobarbital (PB) is a long-acting GABA A-agonist with favorable pharmacokinetics (long half-life and duration of effect) that allows effective treatment of alcohol withdrawal (AW) after administration of a single loading dose. Current evidence suggests that in the setting of AW, PB administration may be associated with decreased hospital admissions and hospital length of stay. The aim of this study was to evaluate the safety outcomes of AW patients who were treated and discharged from the emergency department (ED) after receiving PB for AW. This retrospective chart review included a convenience sample of 33 AW patients who presented to four EDs within an 18-month span. Descriptive statistics (frequencies and percentages) were used to describe demographics, distribution of resources and referrals, and the safety outcomes of PB administration for low-risk AW patients. Patients were selected for inclusion in consultation with a medical toxicologist, treated with PB, and discharged from the ED. Electronic medical records were utilized to gather information on the patient cohort. All patients were treated with at least a single loading dose of 5‒10mg/kg (ideal body weight) of intravenous or per os PB during their ED stay. Only one patient had an unanticipated event after discharge, which was related to driving against advice. Two additional patients had ED revisits for recurrent alcohol use within 72h, and 16 patients had recurrent alcohol use within 30 days. All 33 patients were provided with resources for linkage to treatment. None required hospital admission. ED PB "load and go" may be a safe, effective AW treatment that could help treat AW, facilitate linkage to specific rehabilitation treatments, and decrease hospital admissions.

Alcohol withdrawal and amphetamine co-use in an animal model for attention deficit hyperactivity disorder

ABSTRACT Background: Non-medical use of amphetamine and other stimulants prescribed for treatment of attention deficit/hyperactivity disorder (ADHD) is of special concern when combined with alcohol consumption. In a previous study, we modeled chronic ethanol-amphetamine co-use in adolescent Long-Evans (LE) rats and provided evidence that amphetamine attenuates alcohol withdrawal symptoms. Objectives: This project modeled co-use of amphetamine with alcohol in adolescents with ADHD-like symptoms by examining ethanol-amphetamine administration in adolescent Spontaneously Hypertensive Rats (SHR), an experimental model for the study of ADHD. Withdrawal symptoms were compared among SHR and two control rat strains, LE and Wistar Kyoto (WKY). Methods: At postnatal day 32, parallel groups of 12–24 male SHR, WKY and LE rats were administered a liquid diet containing ethanol (3.6%) and/or amphetamine (20 mg/L). Following administration periods up to 26 days, rats were withdrawn from their treatment and tested for overall severity of alcohol withdrawal symptoms, general locomotor activity, and anxiety-like behavior. Results: Overall withdrawal severity was lower for SHR than for LE (p < .001) or WKY (p = .027). Co-consumption of amphetamine decreased withdrawal severity for LE (p = .033) and WKY (p = .011) but not SHR (p = .600). Only WKY showed increased anxiety-like behavior during withdrawal (p = .031), but not after amphetamine co-administration (p = .832). Conclusion: Alcohol withdrawal severity may be attenuated when co-used with amphetamine. However, as a model for ADHD, SHR adolescents appeared resistant to developing significant signs of alcohol withdrawal following alcohol consumption. Whether alcohol withdrawal symptoms are attenuated or absent, potential consequences could include a decreased awareness of an emerging problem with alcohol use.

Alcohol-related posterior reversible encephalopathy syndrome: a case report of a patient managed with a benzodiazepine-sparing regimen for alcohol withdrawal

ABSTRACT We report a case of posterior reversible encephalopathy syndrome (PRES) during treatment for alcohol withdrawal syndrome with gabapentin and clonidine. The patient developed severe hypertension, confusion and tremor, culminating in bilateral vision loss and a seizure. Imaging revealed posterior cerebral edema. Treatment with benzodiazepines, antihypertensives, and anti-seizure medications led to resolution. One year later, imaging showed resolution of the findings. We review the associated literature and propose the recognition of a PRES sub-entity, Alcohol-Related PRES (ARPRES), which can appear in the setting of alcohol withdrawal syndrome, chronic alcohol use, and acute alcohol intoxication, with or without hypertension.

ANK3 rs10994336 and ZNF804A rs7597593 polymorphisms: genetic interaction for emotional and behavioral symptoms of alcohol withdrawal syndrome

ObjectiveAlcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity.MethodsThe study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR.ResultsSingle-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation.ConclusionThis study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.