Research progress on the relationship between proBDNF and alcohol dependence and its related cognitive impairment

Brain-derived neurotrophic factor(BDNF)plays an important role in the growth,develop-ment,differentiation,injury,repair,survival and apoptosis of nerve cells.Precursor of BDNF(proBDNF)is an im-portant regulator of neurodegeneration,long-term hippo-campal inhibition and synaptic plasticity.Alcohol depen-dence syndrome(ADS)is a group of chronic recurrent diseases with unknown etiology.Current studies believe that proBDNF plays an important role in the occurrence,development and outcome of ADS.Alcohol dependence patients,like other neurodegenerative diseases,will also have different degrees of cognitive impairment.This arti-cle reviews the research progress on the relationship be-tween BDNF,proBDNF,alcohol dependence and cogni-tive impairment.

Effectiveness of psychosocial intervention for internalizing behavior problems among children of parents with alcohol dependence:Randomized controlled trial

BACKGROUND Parental drinking has a direct bearing on children.Behavioral problems such as anxiety and depression are common problems among children whose parents drink heavily.Psychosocial interventions have shown promising results for anxiety and depression among children;however,few studies have been conducted in the context of children of parents with alcohol dependence in India.AIM To evaluate the efficacy of psychosocial intervention for internalizing behavioral problems among children of parents with alcohol dependence.METHODS A randomized controlled trial with a 2×4 factorial design was adopted with longitudinal measurement of outcomes for 6 mo.Two-hundred and eleven children who met the eligibility criteria(at least one parent with alcohol dependence)at government high schools in Bangalore,India,were randomized to the experimental(n=97)or control group(n=98).The psychosocial intervention was administered to the experimental group in eight sessions(biweekly)over 4 wk after baseline assessment.The intervention focused on identifying and modifying negative thoughts,replacing thinking errors with realistic alternatives,modification of maladaptive behavior,developing adaptive coping skills and building self-esteem.The data was collected pre-intervention and at 1,3 and 6 mo after the intervention.Data were analyzed using SPSS 28.0 version.RESULTS Mean age of the children was 14.68±0.58 years,60.5%were male,56%were studying in 9th standard,70.75%were from nuclear families,and mean family monthly income was 9588.1±3135.2 INR.Mean duration of parental alcohol dependence was 7.52±2.94 years and the father was the alcohol-consuming parent.The findings showed that there were significant psychosocial intervention effects in terms of decreasing anxiety and depression scores,and increasing selfesteem level among experimental group subjects over the 6-mo interval,when compared with the control group(P<0.001).CONCLUSION The present study demonstrated that the psychosocial intervention was effective in reducing anxiety and depression,and increasing self-esteem among children of parents with alcohol dependence.The study recommends the need for ongoing psychosocial intervention for these children.

Alcohol use disorder and liver injury related to the COVID-19 pandemic

Alcohol use disorder is a complex and heterogeneous phenomenon that can be studied from several points of view by focusing on its different components.Alcohol is a hepatotoxin whose metabolism creates profound alterations within the hepatocyte.The liver is the central organ in the metabolism of alcohol,a process that also involves other organs and tissues such as the brain,heart and muscles,but the most relevant organ is the liver.The anatomopathological alterations in the liver associated with the prolonged use of alcohol range from the simple accumulation of neutral fats in the hepatocytes,to cirrhosis and hepatocellular carcinoma.Alcohol abuse frequently leads to liver disease such as steatosis,steatohepatitis,fibrosis,cirrhosis,and tumors.Following the spread of coronavirus disease 2019(COVID-19),there was an increase in alcohol consumption,probably linked to the months of lockdown and smart working.It is known that social isolation leads to a considerable increase in stress,and it is also recognized that high levels of stress can result in an increase in alcohol intake.Cirrhotic patients or subjects with liver cancer are immunocompromised,so they may be more exposed to COVID-19 infection with a worse prognosis.This review focuses on the fact that the COVID-19 pandemic has made the emergence of alcohol-induced liver damage a major medical and social problem.

A Clinical Study:Therapeutic Effects of Repetitive Transcranial Magnetic Stimulation and Cognitive Behavioral Therapy on Cognitive Impairment in Alcohol-Dependent Patients

Objective To observe the effects of repetitive transcranial magnetic stimulation(rTMS)and cognitive behavioral therapy(CBT)on cognitive function in alcohol-dependent patients.Methods Data from 285 alcohol-dependent patients were collected from Mudanjiang Medical University and Sun Yat-sen Memorial Hospital at Sun Yat-sen University between 2019 and 2021.The patients were divided into groups depending on alcohol abstinence and non-abstinence.There were 43 patients in the alcohol consumption(AC)group.The patients in the abstinence group were randomly assigned to treatment regimens with different combinations of rTMS and CBT using the Elton system.There were 49 patients in the TB+C0 group,36 in the TB+C1 group,44 in the TL+C0 group,36 in the TL+C1 group,37 in the TR+C0 group,and 40 in the TR+C1 group.Cognitive function was assessed by using the Montreal Cognitive Assessment Scale(MoCA).Results The proportion of patients with cognitive impairment in the AC group at 24 weeks was higher than that at baseline(P<0.05),whereas the proportion of cognitive impairment in the other groups did not differ significantly over time.The percentage of patients with cognitive impairment at 24 weeks was 52.3%in the TL+C0 group and 47.2%in the TL+C1 group,which was significantly lower than that in the AC group(P<0.05).MoCA scores at different time points in the AC group were significantly higher than those in the TB+C0,TL+C0,TL+C1,TR+C0,and TR+C1 groups,respectively.MoCA scores were significantly higher at 12 weeks compared with the baseline in the TB+C0,TL+C0,TL+C1,TR+C0,and TR+C1 groups(P<0.05),and similar changes were observed at 24 weeks.The MoCA scores in the TL+C1 and TL+C0 groups were higher than those in the TR+C0 group at 12 weeks after the intervention(P<0.05).Furthermore,MoCA scores in each of the TB+C1,TL+C1,TL+C0,TR+C1,and TR+C0 groups were higher than those in the AC group at 24 weeks(P<0.05).Conclusion Alcohol consumption impairs cognitive function,as evidenced by a significantly higher proportion of cognitive impairment after 24 weeks of non-abstinence.Most of the tested treatment regimens improved cognitive function.High frequency rTMS of the left dorsolateral prefrontal cortex(DLPFC)was associated with a greater improvement in cognitive function than that of the right DLPFC in alcohol-dependent patients at 12 weeks of abstinence.There does not appear to be a therapeutic advantage of CBT for cognitive impairment in alcohol-dependent patients.Screening for impaired cognitive function should be seriously considered for patients who engage in heavy drinking,and measures should be taken to reduce the risk of dementia induced by alcohol dependence.

Advances in the prediction of biological markers of alcohol dependence relapse

Alcohol dependence is a chronic and re-lapsing disease that causes mental and organ damage due to long-term heavy drinking,which has serious adverse effccts on individuals and socicty.Previous studics have shown that even after inpatient treatment,the relapse rate of alcohol-dependent patients can be as high as 60%-70%within 3 months after discharge.Currently,the mecha-nisms associated with relapse to drinking in alcohol-dependent patients are still unclear.And most of the studies reported in the past have been about the relationship between psychosocial factors and relapse to drinking,while few studies have examined the relationship between bi-ological indicators and relapse to drinking.Therefore,in this paper,we summarize the recent literature to explore the biological markers related to alcohol dependence relapse and discuss the progress of research on relapse pre-diction,in order to provide reference and help to reduce the relapse rate and improve the quality of life of patients.

Pilot Study of Problem Gambling in Specialized Substance Use Disorder Treatment—High Lifetime Prevalence of Problem Gambling in Opioid Maintenance Treatment Patients

Problem gambling is over-represented in patients treated for substance use disorders, but substance-specific prevalence of problem gambling is rarely reported. In specialized addiction treatment facilities for opioid maintenance treatment and for alcohol and prescription drug dependence, respectively, 129 patients were screened for problem gambling using the NODS-CLiP. The lifetime prevalence of problem gambling was markedly higher in opioid maintenance treatment (61 percent) than in alcohol and prescription drug dependence treatment (11 percent, p < 0.001). When controlling for gender and age, problem gambling remained significantly associated with opioid maintenance treatment. The present study demonstrated a very high prevalence of lifetime problem gambling in opioid maintenance treatment patients. This calls for active screening for problem gambling in substance use disorder patients, and mainly in treatment for opioid dependence.

Escitalopram with or without combined electroacupuncture on protracted alcohol withdrawal symptoms(PAWS)among male inpatients with alcohol dependence

Objective:This study is conducted to investigate the effects differences of escitalopram with or without combined electroacupuncture(EA)among male inpatients with a diagnosis of alcohol dependence and comorbid protracted alcohol withdrawal symptoms(PAWS).Methods:A total of 62 participants who met the inclusion criteria were enrolled in a two-arm randomized,placebo controlled,patients-blind trial and allocated to an escitalopram with real-EA group(realEA group,patients=31)and an escitalopram with sham-EA group(sham-EA group,patients=31),respectively.In addition to the oral administration of escitalopram for total four weeks,patients in each group received corresponding EA treatment five days per week and two days off for consecutive four weeks.Both serum homocysteine(Hcy)test and electrophysiological tests,including event-related potentials(ERPs)and exploratory eye movement(EEM)were performed at pre-and post-treatment.Additionally,the global scores of Penn Alcohol Craving Scale(PACS),17-items Hamilton Depression Rating Scale(HAMD-17),and Hamilton Anxiety Scale(HAMA)were used for assessing the subjective emotion experience of patients,respectively.Meanwhile,adverse effects were monitored and recorded.Results:After four-week treatment,the global scores of PACS and HAMD-17 declined significantly in both groups(both P<0.05).Furthermore,the decline in the real-EA group was superior to that in the shamEA group(P<0.05).Meanwhile,the total scores of HAMA only decreased in the real-EA group(P<0.05)but not in the sham-EA group(P>0.05).According to the parameters of ERPs,significant declines for N2PL,P3PL,and P3amp were observed in both two groups(all P<0.05),and the decreases for P3PL and P3amp in the real-EA group was much superior to that in the sham-EA group(both P<0.05).According to the parameters of EEM,significant increase for NEF was observed only in the real-EA group(P<0.05).Besides,there was a dramatic decline for serum Hcy level only in the real-EA group(P<0.05).One case in the sham-EA group withdrew from the trial due to self-reported nausea and bitter taste,and outcomes of the remaining 61 patients were adopted for analysis.Conclusion:(1)Escitalopram with EA may be a potential alternative therapy for mitigating PAWS among male inpatients with alcohol dependence.(2)Escitalopram with EA might improve the alcoholdependence induced cognitive dysfunctions via upregulating the expression of Hcy.

Effect of Zhubin(KI9) Acupuncture in Reducing Alcohol Craving in Patients with Alcohol Dependence:A Randomized Placebo-Controlled Trial

Objective： To examine the effect of acupuncture on Zhubin （KI9） in reducing alcohol craving in alcohol-dependent patients. Methods： Twenty male alcohol-dependent patients were randomly assigned to two groups, a treatment group （10 cases, age 43.0 ± 6.8 years） and a placebo group （10 cases, age 44.5 ± 7.9 years）. The treatment group was treated with real needle acupuncture on Zhubin （KI9） twice a week for 4 weeks, and the control group was treated with placebo needle acupuncture. Both groups were given acupuncture treatment using Park Sham Device （PSD）. Alcohol craving was measured by the Visual Analogue Scale （VAS） before treatment to establish a baseline, and after 1, 2, and 4 weeks of treatment. Repeated measures ANOVA was used to determine the main and interaction effects of time and on the outcome measure （VAS）. Results： There was a significant effect of time on VAS score （dr=3, F=13.3, P〈0.01）. Main effect of group on VAS score was significant （df=1, F=10.9, P〈0.01） and the time × group interaction was also significant （df=3, F=4.7, P〈0.01）. Conclusions： Real-needle acupuncture therapy on Zhubin （KI9） showed effectiveness in reducing alcohol craving. These results strongly suggest the usefulness of acupuncture therapy on Zhubin （KI9） in preventing a relapse in alcohol dependent patients.

ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior

Background Alcohol dependence （AD） is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study （GWAS） is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology. Methods A genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples： 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans. Results Several genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene （ANKRDT） showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-likel （CYTL 1） genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531066 （P = 6.51×10^-8）. The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRDTor CYTL1 gene and alcohol consumption. Conclusion The evidence suggests that ANKRD7 and CYTL 1 genes may play an important role in the variance in AD risk.

Genome-wide association study knowledge-driven pathway analysis of alcohol dependence implicates the calcium signaling pathway

Background Alcohol dependence （AD） is a serious and common public health problem.The identification of genes that contribute to the AD variation will improve our understanding of the genetic mechanism underlying this complex disease.Previous genome-wide association studies （GWAS） and candidate gene genetic association studies identified individual genes as candidates for alcohol phenotypes,but efforts to generate an integrated view of accumulative genetic variants and pathways under alcohol drinking are lacking.Methods We applied enrichment gene set analysis to existing genetic association results to identify pertinent pathways to AD in this study.A total of 1 438 SNPs （P ＜1.0×10-3） associated to alcohol drinking related traits have been collected from 31 studies （10 candidate gene association studies,19 GWAS of SNPs,and 2 GWAS of copy number variants）.Results Among all of the KEGG pathways,the calcium signaling pathway （hsa04020） showed the most significant enrichment of associations （21 genes） to alcohol consumption phenotypes （P=5.4×10-5）.Furthermore,the calcium signaling pathway is the only pathway that turned out to be significant after multiple test adjustments,achieving Bonferroni P value of 0.8×10-3 and FDR value of 0.6×10-2,respectively.Interestingly,the calcium signaling pathway was previously found to be essential to regulate brain function,and genes in this pathway link to a depressive effect of alcohol consumption on the body.Conclusions Our findings,together with previous biological evidence,suggest the importance of gene polymorphisms of calcium signaling pathway to AD susceptibility.Still,further investigations are warranted to uncover the role of this pathway in AD and related traits.