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The purpose of this study was to attempt to verify the existence of a relationship between internal resources (self-esteem and self-efficacy) and motivation (decisional balance) to undergo treatment in prisoners with alcohol addiction participating in voluntary treatment as well as referred to obligatory addiction treatment based on a court decision. The study was carried out in penitentiary units in various parts of Poland in 2018–2019. Participants completed the Decision Balance Scale, Generalized Self–Efficacy Scale, and Multidimensional Self-Esteem Inventory twice – before and after addiction treatment. The study adopted the assumptions of the Transtheoretical Model developed by Prochaska and DiClemente (1984). There were no statistically significant differences between the group of prisoners referred for obligatory treatment and those undergoing voluntary therapy. At the end of the 3-month treatment, there was a significantly smaller number of arguments "for" drinking and less identity integration in both groups studied. The results obtained may indicate that after undergoing therapy, prisoners remain in a contemplation stage due to their inability to adapt therapeutic interactions to individual needs. It seems that changes in identity integration may be indicative of the crisis that is being experienced, which in effect may allow individuals with alcohol addiction to search for and achieve a potentially new, coherent image of themselves. • Addiction treatment, should focus on the resources of the convicted rather than their deficits. • Higher self-esteem increases the motivation to complete therapy and continue it after the end of incarceration. • Motivation plays a significant role in the completion of alcohol therapy, so it is important to diagnose patients in this regard before starting therapy, instead of mistakenly assuming the lack of motivation and the need to induce it. • People who undergo therapy with a court order only begin to realize the problem of alcohol dependence and begin to think about changing their behavior during the therapy. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to compare the serum MicroRNA (miRNA) expression levels on the first day of hospitalization and at the end of the first month of treatment in patients with alcohol use disorder and severe craving symptoms. Through the obtained data, biological agents targeting microRNA for alcohol craving may be developed. Methods: The volunteer group consists of four patients diagnosed with severe alcohol use disorder. Sociodemographic and Clinical Information Form, DSM-5 Structured Clinical Interview-Clinical Version (SCID-5-CV), Penn Alcohol Craving Scale (PACS) were used as clinical assessment tools. Peripheral blood samples were obtained at the time of application and on the 30th day. miRNA isolation was performed. The expression levels of 2578 different mature human miRNAs were measured. Results: The miRNAs showing statistically significant differences in peripheral blood samples taken on the 1st and 30th days from alcohol users are as follows: miR-19a-3p, miR-6849-5p, miR-6726-5p, miR-6848-5p, miR-186-5p, miR-6889-5p, miR-933, miR-370-3p, miR-5739, miR-103a-2-5p, miR-6860, miR-1254, miR-1260a, miR-3921, miR-127-3p, miR-8064, miR-6870-5p, miR-4688 Conclusions: A significant difference was found between the 1st and 30th days in 18 of 2578 miRNAs scanned. It is aimed to investigate these 18 miRNAs in larger sample groups during the alcohol craving period. [ABSTRACT FROM AUTHOR]

Introduction: Currently, there is no scientific consensus on the concept of alcohol addiction recovery beyond substance use control. This conceptual issue challenges the implementation of therapeutic strategies and mental health policies that are unrestricted to symptomatic remission. Aiming to contribute to its definition, this study aimed to examine the recovery experience of individuals with alcohol addiction using dialectical phenomenological psychopathology (DPP) as a theoretical and methodological framework. Methods: A dialectical phenomenological analysis was conducted through an examination of online interviews with eight Brazilian, São Paulo state citizens who were self-declared to be undergoing alcohol addiction recovery (or who declared that they had completely recovered). Results: Participants' reports generated eight categories that were subdivided into two groups. The first group indicated experiential elements of recovery, such as changes in self-relation, changes in interpersonal relations, and changes in time relations, giving new meanings to suffering and alcohol use, and recovery as a continuous process. The second group referred to how the participants interpreted recovery according to their worldviews: as a spiritual experience, moral reformation, and mentality change. Conclusion: These categories can be understood through the lens of DPP as a process of change in the subjects' being in the world, characterized by the continued management of their existential imbalances in the dimensions of spatiality, temporality, selfhood, and intersubjectivity. The results are preliminary when it comes to conceptualizing recovery but may help future studies to develop recovery-oriented therapeutic strategies. Plain Language Summary: In the mental health field, there is still no consensus on what it means to be in alcohol addiction recovery beyond controlling alcohol use, which challenges the development of treatments and policies aimed at promoting more than symptom remission. We believe part of this issue is due to the hegemony of strictly objective approaches that lack theoretical resources to grasp recovery experiences. Hence, we tried to contribute to recovery understanding by analyzing the recovery experiences of individuals with alcohol addiction. For this, we used the dialectical phenomenological psychopathology perspective as a theoretical lens, which consists of a study approach in psychopathology that investigates experiences of mental disorders and their typical ways of relating to the world. Through this perspective, we examined online interviews of 8 Brazilian, São Paulo state citizens, who were self-declared to be undergoing alcohol addiction recovery (or who declared that they had completely recovered). Their reports indicated that recovery was a process that featured changes in self-relation, changes in interpersonal relations, changes in time relation, and giving new meanings to alcohol use and suffering. Those transformations were also interpreted by participants' worldviews of spiritual experience, moral reformation, and mentality change. In the discussion, we understood such changes as transformations in the way they experience an act in the world, which are developed by continued management of their own alcohol addiction vulnerabilities. Although we consider the results preliminary when it comes to conceptualizing recovery, we believe they may help future studies to develop therapeutic strategies committed to promoting patient recovery. [ABSTRACT FROM AUTHOR]

Gut dysbiosis and liver cirrhosis are two corelated complications that highly disturbs the metabolism of a normal human body. Liver cirrhosis is scarring of the hepatic tissue and gut dysbiosis is the imbalance in the microbiome of the gut. Gut dysbiosis in cirrhosis occurs due to increased permeability of the intestinal membrane which might induce immune responses and damage the normal functioning of the body. Dysbiosis can cause liver damage from cirrhosis and can further lead to liver failure by hepatocellular carcinoma. In this review we discuss if eubiosis can revert the poorly functioning cirrhotic liver to normal functioning state? A normal microbiome converts various liver products into usable forms that regulates the overgrowth of microbiome in the gut. The imbalance caused by dysbiosis retards the normal functioning of liver and increases the complications. To correct this dysbiosis, measures like use of antibiotics with probiotics and prebiotics are used. This correction of the gut microbiome serves as a ray of hope to recover from this chronic illness. In case of alcohol induced liver cirrhosis, intervention of microbes can possibly be helpful in modulating the addiction as well as associated complications like depression as microbes are known to produce and consume neurotransmitters that are involved in alcohol addiction. Hence a correction of gut liver brain axis using microbiome can be a milestone achieved not only for treatment of liver cirrhosis but also for helping alcohol addicts quit and live a healthy or at least a near healthy life. [ABSTRACT FROM AUTHOR]

Addiction is an uncontrollable desire for the repetition of a particular obsession, despite its negative impact on health and causing harm to social lives. Although it affects their well-being, people persist in pursuing and maintaining this compulsive behavior. Nowadays, substance addiction issues are emerging prominently in children and adolescents as much as in adults. Alcohol can lead to permanent and serious developmental disorders in the adolescent brain. Among these damages, there is a significant risk of losing mental health and experiencing severe psychiatric illnesses such as psychosis and schizophrenia. Especially during critical periods like childhood and adolescence, early alcohol use poses a biopsychosocial (biological, psychological, and social) problem leading to serious negative consequences in society. This study aims to address alcohol addiction in children and adolescents, discussing risk factors, potential problems they might face, treatment approaches, and providing recommendations for approaching this issue for both families and healthcare professionals.

The paper outlines the role of affective temperaments, as defined by Akiskal, in the development and maintenance of alcohol use disorders with a particular focus on the clinical course of addiction. Among affective temperaments, a cyclothymic temperament seems to play a key role in the development and maintenance of alcohol use disorders, and have the greatest influence on the clinical course of addiction. A high cyclothymic score is associated with inter alia an earlier onset of drinking and alcohol dependence, a negative course of alcohol dependence, relapse and alcohol craving. The structure of affective temperaments is also a predictor of suicidal behavior and drug addiction in the alcohol addict population. Interest has been growing regarding the role of affective temperament in the development and course of alcohol dependence; however, further research in this area is needed. An understanding of the temperamental determinants of alcohol dependence in the affective dimension may significantly support diagnostic and therapeutic procedures. Affective temperament profile may be suggestive of alcohol use disorders and may be a primary prognostic factor of craving and relapse, potential suicide, treatment motivation and the co-occurrence of drug dependence among patients with alcohol use disorder. [ABSTRACT FROM AUTHOR]

Introduction and aim. Since February 24, 2022, military personnel of the Ukrainian Defense Forces have been resisting the military aggression of the Russian Federation. After participating in combat operations, military personnel accumulated combat stress. Drinking alcohol was one of the ways to overcome it. The purpose of the article is to identify the types of coping strategies for the risk of developing alcohol addiction among Ukrainian military personnel who participated in intense hostilities. Material and methods. Ukrainian Defense Forces military personnel (n=162 males, between 20 and 60 years of age) took part in this study. To determine coping strategies and the risk of developing alcohol addiction the AUDIT and the COPE Inventory were used. Results. Cluster analysis made it possible to identify 4 types of coping strategies with different prevalence and levels of risk of developing alcohol addiction among participants. Conclusion. Productive coping has been associated with a reduced risk of alcohol use in military personnel, but the ability to be situational flexible in the use of coping is important. Compulsive alcohol use was preceded by a period of intensive use of social support coping by military personnel. This period is sensitive to the risk of developing alcohol addiction. [ABSTRACT FROM AUTHOR]

This cross-sectional analysis aimed to assess the quality of life (QoL) among hospitalized patients with alcohol use disorder (AUD) in Romania, utilizing the WHOQOL survey. Conducted from January to December 2023 in the Psychiatry Clinic of the "Pius Brinzeu" Emergency Clinical Hospital in Timisoara, this study engaged 70 participants, adhering to ethical standards outlined in the Declaration of Helsinki. Employing the WHOQOL-BREF instrument, the research hypothesized that AUD patients would show significantly lower QoL scores across its domains compared to general population norms. The study focused on identifying the QoL domains most impacted by AUD, exploring correlations between QoL scores and AUD background characteristics, and pinpointing intervention areas for patient care improvement. Participants were predominantly males (88.57%) with a middle-aged average of 55.51 years. Educational backgrounds varied, with a notable percentage having attended college (44.29%) or university (17.14%). Regarding marital status, 41.43% were married. Comorbidities were present in 52.86% of the sample, with hypertension being the most common (34.29%). Results showed mean QoL scores in the physical (61.84 ± 16.05), psychological (64.11 ± 17.16), social (60.48 ± 24.85), and environmental (68.44 ± 17.34) domains, revealing a significant diversity in satisfaction levels across these areas. Statistical analyses highlighted marital status as significantly associated with a better QoL in the physical domain, with married, co-habiting, and divorced participants reporting higher scores compared to single ones. In conclusion, while AUD significantly affects the QoL of hospitalized patients in Romania, marital status emerges as a critical factor in mitigating these effects, particularly in the physical domain of QoL. These findings underscore the complexity of AUD's impact on QoL and the importance of considering sociodemographic factors in patient care practices and interventions. The study contributes valuable insights into the nuanced relationship between AUD and QoL, proposing a foundation for enhancing care outcomes for AUD patients in Romania. [ABSTRACT FROM AUTHOR]

On February 24, 2022, the armed forces of the Russian Federation invaded Ukraine. After participating in hostilities Ukrainian military personnel accumulated combat stress. Drinking alcohol was one of the ways to overcome them. This study aimed to identify the role of negative emotional reactions and states in increasing the risk of alcohol addiction in Ukrainian military personnel after participation in hostilities. Ukrainian Defense Forces military personnel (N= 405, between 20-60 years of age) participated in this study. To determine the risk of developing alcohol addiction the Alcohol Use Disorders Identification Test was used. To determine the negative emotional experiences the Assessment of Negative Mental Reactions and Conditions in Military Personnel Questionnaire was used. Multiple regression analysis, hierarchical cluster analysis, and exploratory factor analysis were used to determine the relationship between negative emotional experiences and states in military personnel and the risk of alcohol abuse. The results showed that not only the strength of negative affect but also its structure, which determines the ability to regulate emotional experience and behavior, is associated with the risk of alcohol abuse among military personnel after participating in combat operations. As a result, after leaving the combat zone, military personnel with high levels of negative affect abused alcohol to relieve stress artificially. Other servicemen who had a less affective reaction to manifestations of combat stress could timely control the manifestation of negative emotions and were able to predict the negative development of the situation and prepare for it. [ABSTRACT FROM AUTHOR]

Abstract Background Alcohol use disorder (AUD) is a major clinical problem in Uganda. Explanatory models (EMs) of illness are important as they have consequences for treatment. Clinicians´ knowledge about patients´ EMs can improve understanding of the latter´s perspectives and adapting treatments. There is a lack of African studies about EMs of AUD. The aim of this study was to explore EMs for AUD among hospitalized patients and their relatives at the alcohol and drug unit (ADU) at Butabika hospital in Uganda. Methods An adapted version of the Explanatory Model Interview Catalogue (EMIC) was used for interviews with ten patients and five relatives to investigate how both hospitalized patients with AUD and their relatives understand the disease. Data were analysed for themes with a qualitative content analysis and support of the software program, OpenCode 4.03. Results Five major themes were identified from the patient interviews: “Context promotes AUD”; “Alcohol is part of culture”; “Spiritual causes of AUD in the community”; “Help through Western medicine and religious sources is preferred” and “Social problems and stigmatization”. Six major themes identified from the interviews with relatives were: “Numerous causes of drinking alcohol”; “Devastating consequences of drinking alcohol”; “Exploiting persons with AUD”; “Others’ suffering”; “Relatives struggling for help” and “Suggested solutions”. Conclusions Patients’ EMs of AUD included social and spiritual explanations. Alcohol is seen as an important part of the Ugandan culture among both patients and their relatives. The results indicate it is important in clinical contexts to investigate the EMs of the patients and relatives to individually tailor treatment interventions.

Harmful alcohol consumption is a major socioeconomic burden to the health system, as it can be the cause of mortality of heavy alcohol drinkers. The dopaminergic (DAergic) system is thought to play an important role in the pathogenesis of alcohol drinking behaviour; however, its exact role remains elusive. Fibroblast growth factor 2 (FGF‐2), a neurotrophic factor, associated with both the DAergic system and alcohol consumption, may play an important role in DAergic neuroadaptations during alcohol abuse. Within this study, we aimed to clarify the role of endogenous FGF‐2 on the DAergic system and whether there is a possible link to alcohol consumption. We found that lack of FGF‐2 reduces the alcohol intake of mice. Transcriptome analysis of DAergic neurons revealed that FGF‐2 knockout (FGF‐2 KO) shifts the molecular fingerprint of midbrain dopaminergic (mDA) neurons to DA subtypes of the ventral tegmental area (VTA). In line with this, proteomic changes predominantly appear also in the VTA. Interestingly, these changes led to an altered regulation of the FGF‐2 signalling cascades and DAergic pathways in a region‐specific manner, which was only marginally affected by voluntary alcohol consumption. Thus, lack of FGF‐2 not only affects the gene expression but also the proteome of specific brain regions of mDA neurons. Our study provides new insights into the neuroadaptations of the DAergic system during alcohol abuse and, therefore, comprises novel targets for future pharmacological interventions. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide 1 (GLP-1) analogues have been commercialized for the management of type 2 diabetes. Recent studies have underscored GLP-1's role as a modulator of alcohol-related behavior. However, the role of the GLP-1 analogue liraglutide on alcohol-withdrawal responses have not been fully elucidated. Liraglutide binds to the G-protein-coupled receptor and activates an adenylyl cyclase and the associated classic growth factor signaling pathway, which acts growth factor-like and neuroprotective properties. The underlying neurobiological mechanisms of liraglutide on alcohol withdrawal remains unknown. This study endeavored to explore the effects of liraglutide on the emotion and memory ability of alcohol-withdrawal mice, and synaptic morphology in the medial prefrontal cortex (mPFC) and the hippocampus (HP), and thus affects the relapse-like drinking of alcohol-withdrawal mice. The alcohol-withdrawal group was reintroduced to a 20% v/v alcohol and water through the two-bottle choice for four consecutive days, a period referred to as alcohol re-drinking. Male C57BL/6J mice were exposed to a regimen of 20% alcohol and water for a duration of 6 weeks. This regimen established the two-bottle choice model of alcohol exposure. Learning capabilities, memory proficiency, and anxiety-like behavior were evaluated using the Morris water maze, open field, and elevated plus maze paradigms. Furthermore, synaptic morphology and the levels of synaptic transport-related proteins were assessed via Golgi staining and Western Blot analysis after a two-week alcohol deprivation period. Alcohol re-drinking of alcohol-withdrawal mice was also evaluated using a two-bottle choice paradigm. Our findings indicate that liraglutide can substantially decrease alcohol consumption and preference (p < 0.05) in the alcohol group and enhance learning and memory performance (p < 0.01), as well as alleviate anxiety-like behavior (p < 0.01) of alcohol-withdrawal mice. Alcohol consumption led to a reduction in dendritic spine density in the mPFC and HP, which was restored to normal levels by liraglutide (p < 0.001). Furthermore, liraglutide was found to augment the levels of synaptic transport-related proteins in mice subjected to alcohol withdrawal (p < 0.01). The study findings corroborate that liraglutide has the potential to mitigate alcohol consumption and ameliorate the memory impairments and anxiety induced by alcohol withdrawal. The therapeutic efficacy of liraglutide might be attributed to its role in counteracting synapse loss in the mPFC and HP regions and thus prevented relapse-like drinking in alcohol-withdrawal mice. [ABSTRACT FROM AUTHOR]

Addiction is an uncontrollable desire for the repetition of a particular obsession, despite its negative impact on health and causing harm to social lives. Although it affects their well-being, people persist in pursuing and maintaining this compulsive behavior. Nowadays, substance addiction issues are emerging prominently in children and adolescents as much as in adults. Alcohol can lead to permanent and serious developmental disorders in the adolescent brain. Among these damages, there is a significant risk of losing mental health and experiencing severe psychiatric illnesses such as psychosis and schizophrenia. Especially during critical periods like childhood and adolescence, early alcohol use poses a biopsychosocial (biological, psychological, and social) problem leading to serious negative consequences in society. This study aims to address alcohol addiction in children and adolescents, discussing risk factors, potential problems they might face, treatment approaches, and providing recommendations for approaching this issue for both families and healthcare professionals. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is a major clinical problem in Uganda. Explanatory models (EMs) of illness are important as they have consequences for treatment. Clinicians´ knowledge about patients´ EMs can improve understanding of the latter´s perspectives and adapting treatments. There is a lack of African studies about EMs of AUD. The aim of this study was to explore EMs for AUD among hospitalized patients and their relatives at the alcohol and drug unit (ADU) at Butabika hospital in Uganda. Methods: An adapted version of the Explanatory Model Interview Catalogue (EMIC) was used for interviews with ten patients and five relatives to investigate how both hospitalized patients with AUD and their relatives understand the disease. Data were analysed for themes with a qualitative content analysis and support of the software program, OpenCode 4.03. Results: Five major themes were identified from the patient interviews: "Context promotes AUD"; "Alcohol is part of culture"; "Spiritual causes of AUD in the community"; "Help through Western medicine and religious sources is preferred" and "Social problems and stigmatization". Six major themes identified from the interviews with relatives were: "Numerous causes of drinking alcohol"; "Devastating consequences of drinking alcohol"; "Exploiting persons with AUD"; "Others' suffering"; "Relatives struggling for help" and "Suggested solutions". Conclusions: Patients' EMs of AUD included social and spiritual explanations. Alcohol is seen as an important part of the Ugandan culture among both patients and their relatives. The results indicate it is important in clinical contexts to investigate the EMs of the patients and relatives to individually tailor treatment interventions. [ABSTRACT FROM AUTHOR]

The reciprocal relationship between psychiatric and substance use disorders is well-known, yet it remains largely unknown whether mental health morbidity causally leads to addictive behaviours. This paper utilises a fixed effects instrumental variables model, which is identified by time-varying sources of plausibly exogenous variations in mental health, and a nationally representative panel dataset from Australia to present robust evidence on the causal impact of mental distress on cigarette smoking and alcohol drinking behaviours. We find that mental distress significantly increases the prevalence and intensity of either cigarette or alcohol consumption. Further analysis reveals that mental distress also substantially increases household monetary expenditures on either tobacco or alcohol. The impact is greater for lower educated individuals or children of smokers, and is slightly higher for males. Our findings highlight the importance of mental health screening and treatment programs, especially among lower educated individuals or children of smokers, to assist in the prevention of addictive activities. [ABSTRACT FROM AUTHOR]

BackgroundThere are few efficient treatment options for alcohol addiction, which continues to be a serious public health concern. The possible contribution of gut microbiota to the onset and progression of alcohol addiction has been brought to light by recent studies. Probiotics have become a cutting-edge intervention in the treatment of alcohol consumption disorder because of its favorable effects on gut health. The purpose of this systematic review is to assess the body of research on the advantages of probiotics in treating alcoholism and associated neuroinflammatory conditions.MethodsTo find pertinent research published from January 2012 to 2023, a thorough search of electronic databases, including PubMed, Scopus, Google Scholar and Web of Science, was carried out. Included were studies looking at how probiotics affect neuroinflammation, gut- brain axis regulation, alcohol addiction, and related behaviors.FindingsSeveral investigations have shown how beneficial probiotics are in reducing systemic inflammation and alcoholic liver disease (ALD). Probiotic treatments successfully corrected the imbalance of microbiota, decreased intestinal permeability, and stopped the passage of bacterial constituents such lipopolysaccharides (LPS) into the bloodstream. Additionally, probiotics helped to regulate neurotransmitter pathways, especially those connected to GABA, glutamate, and dopamine, which are intimately linked to behaviors related to addiction. Furthermore, it was shown that probiotics altered the expression of neurotransmitter signaling and dopamine receptors.ConclusionThere is strong evidence from this systematic study that probiotics have potential advantages in treating alcohol addiction. The potential of probiotic therapies is demonstrated by the way they modulate important neurotransmitter pathways implicated in addiction, decrease neuroinflammation, and restore the balance of gut flora. To fully investigate the therapeutic potential of probiotics in treating alcohol addiction and enhancing the general wellbeing of those afflicted by this condition, more research is necessary.

Introduction: The purpose of this paper is to look at the relationship of post-traumatic growth with both type and intensity of trauma in two clinical groups: schizophrenia patients and alcohol-addicted individuals who have had various experiences of a traumatic nature. Material and methods: The subject matter is an analysis of how personal variables (personality traits, self-efficacy, character strengths) can influence the post-traumatic growth in the samples. The study verifies also what events were perceived by the patients as traumatic and life-changing, as well as what differences could be observed in the level of post-traumatic growth in the samples. The goal of the analysis is to find which group has recorded a higher level of post-traumatic growth overall and on specific subscales. Results: The obtained results show that the analysed groups differ in the levels of post-traumatic growth; the highest level was observed among the alcohol-addicted individuals in the scope of their changed perception of self. Post-traumatic growth can be linked, above all, to such personality traits as extraversion and prudence, but only in the group of alcohol-addicted individuals. The largest number of links was found between post-traumatic growth and character strengths, and in this case the quality and quantity of these links were attributed mostly to the group of addicted persons. Conclusions: Further research and advancement of the knowledge would be necessary in order to make post-traumatic growth in mentally-ill persons a milestone of their recovery; moreover, further studies would be helpful for the adaptation of psychological interventions aimed at achieving post-traumatic growth. [ABSTRACT FROM AUTHOR]

Alcohol Use Disorder (AUD) is a relapsing brain disorder that involves perturbations of brain dopamine (DA) systems, and combined treatment with varenicline + bupropion produces additive effects on accumbal DA output and abolishes the alcohol deprivation effect (ADE) in rats. Also, direct and indirect glycine receptor (GlyR) agonists raise basal DA, attenuate alcohol-induced DA release in the nucleus Accumbens (nAc) and reduce alcohol consumption in rats. This study in rats examines whether the GlyT1-inhibitor Org 24598, an indirect GlyR agonist, enhances the ADE-reducing and DA elevating action of the combined administration of varenicline + bupropion in lower doses than previously applied. Effects on voluntary alcohol consumption, the ADE and extracellular levels of glycine and DA in nAc were examined following treatment with Org 24598 6 and 9 mg/kg i.p., bupropion 3.75 mg/kg i.p. and varenicline 1.5 mg/kg s.c., in monotherapy or combined, using a two-bottle, free-choice alcohol consumption paradigm with an ADE paradigm, and in vivo microdialysis in male Wistar rats. Notably, all treatment regimens appeared to abolish the ADE but only the effect produced by the triple combination (Org24598 + varenicline + bupropion) was significant compared to vehicle. Hence, addition of Org 24598 may enhance the ADE-reducing action of varenicline + bupropion and appears to allow for a dose reduction of bupropion. Treatment with Org 24598 raised accumbal glycine levels but did not significantly alter DA output in monotherapy. Varenicline + bupropion produced a substantial elevation in accumbal DA output that was slightly enhanced following addition of Org 24598. Conceivably, the blockade of the ADE is achieved by the triple combination enhancing accumbal DA transmission in complementary ways, thereby alleviating a hypothesized hypodopaminergia and negative reinforcement to drink. Ultimately, combining an indirect or direct GlyR agonist with varenicline + bupropion may constitute a new pharmacological treatment principle for AUD, although further refinement in dosing and evaluation of other glycinergic compounds are warranted. [ABSTRACT FROM AUTHOR]

Oxidative stress and neuroinflammation are involved in the pathogenesis of alcohol addiction. However, little is known regarding the effect of genetic, behavioral, psychological, and environmental sources of origin on the inflammation and oxidative stress pathways of patients with alcohol addiction. Our study aimed to evaluate the impact of selected common functional single-nucleotide polymorphisms in inflammation and oxidative stress genes on alcohol addiction, and common comorbid psychosymptomatology. Our study included 89 hospitalized alcohol-addicted patients and 93 healthy individuals, all Slovenian males. Their DNA was isolated from peripheral blood and patients were genotyped for PON1 rs705379, rs705381, rs854560, and rs662, SOD2 rs4880, GPX1 rs1050450, IL1B rs1143623, rs16944, and rs1071676, IL6 rs1800795, IL6R rs2228145, and miR146a rs2910164. Kruskal–Wallis and Mann–Whitney tests were used for the additive and dominant genetic models, respectively. Our findings suggested the involvement of IL6 rs1800795 in alcohol addiction. Moreover, our data indicated that the genetic variability of SOD2 and PON1, as well as IL1B and IL6R, may be related to comorbid psychosymptomatology, revealing a potential indirect means of association of both the oxidative stress and inflammation pathways. [ABSTRACT FROM AUTHOR]

Limited data exist on the association between per capita alcohol consumption and incidence of alcohol related liver disease (ARLD). The aims were to analyse this relationship and assess prevalence of ARLD in Iceland and among patients treated for alcohol use disorder (AUD) and its impact on outcomes. A retrospective study on all patients diagnosed with severe ARLD: alcohol related cirrhosis (ARC) and alcohol related hepatitis (ARH) in Iceland 1984–2020. Medical records were scrutinized for clinical features, severity of ARLD, proportion undergoing treatment for AUD, data on abstinence and long-term outcomes. A total of 314 patients, males 76%, median age 56 years, fulfilled the predetermined criteria for ARLD. Median MELD was 17, 73% with Child-Pugh B/C and 70/314 (22%) who had ARH. Incidence of ARLD increased from 0.77 cases per 100 000 inhabitants annually 1984–2000 to 6.1 per 100 000 in 2016–2020. Per capita alcohol consumption increased from 4.3 Liters to 7.5 L in in the same time periods. Overall 220/314 (70%) with ARLD had undergone treatment for AUD. Of all individuals who had AUD treatment during the study period (n = 21.845), 1% were diagnosed with ARLD. Patients who underwent treatment for AUD after the ARLD diagnosis had better prognosis than those who had treatment prior to ARLD diagnosis (hazard ratio 2.5 [95% CI 1.3–5.0]). The incidence of ARLD increased 8-fold during the study period coinciding with 74% increase in per capita alcohol consumption. Patients with prior diagnosis of AUD had worse prognosis that needs special attention. [ABSTRACT FROM AUTHOR]

Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided. [ABSTRACT FROM AUTHOR]

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This cross-sectional analysis aimed to assess the quality of life (QoL) among hospitalized patients with alcohol use disorder (AUD) in Romania, utilizing the WHOQOL survey. Conducted from January to December 2023 in the Psychiatry Clinic of the “Pius Brinzeu” Emergency Clinical Hospital in Timisoara, this study engaged 70 participants, adhering to ethical standards outlined in the Declaration of Helsinki. Employing the WHOQOL-BREF instrument, the research hypothesized that AUD patients would show significantly lower QoL scores across its domains compared to general population norms. The study focused on identifying the QoL domains most impacted by AUD, exploring correlations between QoL scores and AUD background characteristics, and pinpointing intervention areas for patient care improvement. Participants were predominantly males (88.57%) with a middle-aged average of 55.51 years. Educational backgrounds varied, with a notable percentage having attended college (44.29%) or university (17.14%). Regarding marital status, 41.43% were married. Comorbidities were present in 52.86% of the sample, with hypertension being the most common (34.29%). Results showed mean QoL scores in the physical (61.84 ± 16.05), psychological (64.11 ± 17.16), social (60.48 ± 24.85), and environmental (68.44 ± 17.34) domains, revealing a significant diversity in satisfaction levels across these areas. Statistical analyses highlighted marital status as significantly associated with a better QoL in the physical domain, with married, co-habiting, and divorced participants reporting higher scores compared to single ones. In conclusion, while AUD significantly affects the QoL of hospitalized patients in Romania, marital status emerges as a critical factor in mitigating these effects, particularly in the physical domain of QoL. These findings underscore the complexity of AUD’s impact on QoL and the importance of considering sociodemographic factors in patient care practices and interventions. The study contributes valuable insights into the nuanced relationship between AUD and QoL, proposing a foundation for enhancing care outcomes for AUD patients in Romania.

Introduction and objective: Psychoactive substance abusers are characterised by significantly stronger pathology of personality structure compared to non-addicted population. Therefore, identifying psychological resources that may provide a chance for more adequate functioning and effective treatment of these patients seems justified. One such resource is flexibility in coping, which helps reduce emotional tension and reinforces adaptive forms of functioning. The aim of the presented research was to verify whether there is a relationship between the dimensions of personality organisation and flexibility in coping among alcohol-dependent individuals, taking into account the age and gender of respondents. Materials and methods: The study involved 93 alcohol-dependent people, including 27 women (29%) and 66 men (71%) aged 20 to 77 years (mean, M = 43.72; standard deviation, SD = 12.83). The research used the Inventory of Personality Organization (IPO) by Otto F. Kernberg and colleagues (2001) in the Polish adaptation by Agnieszka Izdebska and Beata Pastwa- Wojciechowska (2013) and the Flexibility in Coping with Stress Questionnaire (Kwestionariusz Elastyczności w Radzeniu sobie ze Stresem, KERS-14) by Małgorzata Anna Basińska and colleagues (2021). Results: The research showed that more flexible coping strategies occur among those alcohol-dependent adults who use higher-order defence mechanisms and are characterised by greater identity coherence. The age was found to be a variable associated with a better personality organisation and greater flexibility in coping. Conclusions: Flexibility in coping is partially related to the dimensions of personality organisation in alcohol-dependent adults. [ABSTRACT FROM AUTHOR]

Objective: This paper is aimed at reviewing the literature on oxytocin and attachment relationship among people addicted to alcohol. The paper describes in a holistic way their possible interactions with bio-psycho-social risk factors for the development of addiction. It also indicates the possible practical use of oxytocin in addiction therapy. Material and method: The literature review was made with the use of the following databases: PsycINFO, PubMed and Google Scholar. Each database was searched using the following keywords: 'secure', 'disorganised', 'genetic', and 'therapy'. These keywords were combined with the terms "attachment style", "oxytocin" and each time with "alcohol addiction". Results: The analysis of the literature confirms that people addicted to alcohol are more often characterised by relational problems than healthy people. The association of oxytocin with the attachment relationship is mediated by epigenetic, neurobiological, and environmental factors. Research also confirms that the use of oxytocin in addiction therapy brings positive effects for some patients. Discussion and conclusions: The ability to build satisfactory interpersonal relationships is a protective factor against alcohol use. The article indicates the role that oxytocin plays in building interpersonal relationships and the possibility of its use in addiction therapy. [ABSTRACT FROM AUTHOR]

Long-term use of drugs can sometimes result in brain damage that greatly affects a person's psychology and sometimes become indecent. This paper examines psychological disorders caused by substance abuse by examining literatures that involved machine learning (ML) models. The brain imaging, behavioural kinematics, and memory analysis are studied to gain insights of substance use and its disorder. Review analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In order to help better screen, diagnose and monitor such disorders, ML identifies early onset of substance intake as predictors of disorders. The study measures identified in the articles (N=26) illustrate the exclusive use of ML to bring out insights of substance use disorders. Brain-related factors, behavioural phenotypes, and functional differentiation of the brain can express a great deal about disorders. Findings also identify the insights into various research levels, classification techniques, performance measures, challenges, and future directions related to use of ML. Random forests models are largely used for better performance. In addition, the diversity of interviews, questionnaires, brain imaging and the latest digital tools is part of this review. A longitudinal study with clinical validation could open up new models to explore substance use disorders.

Background: The free‐access (FA) intravenous alcohol self‐administration (IV‐ASA) paradigm is an experimental approach that can identify modulators of alcohol consumption in humans. Moreover, the outcome measures of IV‐ASA paradigms are associated with self‐reported alcohol intake using the timeline follow‐back method (TLFB). To evaluate how FA IV‐ASA reflects drinking in real life, we examined the relationship between an objective marker of recent alcohol intake, phosphatidylethanol in blood (B‐PEth), and TLFB and measures obtained during IV‐ASA in individuals with alcohol use disorder (AUD) and social drinkers (SD). We also explored the associations between these measures and gut‐brain peptides involved in AUD pathophysiology. Methods: Thirty‐eight participants completed a laboratory session in which they self‐administered alcohol intravenously. The safety limit was 200 mg%, and main outcomes were mean and peak breath alcohol concentrations (BrAC). Blood samples were drawn prior to IV‐ASA and subjective alcohol effects were rated during the experiment. Results: The study sample comprised 24 SD and 14 participants with DSM‐5 mild AUD. Although BrACs were not associated with B‐PEth or TLFB in the full sample or AUD subgroup, there was an association with TLFB in SD. In both subgroups, BrACs were associated with alcohol craving but with differential timing. Total ghrelin levels were higher in AUD participants than in SD. Conclusions: No associations between B‐PEth levels and achieved BrACs were observed in the mild AUD group, the SD group, or the full sample. The ability for FA IV‐ASA to reflect recent drinking was confirmed only for TLFB in SD, whereas there were no associations within the smaller subsample of participants with mild AUD or in the full sample. Further studies that include a larger AUD sample are warranted. The association of BrACs with craving for alcohol suggests that the IV‐ASA method may be useful for assessing interventions that target craving. This could be explored by using the FA IV‐ASA model to evaluate the effects on craving of approved pharmacotherapies for AUD. [ABSTRACT FROM AUTHOR]

Understanding the role of mass media in shaping the perception of individual health behavior in India, alcohol promoting advertisement bans were imposed on all mass media platforms. However, minimal research explored how the mass media had influenced the alcohol behavior of Indian individual's overtime after imposing a an. The present study examined the effect of mass media exposure to abate alcohol consumption behavior among the Indian population, adjusting for heterogeneity in the risk of alcohol consumption across India's communities and states. The India Human Development Survey panel data, including 16661 individuals, were used for analysis. Multivariable analyses were performed using three-level random intercept logit models to show the variation in consumption behavior across communities and states. Watching TV, listening to the radio and reading newspapers had no significant influence on alcohol consumption during 2005 and 2012, respectively. We have found a high correlation of alcohol consumption among individuals belonging to the same community and state. The study found an insignificant association of mass media with alcohol consumption but higher heterogeneity at the community and state levels. Thus, it suggests programs and campaigns targeting a particular group to address India's high-risk communities and states. [ABSTRACT FROM AUTHOR]

BACKGROUND: The dearth of and inconsistency in the data on the prevalence, risks of occurrence, comorbidity, and causation of stress-related disorders and alcohol use disorders in Russian veterans of local wars constituted the background for this study. AIM: To study the psychopathological structure, clinical changes, and the reasons for the mental disorders suffered by Russian veterans of local wars; in particular, to study the prevalence, pathogenic factors, comorbidity of alcohol addiction and alcohol abuse, together with symptoms of stress disorders, in Russian veterans undergoing inpatient treatment. METHODS: Our observational case-control study included 685 patients who were undergoing treatment in the psychiatric department of a military hospital: the Main group (veterans) consisted of 264 veterans of armed conflicts who had undergone inpatient treatment from 1992 to 2010; the Control group, 1, 296 patients, all servicemen and military pensioners who had undergone inpatient treatment during a calendar year and had never taken part in combat operations in the past; Control group 2, 125 military personnel (regular and reserve) who had not taken part in combat operations and corresponded to the patients of the main group in terms of the mean age and age distribution curve. We performed a clinical and psychopathological analysis of the symptoms identified in patients from the compared samples and, then, compared them with the ICD-10 criteria of post-traumatic stress disorder (PTSD) and alcohol-related disorders. This allowed us to establish the significance of the difference in their frequency and degree of association at the stage of the data analysis. RESULTS: We uncovered no difference in the prevalence of symptoms of alcohol addiction and alcohol abuse among veterans and other servicemen and military pensioners who had not taken part in combat operations. However, there was a tendency to underdiagnose alcohol addiction in veterans in general and those with symptoms of PTSD, in particular. That is, alcohol addiction was not diagnosed in most cases when the veterans displayed symptoms of stress or other mental disorders, in addition to the signs of alcohol addiction. In most such cases, a stress-related mental disorder or another mental disorder with identified signs was diagnosed and alcohol abuse was described as a concomitant disorder or a complication. There was no significant association between any form of alcohol addiction or abuse and the presence of stress disorder symptoms in our sample of veterans; on the contrary, symptoms of re-experience of trauma were more often observed in veterans who were not prone to frequent drinking. The incidence of combat stressors traced in the medical history did not differ in veterans with any form of alcohol abuse and veterans who were not prone to frequent drinking. However, the main group subjects with alcohol addiction more often displayed cases of addictive behavior during combat operations. Therefore, alcohol abuse during combat operations requires additional research to better establish its prognostic significance. CONCLUSION: This Study found no difference in the incidence of alcohol dependence and alcohol abuse among veterans and other officers. In the sample of veterans, there was no significant association between alcoholism and the presence of PTSD symptoms or a history of combat stressors. It is possible that the same risk of alcohol addiction in different categories of military officers is due to a compact of social stressors that equally had a more significant adverse effect on the entire population of Russian military personnel in the 90s of the last century and the first years of this century, as well as the massive abuse of alcohol, which could also equalize the risks of developing alcohol dependence in all groups of militaries.

Background: Hippocampal and cerebellar neuropathology occurs in individuals with alcohol use disorders (AUD), resulting in impaired cognitive and motor function. Objectives: Evaluate the effects of ethanol on the expression of pro- and anti-inflammatory molecules, as well as the effects of the anti-inflammatory PPAR-γ agonist pioglitazone in suppressing ethanol-induced neuroinflammation. Methods: Adult male and female mice were treated chronically with ethanol for just under a month followed by a single acute binge dose of ethanol. Animals were provided liquid diet in the absence of ethanol (Control; n = 18, 9 M/9F), liquid diet containing ethanol (ethanol; n = 22, 11 M/11F), or liquid diet containing ethanol plus gavage administration of 30.0 mg/kg pioglitazone (ethanol + pioglitazone; n = 20, 10 M/10F). The hippocampus and cerebellum were isolated 24 h following the binge dose of ethanol, mRNA was isolated, and pro- and anti-inflammatory molecules were quantified by qRT-PCR. Results: Ethanol significantly (p <.05) increased the expression of pro-inflammatory molecules IL-1β, TNF-α, CCL2, and COX2; increased the expression of inflammasome-related molecules NLRP3 and Casp1 but decreased IL-18; and altered the expression of anti-inflammatory molecules including TGFβR1 in the hippocampus and cerebellum, though some differences were observed between males and females and the two brain regions. The anti-inflammatory pioglitazone inhibited ethanol-induced alterations in the expression of most, but not all, inflammation-related molecules. Conclusion: Chronic plus binge administration of ethanol induced the expression of inflammatory molecules in adult mice and pioglitazone suppressed ethanol-induced neuroinflammation. [ABSTRACT FROM AUTHOR]

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Alcohol use disorder (AUD) and anxiety/stressor disorders frequently co‐occur and this dual diagnosis represents a major health and economic problem worldwide. The basolateral amygdala (BLA) is a key brain region that is known to contribute to the aetiology of both disorders. Although many studies have implicated BLA hyperexcitability in the pathogenesis of AUD and comorbid conditions, relatively little is known about the specific efferent projections from this brain region that contribute to these disorders. Recent optogenetic studies have shown that the BLA sends a strong monosynaptic excitatory projection to the ventral hippocampus (vHC) and that this circuit modulates anxiety‐ and fear‐related behaviours. However, it is not known if this pathway influences alcohol drinking‐related behaviours. Here, we employed a rodent operant self‐administration regimen that procedurally separates appetitive (e.g. seeking) and consummatory (e.g., drinking) behaviours, chemogenetics and brain region‐specific microinjections, to determine if BLA‐vHC circuitry influences alcohol and sucrose drinking‐related measures. We first confirmed prior optogenetic findings that silencing this circuit reduced anxiety‐like behaviours on the elevated plus maze. We then demonstrated that inhibiting the BLA‐vHC pathway significantly reduced appetitive drinking‐related behaviours for both alcohol and sucrose while having no effect on consummatory measures. Taken together, these findings provide the first indication that the BLA‐vHC circuit may regulate appetitive reward seeking directed at alcohol and natural rewards and add to a growing body of evidence suggesting that dysregulation of this pathway may contribute to the pathophysiology of AUD and anxiety/stressor‐related disorders. [ABSTRACT FROM AUTHOR]

Alcohol abuse is a leading risk factor for the public health burden worldwide. Approved pharmacotherapies have demonstrated limited effectiveness over the last few decades in treating alcohol use disorders (AUD). New therapeutic approaches are therefore urgently needed. Historical and recent clinical trials using psychedelics in conjunction with psychotherapy demonstrated encouraging results in reducing heavy drinking in AUD patients, with psilocybin being the most promising candidate. While psychedelics are known to induce changes in gene expression and neuroplasticity, we still lack crucial information about how this specifically counteracts the alterations that occur in neuronal circuits throughout the course of addiction. This review synthesizes well-established knowledge from addiction research about pathophysiological mechanisms related to the metabotropic glutamate receptor 2 (mGlu2), with findings and theories on how mGlu2 connects to the major signaling pathways induced by psychedelics via serotonin 2A receptors (2AR). We provide literature evidence that mGlu2 and 2AR are able to regulate each other's downstream signaling pathways, either through monovalent crosstalk or through the formation of a 2AR-mGlu2 heteromer, and highlight epigenetic mechanisms by which 2ARs can modulate mGlu2 expression. Lastly, we discuss how these pathways might be targeted therapeutically to restore mGlu2 function in AUD patients, thereby reducing the propensity to relapse. [ABSTRACT FROM AUTHOR]

Background: Hypersexual and hyposexual behaviors are common concomitant of substance use disorders (SUD). On the one hand, the regular consumption of alcohol or illegal drugs can lead to hypersexual or hyposexual behavior due to its effects on the organism; on the other hand, the use of psychotropic substances is also used as a coping strategy concerning already existing sexual impairments. The aforementioned disorders show similarities in terms of their etiology, as traumatic experiences get special attention as potential risk factors for the development of addictions, hypersexual, and hyposexual behavior. Objectives: The study aims to explore the association between SUD characteristics and hypersexual/hyposexual behavior, and a potential moderating effect of early traumatic life events by answering the following research questions: (1) Do people with SUD differ from a sample of people with other psychiatric disorders regarding hypersexual and hyposexual behavior? (2) What are the associations between the presence of sexual problems and different characteristics of the SUD (e.g., mono vs. polysubstance use, type of addictive substance, intensity of the disorder)? (3) What influence do traumatic experiences in childhood and adolescence have on the existence of sexual disorders among adults with a diagnosed SUD? Method: The target group of this cross-sectional ex-post-facto study comprises adults diagnosed with an alcohol- and/or substance use disorder. Data will be collected with an online survey, which will be promoted via several support and networking services for people diagnosed with SUD. Two control groups will be surveyed, one consisting of people with other psychiatric disorders than SUD and traumatic experiences, and one healthy group. Relations between the dependent variables (hypersexual and hyposexual behavior) and independent variables (sociodemographic information, medical and psychiatric status, intensity of the prevalent SUD, traumatic experiences, and symptoms of posttraumatic stress disorder) will be initially calculated via correlations and linear regression. Risk factors will be identified via multivariate regression. Discussion: Gaining relevant knowledge promises new perspectives for prevention, diagnosis, case conception, and therapy of SUDs as well as problematic sexual behaviors. The results can provide more information about the importance of psychosexual impairments regarding the development and maintenance of SUDs. [ABSTRACT FROM AUTHOR]

Objectives: A managed alcohol program (MAP) is a harm reduction strategy that provides regularly, witnessed alcohol to individuals with a severe alcohol use disorder. Although community MAPs have positive outcomes, applicability to hospital settings is unknown. This study describes a hospital-based MAP, characterizes its participants, and evaluates outcomes. Methods: A retrospective chart review of MAP participants was conducted at an academic hospital in Vancouver, Canada, between July 2016 and October 2017. Data included demographics, alcohol/substance use, alcohol withdrawal risk, and MAP indication. Outcomes after MAP initiation included the change in mean daily alcohol consumption and liver enzymes. Results: Seventeen patients participated in 26 hospital admissions: 76% male, mean age of 54 years, daily consumption prehospitalization of a mean 14 alcohol standard drinks, 59% reported previous nonbeverage alcohol consumption, and 41% participated in a community MAP. Most participants were high risk for severe, complicated alcohol withdrawal and presented in moderate withdrawal. Continuation of community MAP was the most common indication for hospital-based MAP initiation (38%), followed by a history of leaving hospital against medical advice (35%) and hospital illicit alcohol use (15%). Hospital-based MAP resulted in a mean of 5 fewer alcohol standard drinks daily compared with preadmission (P = 0.002; 95% confidence interval, 2–8) and improvement in liver enzymes, with few adverse events. Conclusions: Participation in a hospital-based MAP may be an effective safe approach to reduce harms for some individuals with severe alcohol use disorder. Further study is needed to understand who benefits most from hospital-MAP and potential benefits/harms following hospital discharge. [ABSTRACT FROM AUTHOR]

Oxidative stress and neuroinflammation are involved in the pathogenesis of alcohol addiction. However, little is known regarding the effect of genetic, behavioral, psychological, and environmental sources of origin on the inflammation and oxidative stress pathways of patients with alcohol addiction. Our study aimed to evaluate the impact of selected common functional single-nucleotide polymorphisms in inflammation and oxidative stress genes on alcohol addiction, and common comorbid psychosymptomatology. Our study included 89 hospitalized alcohol-addicted patients and 93 healthy individuals, all Slovenian males. Their DNA was isolated from peripheral blood and patients were genotyped for PON1 rs705379, rs705381, rs854560, and rs662, SOD2 rs4880, GPX1 rs1050450, IL1B rs1143623, rs16944, and rs1071676, IL6 rs1800795, IL6R rs2228145, and miR146a rs2910164. Kruskal–Wallis and Mann–Whitney tests were used for the additive and dominant genetic models, respectively. Our findings suggested the involvement of IL6 rs1800795 in alcohol addiction. Moreover, our data indicated that the genetic variability of SOD2 and PON1, as well as IL1B and IL6R, may be related to comorbid psychosymptomatology, revealing a potential indirect means of association of both the oxidative stress and inflammation pathways.

Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.

Alcohol dependence (AD) and mood disorders are not only a serious medical and socio-economic problem for modern society, but also the cause of social adaptation disorders that form even in the early stages of each of these disorders, as well as in case of their comorbidity.Objective: to determine the relationship between the level of subjective assessment of social adaptation and the main clinical, dynamic and psychological characteristics in patients with affective disorders (AFD) with comorbid AD.Patients and methods. The study included 126 patients treated for AFD in the departments of affective or addictive conditions of the clinic of the Research Institute of Mental Health of the Tomsk National Research Medical Center (F31 – F34.1 according to ICD-10; n=83) or AFD comorbid with AD (F10. 2; n=43). The study used clinical-dynamic, psychometric, pathopsychological and statistical methods.Results and discussion. Patients with AFD without comorbidity at admission were characterized by a greater severity of subjective impairment of social adaptation and anhedonia; hypochondriacal, depressive, psychasthenic and schizoid traits predominated in the structure of their personality. At the same time, the condition of patients with AFD and AD comorbidity was objectively assessed as more severe. An inverse correlation was found between the level of subjective assessment of social adaptation and anhedonia in the group of patients with «pure» AFD, and in the group with AFD and AD comorbidity, with the severity of depressive symptoms (due to typical depressive symptoms), as well as with depressive and anxious personality traits of patients.Conclusion. Self-assessment of social adaptation of patients with “pure” AFD depends on the intensity of anhedonia manifestations, and in patients with AFD and AD comorbidity, on depressive symptoms (due to typical depressive symptoms) and on the severity of such psychological characteristics as depression and psychasthenia.

BackgroundHypersexual and hyposexual behaviors are common concomitant of substance use disorders (SUD). On the one hand, the regular consumption of alcohol or illegal drugs can lead to hypersexual or hyposexual behavior due to its effects on the organism; on the other hand, the use of psychotropic substances is also used as a coping strategy concerning already existing sexual impairments. The aforementioned disorders show similarities in terms of their etiology, as traumatic experiences get special attention as potential risk factors for the development of addictions, hypersexual, and hyposexual behavior.ObjectivesThe study aims to explore the association between SUD characteristics and hypersexual/hyposexual behavior, and a potential moderating effect of early traumatic life events by answering the following research questions: (1) Do people with SUD differ from a sample of people with other psychiatric disorders regarding hypersexual and hyposexual behavior? (2) What are the associations between the presence of sexual problems and different characteristics of the SUD (e.g., mono vs. polysubstance use, type of addictive substance, intensity of the disorder)? (3) What influence do traumatic experiences in childhood and adolescence have on the existence of sexual disorders among adults with a diagnosed SUD?MethodThe target group of this cross-sectional ex-post-facto study comprises adults diagnosed with an alcohol- and/or substance use disorder. Data will be collected with an online survey, which will be promoted via several support and networking services for people diagnosed with SUD. Two control groups will be surveyed, one consisting of people with other psychiatric disorders than SUD and traumatic experiences, and one healthy group. Relations between the dependent variables (hypersexual and hyposexual behavior) and independent variables (sociodemographic information, medical and psychiatric status, intensity of the prevalent SUD, traumatic experiences, and symptoms of posttraumatic stress disorder) will be initially calculated via correlations and linear regression. Risk factors will be identified via multivariate regression.DiscussionGaining relevant knowledge promises new perspectives for prevention, diagnosis, case conception, and therapy of SUDs as well as problematic sexual behaviors. The results can provide more information about the importance of psychosexual impairments regarding the development and maintenance of SUDs.

Mitochondrial aldehyde dehydrogenase (ALDH2) is a potential target for the treatment of substance use disorders such as alcohol addiction. Here, we adopted computational methods of molecular dynamics (MD) simulation, docking, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) analysis to perform a virtual screening of FDA-approved drugs, hitting potent inhibitors against ALDH2. Using MD-derived conformations as receptors, butenafine (net charge q = +1 e) and olaparib (q = 0) were selected as promising compounds with a low toxicity and a binding strength equal to or stronger than previously reported potent inhibitors of daidzin and CVT-10216. A few negatively charged compounds were also hit from the docking with the Autodock Vina software, while the MM-PBSA analysis yielded positive binding energies (unfavorable binding) for these compounds, mainly owing to electrostatic repulsion in association with a negatively charged receptor (q = −6 e for ALDH2 plus the cofactor NAD+). This revealed a deficiency of the Vina scoring in dealing with strong charge–charge interactions between binding partners, due to its built-in protocol of not using atomic charges for electrostatic interactions. These observations indicated a requirement of further verification using MD and/or MM-PBSA after docking prediction. The identification of key residues for the binding implied that the receptor residues at the bottom and entrance of the substrate-binding hydrophobic tunnel were able to offer additional interactions with different inhibitors such as π-π, π-alkyl, van der Waals contacts, and polar interactions, and that the rational use of these interactions is beneficial to the design of potent inhibitors against ALDH2. [ABSTRACT FROM AUTHOR]

Improving physical activity (PA) in patients with alcohol use disorder (AUD) has recently emerged as an important component of the global treatment strategy to improve drinking outcomes and quality of life. However, this new approach should focus on AUD patients with insufficient baseline PA and requires this subgroup to be better characterized. In a population of 382 treatment-seeking AUD patients, PA was assessed using the International Physical Activity Questionnaire, and participants were divided into two groups: insufficient PA group and sufficient PA group. The severity of the AUD was assessed using the DSM-5 criteria, the Alcohol Use Disorder Identification Test, and the Severity of Alcohol Dependence Questionnaire. In logistic regression models, individuals with insufficient PA were more likely than other AUD individuals to present a higher Body Mass Index (p < 0.001), a higher number of AUD DSM-5 criteria (p < 0.05), more frequent opioid use (p < 0.05), higher scores at the Fagerström Test for Nicotine Dependence (p < 0.001), State-Trait Anxiety Inventory (p < 0.001), impulsivity scale (p < 0.05), Pittsburgh Sleep Quality Inventory (p < 0.05), and lower WHO Quality of Life (p < 0.001) scores. In AUD, an insufficient baseline PA is associated with several markers of severity, and physical exercise interventions should be part of a multimodal treatment program integrating the global impairments of patients. [ABSTRACT FROM AUTHOR]

Abstract Background Craving for alcohol, in other words powerful desire to drink after withdrawal, is an important contributor to the development and maintenance of alcoholism. Here, we studied the role of GDNF (glial cell line-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) on alcohol-seeking behavior in group-housed female mice. Methods We modeled alcohol-seeking behavior in C57Bl/6J female mice. The behavioral experiments in group-housed female mice were performed in an automated IntelliCage system. We conducted RT-qPCR analysis of Gdnf, Bdnf, Manf and Cdnf expression in different areas of the female mouse brain after alcohol drinking conditioning. We injected an adeno-associated virus (AAV) vector expressing human GDNF or BDNF in mouse nucleus accumbens (NAc) after ten days of alcohol drinking conditioning and assessed alcohol-seeking behavior. Behavioral data were analyzed by two-way repeated-measures ANOVA, and statistically significant effects were followed by Bonferroni’s post hoc test. The student’s t-test was used to analyze qPCR data. Results The RT-qPCR data showed that Gdnf mRNA level in NAc was more than four times higher (p