A study of alcohol dependence in obsessive-compulsive disorder.

Alcohol use disorder (AUD) is one of the deadliest psychiatric conditions. Previous studies indicate that AUD is linked to several neurological biomarkers in the human brain; however, how alcohol use manifests in brain volumes and the relationships between the subcortical brain regions affected by AUD and clinical outcomes are not fully understood. This study attempts to compare subcortical brain volume differences between patients with AUD and healthy controls (HC) to understand how alcohol use relates to brain volume changes. Patients with AUD, as determined by alcohol dependence and abuse criteria from the DSM-IV, (n = 71) were recruited and matched with HC (n = 71) by demographic characteristics. We examined group differences in the volumes of 40 bilateral subcortical structures between patients with AUD and HC. We assessed the relationship between changes in subcortical brain volumes and common co-occurring psychiatric symptoms. Our results revealed a significant increase of third ventricle volume in patients with AUD compared to HC. Moreover, we also found a positive correlation between the third ventricle volume and generalized anxiety in patients with AUD. Our findings indicate significant enlargement of the third ventricle volume in patients with AUD, as well as relatedness between the volume of this area and generalized anxiety. This study is the first in the literature to find volume alterations correlated with clinical outcomes among AUD patients, reflecting a complex relationship between brain volumes and psychological symptoms in this population.

The emerging role of FGF21 in alcohol consumption and dependence: mechanisms and therapeutic prospects.

Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD) are two highly prevalent psychiatric disorders with a high comorbidity rate, which is significantly higher rate than other combinations of mental disorders and substance use disorders. This comorbidity not only imposes a substantial disease burden on individuals but also significantly complicates clinical management, leading to more severe functional impairment, reduced treatment adherence, and increased resistance to monotherapy. AUD diagnosis varies by diagnostic system: DSM-V integrates alcohol dependence and abuse into 11 criteria with severity grading, while ICD-11 retains two subtypes and shows higher diagnostic rates for dependence. MDD, the depressive subtype with the highest AUD comorbidity rate, must be distinguished from alcohol-induced depression. Underlying mechanisms of this comorbidity involve bidirectional pathways as well as core pathophysiological processes including abnormal reward sensitivity, neurotrophic-inflammatory imbalance, dysregulation of neurotransmitter systems and the hypothalamic-pituitary-adrenal (HPA) axis, gut-brain axis disruption, and shared risk factors. Therapeutic strategies encompass multiple modalities: pharmacological interventions include selective serotonin reuptake inhibitors (SSRIs) combined with AUD-targeted therapies, as well as emerging agents like extended-release trazodone and ketamine; psychosocial interventions are dominated by cognitive behavioral therapy (CBT); physical therapies such as repetitive transcranial magnetic stimulation (rTMS) and gut-brain axis-targeted therapies also show therapeutic potential. Notably, integrated treatment models that simultaneously address both disorders have been proven to outperform sequential or parallel approaches. This review systematically synthesizes the latest evidence on the diagnosis, underlying mechanisms, and therapeutic strategies of AUD-MDD comorbidity, aiming to provide evidence-based references for clinical management.

<p><strong>Relevance.</strong> Cultural influences are not only an important factor in the genesis of mental disorders, but also significant in the development of any psychotherapeutic models and technologies. However, the dependence of the latter on cultural influences is poorly taken into account during their implementation and dissemination. The request from routine narcological practice and somatic medicine for motivational psychotherapy targeting patients who use psychoactive substances (PAS) determines the practical significance of the problem. <strong>The aim</strong> of the authors of the article was to substantiate the need to modify motivational psychotherapy proposed for patients with alcohol dependence, taking into account cultural influences that are significant when it is carried out in modern Russia. <strong>Hypothesis.</strong> It was assumed that through a structured survey of expert narcologists, it would be possible to identify aspects of the stated problem that are significant for further study and practical use: the presence of cultural influences that are observed during motivational psychotherapy for a patient with alcohol dependence syndrome. <strong>The material</strong> for the pilot study was data from a survey of 20 Russian expert narcologists, conducted using authors’ questionnaires described in the text of the article. <strong>Results. </strong>A survey of addiction experts identified anti-therapeutic attitudes and beliefs frequently observed in patients with alcohol dependence. These beliefs reflect the patient's view of alcohol usage as a primary form of recreation, a means of relaxation and pastime, and the conviction that external circumstances are the cause of alcoholism. A lack of understanding of chemical dependence as a serious disorder was identified, along with a negative attitude toward addiction treatment and addiction specialists. A belief that others will not accept the patient if they choose a sober lifestyle is present. These attitudes hinder motivation and subsequent treatment. <strong>Conclusions. </strong>The research perspective is to study the cultural aspects of the use of motivational psychotherapy for people with substances dependence in modern Russia for the subsequent improvement of its technologies.</p>

ABSTRACTUnderage drinking has become a global public health concern. One of the major causes of underage drinking is stress. The orexin system has been reported to be involved in both alcohol addiction and stress. However, few studies have examined this system, especially among adolescents. Therefore, we constructed protein–protein interaction (PPI) networks to confirm that orexin receptors are connected to stress‐ and alcohol dependence‐related genes, providing a theoretical basis for our experimental approach. Animal experiments employed the conditioned place preference (CPP), the foot‐shock stress model and the enzyme‐linked immunosorbent assay (ELISA), to elucidate the role of the orexin system in the stress‐induced alcohol addiction‐related behaviour among adolescent mice. Our results revealed that there were interactions among orexin system, chronic/acute stress and alcohol dependence related proteins. Otherwise, chronic stress can increase the animals' vulnerability to alcohol addition‐related behaviour. Additionally, acute foot‐shock can promote alcohol‐seeking behaviour reinstatement and facilitate orexin concentrations in brain regions that have been shown to be associated with reward and addiction. Moreover, the inhibition of orexin receptors can attenuate the formation and reinstatement of alcohol addiction‐like behaviour among adolescent mice. Collectively, our findings indicate that orexin system may be a pivotal target for preventing stress‐induced alcohol addiction and reinstatement among the adolescents.

Decoding the serotonin-alcohol crosstalk: the role of central serotonergic dysregulation in alcohol use disorder.

Impact of alcohol cessation on hepatic metabolic signaling during cancer cachexia.

Alcohol consumption remains an independent risk factor for recurrent presentations of alcohol-associated acute pancreatitis (AAP). Although there are recognised guidelines for alcohol use disorder (AUD), there are no recommendations on targeting alcohol cessation to reduce recurrence of AAP in guidelines for acute pancreatitis. This study describes the uptake of the Addiction Medicine Unit (AMU), a specialist consultative service, in patients with AAP presenting to a tertiary hospital. Retrospective cohort with all inpatients with AAP at a large multisite tertiary health service in Melbourne, Australia from May 2022 to May 2024. Demographics, AUD diagnosis and recommended interventions from the AMU were obtained from medical records. There were 231 patients across 314 admissions with AAP identified with a high prevalence of AUD (91.8%). Referral to AMU occurred in 56.7% of admissions, predominantly among those with AUD (93.8%), with a tendency to refer patients with higher weekly alcohol intake (P = 0.024). The AMU recommended outpatient counselling services to assist with detoxification and rehabilitation in 40.4%, both pharmacological and outpatient interventions in 37.6% and medications alone in 21.9% of admissions. Over the 2-year period, 54 (23.4%) patients were readmitted with AAP. The adjusted analysis did not demonstrate reduced readmission with AAP associated with AMU review. There is a substantial missed opportunity for specialist addiction medicine input in this cohort. AAP should be considered a sentinel alcohol-related hospital presentation, and the observed referral gap identifies an opportunity for more systematic addiction medicine assessment, pharmacotherapy initiation and linkage to longitudinal care.

Alcohol misuse leads to a range of health complications and induces various metabolic perturbations that impacts multiple physiological systems, including the cardiovascular system, liver, and gut microbiota. However, limited research has been reported on these metabolic profile changes, particularly using models of alcohol dependence such as after chronic intermittent ethanol (CIE) vapor exposure. This study investigated CIE-induced metabolomic alterations of CIE were investigated using fecal, liver, and serum samples of adult male and female C57BL/6J mice following 72 hr withdrawal. Significant metabolite changes were observed in both fecal and liver extracts and these changes were sex-specific. Both liver and fecal metabolites had systematic changes, while blood serum influences were limited after CIE. Female fecal samples showed higher metabolite perturbations than male samples according to PCA studies. The female samples showed significant butyrate downregulation and acetate upregulation, which are critical microbial products as beneficial microbe cell energy sources and influence intestinal absorption in the host. In addition, the female fecal samples showed significant downregulation of branched-chain amino acids including leucine, isoleucine, and valine, while male samples showed downregulation of glucose and taurine, with upregulated phenylalanine and tyrosine. In contrast, in the liver study, phenylalanine and tyrosine were upregulated while taurine was downregulated in females. Both sexes showed downregulation of liver glycine and glucose. These data indicate that CIE induces sex-specific metabolic perturbations in the mouse liver and fecal metabolome, and have implications for guy disturbances and liver damage observed following alcohol dependence. This study provides potential targets for future examination of mechanisms and treatment approaches for alcohol dependence.

Chronic alcohol disrupts premotor cortex intrinsic excitability and transmission.

The aim of this study was to determine whether adolescent traumatic brain injury (TBI) is associated with long-term risk of depression, anxiety, suicide ideation, suicide attempt, and substance use disorders, and whether these risks differ by sex and injury severity. This retrospective cohort study used electronic health record data from January 1, 2000, to January 1, 2019, with a 5-year follow-up period. Data were obtained from the TriNetX platform, which aggregates deidentified information from 60 US healthcare organizations across all 50 states. A total of 262,262 adolescents aged 10-18 years diagnosed with mild or moderate to severe TBI were included. Cohorts were stratified by sex and TBI severity and matched to controls without TBI by race, socioeconomic factors, and prior psychiatric or head injury diagnoses. Exposures were defined by ICD-10 codes for TBI severity, and outcomes included incidence of depression, anxiety, alcohol dependence, nicotine dependence, suicide ideation, and suicide attempt within 5 years of TBI diagnosis. Among 262,262 adolescents with TBI (154,149 male and 108,113 female), mild TBI was associated with increased risk of depression, anxiety, suicide ideation, suicide attempt, alcohol dependence, and nicotine dependence in both males and females compared with matched controls. Females with mild TBI had a higher risk of mood disorders and suicidality, whereas males had higher risk of substance use. Moderate to severe TBI was not associated with higher risk for these disorders compared with mild TBI. Adolescent TBI, regardless of severity, was associated with increased risk of psychiatric disorders and substance use, with females showing greater vulnerability to mood disorders and suicidality.

BackgroundCraving is a diagnostic criterion and predictor of relapse in patients with alcohol dependence (AD) and is induced in cue exposure therapy (CET) to prepare patients for real-life risk situations. The benefits of virtual reality (VR) as an innovative tool within treatment for this highly prevalent disorder include increased practicability, standardization, and personalization of CET. Accurate measurement of craving is essential to develop effective virtual reality cue exposure (VR-CE) scenarios. Despite being relevant for diagnostics and therapy, the psychophysiological reaction to alcohol cues and its relationship to subjective craving has not been sufficiently examined.ObjectiveThis study aimed to investigate the induction of subjective craving, its physiological correlates, and their relationship in patients with AD during an innovative VR-CE paradigm, including 2 alcohol-associated risk scenarios (bar and living room) and a neutral baseline scenario.MethodsCraving was analyzed by measuring physiological reactions (electrodermal activity, including nonspecific skin conductance responses [NS-SCR] and skin conductance level [SCL]; heart rate [variability] [HR(V)]; brightness-corrected pupil diameter [BCPD]; and respiration rate [RR]) and subjective craving (visual analog scale) in 61 patients with AD. Linear mixed-effects models were conducted to estimate the effects of VR-CE. Correlations between subjective and physiological craving parameters were analyzed using Spearman correlations.ResultsResults showed that alcohol-associated VR scenarios had significant effects on subjective craving (β values between 9.48, 95% CI 6.02‐12.95 and 15.93, 95% CI 12.47‐19.40, with moderate effect sizes between d=0.56 and d=0.72) and on NS-SCR frequency (β values between 0.97, 95% CI 0.14‐1.80 and 3.06, 95% CI 2.23‐3.89, with small-to-large effect sizes between d=0.31 and d=0.91), BCPD (β values between 0.03, 95% CI 0.01‐0.06 and 0.05, 95% CI 0.02‐0.07, with small effect sizes between d=0.21 and d=0.29), and RR (β values between 0.67, 95% CI 0.06‐1.28 and 1.66, 95% CI 1.05‐2.26, with small effect sizes between d=0.22 and d=0.45), but not on SCL and HR(V). Correlation analyses showed significant but weak correlations between subjective craving and electrodermal activity (SCL: r=0.20, P=.04; NS-SCR frequency: r=0.21, P=.03).ConclusionsThis study showed that subjective and physiological craving (NS-SCR, BCPD, and RR but not SCL and HR[V]) can be successfully induced by VR-CE in patients with AD. These outcomes add to research on the induction of craving using a wide range of psychophysiological and subjective parameters. Furthermore, this study expands the still-limited research on the relationship between subjective and psychophysiological craving in patients with AD. In the long term, this study informs the development of effective VR-CET, which could, by further building on psychophysiological parameters, lead to biofeedback VR-CET as an innovative treatment option for patients with AD.

Domestic violence and abuse (DVA) remains a major public health and human rights concern, with profound consequences for women's physical, psychological, and socioeconomic well-being. We report the case of a 32-year-old married woman and mother of two who experienced prolonged domestic violence, including physical, emotional, and economic abuse, compounded by her husband's alcohol dependence. Economic abuse escalated when debt incurred through a self-help group loan, intended to support the family's livelihood, was transferred to the survivor, reinforcing financial dependency and coercive control. Following a severe episode of physical violence that resulted in her displacement from the marital home, she sought support through a hospital-based crisis center established within a tertiary care women's hospital. Through crisis intervention, structured counseling, legal guidance, child welfare support, and employment assistance, the survivor achieved financial independence, secured safe accommodation, and initiated steps toward legal separation. This case highlights the often-overlooked role of economic abuse and debt bondage as mechanisms of control within abusive relationships. It also demonstrates the value of integrated, hospital-based crisis services and intersectoral collaboration in supporting survivors of violence. Strengthening routine identification of DVA within healthcare settings, expanding access to crisis centers, and promoting women's economic empowerment may contribute to improved safety and long-term recovery for survivors.

Dysregulation of the dynorphin (DYN) / kappa-opioid receptor (KOR) system is heavily implicated in symptoms of alcohol use disorder (AUD) including negative affective-like states that can drive maladaptive behavioral regulation. Substantial efforts have been made towards understanding the neurobiology of DYN / KOR dysregulation; however, the role of dynorphinergic islands of Calleja within the ventral striatum remain poorly understood. Presently, adult male Wistar rats were trained to self-administer 10% alcohol, exposed to either air or alcohol vapor for eight weeks, and alcohol self-administration and 22-kHz ultrasonic vocalizations (USVs) assessed during acute withdrawal. Subsequently, brains were extracted during acute withdrawal and DYN A-like immunoreactivity was measured in the ventral striatum. Alcohol vapor-exposed rats demonstrated increased alcohol consumption and 22-kHz USVs compared to air-exposed controls. Vapor-exposed rats additionally demonstrated increased DYN A-like immunoreactivity in the islands of Calleja. Moreover, the average DYN A neuron size positively correlated with the number of 22-kHz USVs in vapor exposed animals, but not in air-exposed controls. The present findings identify the islands of Calleja as a novel DYN-associated region that may be recruited during alcohol dependence with enhanced DYN plasticity in the islands of Calleja contributing to affective dysregulation in AUD and other neuropsychiatric conditions.

Background and aims: Alcohol-related liver disease (ALD) is a major indication for liver transplantation (LT) and post-LT alcohol relapses remain a key concern. We evaluated the risk and predictors in a nationwide ALD cohort using phosphatidylethanol (PEth), a direct biomarker of alcohol consumption. Methods: We retrospectively analyzed all adults transplanted for ALD in Finland 2018–2023. Alcohol relapse was defined as any relapse (PEth ≥ 0.03 µmol/L) or severe relapse (PEth ≥ 0.30 µmol/L). Cumulative incidence was estimated using competing-risk time-to-event methods, and predictors were examined using univariable Cox proportional hazards models. Results: Among 95 patients (median post-LT follow-up 4.3 years), 29 (31%) experienced any relapse and 13 of those (14%) severe relapse. Limited social support (HR 2.81, 95% CI 1.32–5.95) and insufficient assessment of alcohol use disorder (AUD) (HR 2.93, 95% CI 1.34–6.41) were associated with increased risk of any relapse, while involvement of a relative during LT evaluation (HR 0.28, 95% CI 0.10–0.72) and a formal diagnosis of alcohol dependence (HR 0.15, 95% CI 0.03–0.76) were protective. Older age reduced the risk of severe relapse (HR 0.93 per year, 95% CI 0.88–0.99). Among those transplanted within ≤6 months of pre-transplant abstinence (n = 9), 78% experienced any relapse and 44% developed severe relapse. Conclusion: In this national Finnish ALD cohort, approximately one third of LT recipients experienced alcohol relapse. Short pre-transplant abstinence and indicators of limited support and suboptimal AUD assessment were associated with higher relapse risk, underscoring the need for sustained addiction treatment and consistent support post-LT.

The association between alcohol use and poor mental health is well known. Although psychiatric services and supports are typically delivered in community settings, some individuals require specialist inpatient care for alcohol-related disorders. For many, multiple admissions may be required, referred to as the 'Revolving Door' (RD) phenomenon. This study examines alcohol-related admissions to inpatient psychiatric units during a 10-year period (2015 - 2024) using data from the Irish National Psychiatric Inpatient Reporting System (NPIRS). The study aims to compare characteristics of first admissions and re-admissions to examine factors associated with RD admissions. This study used retrospective, anonymised NPIRS data. Descriptive statistics were conducted, and statistical significance was assessed using Pearson X2 tests. During the study period, 5.9% of all inpatient admissions into psychiatric units were alcohol related and almost two-thirds were readmissions (63.8%). Both first and readmissions were predominantly single, male, employed and aged between 45 - 64 years with a diagnosis of alcohol dependency. Readmissions were significantly more likely to have a longer length of stay. Key sex differences in alcohol-related admissions were noted. Male admissions were significantly more likely to be single and younger. Females were more likely to be older, private patients and have longer inpatient stays. Rural areas accounted for a larger share of alcohol-related admissions. Despite accounting for less than 6% of all psychiatric admissions, alcohol-related psychiatric hospitalisations represent substantial healthcare costs. The findings from this study highlight the need for more targeted, sex-sensitive interventions to reduce the high level of readmissions.

Increased risk of alcohol dependence is recognised following bariatric surgery. Modified gastrointestinal anatomy and neurohormonal profiles lead to altered alcohol metabolism, peak blood alcohol concentrations and enhanced reward circuits and cravings. For patients with metabolic associated fatty liver disease, bariatric surgery has been shown to reduce liver fibrosis; however, the impact of bariatric surgery on alcohol consumption and consequent liver fibrosis has not been well-characterised using validated measures. This study examined the changes in alcohol consumption patterns, alcohol dependence and validated liver fibrosis measures before and after bariatric surgery. A retrospective cohort study assessing patients seeking treatment for alcohol problems with a history of gastric sleeve (GS) or Roux-en-Y Gastric Bypass (RYGB) in a quaternary hospital in Brisbane, Australia. Validated measures of alcohol dependence [Alcohol Use Disorders Identification Test (AUDIT) and brief Michigan Alcohol Screening Test (bMAST)] and non-invasive liver fibrosis (FIB4 and APRI) were compared pre- and post-surgery. Twenty patients were identified with prior GS and 10 patients with RYGB. Following bariatric surgery, body mass index was reduced by 14.5 (±9.39) kg/m2. Metabolic co-morbidities were less frequent post-surgery. Pre-surgery, the mean AUDIT score was 10.2 ± 8.9, with 9 patients having scores indicative of alcohol dependence. Mean AUDIT increased statistically significantly post-surgery (18.1, standard deviation ±11.4; P < 0.001) with 29 patients meeting criteria for alcohol dependence. AUDIT components relating to both consumption (volume, frequency) and harmful consequences of alcohol increased following surgery. Despite surgery lowering metabolic liver fibrosis risk, worsened liver fibrosis was observed [mean FIB4 (0.98 ± 1.8) and APRI (0.41 ± 0.83) increased; P < 0.05]. Within a cohort of adults seeking treatment for alcohol problems, increases in alcohol consumption and alcohol-related harm were observed following bariatric surgery. Despite improvement in risk factors for metabolic-associated fatty liver disease after surgery, non-invasive markers for hepatic fibrosis worsened, likely in the setting of harmful alcohol intake and associated liver injury. This supports the role of bariatric surgery pre-operative assessment and post-operative follow-up to identify and manage alcohol-related problems and associated liver disease risk.

The transition from controlled to escalated drug intake is a core feature of cocaine use disorder (CUD), yet the molecular mechanisms underlying this behavioral escalation remain poorly defined. Our prior genome-wide association study (GWAS) identified ANKS1B as a significant shared genetic risk factor for heroin, methamphetamine, and alcohol dependence, suggesting a broad role in addiction vulnerability. However, the specific function of ANKS1B in cocaine addiction and its associated neural mechanisms were unknown. Here, we found that ANKS1B expression level in the Nucleus Accumbens (NAc) was downregulated after extended cocaine use, and manipulating ANKS1B could selectively influence the escalation of cocaine intake and the subsequent cocaine-seeking behavior in the long-access cocaine self-administration rat model. Molecular experiments reveal that ANKS1B interacts with the histone acetyltransferase CBP to control H3K27 acetylation and extended cocaine intake, via epigenetically repressing the transcription factor FoxO3. Overall, these findings suggest that ANKS1B is a crucial factor influencing the escalation of cocaine use. The ANKS1B-CBP-FoxO3 signaling pathway presents a promising target for potential therapeutic interventions for controlling extended cocaine use.

Lifestyle modification, including dietary interventions, physical activity, and stress management, has proven crucial in the non-pharmacological management of cardiometabolic diseases. However, the implementation of these interventions in the context of cardiometabolic multimorbidity (CMM) within the unique demographic and cultural milieu of India is inadequately explored, despite Indians exhibiting distinct susceptibility to cardiovascular diseases. This community-based study aims to address existing knowledge gaps by implementing a culturally tailored lifestyle toolkit based on the WHO-HEARTS framework among individuals with CMM and exploring the intergenerational preventive dimension. The study adopts a two-arm non-blinded cluster randomised controlled trial (c-RCT) design to include adults diagnosed with CMM, defined by the presence of two or more of diabetes mellitus, hypertension, stroke, or coronary heart disease, aged 18 years and above, providing informed consent, and agreeing to follow-up. The trial spans the 'Epidemiology of Non-communicable Diseases In Rural Areas' (ENDIRA) cohort in Ernakulam, Kerala. The intervention, 'SHRADDHA lifestyle toolkit', integrates guidance on diet, physical activity, stress management, tobacco and alcohol cessation, and drug adherence. It leverages frontline health workers and a digital health platform for implementation. Measurements involve use of point-of-care devices and digital tools. The study duration is 24 months, with a sample size of 2000 participants distributed across 18 clusters. Statistical analysis includes repeated-measures ANOVA and multilevel models, employing an intention-to-treat approach. The study's novelty lies in its holistic approach, addressing various facets of CMM comprehensively.Trial registration: The trial has been registered with the Clinical Trial Registry of India (CTRI) Reference Number-CTRI/2025/08/092529. Registered on August 6, 2025.