Adverse Childhood Experiences, Coping and Resilience in Persons with Alcohol Use Disorder and Their Non-drinking Siblings in High-density Families: A Case-control Study.

Background: Adverse childhood experiences (ACEs) increase the odds of alcohol use disorder (AUD). Aim: To study the ACEs, coping, and resilience in persons with AUD and their non-drinking siblings from high-density families. Methods: The study used a case-control study design. Using purposive sampling, 135 participants were selected; the sample consists of persons with AUD (n = 45), non-drinking siblings (n = 45), and healthy controls (n = 45), selected from out-patient and in-patient services from a government-run de-addiction centre in Bengaluru. Individuals were administered an ACEs questionnaire, Brief-COPE, and Connor-Davison Resilience scale. Descriptive statistics, Friedman's test, and Bonferroni's post-hoc test, Binary Logistic Regression were used for analysis. Results: ACEs, coping, and resilience significantly differ across the three groups. Persons with AUD and their non-drinking siblings are comparable in terms of ACEs and having dysfunctional family members. Non-drinking siblings and healthy controls have similar coping and resilience. None of the healthy controls had dysfunctional family members. Conclusion: ACEs are more prevalent and more frequent in persons with AUD. Individuals with AUD showed higher avoidant coping and lower resilience than their non-drinking siblings and healthy controls. Early identification of ACEs and interventions to build resilience and coping strategies could prevent individuals from developing AUD in high-density families.

Childhood adversities characterize the heterogeneity in the brain pattern of individuals during neurodevelopment.

BACKGROUND: Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development. METHODS: Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort (n = 987, aged 6-23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects). RESULTS: Significant DMD differences were primarily identified in the default mode network (DMN) regions across these groups (p < 0.05, Bonferroni corrected). While the groups were comparable in cognitive performance, the atypical group had more frequent exposure to adversities and faced higher abuses (p < 0.05, Bonferroni corrected). Upon evaluating brain-behavior correlations, we found that correlation patterns between adversity and DMN dynamic modes exhibited age-dependent variations for atypical subjects, hinting at differential utilization of the DMN due to chronic adversities. CONCLUSION: Adversities (particularly abuse) maximally influence the DMN during neurodevelopment and lead to the failure in the development of a coherent DMN system. While DMN's integrity is preserved in typical development, the age-dependent variability in atypically developing individuals is contrasting. The flexibility of DMN might be a compensatory mechanism to protect an individual in an abusive environment. However, such adaptability might deprive the neural system of the faculties of normal functioning and may incur long-term effects on the psyche.

Text message-based Cessation Intervention for People who Smoked or Used Smokeless Tobacco in India: a Feasibility Randomised Controlled Trial.

INTRODUCTION: Despite the high burden of tobacco use in India, users do not have access to adequate help. This pilot trial aimed to evaluate the feasibility and acceptability of a text messaging intervention for tobacco cessation, generate preliminary estimates of its impact, and fine-tune procedures for a definitive trial. METHODS: Parallel two-arm single blind individually randomised controlled pilot trial with nested qualitative study. Participants included adult current tobacco users (smoked and smokeless). Eligible and consenting participants were randomised to receive either (a) text messaging intervention (ToQuit) which covered specific content areas such as psychoeducation about consequences of tobacco use and benefits of quitting and tobacco avoidance strategies or (b) information about tobacco cessation helplines such as the helpline number and the languages in which tobacco cessation support was available (control). Feasibility data included screening and consent rates, treatment dropouts and outcome ascertainment. The primary abstinence outcome was self-reported abstinence from tobacco in the past seven days at three months post-randomisation. In-depth interviews were conducted with a sub-sample of participants primarily to collect acceptability data. The primary abstinence analysis used a chi-squared test and logistic regression (complete-case), and qualitative data analysed using thematic analysis. RESULTS: Ninety eight participants were randomised into the two trial arms; 77 (79%) completed outcome evaluation. No between-arm differences in abstinence were found though findings favoured the intervention (7-day abstinence: ToQuit 23%, control 19%; adjusted odds ratio 1.23, 95% confidence interval 0.38, 3.97). Participants appreciated the language, comprehensibility, and relevance of the messages; and reported overall satisfaction with and positive impact from the intervention on their lives. CONCLUSION: The findings indicate the acceptability and feasibility of ToQuit and if found effective, it could be a potentially scalable first-line response to tobacco use in low resource settings. IMPLICATIONS: Our pilot RCT provides sufficient findings supporting the acceptability and feasibility of an intervention for tobacco cessation which is suitable for a context which has a shortage of healthcare workers and for individuals who use smoked or smokeless tobacco. This is critical on a background of limited contextually relevant interventions for a problem with a high burden in low- and middle- income countries such as India.

Evaluation of Feasibility and Acceptability of a Text-Messaging Intervention for Tobacco Cessation in India.

INTRODUCTION: The aim of our study was to assess the feasibility and acceptability of a brief behavioral intervention for tobacco cessation delivered via mobile phone text messaging in India. AIMS AND METHODS: We conducted an uncontrolled intervention cohort study in adult current users of tobacco. The participants received intervention messages on their mobile phones for eight weeks. We collected qualitative data about participants' perceptions of intervention delivery and receipt, acceptability, and feasibility of the intervention. The outcomes measured at 3 months post-recruitment were self-reported 7- and 28-day point-prevalence abstinence, and Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) risk categories for tobacco-low (0-3), moderate (4-26), and high (≥27). RESULTS: We recruited 26 eligible participants, and 22 completed the outcome assessments. The participants generally perceived the intervention content to be simple to access and useful in facilitating a change in tobacco use. None of the participants indicated that they wanted to discontinue receiving the intervention messages. Some suggestions for enhancing acceptability included supplementing text messaging with more intensive counseling and the use of multimedia content. Eighteen percent of participants reported abstinence in the past 7 and 28 days. A greater proportion of those who used smokeless tobacco were abstinent at follow-up compared to those who smoked (42.9% vs. 6.7%; p = .04). CONCLUSIONS: If effective, simple and low-cost mobile phone text messaging can be used to deliver interventions for tobacco use, and has the potential to be scaled up so it can be delivered to populations of smokers interested in receiving cessation support. IMPLICATIONS: Our study is an important step towards the development of a contextually relevant intervention suited for low- and middle-income countries and which is responsive to the needs of both those who use smoked and smokeless tobacco. If found to be effective, our intervention would be a scalable solution to overcome the human resource related barrier to accessing tobacco cessation services in low resource settings.

A descriptive study of hepatitis C in people who inject drugs.

BACKGROUND OBJECTIVES: The seroprevalence of the hepatitis C virus (HCV) in general population is higher than that of human immunodeficiency virus (HIV) in India. People who inject drugs (PWIDs) constitute a high-risk group for all blood-borne infections. Multiple behavioural surveillance surveys have provided a rich typology of HIV-infected PWIDs, but this information is missing for HCV infection. We describe awareness, transmission risk factors and the treatment continuum for HCV infection among PWID. We also report spatial clustering of HCV infection in PWIDs residing in Bengaluru. METHODS: Information from clinical records was collected and telephonic interviews of retrospectively identified PWIDs who received treatment at a tertiary-level addiction treatment facility between 2016 and 2021 were conducted. RESULTS: We identified 391 PWIDs; 220 (56.26%) received an anti-HCV antibody test (4 th Generation HCV-Tridot). Individuals reporting unsafe injection practices were more often tested than those who did not ( χ2 =44.9, df=1, P <0.01). Almost half of the tested and more than a quarter of the whole sample (109/220, 49.9%; 109/391, 27.9%) were seropositive for HCV infection. The projected seropositivity in this group was between 27.9 per cent (best case scenario, all untested assumed negative) and 71.6 per cent (worst case scenario, all untested assumed positive). Only a minority of participants interviewed were aware of HCV (27/183, 14.7%). HCV infection and its associated risk behaviour (PWID) were clustered in certain localities (Diggle and Chetwynd Test; P =0.001) in Bengaluru in the southern district of Karnataka. INTERPRETATION CONCLUSIONS: Undetected HCV infection is common in PWIDs; awareness and treatment uptake is poor in this group. Spatial clustering of infections in a district shows transmission in close networks and provides opportunities for targeted interventions.

Tobacco use in people with severe mental illness: Findings from a multi-country survey of mental health institutions in South Asia.

INTRODUCTION: People with severe mental illness (SMI) tend to die early due to cardiovascular and respiratory diseases, which may be linked to tobacco use. There is limited information on tobacco use in people with SMI in low- and middle-income countries where most tobacco users reside. We present novel data on tobacco use in people with SMI and their access to tobacco cessation advice in South Asia. METHODS: We conducted a multi-country survey of adults with SMI attending mental health facilities in Bangladesh, India, and Pakistan. Using data collected with a standardized WHO STEPS survey tool, we estimated the prevalence and distribution of tobacco use and assessed receipt of tobacco cessation advice. RESULTS: We recruited 3874 participants with SMI; 46.8% and 15.0% of men and women consumed tobacco, respectively. Smoking prevalence in men varied by country (Bangladesh 42.8%, India 20.1% and Pakistan 31.7%); <4% of women reported smoking in each country. Smokeless tobacco use in men also varied by country (Bangladesh 16.2%, India 18.2% and Pakistan 40.8%); for women, it was higher in Bangladesh (19.1%), but similar in India (9.9%) and Pakistan (9.1%). Just over a third of tobacco users (38.4%) had received advice to quit tobacco. Among smokers, 29.1% (n=244) made at least one quit attempt in the past year. There was strong evidence for the association between tobacco use and the severity of depression (OR=1.29; 95% CI: 1.12-1.48) and anxiety (OR=1.29; 95% CI: 1.12-1.49). CONCLUSIONS: As observed in high-income countries, we found higher tobacco use in people with SMI, particularly in men compared with rates reported for the general population in South Asia. Tobacco cessation support within mental health services offers an opportunity to close the gap in life expectancy between SMI and the general population. STUDY REGISTRATION: ISRCTN88485933; https://doi.org/10.1186/ISRCTN88485933 39.

Mental Health Programme in India: Has the tide really turned?

Mental disorders in India form a major public health concern and the efforts to tackle these dates back to four decades, by way of the National Mental Health Programme (NMHP) and its operational arm, the District Mental Health Programme (DMHP). Although the progress of NMHP (and DMHP) was relatively slower till recently, the last 4-5 years have seen rapid strides with several initiatives, including (i) expansion of DMHPs to 90 per cent of the total districts of the country, (ii) the National Mental Health Policy and (iii) strengthening the Mental Health Legislation by way of providing explicit provisions for rights of persons with mental illnesses. Among others, factors responsible for this accelerated growth include the easily accessible digital technology as well as judicial activism. Federal and State cooperation is another notable feature of this expansion. In this review, the authors summarize the available information on the evolution of implementation and research aspects related to India's NMHP over the years and provide a case for the positive turn of events witnessed in the recent years. However, the authors caution that these are still baby steps and much more remains to be done.

Quantification of Δ9-tetrahydrocannabinol in urine as a marker of cannabis abuse.

BACKGROUND OBJECTIVES: Cannabis use has long been associated with celebration and hospitality, although abuse must be confirmed through testing. It has always been difficult to develop an accurate and reliable confirmatory method for the quantification of tetrahydrocannabinol carboxylic acid (THC-COOH) that meets local requirements. The goal was to develop a rapid, cost-effective analytical technique that can handle large batches. METHODS: Because of the wide metabolite detection window and ease of collection, urine was preferable sample. The extraction of a pre-screened urine sample (adulteration and multidrug screening) was done on Bond Elut cartridges using a positive pressure vacuum manifold, followed by quantification using a gas chromatograph and mass spectrometer. RESULTS: The assay was linear between 15 and 300 ng/ml ( r2 of 0.99). The intra-day precision was 8.69 per cent and the inter-day precision was 10.78 per cent, respectively with a 97.5 per cent recovery rate for the lowest concentration. A total of 939 urine samples were examined, with 213 detecting cannabis. Sixty per cent of the total individuals tested positive for simply cannabinoids, 33 per cent for cannabinoids and sedatives, five per cent for cannabinoids and morphine and one for cannabis, morphine and cocaine. INTERPRETATION CONCLUSIONS: Assay characteristics included modest sample preparation, rapid chromatography, high specificity and small sample volume with a processing time of 12 h. The assay described here can be applied for diagnostic laboratories and in forensic settings as well.

Behavioral Activation for Comorbid Depression in People With Noncommunicable Disease in India: Protocol for a Randomized Controlled Feasibility Trial.

BACKGROUND: The increasing burden of depression and noncommunicable disease (NCD) is a global challenge, especially in low- and middle-income countries, considering the resource constraints and lack of trained human resources in these settings. Effective treatment of depression in people with NCDs has the potential to enhance both the mental and physical well-being of this population. It will also result in the effective use of the available health care resources. Brief psychological therapies, such as behavioral activation (BA), are effective for the treatment of depression. BA has not been adapted in the community health care services of India, and the feasibility of using BA as an intervention for depression in NCD and its effectiveness in these settings have not been systematically evaluated. OBJECTIVE: Our objective is to adapt BA for the Indian NCD context and test the acceptability, feasibility, and implementation of the adapted BA intervention (BEACON intervention package [BIP]). Additionally, we aim to test the feasibility of a randomized controlled trial evaluation of BIP for the treatment of depression compared with enhanced usual care. METHODS: Following well-established frameworks for intervention adaptation, we first adapted BA (to fit the linguistic, cultural, and resource context) for delivery in India. The intervention was also adapted for potential remote delivery by telephone. In a randomized controlled trial, we will be testing the acceptability, feasibility, and implementation of the adapted BA intervention (BIP). We shall also test if a randomized controlled feasibility trial can be delivered effectively and estimate important parameters (eg, recruitment and retention rates and completeness of follow-up) needed to design a future definitive trial. RESULTS: Following the receipt of approval from all the relevant agencies, the development of the BIP was started on November 28, 2020, and completed on August 18, 2021, and the quantitative data collection was started on August 23, 2021, and completed on December 10, 2021. Process evaluation (qualitative data) collection is ongoing. Both the qualitative and quantitative data analyses are ongoing. CONCLUSIONS: This study may offer insights that could help in closing the gap in the treatment of common mental illness, particularly in nations with limited resources, infrastructure, and systems such as India. To close this gap, BEACON tries to provide BA for depression in NCDs through qualified NCD (BA) counselors integrated within the state-run NCD clinics. The results of this study may aid in understanding whether BA as an intervention is acceptable for the population and how feasible it will be to deliver such interventions for depression in NCD in South Asian countries such as India. The BIP may also be used in the future by Indian community clinics as a brief intervention program. TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2020/05/025048; https://tinyurl.com/mpt33jv5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41127.

Relationship of personality, psychological distress, and substance use with social network characteristics of college going young adults.

Background: Causes of substance use are multifactorial. Factors such as personality, psychological distress, and the person's social ties contribute to the understanding of substance use problems of college students. Aim: The current study aimed to investigate the association between personality traits and psychological distress with ego-centric social networks of substance-using and non-using college students. Method: This cross-sectional descriptive study involved 902 undergraduate students from the government (n = 2) and government-aided (n = 9) colleges. The socio-demographic data sheet, Big Five Personality Inventory, Depression Anxiety and Stress Scale, and the semi-structured Ego-centric Social Network Questionnaire were used to collect data. Results: Of 902 participants, 26.9% of participants used substances. The mean score of anxiety (P < 0.002) and depression (P < 0.002) was significantly higher among the substance users compared with non-users. Agreeableness (P < 0.001) and conscientiousness (P < 0.001) scores were significantly higher among non-users. Depression (P < 0.01), anxiety (P < 0.01), and stress (P < 0.01) correlated positively with the total number of substance users in the network. Agreeableness (P < 0.01) and conscientiousness (P < 0.01) were positively correlated with parents and siblings in the network. Stress emerged as a predictor (OR 1.61, CI 1.09-3.04, P < 0.001) for considering substance users to the social network. Conclusion: Personality and psychological distress are associated with an individual's social network and significantly contribute to student substance use problems.

A study of genetic variants, genetic risk score and DNA methylation of PNPLA3 and TM6SF2 in alcohol liver cirrhosis.

BACKGROUND: Genetic and epigenetic factors are associated with the development of alcohol-associated liver disease (AALD). The single nucleotide polymorphisms (SNPs), rs738409 in Patatin-like phospholipase domain-containing protein (PNPLA3) and rs58542926 in Transmembrane 6 Superfamily Member 2 (TM6SF2) are strongly associated with AALD in different global populations, Hence, we analyzed the genetic risk score for these variants and deoxyribonucleic acid (DNA) methylation levels of the PNPLA3 and TM6SF2 genes among cases (alcohol liver cirrhosis) and controls (heavy drinkers without cirrhosis). METHOD: We studied patients with alcohol use disorder (AUD) with cirrhosis (AUD-C + ve, n = 136) and without cirrhosis (AUD-C-ve, n = 107) drawn from the clinical services of St. John's Medical College Hospital (SJMCH) (Gastroenterology and Psychiatry) and Centre for Addiction Medicine (CAM), National Institute of Mental Health and Neurosciences, (NIMHANS). Genotype data was generated for rs738409 (PNPLA3) and rs58542926 (TM6SF2) and used to calculate unweighted genetic risk score (uGRS) and weighted genetic risk scores (wGRS). DNA methylation levels were estimated by pyrosequencing at PNPLA3 and TM6SF2 loci. RESULTS: Overall we observed a significantly higher genetic risk score (weighted genetic risk score, wGRS) in individuals with alcohol use disorder compared to control population (p = < 0.01). Further, uGRS and wGRS were associated with the diagnosis of cirrhosis, even after correcting for age of onset, quantity and frequency of drinking. We also found hypomethylation at CpG2 of TM6SF2 gene in AUD-C + ve compared to AUD-C-ve (P = 0.02). CONCLUSION: We found that a genetic risk score based on SNPs in the PNPLA3 and TM6SF2 genes was significantly associated with cirrhosis in patients with AUD, suggesting a potential utility in identifying patients at risk and providing pre-emptive interventions. These may include interventions that aim to alter DNA methylation, which may be one of the mechanisms through which elevated genetic risk may influence the development of cirrhosis.

Exploring the early history of convulsive therapies at the Mysore Government Mental Hospital (currently NIMHANS).

OBJECTIVE: The paper describes the introduction, and early use of chemically and electrically induced convulsive therapies, at the Mysore Government Mental Hospital (MGMH), now the National Institute of Mental Health and Neuro Sciences, Bangalore, India. Cardiazol and ammonium chloride were used at MGMH before the introduction of electroconvulsive therapy (ECT). The study examines the early history, clinical correlates and outcome of convulsive therapies and attempts to contextualize how local conditions influenced implementation. METHOD: Three sets of archival case-records from 1938 to 1948, each of a period of 9 months following the implementation of a particular mode of convulsive therapy were reviewed. RESULTS: During the examined timeframe, 40 patients received cardiazol, 95 ammonium chloride and 50 unmodified ECT. Schizophrenia was the commonest clinical indication for convulsive therapy across all modalities of treatment. When outcomes were examined, 45%, 48.4% and 62% of patients were clinically reported to have been either cured/improved after receiving cardiazol, ammonium chloride and ECT respectively. Those receiving cardiazol had a high mortality of 22.5%, compared to 3.1% for ammonium chloride and 4% with ECT. CONCLUSIONS: Convulsive therapies were one of the first somatic psychiatric treatments, introduced around 1930s and 1940s all over the world, including in India. Our archival records suggest that many international ideas about somatic treatments were quickly adopted in India. Electroconvulsive therapy and other novel neuromodulatory interventions continue to be used and actively researched in India.

Clinical Profile, Course and Outcomes of Male Inpatients with Mental Illness Charged with Homicide: A Chart Review from an Indian Tertiary Care Hospital.

Background: The relationship between imprisonment and mental illness is bidirectional. The clinical outcomes of prisoners with mental illness have not been widely studied, especially in developing countries. This study was conducted to assess the same among male inpatients under judicial custody with charges of homicide. Methods: A retrospective chart review of male forensic ward inpatients admitted between January 1, 2003, and December 31, 2016, was conducted. Diagnosis in the files was based on the International Classification of Diseases (ICD)-10 criteria. The Clinical and Global Improvement-Severity (CGI-S) scale was used to measure the severity of illness. Mean CGI-S assessment was carried out at baseline, end of 1 year, 5 years, and 15 years. The data were analyzed using descriptive statistics, Friedman's test, and Dunn's post hoc test. Results: Schizophrenia spectrum disorders and other psychotic disorders, mood disorders, and alcohol use disorders were diagnosed in 62(49.6%), 22(17.6%), and 44(35.2%) subjects, respectively. Forty-one (32.8%) subjects had at least one readmission. The average CGI-S score for the total subjects was 5 (markedly ill) at baseline and 2 (borderline ill) at the end of their latest contact with the tertiary care hospital. For the 34 subjects (27.2%) who had follow-up information of 15 years, the average CGI-S score was 1 (normal, not at all ill) at the end of 15 years (P < 0.001). Conclusion: Clinical outcomes of prisoners with mental illness seem promising, subject to the seamless availability of services. Studies from other parts of the country are required for a more systematic understanding of the requirements of care.

Physical and chemical characterization of smokeless tobacco products in India.

The rapid proliferation of smokeless tobacco (SLT) in India has occurred without adequate information on the possible dangers and toxicity of these products. Tobacco flavors as well as nicotine (both protonated and un-protonated) are responsible for health dangers and addiction. The study aimed to offer information on the physical characteristics of commonly used smokeless tobacco products (including microscopic analysis), along with nicotine content (both total and un-protonated), pH, moisture, and flavors. The Standard Operating Procedures (SOPs) validated by the World Health Organization (WHO) recognized Tobacco Testing Laboratory TobLabNet) were applied for the analysis of various constituents of the SLTs. The microscopic analysis indicated that some of the SLT products like khaini were finely processed and available in filter pouches for users' convenience and prolonged use leading to prolonged retention and addiction potential. Nicotine absorption and availability (both protonated and un-protonated) are affected by moisture and pH. Essences provide a pleasant aroma and flavor, with an increased risk of misuse and other health problems. Few chewing tobacco and Zarda had the lowest levels of un-protonated nicotine (0.10-0.52% and 0.15-0.21%, respectively), whereas Gul, Gudhaku, and Khaini had the highest levels, ranging from 95.33 to 99.12%. Moisture and pH ranged from 4.54 to 50.19% and 5.25-10.07 respectively. Menthol (630.74-9681.42 µg/g) was the most popular flavour, followed by Eucalyptol (118.16-247.77 µg/g) and camphor (148.67 and 219.317 µg/g). SLT's health concerns and addiction dangers are exacerbated by the high proportion of bioavailable nicotine coupled with flavors. The findings of this study have important implications for the regulation and use of SLT in countries where use of SLT is prevalent.

Gender differences in the young-onset persistent delusional disorder.

We conducted a retrospective chart review to examine the gender differences in young onset Persistent Delusional Disorder (PDD) subjects (N = 236) with onset of illness before the age of 30 years. Gender differences in marital and employment status were significant (p-0.001). Delusion of infidelity and erotomania were more common in females, while males had more body dysmorphic and persecutory delusions (X2-20.45, p-0.009). Males had more substance dependence (X2-21.31, p < 0.001), as well as a family history of substance abuse and PDD (X2-18.5, p < 0.01). To conclude, gender differences in PDD comprised some psychopathology, co-morbidity, and family history among those with young onset PDD.

IMPACT smoking cessation support for people with severe mental illness in South Asia (IMPACT 4S): A protocol for a randomised controlled feasibility trial of a combined behavioural and pharmacological support intervention.

INTRODUCTION: The prevalence of smoking is high among people living with severe mental illness (SMI). Evidence on feasibility, acceptability and effectiveness of smoking cessation interventions among smokers with SMI is lacking, particularly in low- and middle-income countries. We aim to test the feasibility and acceptability of delivering an evidence-based intervention,i.e., the IMPACT smoking cessation support for people with severe mental illness in South Asia (IMPACT 4S) intervention that is a combination of behavioural support and smoking cessation pharmacotherapies among adult smokers with SMI in India and Pakistan. We will also test the feasibility and acceptability of evaluating the intervention in a randomised controlled trial. METHODS: We will conduct a parallel, open label, randomised controlled feasibility trial among 172 (86 in each country) adult smokers with SMI in India and Pakistan. Participants will be allocated 1:1 to either Brief Advice (BA) or the IMPACT 4S intervention. BA comprises a single five-minute BA session on stopping smoking. The IMPACT 4S intervention comprises behavioural support delivered in upto 15 one-to-one, face-to-face or audio/video, counselling sessions, with each session lasting between 15 and 40 minutes; nicotine gum and/or bupropion; and breath carbon monoxide monitoring and feedback. Outcomes are recruitment rates, reasons for ineligibility/non-participation/non-consent of participants, length of time required to achieve required sample size, retention in study and treatments, intervention fidelity during delivery, smoking cessation pharmacotherapy adherence and data completeness. We will also conduct a process evaluation. RESULTS: Study will address- uncertainty about feasibility and acceptability of delivering smoking cessation interventions, and ability to conduct smoking cessation trials, among adult smokers with SMI in low- and middle-income countries. CONCLUSIONS: This is to inform further intervention adaptation, and the design and conduct of future randomised controlled trials on this topic. Results will be disseminated through peer-review articles, presentations at national, international conferences and policy-engagement forums. TRIAL REGISTRATION: ISRCTN34399445 (Updated 22/03/2021), ISRCTN Registry https://www.isrctn.com/.

Hypomethylation of Long Interspersed Nucleotide Elements and Aldehyde Dehydrogenase in Patients of Alcohol Use Disorder with Cirrhosis.

Alcohol use disorder (AUD) and cirrhosis are key outcomes of excessive alcohol use, and a genetic influence in these outcomes is increasingly recognized. While 80-90% of heavy alcohol users show evidence of fatty liver, only 10-20% progress to cirrhosis. There is currently no clear understanding of the causes of this difference in progression. The aim of this study is to evaluate genetics and epigenetics at the aldehyde dehydrogenase (ALDH2) locus in patients with AUD and liver complications. Study participants were inpatients from the clinical services of Gastroenterology and Psychiatry at St. John's Medical College Hospital (SJMCH) and the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Men diagnosed as having AUD with cirrhosis (AUDC+ve, N = 136) and AUD without cirrhosis (AUDC-ve, N = 107) were assessed. FibroScan/sonographic evidence was used to rule out fibrosis in the AUDC-ve group. Genomic DNA was used for genotyping at the ALDH2 (rs2238151) locus. A subset of 89 samples was used for DNA methylation (AUDC+ve, N = 44; and AUDC-ve, N = 45) analysis at long interspersed nucleotide element 1 (LINE-1) and ALDH2 cytosine-phosphate-guanine (CpG) loci by pyrosequencing. ALDH2 DNA methylation was significantly lower in the AUDC+ve group compared with the AUDC-ve group (p < 0.001). Lower methylation was associated with a risk allele (T) of the ALDH2 locus (rs2238151) (p = 0.01). Global (LINE-1) DNA methylation levels were also significantly lower in the AUDC+ve group compared with the AUDC-ve group (p = 0.01). Compromised global methylation (LINE-1) and hypomethylation at the ALDH2 gene was observed in patients with cirrhosis compared with those without cirrhosis. DNA methylation could be explored as a biomarker for cirrhosis and liver complications.

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India.

Importance: Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. Objective: To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their underlying brain mechanisms. Design, Setting, and Participants: This multicenter population-based cohort study analyzed cross-sectional data of the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, recruited between November 4, 2016, and May 4, 2019. Participants aged 6 to 23 years were characterized using deep phenotyping measures of behavior, neuropsychology, psychopathology, brain neuroimaging, and exposure to developmental adversities and environmental neurotoxins. All analyses were performed between June 1, 2020, and December 31, 2021. Exposure: Arsenic levels were measured in urine as an index of exposure. Main Outcomes and Measures: Executive function measured using the cVEDA neuropsychological battery, gray matter volume (GMV) from T1-weighted magnetic resonance imaging, and functional network connectivity measures from resting state functional magnetic resonance imaging. Results: A total of 1014 participants aged 6 to 23 years (589 male [58.1%]; mean [SD] age, 14.86 [4.79] years) were included from 5 geographic locations. Sparse-partial least squares analysis was used to describe a negative association of arsenic exposure with executive function (r = -0.12 [P = 5.4 × 10-4]), brain structure (r = -0.20 [P = 1.8 × 10-8]), and functional connectivity (within network, r = -0.12 [P = 7.5 × 10-4]; between network, r = -0.23 [P = 1.8 × 10-10]). Alterations in executive function were partially mediated by GMV (b = -0.004 [95% CI, -0.007 to -0.002]) and within-network functional connectivity (b = -0.004 [95% CI, -0.008 to -0.002]). Socioeconomic status and body mass index moderated the association between arsenic and GMV, such that the association was strongest in participants with lower socioeconomic status and body mass index. Conclusions and Relevance: The findings of this cross-sectional study suggest that low-level arsenic exposure was associated with alterations in executive functioning and underlying brain correlates. These results indicate potential detrimental consequences of arsenic exposure that are below the currently recommended guidelines and may extend beyond endemic risk areas. Precision medicine approaches to study global mental health vulnerabilities highlight widespread but potentially modifiable risk factors and a mechanistic understanding of the impact of low-level arsenic exposure on brain development.

High craving is associated with fewer abstinent days and lesser time to relapse during treatment in severe alcohol use disorder.

Background: Craving, an integral aspect of addictive processes, underlies heavy alcohol consumption and alcohol use disorder (AUD). Western studies point out that craving is associated with relapse risks in AUD treatment. The feasibility of assessing and following up with craving dynamicity is not studied in the Indian context. Aim: We aimed to capture craving and explore its association with relapse in an outpatient facility. Methods: Among 264 treatment-seeking male participants (mean [SD] age = 36 [6.7] years) with severe AUD, craving was assessed according to the Penn Alcohol Craving Scale (PACS) at treatment initiation and two follow-up visits (median follow-up: 1, 2 weeks). Days to drink and percentage of days abstinent were acquired during the follow-ups (maximum follow-up days = 355). Those lost to follow-up were censored and considered as having relapsed. Results: High craving was associated with fewer days to drink when considered as a sole predictor (P = 0.030). With covariates including medication at treatment initiation, high craving was marginally associated with fewer days to drink (P = 0.057). Baseline craving was negatively associated with proximal percentage of days abstinent (P = 0.015) and cravings at follow-ups negatively correlated with cross-sectional abstinent days (FU1: P = 0.009, FU2: P = 0.019). Craving reduced significantly over time (P < 0.001), irrespective of the drinking status in follow-ups. Conclusion: Relapse is a real challenge in AUD. The utility of craving assessment in identifying relapse risk in an outpatient facility helps in identifying an at-risk population for future relapse. Thus better-targeted approaches in treating AUD can be developed.