Combined Addiction and Neurobiological Targets: An In Silico Analysis of Areca Nut and Areca Nut with Tobacco Biomolecules.

BACKGROUND: The addictive potential of areca nut (AN) and tobacco is well-documented, but their combined neurobiological effects in AN-containing tobacco products (ANTP) remain obscure. This study employed a three-stage in silico approach to investigate the potential targets and pathways associated with the addictive properties of AN alone and in ANTP. MATERIALS AND METHODS: Bioactive molecules were retrieved for AN and tobacco, followed by target prediction and pathway enrichment analysis. The identified biomolecules were categorized into AN and ANTP groups. RESULTS: A total of 195 bioactive molecules were identifid (38 to AN, 157 to tobacco). Absorption, distribution, metabolism, and excretion (ADME) details were retrieved. Predicted bioactivity (gene/protein interaction probability ≥80%) was analysed, revealing 13 shared targets between AN and tobacco, 12 exclusive to AN, and 33 exclusive to tobacco. AN and ANTP influenced 21 and 27 pathways (FDR ≤ 0.05), respectively, with distinct footprints. Notably, GABAergic and cholinergic synapses, nicotine addiction, calcium signaling, and morphine addiction pathways were differentially enriched between AN and ANTP. DISCUSSION: This study highlights the distinct and synergistic neurobiological effects of AN and tobacco in ANTP. The identified differences in target genes and pathways underscore the need for tailored interventions and cessation strategies for users of AN and ANTP products. Further research is warranted to validate these findings, explore interplay between diverse addiction factors, and develop effective prevention and treatment programs. (Neuropsychopharmacol Hung 2024; 26(3): 133-143)

Exploring the incidence and etiopathogenesis of pathological yawning as adverse side effect of psychotropic drugs.

INTRODUCTION: Yawning is a normal, stereotyped physiological event in humans and animal kingdom. When excessive (>3 per 15 minutes), it is termed as pathological yawning (PY). PY could be due to many causes but more commonly associated with side-effect of drugs, notably involving those used in psychopharmacology. Though there are isolated case reports and case-series, there are no large-scale reports of PY. This work attempted to address this lacuna. MATERIAL AND METHODS: The current work attempted to identify characteristics of PY as collated from adverse drug effect databases of Australia (Database of Adverse Event Notifications), Canada (Canada Vigilance Adverse Reaction Online Database) and the United States of America (FDA Adverse Event Reporting System - FAERS). These databases collect and provide public access to reports of adverse events related to drugs and therapeutic goods. They act as a prime pharmacovigilance tool as well as a first-line resource for healthcare professionals, researchers, and the public to monitor the safety of these products and make informed decisions. In the first week of June 2023, open access, unrestricted adverse effect of drug databases were explored, using the word "YAWNING" as the only search term for the side effect of any drug without any restrictions. The collected details of PY cases with their gender, age, reason for drug use, other concomitant complaints as well as the nature of adverse event(s) and its treatment requirements were assessed. Descriptive statistics were used. RESULT: Of the 2655 instances in USA database, 398(15%) had more than 1 suspect drug and in total 578 medications involved. The most commonly involved drugs were apomorphine, sertraline, fluoxetine and paroxetine. In all 341(12.8%) cases reported of YAWN alone or with one another sleep disorder, the most common off ending drug were fluoxetine hydrochloride. DISCUSSION AND CONCLUSION: The neural mechanism and physiology of yawning are explained. This study stresses that a health care professional, particularly mental health professionals and neurologists, should be aware of the importance of PY to deliver the best for the patients under their care. (Neuropsychopharmacol Hung 2023; 25(4): 194-205)

Statewide Survey of Psychological Distress Among People of Tamil Nadu in the COVID-19 Pandemic.

BACKGROUND: COVID-19-driven pandemic has caused panic, fear, and stress among all strata of society. The study aimed to assess stress and the factors that influence it in a representative population in the state of Tamil Nadu (TN)-a state in the southern India where the levels of stress have not been measured yet. METHODS: From April 13 to April 25, 2020, we conducted an online survey among the TN population using the snowball sampling technique, collecting basic demographic data. COVID-19-perceived stress was collected through COVID-19 Peritraumatic Distress Index (CPDI). Binomial regression analysis was used to identify the extent of the relationship between CPDI and sociodemographic factors by estimating the odds of having significant stress. P ≤ 0.05 was considered significant. RESULTS: A total of 2,317 valid responses were received. Of the respondents, 830 (35.82%) were males, 1,084 (46.79%) were below 25 years of age, and 2,297 (99.14%) were native residents of TN. The mean(±SD) CPDI was 20.66±12.03. While 1,830 (77.2%) respondents had low or no stress, 478 (20.2%) had mild to moderate stress, and 63 (2.7%) had severe stress. The bivariate model included marital status, age, nativity, and income. The odds of having significant stress (mild-moderate or severe) for a 25-34 year age group as compared to >55 years group was 2.38 (P < 0.001). As compared to widowed, the married had higher odds ratio (3.41, P = 0.05). Compared to those with >10 lakh annual income, those with 2.5-5 lakhs annual income had odds ratio of 1.65 (95% CI = 1.01 to 2.7, P = 0.05). CONCLUSIONS: During the lockdown due to COVID-19, every 1 in 5 TN population had some form of stress, as measured by CPDI. Our model identified certain factors driving the stress, which would help policy framers to initiate an appropriate response.

Salivary Flow Alteration in Patients Undergoing Treatment for Schizophrenia: Disease-Drug-Target Gene/Protein Association Study for Side-effects.

BACKGROUND: Salivary flow alteration (SA), is a known unwarranted effect of schizophrenic medications. It manifest either as reduced (xerostomia) or increased (sialorrhea) SA, among treated schizophrenic patients. It is believed that the SA is due to action of the drugs/disease process involving the muscarinic receptor-3 to process acetyl choline, the common neurotransmitter. The genetic mediation behind the SA in such patients remains largely unexplored. We aimed to address the same by using curated literary databases to identify such relationship, if any existed. MATERIAL AND METHODS: Curated databases of Gene-Disease Association, www.DisGeNet.org and www.networkanalyst.ca were effectively used to identify the probable genes, strength of association and the drug-genes pathway that could be possibly be involved. The genes associated with schizophrenia and SA were analyzed in detail. Protein-Protein interaction (PPI) network proven experimentally in humans were used to identify the missing or unreported links. RESULTS: In all 28 genes associated with schizophrenia were linked to SA. The genetic network of schizophrenia and xerostomia involved FGFR2 gene prominently and network module was statistically significant (P = 9.87*10-8) was achieved that had xerostomia as a node, while schizophrenia (P = 0.025) had statistical significance. Sialorrhea had no statistical significance (P = 0.555). When schizophrenia and sialorrhea connections were analyzed for genetic interaction, only gene GCH1 emerged. On combining the three disease entities, the association of TAC1 gene with sialorrhea was also identified. Using PPI, the coordination of CHRM3, TAC1 and GPRASP1 gene were identified. This network involved several genes that has significant influence on calcium signaling pathway (P = 7.74*10-16), cholingeric synapse(P = 6 × 10-4), salivary secretion(P = 4.38*10-3), endocytosis(P = 8.23*10-4), TGFß signaling pathway(P = 0.0031), gap junction (P = 4.08*10-3) and glutamergic synapse(P = 6.4*10-3). The involvement of G-receptor signaling protein product, GNAQ was established. DISCUSSION AND CONCLUSION: The possible genetic pathway of SA in schizophrenic patients are discussed in light of pharmacotherapeutics. Using the knowledge effectively would help to increase the quality of life of schizophrenic besides increasing the understanding to use saliva as a biomarker of prognosis of schizophrenia and its drug effects.

An Audit of Indian Health Insurance Claims for Mental Illness from Pooled Insurance Information Bureau's Macroindicator Data.

INTRODUCTION: Information on the social and voluntary insurance coverage of mental illness in India is scarce. We attempted to address this lacuna, utilizing a secondary macrodata approach for 3 years. Mental illness per se is not covered by most of existing Indian health insurance policies. MATERIALS AND METHODS: Publicly available de-identified claim macrodata for all health (nonlife) insurance for Indian financial year from 2011-2012 to 2013-2014 were collected. The age group, gender, amount of claims, proportion of claims, and details of number of days of hospitalization were collected and analyzed. Descriptive statistics, Chi-square test, and Wilcoxon tests were used appropriately. P ≤ 0.05 was considered statistically significant. RESULTS: In 2011-2012, there were 2864 claims from the registered 2,591,781 members citing mental illness (0.11%) which decreased to 0.03% in 2012-2013 and marginally rose to 0.07% of all claims. The total amount of claims paid for mental illness was Rs. 51.7 millions in 2011-2012, Rs. 97.2 million in 2012-2013, and Rs. 150 million in 2013-2014. Statistically significant difference emerged in terms of age group, gender, amount and proportion of claim, and number of days of hospitalization. CONCLUSION: The penetration of health insurance is low and claim for mental illness remains low. The difference in patterns of age, gender, amount of claims, and number of days for mental illness provides detailed relevant information to formulate future policies.

Influence of legislations and news on Indian internet search query patterns of e-cigarettes.

BACKGROUND: There is a paucity of data on the use of electronic nicotine delivery systems (ENDS) in India. In addition, the Indian internet search pattern for ENDS has not been studied. We aimed to address this lacuna. Moreover, the influence of the tobacco legislations and news pieces on such search volume is not known. Given the fact that ENDS could cause oral lesions, these data are pertinent to dentists. METHODS: Using a time series analysis, we examined the effect of tobacco-related legislations and news pieces on total search volume (TSV) from September 1, 2012, to August 31, 2016. TSV data were seasonally adjusted and analyzed using time series modeling. The TSV clocked during the month of legislations and news pieces were analyzed for their influence on search pattern of ENDS. RESULTS: The overall mean ± standard deviation (range) TSV was 22273.75 ± 6784.01 (12310-40510) during the study with seasonal variations. Individually, the best model for TSV-legislation and news pieces was autoregressive integrated moving average model, and when influence of legislations and news events were combined, it was the Winter's additive model. In the legislation alone model, the pre-event, event and post-event month TSV was not a better indicator of the effect, barring for post-event month of 2nd legislation, which involved pictorial warnings on packages in the study period. Similarly, a news piece on Pan-India ban on ENDS influenced the model in the news piece model. When combined, no "events" emerged significant. CONCLUSIONS: These findings suggest that search for information on ENDS is increasing and that these tobacco control policies and news items, targeting tobacco usage reduction, have only a short-term effect on the rate of searching for information on ENDS.

Ideological Cause and Hero Worship Related Suicides: Indian Perspective and Changing Trends During 2001-2014: An Exploratory Study.

BACKGROUND: Of the various causes of suicides in India, very less number commit it for an ideological cause or due to hero worship (IHW). The prevalence and changing trends in IHW suicides are not much discussed. An attempt is made to draw attention to this subset of suicides during 2001-2014. MATERIALS AND METHODS: Accessible data from the National Crime Bureau Records in open domain was employed for this study. As only whole sum numbers associated with state, age groups, and genders and years were only available parameters, descriptive statistics of rate of suicides, linear trend with age groups, gender, and geographical divisions are presented. RESULTS: In 14 years period, 1,721,946 suicides with an average of 122,996 suicides per year were observed. In total, a sum of 2395 IHW related suicides was noted accounting an average 171 suicides per year was observed. The difference among genders and age group with respect to various parts of India is presented. Southern India and in particular, Tamil Nadu consistently had the highest IHW related suicides. DISCUSSION: The possible causes behind this unique phenomenon, cultural ethos, and implication are presented. In addition, the implication of changing trends in terms of geographical distribution, age group distribution, and gender dynamics are presented and discussed.

A study on suicide among Indians living with cancer during 2001-2014.

BACKGROUND: A small subset of Indian people living/diagnosed with cancer commits suicide. The prevalence and changing trends in such cancer-related suicides are not much reported in literature. An attempt is made to address this subset of suicides during 2001-2014. MATERIALS AND METHODS: Data for this study were collected from the Indian National Crime Bureau Record, cancer registry publication in open domain, and published literature. Trends in the number of suicides associated with state, age groups, genders, and years were the only available parameters. Using these data, descriptive statistics of the rate of suicides, linear trend with age groups, gender, and geographical divisions are presented. RESULTS: During the study period of 14 years, 1,721,946 suicides with an average of 122,996 suicides per year were observed. One in five suicides was related to illness. In total, a sum of 10,421 cancer-related suicides were noted accounting a mean of 744 suicides per year. Males were commonly involved than females. The commonly involved age group was 45-59 years. Southern parts of India had more instances of cancer-related suicides. Among Indian states, West Bengal reported the highest of such instances. DISCUSSION: Suicide trends among Indians living with cancer during 2001-2014 are presented. The possible causes behind this phenomenon and implications are presented. The effect of changes in the trends in terms of geographical distribution, age group distribution, and gender dynamics is presented and discussed in this context. CONCLUSION: Suicide among PLWC is a multi-dimensional, complex phenomenon, orchestrated by several factors, including mental health. The nascent field of psycho-oncology in India needs to explore this through large scale validated studies.

Contribution of Indian Psychiatrists to PubMed Listed Mental Health Literature During 1995-2013: an Exploratory Study.

INTRODUCTION: Contribution of Indian Psychiatrists as publications in peer-reviewed journals listed with PubMed and their impact has not been studied. The aim of this manuscript is to assess such contribution using a new article level metric measure. The relative citation ratio (RCR) has been used to assess the quality, quantity, and impact of research output of Indian Psychiatrists. MATERIALS AND METHODS: Publications by Indian psychiatrists in PubMed during 1995-2013 were collected, their RCR and associated factors estimated. The nationality of the journals, type of manuscripts, PubMed Central (PMC) visibility and the type of the journals were factored in. The data collected was analyzed. Descriptive statistics, Chi-square tests, correlations, and linear regression were performed. P ≤ 0.05 was taken as significant. RESULTS: Using the criteria set, 1914 manuscripts were identified. Of the 1914 manuscripts, 1007 were cited at least once and among this, 40.7% were listed with PubMed while of the 907 non-PMC listed manuscripts, only 180 were never cited (P = 0.000). Of the 1032 manuscripts published in Indian journals, 474 were never cited while 214 of the manuscripts published with non-India based journals were never cited even once (P = 0.000). DISCUSSION: The difference in terms of manuscripts visibility in PMC, nationality of journals and article type in analysis indicate that there exists an innate difference between the cited and noncited manuscripts. The probable explanation behind this and its associated phenomenon are discussed.

Employability of mentally ill persons in India: A self-report-based population study.

INTRODUCTION: The employment status of mentally ill patients is a reflection of their productivity, control of illness besides providing therapeutic benefits and integration into mainstream society. Owing to the associated stigma, self-reporting of mental illness (SRMI) often is rare. Census exercise of India in 2011 provides an insight of SRMI and employment status of such people. This study was undertaken to consider the role of gender, age group, and place on the employment status of SRMI. METHODOLOGY: Frequency of SRMI, age group, gender, and employment status was gathered from Indian 2011 census sources. Descriptive statistics and logistic regression were employed. P ≤ 0.05 was taken as significant. RESULTS: Majority (68.6%) of the SRMI people resides in rural areas, in the economically productive age group of 15-59 years (75.88%) and often males (57.51%). Of the SRMI as reported in the data, 78.62% were not employed while 2.4% of them were currently employed. The employability frequency distributions of SMRIs were statistically different in terms of area, age group, and gender with significance. DISCUSSION: Although the mental illness data of 2011 census was rejected by mental health professionals citing discrepancy and underestimating of the prevalence of mental illness, it provides a robust estimate of the employability, self-reporting tendency of mental illness. The association of the factors provides a unique insight into SRMIs in India. CONCLUSION: Understanding the interplay of factors may yield robust estimates and clues for policy framers to formulate employment-related policies for employment opportunities for mentally ill patients.

Using smartphone video "selfies" to monitor change in toothbrushing behavior after a brief intervention: A pilot study.

BACKGROUND: Attempts to refine toothbrushing (TB) technique, an ingrained habit in adults, can meet with some challenges. Recently, the role of proactive interference as a barrier to improving the learning of proper brushing has been proposed. This pilot feasibility study was designed to investigate TB behavior and to see how it changes after training. Smartphone video "selfies" (SPVSs) are increasingly being used in the medical field to assess, monitor, and determine the progression of diseases. MATERIALS AND METHODS: We used SPVS to study TB skills in a small sample of volunteers. Over a period of 14 days, after a one-time group training session, we observed TB behavior of volunteers using self-captured SPVS. RESULTS: Following the brief intervention, we observed an 8% of improvement in TB skills. DISCUSSION: To the best of our knowledge, this is the first report using SPVS to study TB behavior. We demonstrated initial feasibility of using SPVS in the dental setting. We observed modest improvements in toothbrushing accuracy and quality, and we generated important experiences about the use of Selfies for TB monitoring and intervention, and some interesting insights about where in the toothbrushing is more or less effective. CONCLUSION: Further investigation using a larger sample size is needed to thoroughly assess the effectiveness of this approach to improve TB skills and better understand the role of proactive interference.

Drilling Deeper into tooth brushing skills: Is proactive interference an under-recognized factor in oral hygiene behavior change?

Proper tooth brushing is a seemingly simple motor activity that can promote oral health. Applying health theories, such as the Information-Motivation-Behavioral Skills (IMB) model, Motivational Interviewing (MI) and Integrated Health Coaching (IHC), may help optimize tooth brushing technique in those with suboptimal skills. Some motor activities, including tooth brushing, may over time become rote and unconscious actions, such that an existing habit can inhibit new learning, i.e., exert proactive interference on learning the new skill. Proactive interference may impede the acquisition of new tooth brushing skills; thus, in this report, we: (1) Review how the habit of tooth brushing is formed; (2) Postulate how proactive interference could impede the establishment of proper tooth brushing retraining; (3) Discuss the merits of this hypothesis; and (4) Provide guidance for future work in this topic within the context of an approach to behavior change that integrates IMB, MI and IHC methodology.