Therapeutic potential of GHSR-1A antagonism in alcohol dependence, a review.

Growth hormone secretagogue receptor type 1A (GHSR-1A) is a functional receptor of orexigenic peptide ghrelin and is highly expressed in mesolimbic dopaminergic systems that regulate incentive value of artificial reward in substance abuse. Interestingly, GHSR-1A has also shown ligand-independent constitutive activity. Alcohol use disorder (AUD) is one of the growing concerns worldwide as it involves complex neuro-psycho-endocrinological interactions. Positive correlation of acylated ghrelin and alcohol-induced human brain response in the right and left ventral striatum are evident. In the last decade, the beneficial effects of ghrelin receptor (GHSR-1A) antagonism to suppress artificial reward circuitries and induce self-control for alcohol consumption have drawn significant attention from researchers. In this updated review, we summarize the available recent preclinical, clinical, and experimental data to discuss functional, molecular actions of central ghrelin-GHSR-1A signaling in different craving levels for alcohol as well as to promote "GHSR-1A antagonism" as one of the potential therapies in early abstinence.

A Primer on the Evolution of Aducanumab: The First Antibody Approved for Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia with global burden projected to triple by 2050. It incurs significant biopsychosocial burden worldwide with limited treatment options. Aducanumab is the first monoclonal antibody recently approved by the US-FDA for mild AD through the accelerated approval pathway. It is the first molecule to be approved for AD since 2003 and carries with it a therapeutic promise for the future. As the definition of AD has evolved from a pathological entity to a Clinico-biological construct over the years, the amyloid-ß (Aß) pathway has been increasingly implicated in its pathogenesis. The approval of Aducanumab is based on reduction of the Aß load in the brain, which forms a surrogate marker for this pathway. The research populace has, however, been globally divided by skepticism and hope regarding this approval. Failure to meet clinical endpoints in the trials, alleged transparency issues, cost-effectiveness, potential adverse effects, need for regular monitoring, and critique of 'amyloid cascade hypothesis' itself are the main caveats concerning the antibody. With this controversy in background, this paper critically looks at antibody research in AD therapeutics, evidence, and evolution of Aducanumab as a drug and the potential clinical implications of its use in future. While the efficacy of this monoclonal antibody in AD stands as a test of time, based on the growing evidence it is vital to rethink and explore alternate pathways of pathogenesis (oxidative stress, neuroinflammation, cholesterol metabolism, vascular factors, etc.) as possible therapeutic targets that may help elucidate the enigma of this complex yet progressive and debilitating neurodegenerative disorder.

Physician assisted suicide in dementia: A critical review of global evidence and considerations from India.

BACKGROUND: Dementias are a group of gradually progressing neurodegenerative conditions, leading to significant impairment in cognition, functioning, decision-making, capacity and autonomy. With the rise of human rights and patient-centred perspectives in psychogeriatric management, physician-assisted suicide (PAS) has emerged as an important and integral part of end-of-life care in advanced dementias. METHODS: With only few original studies in the area, this paper takes a narrative and critical approach to review the global legislations, treatment decisions, debates as well as perspectives from patients, families and medical professionals. RESULTS: PAS and euthanasia are legally allowed in countries like Belgium, Netherlands, Switzerland and few states of the United States (U.S.). Germany has fewer clearer legislations in this regard. The Oregon state requirement and care criteria of the Dutch euthanasia act form the basis of most such laws. Even in the presence of these provisions, PAS is fraught with multiple medical, ethical, moral and legal dilemmas and physicians as well as caregivers are quite heterogenous in their outlook. While right to live with dignity and need to end incurable suffering form the main arguments for PAS, several arguments against it are possibility of undue influence, impaired judgement leading to biased decision-making such as depression and suicidality, inappropriate assessment of capacity, and that all deaths are not necessarily painful. These dilemmas are critically discussed in light of autonomy, decision-making and advanced directives in people living with dementia as well as the rationality of ending life and 'right to live vs right to die'. Based on the findings, certain balanced strategies are highlighted for the health professionals. CONCLUSION: The 'slippery slope' of PAS needs to be carefully evaluated from a social justice and human rights perspective to improve dignified end-of-life care in dementia. Considerations are also discussed from India, a rapidly-ageing nation with no current provisions for PAS.

Perceived stress, marital satisfaction, and sexual satisfaction in spouses of males having bipolar disorder with and without alcohol use disorder: A cross-sectional study.

BACKGROUND: Bipolar affective disorder (BPAD) and alcohol use disorder (AUD) are frequently comorbid and affect the social, occupational, and personal domains of patients and their spouses. AIM: This cross-sectional study was conducted to assess and compare the levels of stress, marital satisfaction, and sexual satisfaction between the spouses of males with BPAD + AUD and of those without AUD. MATERIALS AND METHODS: Spouses of 100 males with diagnosed BPAD, currently in remission, including fifty patients having comorbid AUD, were recruited as participants. Participants were assessed with Perceived Stress Scale-10, Dyadic Adjustment Scale, and Sexuality Scale. STATISTICAL ANALYSIS: Descriptive statistics, Chi-square, t-test, analysis of variance, and correlation on SPSS were used for statistical analysis. RESULTS: More stress (59%), poorer marital (53%) and sexual satisfaction (89%) were found in the majority participants, with significantly higher stress in the group with husbands having both BPAD + AUD (P < 0.01). Duration of cohabitation had a direct, and education and family income had inverse relations with stress. CONCLUSIONS: BPAD worsens stress, marital satisfaction, and sexual satisfaction in the study participants, the stress increasing further with comorbid AUD. Education, family income, and duration of cohabitation have a significant bearing on stress.

COVID-19 Vaccination: crucial roles and opportunities for the mental health professionals.

Besides addressing the increased prevalence of psychiatric disorders, social challenges, and building community resilience during the crisis, mental health professionals (MHPs) are in a unique position to assist the vaccination drive against coronavirus disease-2019 (COVID-19) in various nations. Vaccination programs are adversely affected by misinformation, fake news and vaccine hesitancy fuelled by social media. MHPs can enable this vital public health strategy by prioritizing vaccination for individuals with severe mental illness (SMI) and substance use disorders, promote awareness and public education, debunk misinformation and integrate psychosocial care into the vaccination drives. In order to target the health inequity and discrimination faced by people with SMI coupled with their additional risks, the authors urge the global mental health fraternity to tailor these crucial roles with respect to COVID-19 vaccination based on the regional needs and contexts.

Heavy Metals in Indian Traditional Systems of Medicine: A Systematic Scoping Review and Recommendations for Integrative Medicine Practice.

Introduction: Ayurveda and Siddha are two important components of the traditional Indian medicine (TIM). The regulatory mechanisms have been insufficient, and heavy metal toxicity with TIM preparations continues to be a public health nuisance, putting integrated medicine practice in jeopardy. The current study was undertaken to review the potential health hazards of the heavy metal content in the TIM and formulate patient-safety recommendations for integrative medical practice. Materials and Methods: Systematic MEDLINE searches were performed using a combination of relevant MeSH terms and keywords, and case report/series of Ayurveda or Siddha-induced heavy metal toxicity, published in the previous two decades, were included. Risk of bias was assessed with the tool by Murad et al. Results: A total of 220 cases (51 case reports and 14 case series) were found (lead, n = 156; arsenic, n = 11; mercury, n = 47; thallium, n = 1; gold, n = 1; combination of heavy metals, n = 4) after screening for the inclusion and exclusion criteria. Among them, 169 (76.8%) had a low risk of bias, 113 (out of 135 [83.7%] analyzed) contained higher-than-permissible heavy metal content in the drug samples, and the majority showed elevated biological levels of the heavy metals in the body. Conclusion: The heavy metals in TIM are often the result of adulteration or improper manufacturing and prescribing practices, despite national and international guidelines recommending quality standards and protocols for preparing and dispensing TIM. We thus propose multipronged approaches and provide recommendations at various levels, including individual, institutional, national policy decisions essential to establish patient safety of TIM.