Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Ongoing Use of SSRIs Does Not Alter Outcome in Hospitalized COVID-19 Patients: A Retrospective Analysis

SARS-CoV-2 continues to have devastating consequences worldwide. Though vaccinations have helped reduce spread, new strains still pose a threat. Therefore, it is imperative to identify treatments that prevent severe COVID-19 infection. Recently, acute use of SSRI antidepressants in COVID+ patients was shown to reduce symptom severity. The aim of this retrospective observational study was to determine whether COVID+ patients already on SSRIs upon hospital admission had reduced mortality compared to COVID+ patients not on chronic SSRI treatment. Electronic medical records of 9044 patients with laboratory-confirmed COVID-19 from six hospitals were queried for demographic and clinical information. Using R, a logistic regression model was run with mortality as the outcome and SSRI status as the exposure. In this sample, no patients admitted on SSRIs had them discontinued. There was no significant difference in the odds of dying between COVID+ patients on chronic SSRIs vs. those not taking SSRIs, after controlling for age category, gender, and race. This study shows the utility of large clinical databases in determining what commonly prescribed drugs might be useful in treating COVID-19. During pandemics due to novel infectious agents, it is critical to evaluate safety and efficacy of drugs that might be repurposed for treatment

Ongoing Use of SSRIs Does Not Alter Outcome in Hospitalized COVID-19 Patients: A Retrospective Analysis.

SARS-CoV-2 continues to have devastating consequences worldwide. Though vaccinations have helped reduce spread, new strains still pose a threat. Therefore, it is imperative to identify treatments that prevent severe COVID-19 infection. Recently, acute use of SSRI antidepressants in COVID+ patients was shown to reduce symptom severity. The aim of this retrospective observational study was to determine whether COVID+ patients already on SSRIs upon hospital admission had reduced mortality compared to COVID+ patients not on chronic SSRI treatment. Electronic medical records of 9044 patients with laboratory-confirmed COVID-19 from six hospitals were queried for demographic and clinical information. Using R, a logistic regression model was run with mortality as the outcome and SSRI status as the exposure. In this sample, no patients admitted on SSRIs had them discontinued. There was no significant difference in the odds of dying between COVID+ patients on chronic SSRIs vs. those not taking SSRIs, after controlling for age category, gender, and race. This study shows the utility of large clinical databases in determining what commonly prescribed drugs might be useful in treating COVID-19. During pandemics due to novel infectious agents, it is critical to evaluate safety and efficacy of drugs that might be repurposed for treatment

Mild-to-Moderate Traumatic Brain Injury: A Review with Focus on the Visual System

Traumatic Brain Injury (TBI) is a major global public health problem. Neurological damage from TBI may be mild, moderate, or severe and occurs both immediately at the time of impact (primary injury) and continues to evolve afterwards (secondary injury). In mild (m)TBI, common symptoms are headaches, dizziness and fatigue. Visual impairment is especially prevalent. Insomnia, attentional deficits and memory problems often occur. Neuroimaging methods for the management of TBI include computed tomography and magnetic resonance imaging. The location and the extent of injuries determine the motor and/or sensory deficits that result. Parietal lobe damage can lead to deficits in sensorimotor function, memory, and attention span. The processing of visual information may be disrupted, with consequences such as poor hand-eye coordination and balance. TBI may cause lesions in the occipital or parietal lobe that leave the TBI patient with incomplete homonymous hemianopia. Overall, TBI can interfere with everyday life by compromising the ability to work, sleep, drive, read, communicate and perform numerous activities previously taken for granted. Treatment and rehabilitation options available to TBI sufferers are inadequate and there is a pressing need for new ways to help these patients to optimize their functioning and maintain productivity and participation in life activities, family and community

Toxic External Exposure Leading to Ocular Surface Injury

The surface of the eye is directly exposed to the external environment, protected only by a thin tear film, and may therefore be damaged by contact with ambient particulate matter, liquids, aerosols, or vapors. In the workplace or home, the eye is subject to accidental or incidental exposure to cleaning products and pesticides. Organic matter may enter the eye and cause infection. Ocular surface damage can trigger a range of symptoms such as itch, discharge, hyperemia, photophobia, blurred vision, and foreign body sensation. Toxin exposure can be assessed clinically in multiple ways, including via measurement of tear production, slit-lamp examination, corneal staining, and conjunctival staining. At the cellular level, environmental toxins can cause oxidative damage, apoptosis of corneal and conjunctival cells, cell senescence, and impaired motility. Outcomes range from transient and reversible with complete healing to severe and sight-compromising structural changes. Classically, evaluation of tolerance and safety was carried out using live animal testing; however, new in vitro and computer-based, in silico modes are superseding the gold standard Draize test. This review examines how environmental features such as pollutants, temperature, and seasonality affect the ocular surface. Chemical burns to the eye are considered, and approaches to protect the ocular surface are detailed

Long COVID, the Brain, Nerves, and Cognitive Function

SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may arise from a virus-induced hypercoagulable state. COVID-19 may incite changes in brain function with a wide range of lingering symptoms. Patients often experience fatigue and may note brain fog, sensorimotor symptoms, and sleep disturbances. Prolonged neurological and neuropsychiatric symptoms are prevalent and can interfere substantially in everyday life, leading to a massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection causes neurological sequelae are an important subject of ongoing research. Inflammation- induced blood-brain barrier permeability or viral neuro-invasion and direct nerve damage may be involved. Though the mechanisms are uncertain, the resulting symptoms have been documented from numerous patient reports and studies. This review examines the constellation and spectrum of nervous system symptoms seen in long COVID and incorporates information on the prevalence of these symptoms, contributing factors, and typical course. Although treatment options are generally lacking, potential therapeutic approaches for alleviating symptoms and improving quality of life are explored