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Rubin, L. H.

Publications and source records attributed to Rubin, L. H..

2 recordsLinked to original sources

Social Stress Alters Immune Response and Results in Higher Viral Load During Acute SIV Infection in a Pigtailed Macaque Model of HIV

While social distancing is a key public health response during viral pandemics, social stress, which can be induced by social isolation, has been implicated in adverse health outcomes in general1 and in the context of infectious disease, such as HIV2,3. A comprehensive understanding of the direct pathophysiologic effects of social stress on viral pathogenesis is needed to provide strategic and comprehensive care to patients with viral infection. To determine the effect of social stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly and socially housed SIV-infected pigtailed macaques (Macaca nemestrina). Singly housed macaques had a higher viral load in the plasma and cerebrospinal fluid and demonstrated greater CD4 T cell declines and greater CD4 and CD8 T cell activation compared to socially housed macaques throughout acute infection. These data demonstrate that social stress directly impacts the pathogenesis of acute HIV infection and imply that social stress may act as an integral variable in the progression of HIV infection and potentially of other viral infections.

microbiology

Risperidone-induced changes in DNA methylation from peripheral blood in first-episode schizophrenia parallel neuroimaging and cognitive phenotype

Today, second generation anti-psychotics such as clozapine and risperidone are the favored treatment for schizophrenia. Yet, the absence of relevant biomarkers that can decode their neurobiological effect shackles our ability to accurately predict and track response to treatment. While researchers have investigated DNA methylation as a biomarker for schizophrenia risk, none have performed a systematic analysis of the effect of antipsychotics upon DNA methylation. We hypothesize that disease-related methylation changes occur before treatment, and that acute antipsychotic treatment may affect DNA methylation. We designed a longitudinal DNA methylation study to estimate risperidones effect on DNA methylation and how changes in DNA methylation might influence risperidones therapeutic effect on behavioral and neuroimaging phenotypes. Thirty-eight patients with first-episode drug-naive schizophrenia (FES) and 38 demographically-matched individuals (healthy controls) participated. We identified brain related pathways enriched in 8,204 FES-associated methylation sites. Risperidone administration altered methylation in 6,143 CpG DNA sites. Post-treatment FES associated with methylation in 6760 CpG sites. Majority of the DNA methylation changes were treatment effect in the overall CpG sites, the FES associated CpG sites, and risperidone associated CpG sites, except for the post-treatment FES associated CpG sites. There were 590 DNA methylation cites normalized by risperidone treatment. The methylation changes of these 590 CpG sites were related to alterations in symptom severity, spontaneous neurophysiological activity, and cognitive function. To our knowledge, this is the first longitudinal methylation study of drug treatment effect and side effect in psychiatric disorders to include parallel studies of neuroimaging and cognitive phenotypes. We identified FES-associated CpG sites not confounded by drug treatment as potential SCZ biomarkers. The normalization effect of risperidone monotherapy suggests that DNA methylation changes may serve as a predictive biomarker for treatment effect. The constructed methylation-phenotype network revealed a relationship between methylation and a wide range of biological and psychological variables.

pharmacology and toxicology