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Papers of the Week

Papers: 15 Jun 2024 - 21 Jun 2024

2024 Jun 15

Mol Psychiatry


The single-cell opioid responses in the context of HIV (SCORCH) consortium.


Ament SA, Campbell RR, Lobo MK, Receveur JP, Agrawal K, Borjabad A, Byrareddy SN, Chang L, Clarke D, Emani P, Gabuzda D, Gaulton KJ, Giglio M, Giorgi FM, Gok B, Guda C, Hadas E, Herb BR, Hu W, Huttner A, Ishmam MR, Jacobs MM, Kelschenbach J, Kim DW, Lee C, Liu S, Liu X, Madras BK, Mahurkar AA, Mash DC, Mukamel EA, Niu M, O'Connor RM, Pagan CM, Pang APS, Pillai P, Repunte-Canonigo V, Ruzicka WB, Stanley J, Tickle T, Tsai SA, Wang A, Wills L, Wilson AM, Wright SN, Xu S, Yang J, Zand M, Zhang L, Zhang J, Akbarian S, Buch S, Cheng CS, Corley MJ, Fox HS, Gerstein M, Gummuluru S, Heiman M, Ho YC, Kellis M, Kenny PJ, Kluger Y, Milner TA, Moore DJ, Morgello S, Ndhlovu LC, Rana TM, Sanna PP, Satterlee JS, Sestan N, Spector SA, Spudich S, Tilgner HU, Volsky DJ, White OR, Williams DW, Zeng H


Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.