Adversity in early life and pregnancy are immunologically distinct from total life adversity: macrophage-associated phenotypes in women exposed to interpersonal violence

• Type of Material: Article
• Authors: Kirstin Aschbacher, University of California, San Francisco; Melissa Hagan, University of California, San Francisco; Iris M Steine, University of California, Berkeley; Steven Cole, Emory University; Luisa Rivera, Emory University; Alyssa Baccarella, Columbia University; Elissa S Epel, University of California, San Francisco; Alicia Lieberman, University of California, San Francisco; Nicole R Bush, University of California, San Francisco
• Language: English
• Date: 2021-07-20
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41398-021-01498-1
• Title of Journal or Parent Work: Translational Psychiatry
• Volume: 11
• Grant/Funding Information: Dr. Bush is the Lisa and John Pritzker Distinguished Professor of Developmental and Behavioral Health and receives support from the John and Lisa Pritzker Family Foundation.; The research was supported by awards from the SAMHSA Grant Number 5U79SM080030 (PI Alicia Lieberman) and from the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 TR000004 to (sub PI Nicole Bush).; Additional support was provided by the JPB Research Network on Toxic Stress funded by the JPB Foundation of New York (PIs W. Thomas Boyce and Nicole Bush), the Institute for Integrative Health (TIIH; PI Kirstin Aschbacher), and the Robert Wood Johnson Foundation Health Disparity Seed Grant (M Hagan).; The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript; its contents are solely the responsibility of the authors and do not necessarily represent the official views of the funders.
• Keywords: Predictive markers; Physiology; Human behaviour
• Research Categories: Psychology, Behavioral; Health Sciences, Mental Health; Anthropology, Medical and Forensic

Abstract

Early childhood and pregnancy are two sensitive periods of heightened immune plasticity, when exposure to adversity may disproportionately increase health risks. However, we need deeper phenotyping to disentangle the impact of adversity during sensitive periods from that across the total lifespan. This study examined whether retrospective reports of adversity during childhood or pregnancy were associated with inflammatory imbalance, in an ethnically diverse cohort of 53 low-income women seeking family-based trauma treatment following exposure to interpersonal violence. Structured interviews assessed early life adversity (trauma exposure ≤ age 5), pregnancy adversity, and total lifetime adversity. Blood serum was assayed for pro-inflammatory (TNF-a, IL-1ß, IL-6, and CRP) and anti-inflammatory (IL-1RA, IL-4, and IL-10) cytokines. CD14+ monocytes were isolated in a subsample (n = 42) and gene expression assayed by RNA sequencing (Illumina HiSeq 4000; TruSeq cDNA library). The primary outcome was a macrophage-associated M1/M2 gene expression phenotype. To evaluate sensitivity and specificity, we contrasted M1/M2 gene expression with a second, clinically-validated macrophage-associated immunosuppressive phenotype (endotoxin tolerance) and with pro-inflammatory and anti-inflammatory cytokine levels. Adjusting for demographics, socioeconomic status, and psychopathology, higher adversity in early life (ß = .337, p = 0.029) and pregnancy (ß = .332, p = 0.032) were each associated with higher M1/M2 gene expression, whereas higher lifetime adversity (ß = −.341, p = 0.031) was associated with lower immunosuppressive gene expression. Adversity during sensitive periods was uniquely associated with M1/M2 imbalance, among low-income women with interpersonal violence exposure. Given that M1/M2 imbalance is found in sepsis, severe COVID-19 and myriad chronic diseases, these findings implicate novel immune mechanisms underlying the impact of adversity on health.