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Childhood adversity increases susceptibility to addiction via immune response

July 17, 2018

Philadelphia, July 17, 2018

Childhood adversity permanently alters the peripheral and central immune systems, increasing the sensitivity of the body's immune response to cocaine, reports a study by researchers at the IRCCS Santa Lucia Foundation and University of Rome "La Sapienza", Italy.

The study, published in Biological Psychiatry, showed that exposure to psychosocial stress early in life altered the structure of immune cells and inflammatory signals in mice and led to increased drug-seeking behavior. Exposure to early psychosocial stress in mice, or a difficult childhood in humans, increased the immune response to cocaine in adulthood, revealing a shared mechanism in the role of immune response in the effects of early life stress on cocaine sensitivity in mice and humans.

The findings help explain why as many as 50 percent of people who experience childhood maltreatment develop addiction problems. The results in mice and humans suggest that exposure to adversity during childhood triggers activation of the immune system, leading to permanent changes that sensitize the immune system and increase susceptibility to the effects of cocaine in adulthood.

"This paper suggests the existence of an extraordinary degree of interplay between the neural and immune systems related to the impact of early life stress on later risk for cocaine misuse. It both highlights the complex impact of early life stress and suggests an immune-related mechanism for reducing later addiction risk," said John Krystal, MD, Editor of Biological Psychiatry.

After inducing psychosocial stress in 2-week-old mice by exposing them to a threatening male, first author Luisa Lo Iacono, PhD, and colleagues examined brain immune cells, called microglia, in adulthood. Early social stress altered the structure of microglia in the ventral tegmental area, a brain region important for the reward system and drug-seeking, and increased the response of microglia to cocaine. In the peripheral immune system, early social stress increased the release of inflammatory molecules from white blood cells, which was further amplified by exposure to cocaine, compared with control mice.

"Remarkably, pharmacologically blocking this immune activation during early life stress prevents the development of the susceptibility to cocaine in adulthood," said senior author Valeria Carola, PhD. Mice who received an antibiotic to prevent activation of immune cells during social stress did not have cellular changes or drug-seeking behavior.

The study also compared immune system function of 38 cocaine addicts and 20 healthy volunteers. Those who experienced childhood maltreatment had increased expression levels of genes important for immune system function. And the highest levels were found in cocaine addicts who had experienced a difficult childhood.

The findings add to the growing collection of evidence from the research group for the negative effects of early life trauma on brain development. "Our work emphasizes once again the importance of the emotional environment where our children are raised and how much a serene and stimulating environment can provide them with an extra 'weapon' against the development of psychopathologies," said Dr. Carola.
-end-
Notes for editors
The article is "From traumatic childhood to cocaine abuse: the critical function of the immune system," by Luisa Lo Iacono, Clarissa Catale, Alessandro Martini, Alessandro Valzania, Maria Teresa Viscomi, Valerio Chiurchiù, Ezia Guatteo, Silvia Bussone, Fabiana Perrone, Paola Di Sabato, Eleonora Aricò, Alberto D'Argenio, Alfonso Troisi, Nicola B. Mercuri, Mauro Maccarrone, Stefano Puglisi-Allegra, Pietro Casella, and Valeria Carola (https://doi.org/10.1016/j.biopsych.2018.05.022). It appears in Biological Psychiatry, published by Elsevier.

Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at Biol.Psych@UTSouthwestern.edu">Biol.Psych@UTSouthwestern.edu or +1 214 648 0880. Journalists wishing to interview the authors may contact Valeria Carola at valeria.carola@uniroma1.it">valeria.carola@uniroma1.it, v.carola@hsantalucia.it">v.carola@hsantalucia.it or +39 06 5017 03075.

The authors' affiliations and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.

AboutBiological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 6th out of 142 Psychiatry titles and 9th out of 261 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2017 Impact Factor score for Biological Psychiatry is 11.982. http://www.sobp.org/journal

About ElsevierElsevier is a global information analytics business that helps institutions and professionals advance healthcare, open science and improve performance for the benefit of humanity. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support and professional education, including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, more than 38,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX Group, a global provider of information and analytics for professionals and business customers across industries. http://www.elsevier.com

Media contact
Rhiannon Bugno
Editorial Office, Biological Psychiatry
+1 214 648 0880
Biol.Psych@UTSouthwestern.edu">Biol.Psych@UTSouthwestern.edu

Elsevier

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