Elsevier

Brain, Behavior, and Immunity

Volume 21, Issue 8, November 2007, Pages 1000-1008
Brain, Behavior, and Immunity

Named Series: Twenty Years of Brain, Behavior, and Immunity
Psychosocial influences on immunity, including effects on immune maturation and senescence

https://doi.org/10.1016/j.bbi.2007.06.015Get rights and content

Abstract

Studies investigating the influence of psychosocial factors on immunity played a critical and formative role in the field of psychoneuroimmunology (PNI), and have been a major component of articles published in Brain, Behavior and Immunity (BBI). An analysis of papers during the first two decades of BBI from 1987–2006 revealed three behavior-related topics were most prominent: (1) stress-induced changes in immune responses, (2) immune correlates of psychopathology and personality, and (3) behavioral conditioning of immunity. Important subthemes included the effect of early rearing conditions on immune maturation in the developing infant and, subsequently, psychosocial influences affecting the decline of immunity in the senescent host. The responsiveness of cell functioning in the young and elderly helped to validate the view that our immune competence is malleable. Many technical advances in immune methods were also evident. Initially, there was a greater reliance on in vitro proliferative and cytolytic assays, while later studies were more likely to use cell subset enumerations, cytokine quantification, and indices of latent virus reactivation. The reach of PNI extended from the traditional clinical entities of infection, autoimmunity, and cancer to attain a broader relevance to inflammatory physiology, and thus to asthma, cardiovascular and gastrointestinal disease. There continue to be many theoretical and applied ramifications of these seminal findings. Fortunately, the initial controversies about whether psychological processes could really impinge upon and modify immune responses have now receded into the pages of history under the weight of the empirical evidence.

Introduction

Although the P aspects of the PNI acronym for psychoneuroimmunology were a essential driving force that led up to the coalescence of this scientific field, they were once considered to be the most controversial component. The early and sometimes intense debates about the significance of the P domain have subsided but lingering feelings still resurface occasionally in discussions about whether the field’s name should have emphasized just the physiological aspects of the brain–immune relationship, with a more circumscribed term, such as ‘neuroimmunomodulation’. The primary issue of concern several decades ago was whether immunologists, as well as some clinicians, might respond skeptically to the once less substantiated claim that psychological processes can meaningfully affect immune processes to such a degree that they undermine health or exacerbate the pathophysiology of disease. For many, then and now, this intellectual tension was unwarranted because it had already been established that psychological processes can significantly alter the activity of the same neural and endocrine pathways that were more readily accepted as being able to modify immune responses.

The boundary lines for the possible P factors that affect immune responses have never been explicitly drawn. However, they certainly encompass the influence of psychosocial processes, such as personality and psychopathology, on immunity. Environmental and behavioral factors that challenge psychological well-being sufficiently to exert immune-modulating effects are also usually included. Much of the latter research has been concerned with the changes in immune responses that occur after stressful or traumatic events. For example, the alterations in the number and types of leukocytes in the blood stream or stress-induced reductions in the levels of antibody generated following immunization. Perhaps as importantly, researchers investigating these psychological influences have also had an abiding interest in those factors that buffer the individual against adversity and thereby lessen or prevent the negative immune changes from occurring. Recently, there have been a number of articles advocating positive and salubrious influences that might actually enhance physical well-being, perhaps by stimulating or sustaining some aspects of immunity (Marsland et al., 2006). For example, PNI research has contributed to a growing literature on ‘successful aging’: the view that our life style and outlook enable us to postpone what was once thought to be the inevitable and strictly biological processes accounting for physical decline and immune senescence at the end of the life span.

The primary aim of this short review is to trace some of the historical trends since the journal BBI came into existence, and to highlight landmark studies that helped to advance and refine our thinking about the psychological aspects of PNI. Following the expository style and outlines employed by other reviews in this series, we begin with the knowledge extant in the early 1980s and then progress sequentially in two incremental steps through the periods from 1987 to 1996 and from 1997 to 2006. In embarking on this journey, it goes without saying that there were many who made pioneering contributions before the decade of our embarkation and that page constraints necessitate a delimited summary. Numerous important papers might not be cited in a selective review, and other authors could certainly argue that the unmentioned discoveries were just as pivotal to the field’s progress.

In reconstructing the past, historians must tread warily on the dimly lit and shrouded ground, because they bring their own perceptions to the task, and introduce the inevitable bias of looking back from today’s vantage point. Not all of the promising avenues and lines of inquiry from the early days of PNI were pursued with equal vigor, in part because funding priorities soon constrained the initial diversity and helped to select which topics rose to greater prominence. Especially in the mid-1980s, the urgency to learn more about factors that might influence viral infection and the progression of AIDS was key in guiding the types of PNI research supported by the NIMH, the primary source of funding for psychological studies at that time. In particular, there was considerable interest in the protective benefits of social support and how stress or certain personality attributes might affect survival. The immune correlates of depression continued to be an area of active investigation over time (Zorrilla et al., 2001; see also 2002 Special Issue on “Cytokines and Depression”, 16:5), whereas research on the immune dysfunction associated with schizophrenia has waned (notwithstanding the provocative findings summarized in the 2001 Special Issue on the “Immunobiology of Serious Psychiatric Diseases”, 15:4). There would also be a growth of interest in the hormone and immune correlates of posttraumatic stress disorder (PTSD), a topic barely on the horizon in early days of PNI research (Laudenslager et al., 1998, Yehuda, 2003).

Section snippets

Pre-1987

An examination of the publications and state of knowledge in the early 1980s reveals an overarching framework not too dissimilar from views prevailing today. Fig. 1 illustrates the perspective advocated by Cunningham (1981), an immunologist interested in PNI, in which he envisioned the immune system as subject to influences by the brain (mind) and its many interactions with the body’s other physiological systems. In turn, these complex and reciprocally linked biological processes within the

1987–1996

Publications in BBI during its inaugural year of 1987 heralded several of the topics that would hold the field’s attention and interest for the next 20 years (Fig. 2). The Tables of Contents include titles on the topics of both stress and bereavement, as well as psychopathology (Irwin et al., 1987). Over time these subjects would rival the numbers published on the conditioning of immune responses (Fig. 2). In welcoming authors to submit papers, the founding Editors wrote in the first issue that

1997–2006

In light of this review’s focus on the contributions of psychological research, it is of some historical interest that the first BBI issue in 1997 opened instead with a short commentary entitled “Where is the “Neuro” in psychoneuroimmunology?” (Altman, 1997). Summarizing conclusions of a workshop held at the prior PsychoNeuroImmunology Research Society (PNIRS) meeting, the NIMH Program Director for AIDS-related research at that time, highlighted that the latest tools of neuroimaging and

Retrospective and prospective reflections

This historical review of psychologically oriented papers published during the first two decades of BBI captures a remarkably productive period spanning several important transitions for the field of PNI. At the outset, the subject of psychological influences on immunity was still considered controversial by many scientists and clinicians. Twenty years later, the weight of the evidence has now definitively documented that the perspectives of PNI are not only credible, but that immunomodulation

Acknowledgments

ML was supported in part by NIH grants MH37373 and AA013973. CLC was supported in part by AI067518, HD39386, AG20166, AG008768, and AG011915.

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