Psychoneuroendocrinology (2013) 38, 1832—1834
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Introduction to Special Issue of
Psychoneuroendocrinology ‘‘Enduring effects of
Traumatic Stress: Molecular and Hormonal
Mechanisms’’
This special issue summarizes many of the symposia pre-
sented at the 42nd annual meeting of the International
Society for Psychoneuroendocrinology, held on September
11—13, 2012 in New York. The purpose of the conference was
to take a broader view of the biobehavioral consequences of
stress and traumatic stress, and draw attention to a concept
that has become increasingly evident in recent years — that
effects of stress, particularly traumatic stress, can be endur-
ing. Prior concepts of stress as they have been discussed in
previous international meetings, symposia, and scientific
papers, have generally focused on the transient nature of
the psychoneuroendocrine response to stress. With the abil-
ity to examine more enduring mechanisms associated with
stress, such as epigenetic and other molecular underpin-
nings, it has become possible to learn a great deal more
about aspects of stress responses that can persist for many
decades, including those that can be ‘‘transmitted’’ inter-
generationally. Moreover, the 42nd ISPNE meeting was also
designed to take a broader view of the effects of stress and
responses to it, including those that might reflect resilience
and increased adaptability (Yehuda et al., 2006). This agenda
has been critical as stress has been a much maligned concept,
blamed for causing numerous negative mental, physical,
cognitive, behavioral, and social consequences. Finally,
the focus on traumatic stress was designed to acknowledge
the very important 11th anniversary of the 9/11 attack on the
World Trade Center. In fact, the conference venue, the New
York Academy of Sciences, at their new location at 7 World
Trade Center with a striking view of the construction site,
catalyzed discussions about long term effects and resilience.
The idea that stress effects are varied, and include those
associated with resilience and even post-traumatic growth,
are consistent with original concepts of stress as delineated
by Walter Cannon, who spoke of the ‘‘Wisdom of the Body’’
(Cannon, 1932), as well as those described by Hans Selye,
who described hormonal responses to stress as part of the
‘‘General Adaptation Syndrome’’ (Selye, 1950). Indeed, the
0306-4530/$ — see front matter. Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.psyneuen.2013.06.018
cortisol response to stress was meant to directly aid normal
metabolic and anti-inflammatory responses of the body,
leading to numerous other theories, such as those of Munck
et al. (1984), describing the role of corticosteroids in the
containment of maladaptive, neuronal and defensive
responses to stress. On the other hand, the idea that stress
effects can have long-term or enduring consequences is one
that generally departs from original notions that posited that
removal of the stressor or challenge to the organism will
result in homeostasis. Another departure from original con-
cepts of the stress response is the idea that similar exposure
can result in quite different responses depending on a range
of individual differences including genetic make-up, prior
stress/trauma history, and other environmental influences
(Mason, 1968).
The first paper describes ground-breaking studies on stress
and telomere biology throughout the lifespan. This paper,
authored by Shalev and colleagues summarizes recent find-
ings on the study of telomere length and the types of stress
associated with alterations in this system that is crucial to
reliable cellular replication. The authors discuss the poten-
tial in utero mechanisms responsible for genetic transmission
of telomere length and summarize the emerging field of study
particularly in relation to specific types of early childhood
trauma. The authors then attempt to link telomere length to
mental health outcomes, noting several methodological lim-
itations to research in this area. They conclude with a formal
discussion of the health behaviors that are associated with
maintaining telomere length, including exercise, dietary
intake, and sleep.
The review by Reynolds and colleagues describes how
biological effects of stress can be transmitted from mother
to child through in utero exposures. This work has many
important implications for the physical and behavioral health
of offspring. For example, epidemiological studies have
shown associations between low birth weight, a surrogate
marker of adverse intrauterine environment, and many
Introduction to Special Issue of Psychoneuroendocrinology
physical diseases including cardiometabolic and psychiatric
diseases. Animal studies have been able to demonstrate that
many of these effects are mediated through hormonal
changes that result in developmental programming. A variety
of important epigenetic mechanisms have been noted that
explain these very important consequences. The authors
review these mechanisms and conclude with suggestions
about future interventions for mitigating risks transmitted
via stress during preconception, pregnancy, and early-life.
The review by Elhert et al. describes longitudinal research
examining the interplay between adverse living conditions
and the genetic, epigenetic, and immunological conse-
quences that mediate a range of psychiatric and physical
correlates associated with childhood adversity. The paper
presents findings from recent studies targeting aspects of
these vulnerabilities that include the genetic and epigenetic
effects of glucocorticoid receptor (GR) chaperone, FBKP5, on
the glucocorticoid and CRH systems as well as similar vulner-
abilities transmitted by alterations to BDNF function. The
paper further describes how these effects may be trans-
mitted in utero, suggesting a range of developmentally
sensitive periods for these effects to occur, continuing many
of the themes that are set forth in Reynolds et al., but with a
focus on postnatal experiences. Elhert et al. conclude by
discussing emerging evidence that childhood maltreatment
yields persistent alterations to inflammatory markers that
may offer some explanation for a variety of health outcomes
associated with childhood maltreatment.
Continuing on this theme, the next review by Daskalakis
and colleagues offers a formal discussion of the three-hit
model of psychopathology, including genetic background,
development and early life stress, and later life stress.
Indeed, early environmental effects can result not only in
pathology, but also, resilience. The authors review evidence
from rodent, non-human primate, and human studies to
suggest that mild early life adversity later predicts resilience
when the stressors are similar and vulnerability when the
stressors are mismatched. The question of how different
formative experiences may shape adaptive vs. maladaptive
responses in the adult has been of great interest, and such
models help understand how important individual differ-
ences, such as in coping, can be fostered early in life. The
authors conclude with a discussion of how this model can be
useful in explaining different psychiatric outcomes for indi-
viduals with the same genetic background and similar life
circumstances.
The review by van Anst and colleagues summarizes the
literature on corticosteroids and memory with a focus on the
molecular mechanisms that contribute to intra-individual
variability. The authors focus on new research examining the
role of the mineralocorticoid and glucocorticoid receptors
on different aspects of memory reconsolidation and retrie-
val, and discuss how these mechanisms interact with dis-
positional factors and the environmental contexts
associated with learning. Despite great advances in under-
standing variables that are associated with variability in the
effects of cortisol, cortisol modulators remain a poorly
understood area of research. These mechanisms associated
with cortisol effects will be important for developing a
better understanding of how learning can be enhanced
or disrupted and to aid in treatment for PTSD and other
1833
psychopathology characterized by alterations to learning
and memory.
Olff and colleagues offer a summary of new findings on the
role of oxytocin in moderating stress response. The authors
summarize what is known about individual differences in
oxytocin levels and response and how specific context is
important for eliciting desired effects of oxytocin adminis-
tration. Primarily, oxytocin promotes social functioning and
regulates stress reactivity in animals and humans, and as
such, may promote agonistic characteristics, including bet-
ter attachments and pro-social behaviors. The authors con-
clude with recommendations for future research on the use
of oxytocin to treat a range of psychopathologies.
Daskalakis and colleagues take on the topic of animal
models in translational studies of PTSD, offering a critique
of current approaches that conflate the consequences of
exposure with those associated with the prolonged response
of PTSD. Animal models of PTSD are needed to capture the
complexity of the PTSD behavioral consequences, as well as
the lack of recovery observed. The authors review three
established animal models of PTSD and discuss their use in
drug discovery for PTSD. They further discuss the value of
studying gene  environment interactions and the need for
use of modern genetic and genomic techniques to guide the
search for robust biomarkers of PTSD.
The volume also contains two commentaries that sum-
marize day-long satellite symposia that served to book-end
the meeting. Yehuda et al., describe the state of the science
in identification of PTSD biomarkers and defines different
classes of biomarkers pertaining to PTSD. The discussion on
identification of biomarkers for PTSD risk, diagnosis, symp-
tom severity and treatment response, is supplemented with
the presentation of salient issues regarding biomarker devel-
opment, as well as special considerations for the use of
biomarkers in the military.
Finally, the commentary by Hildebrandt and Grief sum-
marizes the research presented at a satellite conference on
sex differences in eating and addiction. The authors discuss
the importance of examining interactions between gonadal
and stress hormones on motivation and reward. They first
review promising research on the interaction between stress
and gonadal hormones in reward sensitivity and reward
learning as one mechanism to explain sex differences in
the abuse of and dependence on drugs and alcohol. They
then provide a summary of how these types of models are
being applied to other forms of psychopathology such as
eating disorders. They conclude with highlights of the con-
troversies about whether these types of models should be
used to understand obesity as type of addiction.
We take this opportunity to thank the many persons who
contributed to this volume and who presented their exciting
work at the 42nd Annual conference of the International
Society for Psychoneuroendocrinology. All the abstracts of
the meeting can be found at: http://dx.doi.org/10.3402/
ejpt.v3i0.19554 (Supplement, 2012).
Acknowledgements
We wish to thank the authors for their excellent contribu-
tions, and the reviewers for their outstanding reports. We
thank the many persons involved in executing the ISPNE
1834
meeting, particularly Rebecca Greif, Kelly Ryberg, Heather
Bader, Jenna Katz, Amy Ransohoff, Susie Forzano Norton, and
of course, ISPNE administrator, Lori Peterson. We also wish to
thank the PNEC editorial board, editorial assistants, and
editors-in-chief for their advice, and for their trust in this
project, particularly Dr. Robert Dantzer, who was assigned to
this special volume. Very special gratitude goes to Rose-Marie
Bluthé, who showed enormous dedication and worked vigor-
ously with the authors and the special editors to make this
special issue a reality.
References
Cannon, W.B., 1932. The Wisdom of the Body. W.W. Norton &
Company, Inc..
Mason, J.W., 1968. A review of psychoendocrine research on the
pituitary-adrenal cortical system. Psychosom. Med. 30 (Suppl.)
576—607.
Munck, A., Guyre, P.M., Holbrook, N.J., 1984. Physiological functions
of glucocorticoids in stress and their relation to pharmacological
actions. Endocr. Rev. 5, 25—44.
Selye, H., 1950. The Physiology and Pathology of Exposure to Stress. A
Treatise Based on the Concepts of the General-Adaptation-Syn-
drome and the Diseases of Adaptation. Montreal. .
Supplement, 2012. Abstracts from the 42nd Annual Conference:
Effects of Traumatic Stress — Molecular and Hormonal Mecha-
nisms. Eur. J. Psychotraumatol. 3 .
Yehuda, R., Flory, J.D., Southwick, S., Charney, D.S., 2006. Devel-
oping an agenda for translational studies of resilience and vul-
nerability following trauma exposure. Ann. N. Y. Acad. Sci. 1071,
379—396.
Introduction to Special Issue of Psychoneuroendocrinology
Rachel Yehudaa, b,c, *, Tom Hildebrandtd, David Spiegele,
a
Traumatic Stress Studies Division, Department of Psychiatry,
Icahn School of Medicine at Mount Sinai, New York, NY, USA
b
Mental Health Care Center, James J. Peters Veterans
Affairs Medical Center, Bronx, NY, USA
c
Fishberg Department of Neuroscience, Icahn School of Medicine
at Mount Sinai, New York, NY, USA
d
Eating and Weight Disorders Program, Department of
Psychiatry, Icahn School of Medicine at Mount Sinai, New York,
NY, USA
e
Department of Psychiatry, School of Medicine,
Stanford University, Stanford, CA, USA
*Corresponding author at: Traumatic Stress Studies Division,
Department of Psychiatry, Mount Sinai School of Medicine,
James J. Peters Veterans Affairs Medical Center,
526 OOMH PTSD 116/A, 130 West Kingsbridge Road,
Bronx, NY 10468, USA.
Tel.: +1 718 741 4000; fax: +1 718 741 4775
E-mail addresses: rachel.yehuda@va.gov
rachel6964@gmail.com (R. Yehuda)
Received 12 June 2013
accepted 13 June 2013