Available via license: CC BY
Content may be subject to copyright.
fnins-13-00384 April 19, 2019 Time: 17:29 # 1
MINI REVIEW
published: 24 April 2019
doi: 10.3389/fnins.2019.00384
Edited by:
Deborah Suchecki,
Federal University of São Paulo, Brazil
Reviewed by:
Charles Barnet Nemeroff,
The University of Texas at Austin,
United States
Marisa Toups,
University of Texas Dell
Medical School, United States,
in collaboration with reviewer CBN
Bruno Bonaz,
Centre Hospitalier Universitaire
de Grenoble, France
*Correspondence:
Viktoriya Maydych
maydych@ifado.de
Specialty section:
This article was submitted to
Neuroendocrine Science,
a section of the journal
Frontiers in Neuroscience
Received: 10 January 2019
Accepted: 02 April 2019
Published: 24 April 2019
Citation:
Maydych V (2019) The Interplay
Between Stress, Inflammation,
and Emotional Attention: Relevance
for Depression.
Front. Neurosci. 13:384.
doi: 10.3389/fnins.2019.00384
The Interplay Between Stress,
Inflammation, and Emotional
Attention: Relevance for Depression
Viktoriya Maydych*
Department Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, TU
Dortmund (IfADo), Dortmund, Germany
Depression is among the most significant public mental health issues. A growing body
of research implicates inflammation in the etiology and pathophysiology of depression.
Yet, the results are somewhat inconsistent, leading to burgeoning attempts to identify
associations between components of innate immune system involved in inflammation
and specific symptoms of depression, including attention to emotional information.
Negative attentional bias, defined as a tendency to direct attention toward negatively
valenced information, is one of the core cognitive features of depression and is reliably
demonstrated in depressed and vulnerable individuals. Altered attentional processing of
emotional information and immunological changes are often precipitated by stressful
events. Psychological stress triggers inflammatory activity and affective-cognitive
changes that play a critical role in the onset, maintenance, and recurrence of depression.
Using various designs, recent studies have reported a positive relationship between
markers of inflammation and negative attentional bias on behavioral and neural levels,
suggesting that the association between inflammation and emotional attention might
represent a neurobiological pathway linking stress and depression. This mini-review
summarizes current research on the reciprocal relationships between different types of
stressors, emotional attention, inflammation, and depression, and discusses potential
neurobiological mechanisms underlying these interactions. The integration provided
aims to contribute toward understanding how biological and psychological processes
interact to influence depression outcomes.
Keywords: inflammation, cytokines, psychological stress, emotional attention, attentional bias, negative bias,
depression, depressive disorders
INTRODUCTION
Depression is a highly prevalent mood disorder in modern society and is associated with significant
impairments in the patients’ quality of life. A multitude of basic research and clinical studies have
been performed, with the aim of understanding the interaction between biological, psychological,
and environmental factors involved in the etiology of depression. There is growing evidence
Frontiers in Neuroscience | www.frontiersin.org 1April 2019 | Volume 13 | Article 384
fnins-13-00384 April 19, 2019 Time: 17:29 # 2
Maydych Stress, Inflammation and Emotional Attention
implicating increased levels of markers of inflammation in
the pathogenesis of depressive disorders (Raison et al., 2006).
Inflammation is a part of the innate immune system’s response
to infection or injury. The main mediators of the inflammatory
response, proinflammatory cytokines, such as interleukin (IL)-
1β, interleukin (IL)-1 receptor antagonist (RA), interleukin
(IL)- 6, tumor necrosis factor (TNF)-α, and interferon (IFN)-
γ, have been recently shown to communicate with the brain
and affect neurotransmission, neuroendocrine activity, and
brain structure and functions, thereby inducing emotional,
cognitive, and behavioral changes (Haroon et al., 2012). If the
inflammatory response remains unresolved, the chronic release
of proinflammatory cytokines can promote pathology, including
depression. Different studies using a variety of study designs and
populations have found positive associations between increased
levels of proinflammatory cytokines and symptoms of depression
(Dowlati et al., 2010;Valkanova et al., 2013). However, findings
have not been entirely consistent for all types of depression
(Rothermundt et al., 2001), raising the need for identifying
more specific links between inflammation and different somatic
and affective-cognitive symptoms, rather than merely testing
associations between increased inflammation and categorically
defined depression.
According to cognitive models of depression, one of the
key features of depressed and vulnerable individuals is biased
cognitive processing of emotional and social information.
Cognitive biases manifest themselves in a consistent shift
toward (self-referential) negative or threatening information
in all aspects of cognition, including perception, attention,
interpretation, memory, or sensitivity to feedback (Miskowiak
and Carvalho, 2014). Negatively biased processing of emotional
information is usually regarded both as a neuropsychiatric
symptom and as a lingering trait factor that confers cognitive
vulnerability to depression and may, when triggered by adverse
environmental factors (e.g., stress), initiate the development
or reoccurrence of depression (Ingram et al., 1998). The
following mini-review focuses primarily on one cognitive
domain: attention.
Heightened inflammation and negative attentional bias (AB)
are often the results of psychological stress. Acute stressful
challenges lead to increases in inflammatory activity and
other neurophysiological changes that modulate affective,
cognitive, and behavioral processes (Allen et al., 2014;
Slavich and Irwin, 2014). Chronic exposure to stressors causes
endocrine and immune system dysfunction that contributes
to sustained low-grade inflammation, which is involved in
the pathogenesis of depressive symptoms (Rohleder, 2014). In
parallel, acute stress has been shown to trigger affective and
cognitive changes similar to biased information processing
characteristic to depression (Gotlib and Joormann, 2010).
This evidence has recently led to promising attempts to
investigate interactions between emotional attention and
inflammation in the context of stress, thereby identifying
specific neurocognitive pathways that may be relevant for the
etiology of depression and development of novel treatments.
The aim of this mini-review is to summarize independent lines
of inquiry focusing on the effects of stress (1) on inflammation
and (2) emotional attention as well as the potential link
between stress-inflammation and stress-cognition pathways
(3), and depression.
INFLAMMATION, STRESS, AND
DEPRESSION
A considerable body of evidence suggests that individuals
with diagnosed depression exhibit significantly higher
levels of IL-1, IL-6, TNF-α, and C-reactive protein (CRP)
compared to non-depressed counterparts (Howren et al., 2009;
Dowlati et al., 2010). Concurrently, depressive symptoms
are more frequent in patients with conditions involving
inflammation (e.g., autoimmune diseases) and can be reversed
through the use of anti-inflammatory drugs (Kojima et al.,
2009;Köhler et al., 2014). Notably, increased inflammatory
activity has been documented only in some patients with
depression. This indicates that the depression-inflammation
link may be modulated by further vulnerability factors,
such as genes or cognitive vulnerability. Alternatively,
since depression is a heterogeneous disorder, it is also
plausible that the association between cytokine-mediated
inflammatory processes and depression is more nuanced
in terms of the groups of depressive symptoms (somatic
vs. affective-cognitive). In support of this notion, a large
data set has documented mechanistic links between somatic
symptoms of depression and increased inflammation in animals
and humans (DellaGioia and Hannestad, 2010); however,
studies are lacking in affective-cognitive changes related to
inflammatory activity. There is some evidence that inflammatory
processes may have differential effects on somatic and affective-
cognitive depressive symptoms that are based on distinct
neurophysiological mechanisms. For example, studies examining
the development of depressive symptoms during the course
of IFN-αtherapy found that all patients developed somatic
symptoms, including fatigue, altered sleep and appetite, motor
slowing, during the first weeks of therapy (Capuron and
Miller, 2004). In contrast, only 30–50% of patients developed
affective-cognitive symptoms such as negative mood, anhedonia,
or cognitive impairment during the later stages of therapy.
Strikingly, the development of this group of symptoms could
be prevented by prophylactic antidepressant administration
(Musselman et al., 2001).
There is considerable evidence that psychological stress can
activate the inflammatory response. Different types of stressors
are capable of eliciting increases in inflammatory activity in
a manner that may promote depressive symptoms (Slavich
and Irwin, 2014). Moreover, the link between stressor-evoked
increases in CRP and proinflammatory cytokines and depression
appears to be bidirectional, as chronic stressors and current
depressive symptoms, both associated with neurophysiological
changes (e.g., glucocorticoid resistance), were found to increase
stress reactivity, including cytokine changes in response to
stressful challenges.
One of the most robust predictors of increased levels of
proinflammatory cytokines is early life adversity (ELA). Usually
Frontiers in Neuroscience | www.frontiersin.org 2April 2019 | Volume 13 | Article 384
fnins-13-00384 April 19, 2019 Time: 17:29 # 3
Maydych Stress, Inflammation and Emotional Attention
indicated by parental maltreatment and low socioeconomic
status during childhood, ELA is considered as a chronic and
severe stressor causing long-lasting psychological and biological
abnormalities that considerably increase the risk of depression
(Hostinar et al., 2018). Psychological alterations are manifested
in exaggerated reactivity to negative information and stress;
biological abnormalities include HPA axis activity dysregulation
(in most cases hyperactivity leading to glucocorticoid resistance),
low parasympathetic activity, and frontolimbic circuit alterations
that promote reactivity to threatening stimuli (Callaghan
and Tottenham, 2016). For example, individuals exposed to
ELA showed stronger increases in proinflammatory cytokines
in response to laboratory stress than those who were not
(Pace et al., 2006). Moreover, exposure to ELA was prospectively
and retrospectively associated with an increased inflammation
in later life (Danese et al., 2008;Kiecolt-Glaser et al., 2011;
Coelho et al., 2014).
The causal role of stress in inflammatory activity was also
examined in laboratory settings that enable the assessment of
temporal patterns of cytokine responses and use of standardized
stress induction procedures such as the Trier Social Stress Test
(TSST) (Kirschbaum et al., 1993;Slavich and Irwin, 2014).
Laboratory studies showed that acute stress was associated
with significant increases in IL-1β(Yamakawa et al., 2009),
IL-1RA and IL-6 (Goebel et al., 2000;O’Donnell et al.,
2008;Hackett et al., 2012), and TNF-α(O’Donnell et al.,
2008), with IL-β, IL-6, and TNF-αdemonstrating the most
robust increases (Marsland et al., 2017). At the same time,
higher cytokine levels were reported to be associated with
increases in negative mood and anxiety in some studies
(Yamakawa et al., 2009;Moons et al., 2010;Carroll et al.,
2011). The notion that increases in inflammatory activity
can lead to negative emotional states was also supported
by studies that induced low-grade inflammation through
the injection of bacterial endotoxin (i.e., lipopolysaccharide,
LPS) or vaccines (i.e., flu, typhoid). Stimulated increases in
proinflammatory cytokines were associated with symptoms such
as fatigue, negative mood, anhedonia, cognitive impairment,
social withdrawal, motor slowing – a variety of symptoms
collectively referred to as sickness behavior and resembling
those of affective-cognitive and somatic symptoms of depression
(Dantzer et al., 2008;Eisenberger et al., 2010). Moreover,
the associations between inflammatory activity and sickness
behavior were not restricted to the laboratory, but also
predicted depressive symptoms and cognitive impairment 1 week
later (Kuhlman et al., 2018). Similarly, increases in IL-1β
in response to TSST predicted the increase of depressive
symptoms 1 year later (Aschbacher et al., 2012). Individuals
with diagnosed depression have demonstrated stronger increases
in proinflammatory cytokines in response to laboratory stress
than non-depressed individuals (Weinstein et al., 2010;Fagundes
et al., 2013), indicating an increased inflammatory stress
responsiveness in depression. Although the aforementioned
studies provide interesting findings, the ecological validity of
most results is limited due to laboratory settings and mainly
samples of healthy young adults. Future research could seek
to examine whether naturalistic stressor-induced increases in
proinflammatory cytokines are prospectively associated with
depressive symptoms.
EMOTIONAL ATTENTION, STRESS, AND
DEPRESSION
Cognitive symptoms of depression include attentional biases
(AB) toward negative information (Mathews and MacLeod,
2005). A number of studies using different attention allocation
tasks (MacLeod et al., 1986) demonstrated that compared
to non-depressed counterparts, depressed individuals exhibit
increased difficulty in disengaging their attention from negative
stimuli than from positive or neutral stimuli, especially when
negative material is related to depression (e.g., feelings of
worthlessness, guilt) (Gotlib et al., 2004a,b;Koster et al., 2005;
Caseras et al., 2007). Negative AB has been also documented in
patients with remitted depression and in individuals exposed to
ELA (Luecken and Appelhans, 2005;Joormann and Gotlib, 2007;
Raymond et al., 2018).
The common assumption of cognitive stress-diathesis models
is that depression is a result of the interaction between cognitive
vulnerability and stressful life events (Ingram et al., 1998).
Therefore, given cognitive vulnerability, experiencing stressful
events can initiate a depressive episode. Although the causal
role of stress and cognitive biases that jointly increase the
subsequent depression risk is theoretically now well-established,
surprisingly few studies have examined this etiological pathway
with assessments of stressful events and attention measures
that do not rely on the participants’ self-report. A number
of laboratory-based studies have examined whether laboratory
stress would increase negative AB and whether attention shift
would be associated with mood change. Indeed, AB toward
negative vs. neutral material has been shown to be increased
after a stressful challenge (Ellenbogen et al., 2002;Tsumura
and Shimada, 2012). Moreover, attention shift toward negative
information was associated with mood lowering (Ellenbogen
et al., 2002, 2006) cortisol responses (Ellenbogen et al., 2010;
Roelofs et al., 2007) in healthy participants and slower stress
recovery in a depressed cohort (Sanchez et al., 2017). Although
these results suggest a causal link between stressor-evoked AB
and negative mood, the main limitation of this work is that
stress effects on AB and mood change reflect short-term prime
effects rather than providing ecologically valid evidence of the
stress-diathesis hypothesis. To examine the long-term effects,
several studies examined whether baseline or stressor-related
negative AB shifts would prospectively predict depressive
symptoms. These studies reported that AB shift following
induction of negative mood interacted with subsequent stressful
events in predicting increases in dysphoria 7 weeks later
in dysphoric students (Beevers and Carver, 2003). Similarly,
negative AB was predictive of the exacerbation of depressive
symptoms in adults with subclinical depression after 5 weeks
(Disner et al., 2017). Finally, a significant interaction effect
of stressful life events and dysfunctional attitudes on clinical
depression incidence after 12 months has been reported
(Lewinsohn et al., 2001).
Frontiers in Neuroscience | www.frontiersin.org 3April 2019 | Volume 13 | Article 384
fnins-13-00384 April 19, 2019 Time: 17:29 # 4
Maydych Stress, Inflammation and Emotional Attention
STRESS, INFLAMMATION, AND
EMOTIONAL ATTENTION
As outlined in previous sections, distinct lines of research
show that different stressors can trigger inflammatory activity
and increase the attentional processing of negative information.
Both inflammatory processes and cognitive stressor-evoked
changes were associated with mood lowering and an increase in
anxiety and depressive symptoms. Stressor-evoked elevations in
proinflammatory cytokines and attention shift toward negative
information can represent stress responses at multiple levels that
independently contribute to depressive symptoms. Alternatively,
inflammatory and cognitive stress responses may act together,
potentiating one another’s impact on promoting depression. The
following section provides a summary of studies that examined
the relationship between AB and markers of inflammation.
BEHAVIORAL STUDIES
To analyze an association between negative AB and increased
inflammatory activity, several cross-sectional and clinical studies
examined performance in attention tasks using emotional
material and tested for relationships with inflammatory markers.
Levels of CRP were reported to positively correlate with increased
AB toward sad vs. happy and angry faces in breast cancer
survivors (Boyle et al., 2017). In addition, hepatitis C patients
showed an AB away from positive vs. neutral and fearful faces
and an increase in symptoms of depression, anxiety, and fatigue
6–7 weeks after commencing IFN-αtherapy (Cooper et al., 2018).
Concurrently, a greater increase in AB toward self-referential
positive vs. negative words and improvement of affective-
cognitive and somatic depressive symptoms was observed after
completion of anti-TNF-αtherapy in patients with inflammatory
bowel disease (Gray et al., 2018). This preliminary evidence
suggests that affective processing and depressive symptoms may,
at least, be partially driven by inflammatory activity. The pattern
of AB toward negative and away from positive information is
consistent with AB usually observed in depression. However,
the influence of disease or environmental confounding factors
cannot be ruled out in these studies.
To examine whether a causal relationship exists between
stressor-evoked inflammatory response and AB, a number of
experimental studies investigated the effects of acute stress or
mood induction on cytokine levels and emotional attention
in healthy and depressed individuals; however, the findings
have been mixed. Significant increases in both pro- and
anti-inflammatory cytokines following laboratory stress were
reported by some studies (Boyle, 2018;Maydych et al., 2018).
Elevations of cytokine levels were, in turn, positively associated
with increased AB toward negative and decreased AB toward
positive information. While these findings provide support for
the notion that stressor-evoked cytokine increases may drive,
at least, short-term changes in attention processing with these
effects depending on the valence of emotional material, other
studies could not confirm this hypothesis (Benson et al., 2017;
Niemegeers et al., 2019). The inconsistency of the findings may
stem from methodological and design issues, especially from
differences in stress/mood induction procedures, the timing
of cytokine assessments, and types of attention tasks. It is
also plausible that endogenous concentrations of cytokines, in
particular in healthy samples, even after a stressful challenge,
may be too low to map on behavioral attention measures.
Alternatively, attention tasks may not be sensitive enough to the
cognitive changes produced by cytokines.
Increased inflammatory activity appears not only to be
associated with AB toward negative information but has also
been suggested to increase stress reactivity (Dooley et al.,
2018). As outlined earlier, depressed individuals and those
exposed to ELA exhibit higher increases in proinflammatory
cytokines in response to acute stress. Thus, it is possible that
exogenously induced inflammation prior to stress manipulation
would increase stress reactivity and drive even stronger changes
in emotional processing than individual treatments. Increases in
IL-6 levels have been demonstrated to be positively associated
with negative AB only in response to typhoid vaccine in women
with partially remitted depression, but not in response to
laboratory stress or both treatments (Niemegeers et al., 2019).
In another study, slower processing of negative information was
observed in response to LPS treatment and at a trend level in
combined LPS and negative mood induction condition in healthy
males (Benson et al., 2017).
In summary, the findings from various behavioral studies
indicate that stressor-related or endotoxin-induced increases in
inflammatory activity may affect emotional attention similar to
AB in depression. Yet, there were some inconsistent results and
null results, which can reflect methodological differences between
studies. In addition, the results obtained in laboratory studies
do not allow for conclusions on long-term causal relationships
between immune and cognitive processes. Future studies should
determine whether increased inflammation can prospectively
predict alterations in emotional attention.
FUNCTIONAL NEUROIMAGING STUDIES
Although the literature is rather sparse at present, the effects
of inflammation on neural activity and functional connectivity
during the processing of emotional stimuli have also been
the subject of investigation. The experimental designs of these
studies induced increased inflammation through either LPS,
vaccines, or laboratory stress and measured neural activity
and connectivity during exposure to emotional stimuli or
receiving social feedback. LPS-induced inflammation was shown
to increase amygdala activity while viewing negative facial
expression images (Inagaki et al., 2012). Furthermore, peripheral
levels of IL-6 were associated with increased activation of
the amygdala and increased functional connectivity between
the amygdala and dorsomedial prefrontal cortex (dmPFC) in
response to negative social feedback (Muscatell et al., 2015).
Laboratory stressor-evoked increases in the soluble TNF-α
receptor (sTNFαRII) have been shown to be positively correlated
with increased activation in dorsal anterior cingulate cortex
(dACC) and anterior insula (AI) in response to social rejection
Frontiers in Neuroscience | www.frontiersin.org 4April 2019 | Volume 13 | Article 384
fnins-13-00384 April 19, 2019 Time: 17:29 # 5
Maydych Stress, Inflammation and Emotional Attention
(Slavich et al., 2010;Muscatell et al., 2016). Comparatively, the
LPS-stimulated increase in IL-6 was positively associated with
increased activation of the bilateral amygdala, dACC, and dorsal
prefrontal cortex (dPFC) in response to negative feedback from
the confederate based on a 10-min interview previously provided
by participants (Muscatell et al., 2016). Other studies reported on
the enhanced activity of right inferior orbitofrontal cortex (iOFC)
(Kullmann et al., 2013) and subgenual ACC (Harrison et al., 2009)
in response to viewing emotional pictures and faces, respectively.
Although the data is not yet sufficient to draw generalized
conclusions, the majority of studies have documented the
increased activity of amygdala and dACC in response to increases
in inflammatory activity and negative social stimuli/feedback.
This is consistent with the literature on AB in depressive or at-risk
individuals (e.g., those exposed to ELA) that found enhanced and
long-lasting activity of amygdala in response to negative material
(Disner et al., 2011). A simultaneous activation increase in of PFC
and ACC was attributed to cortical insufficiency and abnormal
frontolimbic circuit function (Wagner et al., 2006;Matsuo et al.,
2007). Along with amygdala and AI, dACC was suggested to
constitute a so-called “neural alarm system,” which is responsible
for the detection of environmental threats and the regulation of
responses to danger including SNS system and HPA axis response
(Muscatell and Eisenberger, 2012).
MECHANISMS LINKING INFLAMMATION
TO EMOTIONAL ATTENTION
Peripherally released cytokines communicate with the brain and
are capable of eliciting changes in emotional processing that
mimic affective-cognitive symptoms of depression. Research has
identified several pathways by which cytokine signals can access
the brain (Haroon et al., 2012). Briefly, cytokines can enter the
brain through leaky regions in the blood-brain barrier (e.g.,
circumventricular organs) or activated monocytes/macrophages
recruited to the brain. In addition, cytokine release can be
stimulated through brain blood vessel cells (e.g., endothelial
cells). Furthermore, afferent vagus nerve fibers can be stimulated
to transduce cytokine signals from the periphery into the brain,
where the cytokine signals activate cytokine-producing glia cells.
One of the most important molecular mechanisms
linking inflammation to emotional cognition is the cytokine
effect on the serotonergic system (Capuron and Castanon,
2016). Proinflammatory cytokines activate indoleamine-2,3-
dioxygenase (IDO), an enzyme involved in the synthesis of
kynurenine from dietary tryptophan. Central and peripheral
activation of IDO causes increased catabolism of tryptophan, an
important precursor of serotonin, leading to serotonin deficiency
(O’connor J. et al., 2009;O’Connor J.C. et al., 2009). Furthermore,
the products of kynurenine metabolism, such as quinolinic acid,
stimulate the N-methyl-D-aspartate (NMDA) receptor, thereby
unfolding neurotoxic effects leading to neuronal damage
(Campbell et al., 2014).
Another mechanism linking inflammation with cognition
is the effect of cytokines on the HPA axis. Cytokines can
act on glucocorticoid receptors and indirectly upregulate
the synthesis of corticotrophin-releasing hormone (CRH),
adrenocorticotropic hormone (ACTH), and cortisol (Raison
and Miller, 2003). The extent to which cytokines induce
the release of ACTH and cortisol is predictive of the
development of affective-cognitive but not of somatic symptoms
of depression (Capuron et al., 2003). This implies that HPA axis
sensitivity to inflammatory stimulation is particularly relevant for
the development of affective-cognitive symptoms of depression.
Finally, the parasympathetic nervous system has been
suggested to modulate affective-cognitive and immune processes
involved in stress cascade and depression (Thayer and Sternberg,
2006;Ondicova et al., 2010). Lower activity of the vagus nerve
is predictive of higher levels of cortisol and cytokine acute
stress response (Hamer and Steptoe, 2007;Smeets, 2010;Woody
et al., 2017) as well as slower stress recovery (Weber et al.,
2010). In addition, the vagal tone has been implicated in the
detection and (down-) regulation of inflammatory processes.
The anti-inflammatory effects are mediated by the vagal release
of acetylcholine, which activates a7 nicotinic Ach receptors in
macrophages, thereby inhibiting the release of proinflammatory
cytokines from these lymphocytes (the mechanism referred to
as “cholinergic anti-inflammatory reflex”) (Rosas-Ballina and
Tracey, 2009). It has been also suggested that reduced activity of
the vagus nerve is associated with disturbed emotion regulation
and further affective-cognitive symptoms that stem from the
impaired inhibitory control of the prefrontal cortex over the
limbic system (Thayer and Sternberg, 2006;Thayer et al., 2012)
as well as deficiency in monoamines (Dorr and Debonnel, 2006).
CONCLUSION
In summary, preliminary evidence suggests that acute and
chronic stress is associated with increased inflammatory activity
and enhanced attentional processing of negative information.
Both are predictive of negative mood and depression symptoms
that, in turn, increase inflammatory and cognitive stress
reactivity. Increased inflammation was associated with a pattern
of attentional changes characteristic to depression, whereas
affective-cognitive states were predictive of inflammatory stress
responses. These findings indicate that immune and affective-
cognitive processes are interconnected and may potentiate
one another’s impact on depression onset, maintenance or
recurrence. An improved understanding of the interplay between
inflammatory activity and emotional cognition in the context of
stress may help to optimize treatment strategies for depression.
AUTHOR CONTRIBUTIONS
VM has conceptualized and written the manuscript.
ACKNOWLEDGMENTS
The author thanks Dr. Thomas Kleinsorge for proofreading of the
first version of the manuscript. The publication of this article was
funded by the Open Access Fund of the Leibniz Association.
Frontiers in Neuroscience | www.frontiersin.org 5April 2019 | Volume 13 | Article 384
fnins-13-00384 April 19, 2019 Time: 17:29 # 6
Maydych Stress, Inflammation and Emotional Attention
REFERENCES
Allen, A. P., Kennedy, P. J., Cryan, J. F., Dinan, T. G., and Clarke, G. (2014).
Biological and psychological markers of stress in humans: focus on the Trier
Social Stress Test. Neurosci. Biobehav. Rev. 38, 94–124. doi: 10.1016/j.neubiorev.
2013.11.005
Aschbacher, K., Epel, E., Wolkowitz, O., Prather, A., Puterman, E., and
Dhabhar, F. (2012). Maintenance of a positive outlook during acute
stress protects against pro-inflammatory reactivity and future depressive
symptoms. Brain Behav. Immun. 26, 346–352. doi: 10.1016/j.bbi.2011.
10.010
Beevers, C. G., and Carver, C. S. (2003). Attentional bias and mood persistence
as prospective predictors of dysphoria. Cognit. Ther. Res. 27, 619–637.
doi: 10.1023/A:1026347610928
Benson, S., Brinkhoff, A., Lueg, L., Roderigo, T., Kribben, A., Wilde, B., et al. (2017).
Effects of acute systemic inflammation on the interplay between sad mood
and affective cognition. Transl. Psychiatry 7, 1281. doi: 10.1038/s41398-017-
0043-0
Boyle, C. C. (2018). Stress, Inflammation and Reward Processing: Implications for
Major Depressive Disorder. Los Angeles, US: UCLA.
Boyle, C. C., Ganz, P. A., Van Dyk, K. M., and Bower, J. E. (2017). Inflammation
and attentional bias in breast cancer survivors. Brain Behav. Immun. 66, 85–88.
doi: 10.1016/j.bbi.2017.05.016
Callaghan, B. L., and Tottenham, N. (2016). The stress acceleration hypothesis:
effects of early-life adversity on emotion circuits and behavior. Curr. Opin.
Behav. Sci. 7, 76–81. doi: 10.1016/j.cobeha.2015.11.018
Campbell, B. M., Charych, E., Lee, A. W., and Möller, T. (2014). Kynurenines
in CNS disease: regulation by inflammatory cytokines. Front. Neurosci. 8:12.
doi: 10.3389/fnins.2014.00012
Capuron, L., and Castanon, N. (2016). “Role of inflammation in the development
of neuropsychiatric symptom domains: evidence and mechanisms,” in
Inflammation-Associated Depression: Evidence, Mechanisms and Implications,
eds R. Dantzer and L. Capuron (Berlin: Springer), 31–44. doi: 10.1007/7854_
2016_14
Capuron, L., and Miller, A. H. (2004). Cytokines and psychopathology: lessons
from interferon-α.Biol. Psychiatry 56, 819–824. doi: 10.1016/j.biopsych.2004.
02.009
Capuron, L., Raison, C. L., Musselman, D. L., Lawson, D. H., Nemeroff, C. B.,
and Miller, A. H. (2003). Association of exaggerated HPA axis response to
the initial injection of interferon-alpha with development of depression during
interferon-alpha therapy. Am. J. Psychiatry 160, 1342–1345. doi: 10.1176/appi.
ajp.160.7.1342
Carroll, J. E., Low, C. A., Prather, A. A., Cohen, S., Fury, J. M., Ross, D. C.,
et al. (2011). Negative affective responses to a speech task predict changes in
interleukin (IL)-6. Brain Behav. Immun. 25, 232–238. doi: 10.1016/j.bbi.2010.
09.024
Caseras, X., Garner, M., Bradley, B. P., and Mogg, K. (2007). Biases in visual
orienting to negative and positive scenes in dysphoria: an eye movement study.
J. Abnorm. Psychol. 116, 491. doi: 10.1037/0021-843X.116.3.491
Coelho, R., Viola, T., Walss-Bass, C., Brietzke, E., and Grassi-Oliveira, R. (2014).
Childhood maltreatment and inflammatory markers: a systematic review. Acta
Psychiatr. Scand. 129, 180–192. doi: 10.1111/acps.12217
Cooper, C. M., Godlewska, B., Sharpley, A. L., Barnes, E., Cowen, P. J., and Harmer,
C. J. (2018). Interferon-αinduces negative biases in emotional processing in
patients with hepatitis C virus infection: a preliminary study. Psychol. Med. 48,
998–1007. doi: 10.1017/S0033291717002379
Danese, A., Moffitt, T. E., Pariante, C. M., Ambler, A., Poulton, R., and Caspi, A.
(2008). Elevated inflammation levels in depressed adults with a history of
childhood maltreatment. Arch. Gen. Psychiatry 65, 409–415. doi: 10.1038/
nrn2297
Dantzer, R., O’Connor, J. C., Freund, G. G., Johnson, R. W., and Kelley, K. W.
(2008). From inflammation to sickness and depression: when the immune
system subjugates the brain. Nat. Rev. Neurosci. 9:46. doi: 10.1001/archpsyc.65.
4.409
DellaGioia, N., and Hannestad, J. (2010). A critical review of human endotoxin
administration as an experimental paradigm of depression. Neurosci. Biobehav.
Rev. 34, 130–143. doi: 10.1016/j.neubiorev.2009.07.014
Disner, S. G., Beevers, C. G., Haigh, E. A., and Beck, A. T. (2011). Neural
mechanisms of the cognitive model of depression. Nat. Rev. Neurosci. 12:467.
doi: 10.1038/nrn3027
Disner, S. G., Shumake, J. D., and Beevers, C. G. (2017). Self-referential schemas
and attentional bias predict severity and naturalistic course of depression
symptoms. Cognit. Emot. 31, 632–644. doi: 10.1080/02699931.2016.1146123
Dooley, L. N., Kuhlman, K. R., Robles, T. F., Eisenberger, N. I., Craske, M. G., and
Bower, J. E. (2018). The role of inflammation in core features of depression:
Insights from paradigms using exogenously-induced inflammation. Neurosci.
Biobehav. Rev. 94, 219–237. doi: 10.1016/j.neubiorev.2018.09.006
Dorr, A. E., and Debonnel, G. (2006). Effect of vagus nerve stimulation on
serotonergic and noradrenergic transmission. J. Pharmacol. Exp. Therap. 318,
890–898. doi: 10.1124/jpet.106.104166
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., et al.
(2010). A meta-analysis of cytokines in major depression. Biol. Psychiatry 67,
446–457. doi: 10.1016/j.biopsych.2009.09.033
Eisenberger, N. I., Berkman, E. T., Inagaki, T. K., Rameson, L. T., Mashal, N. M.,
and Irwin, M. R. (2010). Inflammation-induced anhedonia: endotoxin reduces
ventral striatum responses to reward. Biol. Psychiatry 68, 748–754. doi: 10.1016/
j.biopsych.2010.06.010
Ellenbogen, M. A., Carson, R. J., and Pishva, R. (2010). Automatic emotional
information processing and the cortisol response to acute psychosocial stress.
Cognit. Affect. Behav. Neurosci. 10, 71–82. doi: 10.3758/CABN.10.1.71
Ellenbogen, M. A., Schwartzman, A. E., Stewart, J., and Walker, C.-D. (2002). Stress
and selective attention: the interplay of mood, cortisol levels, and emotional
information processing. Psychophysiology 39, 723–732. doi: 10.1111/1469-8986.
3960723
Ellenbogen, M. A., Schwartzman, A. E., Stewart, J., and Walker, C.-D. (2006).
Automatic and effortful emotional information processing regulates different
aspects of the stress response. Psychoneuroendocrinology 31, 373–387. doi: 10.
1016/j.psyneuen.2005.09.001
Fagundes, C. P., Glaser, R., Hwang, B. S., Malarkey, W. B., and Kiecolt-Glaser, J. K.
(2013). Depressive symptoms enhance stress-induced inflammatory responses.
Brain Behav. Immun. 31, 172–176. doi: 10.1016/j.bbi.2012.05.006
Goebel, M. U., Mills, P. J., Irwin, M. R., and Ziegler, M. G. (2000). Interleukin-6 and
tumor necrosis factor-αproduction after acute psychological stress, exercise,
and infused isoproterenol: differential effects and pathways. Psychos. Med. 62,
591–598. doi: 10.1097/00006842-200007000- 00019
Gotlib, I. H., and Joormann, J. (2010). Cognition and depression: current status and
future directions. Annu. Rev. Clin. Psychol. 6, 285–312. doi: 10.1146/annurev.
clinpsy.121208.131305
Gotlib, I. H., Kasch, K. L., Traill, S., Joormann, J., Arnow, B. A., and Johnson,
S. L. (2004a). Coherence and specificity of information-processing biases in
depression and social phobia. J. Abnorm. Psychol. 113, 386. doi: 10.1037/0021-
843X.113.3.386
Gotlib, I. H., Krasnoperova, E., Yue, D. N., and Joormann, J. (2004b). Attentional
biases for negative interpersonal stimuli in clinical depression. J. Abnorm.
Psychol. 113, 127. doi: 10.1037/0021-843X.113.1.121
Gray, M. A., Chao, C. Y., Staudacher, H. M., Kolosky, N. A., Talley, N. J., and
Holtmann, G. (2018). Anti-TNFαtherapy in IBD alters brain activity reflecting
visceral sensory function and cognitive-affective biases. PLoS One 13:e0193542.
doi: 10.1371/journal.pone.0193542
Hackett, R. A., Hamer, M., Endrighi, R., Brydon, L., and Steptoe, A. (2012).
Loneliness and stress-related inflammatory and neuroendocrine responses in
older men and women. Psychoneuroendocrinology 37, 1801–1809. doi: 10.1016/
j.psyneuen.2012.03.016
Hamer, M., and Steptoe, A. (2007). Association between physical fitness,
parasympathetic control, and proinflammatory responses to mental stress.
Psychos. Med. 69, 660–666. doi: 10.1097/PSY.0b013e318148c4c0
Haroon, E., Raison, C. L., and Miller, A. H. (2012). Psychoneuroimmunology
meets neuropsychopharmacology: translational implications of the impact of
inflammation on behavior. Neuropsychopharmacology 37:137. doi: 10.1038/
npp.2011.205
Harrison, N. A., Brydon, L., Walker, C., Gray, M. A., Steptoe, A., and Critchley,
H. D. (2009). Inflammation causes mood changes through alterations in
subgenual cingulate activity and mesolimbic connectivity. Biol. Psychiatry 66,
407–414. doi: 10.1016/j.biopsych.2009.03.015
Frontiers in Neuroscience | www.frontiersin.org 6April 2019 | Volume 13 | Article 384
fnins-13-00384 April 19, 2019 Time: 17:29 # 7
Maydych Stress, Inflammation and Emotional Attention
Hostinar, C. E., Nusslock, R., and Miller, G. E. (2018). Future directions in the
study of early-life stress and physical and emotional health: implications of the
neuroimmune network hypothesis. J. Clin. Child Adolesc. Psychol. 47, 142–156.
doi: 10.1080/15374416.2016.1266647
Howren, M. B., Lamkin, D. M., and Suls, J. (2009). Associations of depression with
C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychos3. Med. 71, 171–186.
doi: 10.1097/PSY.0b013e3181907c1b
Inagaki, T. K., Muscatell, K. A., Irwin, M. R., Cole, S. W., and Eisenberger,
N. I. (2012). Inflammation selectively enhances amygdala activity to socially
threatening images. Neuroimage 59, 3222–3226. doi: 10.1016/j.neuroimage.
2011.10.090
Ingram, R. E., Miranda, J., and Segal, Z. V. (1998). Cognitive Vulnerability to
Depression. New York, NY: Guilford Press.
Joormann, J., and Gotlib, I. H. (2007). Selective attention to emotional faces
following recovery from depression. J. Abnorm. Psychol. 116:80. doi: 10.1037/
0021-843X.116.1.80
Kiecolt-Glaser, J. K., Gouin, J. P., Weng, N. P., Malarkey, W. B., Beversdorf, D. Q.,
and Glaser, R. (2011). Childhood adversity heightens the impact of later-life
caregiving stress on telomere length and inflammation. Psychos. Med. 73:16.
doi: 10.1097/PSY.0b013e31820573b6
Kirschbaum, C., Pirke, K.-M., and Hellhammer, D. H. (1993). The ‘Trier Social
Stress Test’–a tool for investigating psychobiological stress responses in a
laboratory setting. Neuropsychobiology 28, 76–81. doi: 10.1159/000119004
Köhler, O., Benros, M. E., Nordentoft, M., Farkouh, M. E., Iyengar, R. L.,
Mors, O., et al. (2014). Effect of anti-inflammatory treatment on depression,
depressive symptoms, and adverse effects: a systematic review and meta-
analysis of randomized clinical trials. JAMA Psychiatry 71, 1381–1391.
doi: 10.1001/jamapsychiatry.2014.1611
Kojima, M., Kojima, T., Suzuki, S., Oguchi, T., Oba, M., Tsuchiya, H., et al. (2009).
Depression, inflammation, and pain in patients with rheumatoid arthritis.
Arthritis Care Res. 61, 1018–1024. doi: 10.1002/art.24647
Koster, E. H., De Raedt, R., Goeleven, E., Franck, E., and Crombez, G. (2005).
Mood-congruent attentional bias in dysphoria: maintained attention to and
impaired disengagement from negative information. Emotion 5:446. doi: 10.
1037/1528-3542.5.4.446
Kuhlman, K. R., Robles, T. F., Dooley, L. N., Boyle, C. C., Haydon, M. D., and
Bower, J. E. (2018). Within-subject associations between inflammation and
features of depression: Using the flu vaccine as a mild inflammatory stimulus.
Brain Behav. Immun. 69, 540–547. doi: 10.1016/j.bbi.2018.02.001
Kullmann, J. S., Grigoleit, J. S., Lichte, P., Kobbe, P., Rosenberger, C., Banner, C.,
et al. (2013). Neural response to emotional stimuli during experimental human
endotoxemia. Hum. Brain Mapp. 34, 2217–2227. doi: 10.1002/hbm.22063
Lewinsohn, P. M., Joiner, T. E., and Rohde, P. (2001). Evaluation of cognitive
diathesis-stress models in predicting major depressive disorder in adolescents.
J. Abnorm. Psychol. 110:203. doi: 10.1037/0021-843X.110.2.203
Luecken, L. J., and Appelhans, B. (2005). Information-processing biases in young
adults from bereaved and divorced families. J. Abnorm. Psychol. 114:309.
doi: 10.1037/0021-843X.114.2.309
MacLeod, C., Mathews, A., and Tata, P. (1986). Attentional bias in emotional
disorders. J. Abnorm. Psychol. 95:15. doi: 10.1037/0021-843X.95.1.15
Marsland, A. L., Walsh, C., Lockwood, K., and John-Henderson, N. A. (2017). The
effects of acute psychological stress on circulating and stimulated inflammatory
markers: a systematic review and meta-analysis. Brain Behav. Immun. 64,
208–219. doi: 10.1016/j.bbi.2017.01.011
Mathews, A., and MacLeod, C. (2005). Cognitive vulnerability to emotional
disorders. Annu. Rev. Clin. Psychol. 1, 167–195. doi: 10.1146/annurev.clinpsy.
1.102803.143916
Matsuo, K., Glahn, D., Peluso, M., Hatch, J., Monkul, E., Najt, P., et al.
(2007). Prefrontal hyperactivation during working memory task in untreated
individuals with major depressive disorder. Mol. Psychiatry 12:158. doi: 10.
1038/sj.mp.4001894
Maydych, V., Claus, M., Watzl, C., and Kleinsorge, T. (2018). Attention to
emotional information is associated with cytokine responses to psychological
stress. Front. Behav. Neurosci. 12:687. doi: 10.3389/fnins.2018.00687
Miskowiak, K. W., and Carvalho, A. F. (2014). Hot cognition in major depressive
disorder: a systematic review. CNS Neurol. Disord. Drug Targets 13, 1787–1803.
doi: 10.2174/1871527313666141130205713
Moons, W. G., Eisenberger, N. I., and Taylor, S. E. (2010). Anger and fear responses
to stress have different biological profiles. Brain Behav. Immun. 24, 215–219.
doi: 10.1016/j.bbi.2009.08.009
Muscatell, K. A., Dedovic, K., Slavich, G. M., Jarcho, M. R., Breen, E. C., Bower, J. E.,
et al. (2015). Greater amygdala activity and dorsomedial prefrontal-amygdala
coupling are associated with enhanced inflammatory responses to stress. Brain
Behav. Immun. 43, 46–53. doi: 10.1016/j.bbi.2014.06.201
Muscatell, K. A., and Eisenberger, N. I. (2012). A social neuroscience perspective on
stress and health. Soc. Pers. Psychol. Compass 6, 890–904. doi: 10.1111/j.1751-
9004.2012.00467.x
Muscatell, K. A., Moieni, M., Inagaki, T. K., Dutcher, J. M., Jevtic, I., Breen,
E. C., et al. (2016). Exposure to an inflammatory challenge enhances neural
sensitivity to negative and positive social feedback. Brain Behav. Immun. 57,
21–29. doi: 10.1016/j.bbi.2016.03.022
Musselman, D. L., Lawson, D. H., Gumnick, J. F., Manatunga, A. K., Penna, S.,
Goodkin, R. S., et al. (2001). Paroxetine for the prevention of depression
induced by high-dose interferon alfa. N. Engl. J. Med. 344, 961–966. doi: 10.
1056/NEJM200103293441303
Niemegeers, P., de Boer, P., Schuermans, J., Dumont, G. J., Coppens, V.,
Spittaels, K., et al. (2019). Digging deeper in the differential effects of
inflammatory and psychosocial stressors in remitted depression: effects on
cognitive functioning. J. Affect. Disord. 245, 356–363. doi: 10.1016/j.jad.2018.
11.020
O’connor, J., Lawson, M., Andre, C., Moreau, M., Lestage, J., Castanon, N., et al.
(2009). Lipopolysaccharide-induced depressive-like behavior is mediated by
indoleamine 2, 3-dioxygenase activation in mice. Mol. Psychiatry 14:511. doi:
10.1038/sj.mp.4002148
O’Connor, J. C., Lawson, M. A., André, C., Briley, E. M., Szegedi, S. S., Lestage, J.,
et al. (2009). Induction of IDO by bacille calmette-guerin is responsible for
development of murine depressive-like behavior. J. Immunol. 182, 3202–3212.
doi: 10.4049/jimmunol.0802722
O’Donnell, K., Brydon, L., Wright, C. E., and Steptoe, A. (2008). Self-esteem levels
and cardiovascular and inflammatory responses to acute stress. Brain Behav.
Immun. 22, 1241–1247. doi: 10.1016/j.bbi.2008.06.012
Ondicova, K., Pecenak, J., and Mravec, B. (2010). The role of the vagus nerve in
depression. Neuroendocrinol. Lett. 31:602.
Pace, T. W., Mletzko, T. C., Alagbe, O., Musselman, D. L., Nemeroff, C. B., Miller,
A. H., et al. (2006). Increased stress-induced inflammatory responses in male
patients with major depression and increased early life stress. Am. J. Psychiatry
163, 1630–1633. doi: 10.1176/ajp.2006.163.9.1630
Raison, C. L., Capuron, L., and Miller, A. H. (2006). Cytokines sing the blues:
inflammation and the pathogenesis of depression. Trends Immunol. 27, 24–31.
doi: 10.1016/j.it.2005.11.006
Raison, C. L., and Miller, A. D. (2003). When not enough is too much: the
role of insufficient glucocorticoid signaling in the pathophysiology of stress-
related disorders. Am. J. Psychiatry 160, 1554–1565. doi: 10.1176/appi.ajp.160.9.
1554
Raymond, C., Marin, M.-F., Majeur, D., and Lupien, S. (2018). Early child adversity
and psychopathology in adulthood: HPA axis and cognitive dysregulations
as potential mechanisms. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 85,
152–160. doi: 10.1016/j.pnpbp.2017.07.015
Roelofs, K., Bakvisa, P., Hermans, E. J., van Pelt, J., and van Honk, J. (2007).
The effects of social stress and cortisol responses on the preconscious selective
attention to social threat. Biol. Psychol. 75, 1–7. doi: 10.1016/j.biopsycho.2006.
09.002
Rohleder, N. (2014). Stimulation of systemic low-grade inflammation
by psychosocial stress. Psychos. Med. 76, 181–189. doi: 10.1097/PSY.
0000000000000049
Rosas-Ballina, M., and Tracey, K. J. (2009). Cholinergic control of inflammation.
J. Int. Med. 265, 663–679. doi: 10.1111/j.1365-2796.2009.02098.x
Rothermundt, M., Arolt, V., Peters, M., Gutbrodt, H., Fenker, J., Kersting, A., et al.
(2001). Inflammatory markers in major depression and melancholia. J. Affect.
Disord. 63, 93–102. doi: 10.1016/S0165-0327(00)00157- 9
Sanchez, A., Romero, N., and De Raedt, R. (2017). Depression-related difficulties
disengaging from negative faces are associated with sustained attention to
negative feedback during social evaluation and predict stress recovery. PLoS
One 12:e0175040. doi: 10.1371/journal.pone.0175040
Frontiers in Neuroscience | www.frontiersin.org 7April 2019 | Volume 13 | Article 384
fnins-13-00384 April 19, 2019 Time: 17:29 # 8
Maydych Stress, Inflammation and Emotional Attention
Slavich, G. M., and Irwin, M. R. (2014). From stress to inflammation and major
depressive disorder: a social signal transduction theory of depression. Psychol.
Bull. 140:774. doi: 10.1037/a0035302
Slavich, G. M., Way, B. M., Eisenberger, N. I., and Taylor, S. E. (2010). Neural
sensitivity to social rejection is associated with inflammatory responses to
social stress. Proc. Natl. Acad. Sci. U.S.A. 107:201009164. doi: 10.1073/pnas.
1009164107
Smeets, T. (2010). Autonomic and hypothalamic-pituitary-adrenal stress
resilience: impact of cardiac vagal tone. Biol. Psychol. 84, 290–295.
doi: 10.1016/j.biopsycho.2010.02.015
Thayer, J. F., Åhs, F., Fredrikson, M., Sollers, J. J. Jr., and Wager, T. D.
(2012). A meta-analysis of heart rate variability and neuroimaging
studies: implications for heart rate variability as a marker of stress and
health. Neurosci. Biobehav. Rev. 36, 747–756. doi: 10.1016/j.neubiorev.2011.
11.009
Thayer, J. F., and Sternberg, E. (2006). Beyond heart rate variability: vagal
regulation of allostatic systems. Ann. N. Y. Acad. Sci. 1088, 361–372. doi: 10.
1196/annals.1366.014
Tsumura, H., and Shimada, H. (2012). Acutely elevated cortisol in response to
stressor is associated with attentional bias toward depression-related stimuli but
is not associated with attentional function. Appl. Psychophysiol. Biofeedback 37,
19–29. doi: 10.1007/s10484-011- 9172-z
Valkanova, V., Ebmeier, K. P., and Allan, C. L. (2013). CRP, IL-6 and depression:
a systematic review and meta-analysis of longitudinal studies. J. Affect. Disord.
150, 736–744. doi: 10.1016/j.jad.2013.06.004
Wagner, G., Sinsel, E., Sobanski, T., Köhler, S., Marinou, V., Mentzel, H.-J.,
et al. (2006). Cortical inefficiency in patients with unipolar depression: an
event-related FMRI study with the Stroop task. Biol. Psychiatry 59, 958–965.
doi: 10.1016/j.biopsych.2005.10.025
Weber, C. S., Thayer, J. F., Rudat, M., Wirtz, P. H., Zimmermann-Viehoff, F.,
Thomas, A., et al. (2010). Low vagal tone is associated with impaired post
stress recovery of cardiovascular, endocrine, and immune markers. Eur. J. Appl.
Physiol. 109, 201–211. doi: 10.1007/s00421-009-1341-x
Weinstein, A. A., Deuster, P. A., Francis, J. L., Bonsall, R. W., Tracy, R. P., and Kop,
W. J. (2010). Neurohormonal and inflammatory hyper-responsiveness to acute
mental stress in depression. Biol. Psychol. 84, 228–234. doi: 10.1016/j.biopsycho.
2010.01.016
Woody, A., Figueroa, W. S., Benencia, F., and Zoccola, P. M. (2017). Stress-induced
parasympathetic control and its association with inflammatory reactivity.
Psychos. Med. 79, 306–310. doi: 10.1097/PSY.0000000000000426
Yamakawa, K., Matsunaga, M., Isowa, T., Kimura, K., Kasugai, K., Yoneda, M.,
et al. (2009). Transient responses of inflammatory cytokines in acute stress. Biol.
Psychol. 82, 25–32. doi: 10.1016/j.biopsycho.2009.05.001
Conflict of Interest Statement: The author declares that the research was
conducted in the absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Copyright © 2019 Maydych. This is an open-access article distributed under the
terms of the Creative Commons Attribution License (CC BY). The use, distribution
or reproduction in other forums is permitted, provided the original author(s) and
the copyright owner(s) are credited and that the original publication in this journal
is cited, in accordance with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with these terms.
Frontiers in Neuroscience | www.frontiersin.org 8April 2019 | Volume 13 | Article 384
