Angela Clayborne

ENC 1102
Bibliography
This bibliography is intended to give a broad scope on the research of
psychoneuroimmunology, the study of the interaction between the nervous and immune
systems and psychological processes, over the past 20 years and some current research,
but mainly to describe and analyze the bidirectional communication between the nervous
an immune systems and how cytokines, immune cells, can affect mood (leading to mood
disorders), behavior, and cognition, particularly in patients with autoimmune diseases.
How this research can be translated into treatments for psychiatric disorders is still being
studied and is therefore beyond the scope of this investigation. In addition, this
bibliography mainly focuses on the effects of cytokines that help play a role in the
development of depression in patients and not so much other psychiatric diseases like
schizophrenia or bipolar disorder, for example.

The information relayed in this investigation all came from academic articles from
various research journals, with the exception of one presidential address from the journal
of Brain, Behavior, and Immunity. It is this type of work that is considered to be valid
sources for this investigation because these academic articles give an accurate and precise
insight into the bidirectional communication between the immune system and the nervous
system and the effects of cytokines on mood, behavior and cognition. Also, the authors of
the academic articles all have an extensive background into this type of research, thus
allowing them to be considered experts on the topic and ensuring that the information
will be valid. Of all the academic articles, the ones that included how the immune system

and nervous system communicate bidirectionally and/or the relationship of proinflammatory cytokines to the development of depression in patients were selected.
Academic articles that explored the possible effects of immune activation on behavior
were selected as well. If the article did not include information on at least one of these
topics, it was not included in this bibliography.

Capuron, L., & Dantzer, R. (2003). Cytokines and depression: The need for a new
paradigm. Brain, Behavior, and Immunity, 17, 119-124.
In this academic journal article, the authors, who are professors in the Department of
Psychiatry and Behavioral Sciences at the Emory University School of Medicine,
discuss a little bit of the background of the relationship between cytokines and
depression. These cytokines can cause changes in brain function causing patients
suffering with depression to face social withdrawal, cognitive impairment, and
altered neurotransmission. The authors also talk about the controversy on innate
immune system activation and whether it really helps depressed patients. The rest
of the article speaks on how new data on this topic could possibly lead to
advances in understanding and management of neurobehavioral symptoms
related to cancer. It is evident that cytokines play a particular role in changes in
mood and cognition in cancer patients, but identification of cytokines role and
their mode of action has not been achieved yet. However, once this is, it will
greatly benefit people suffering from psychiatric diseases. This article is relevant
to my research topic in its discussion of the relationship between cytokines and

depression and of its explanation of immune activation and how it could possibly
help patients suffering from depressive symptoms.

Dantzer, R., O'Connor, J., Freund, G., Johnson, R., & Kelley, K. (2008). From
Inflammation To Sickness And Depression: When The Immune System
Subjugates The Brain. Nature Reviews Neuroscience, 9, 46-56.
The authors of this scholarly academic article, who are researchers/professors at the
University of Illinois, examine innate immune cells and how their role in the
body can lead to depression. They say that these immune cells produce proinflammatory cytokines that work on the brain causing a sickness behavior in the
body. When this activation is unfaltering, in situations like infections, cancer, and
autoimmune diseases, the immune signaling to the brain can lead to the
development of depression. They feel that this finding can be an explanation for
the rising occurrence of clinical depression in people with physical sicknesses.
They conclude by stating that The identification of the intracellular molecular
mechanisms that are at the origin of the association between inflammation and
depression will provide valuable targets for the development of new
antidepressant drugs only if the activation of brain pro-inflammatory cytokine
signaling is proven to represent the final pathway for the various conditions that
lead to depression. This is especially important to my research because it
explains just how immune cells can possibly cause depression in patients with
autoimmune diseases.
Farzi. (n.d.). The homeostatic role of neuropeptide Y in immune function and its impact

on mood and behaviour. Acta Physiologica, 213(3), 603-627.

Farzi, Reichmann, and Holzer, researchers at the Institute of Experimental and
Clinical Phamacology, discuss the neuropeptide Y (NPY), a highly abundant
peptide in the nervous system, and how it regulates mood, brain activity, stress
coping, and directly affects cells a part of the immune system. They reflect on
how there is a special relationship between stress, the immune system, and mood
disorders and how NPY can help prevent the development of depression. So,
NPY helps to balance disruptions of physiological systems caused by immune
challenges and can counteract the negative impact of these challenges stress
coping, mood, and emotional processing. This article shows relevance to my
research topic because it discusses a part of the relationship between the nervous
and immune systems and how this certain peptide can counteract the depressive
symptoms that the immune system can cause.

Innate Immunity at the Forefront of Psychoneuroimmunology. (2004). Brain, Behavior,

and Immunity, 18, 1-6.
In this presidential address by an unknown author, the topic of
psychoneuroimmunology is explored. The address gives a slight insight into
what psychoneuroimmunology is, what research it involves, and the main
discoveries and progress this field of research has achieved. The remainder of the
address is focused on the main methodological and conceptual developments
that have allowed such progress. Some of these developments include the
impact of inflammation, how the brain mirrors the inflammation response, and

the effect of cytokines and how it can lead to depressive symptoms in patients
with immune diseases. The address concludes by stating that a healthy subject is
a one whose immune system remains quiet and does not interfere with brain
processing of external information. This article is relevant to my topic in its
definition of Psychoneuroimmunology and discussion of the past progresses that
this field has obtained on the topic of the nervous system and the immune
system.
Irwin, M., & Miller, A. (2007). Depressive Disorders And Immunity: 20 Years Of
Progress And Discovery. Brain, Behavior, and Immunity, 21, 374-383. The
authors of this academic journal article, who are researchers at the Center
for Psychoneuroimmunology at the University of California and the
Department of Psychiatry and Behavioral Sciences at the Emory
University School of Medicine, talk about the many developments
regarding the relationship between depression and the immune system that
has occurred over the past 20 years and how these developments have
revealed the importance of psychoneuroimmunology in a clinical context.
They discuss some initial studies of the impact of depression on defined
immunologic endpoints, how these studies have led to more recent
studies on the effects on depression on immune based diseases, and how
influences of the immune system on the brain can affect behavior and
mood. They state that more data now shows that activating the immune
system can affect many parts of the central nervous system function like
neurotransmitter metabolism and information processing that can lead to

behavior changes in humans. They conclude this article by stating that

there is significant evidence to conclude that depression involves
alterations in multiple aspects of immunity that may not only contribute to
the development of exacerbation of a number of medical disorders but also
may contribute to the pathophysiology of the disease itself. They also
conclude that psychoneuroimmunology may have significant implications
on the problems and treatment of depression. This article is very important
to my research because it relates to the information discussed in the
previous article and it also discusses not only past discoveries but also
more recent studies on how the immune system can play a role in
depression and how immune activation can affect human behavior.

Irwin, M. (2008). Human psychoneuroimmunology: 20 Years of discovery. Brain,

Behavior, and Immunity, 22, 129-139.
This scholarly journal article written by Michael Irwin, a researcher at the
Center for Psychoneuroimmunology and the Institute for Neuroscience at
the University of California, examines psychoneuroimmunology and how
its research reveals ways that behavior and health are interrelated. This
article discusses the perspective of his laboratory over the last 20 years to
define the many aspects of the inter-relationship between behavior and
immunity. Some of these aspects include the hypothalamic pituitary
adrenal and autonomic mechanisms that link the central nervous system
and immune responses, the clinical implications of immune alterations

during depression or life stress on inflammatory and infectious disease

risk, and the reciprocal role of immune mediators on behavior in humans.
At the conclusion, Irwin discusses how the nervous, endocrine, and
immune systems have a bidirectional communication through the means
of common hormones, neuropeptides, and cytokines. Even though there is
a lot of research on the communication between the brain and the immune
system, there is little to no definitive research on the immune-to-brain
communication pathway on the cellular and molecular level. This article
is important to this research discussion because it gives another definition
of the field of Psychoneuroimmunology and explores the bidirectional
communication between the nervous and immune system and the means of
how this communication is possible.

Jones, K., & Thomsen, C. (n.d.). The role of the innate immune system in psychiatric
disorders. Molecular and Cellular Neuroscience, 52-62.
In this scholarly journal article, two researchers a part of Lundbeck Research USA,
examine biochemical, cellular, and animal disease models, and clinical
observations to uncover the relationship between the immune system and
psychiatric disorders. It has been discovered that some cytokines have special
and unique actions on neurons and circuits in the central nervous system that
effect neurotransmission, memory, and animal behaviors like social withdrawal,
for example. It also points out directions for future studies for discovering and
developing new ways for treating psychiatric illnesses. The article is important

because it gives an inside look how just how the immune system has a
relationship with psychiatric disorders and exactly what behaviors are changed in
response to cytokines.
Kiecolt-Glaser, J., McGuire, L., Robles, T., & Glaser, R. (2002).
EMOTIONS,MORBIDITY, AND MORTALITY: New Perspectives from
Psychoneuroimmunology. 83-107.
The authors, who are researchers at the Ohio State University College of Medicine,
analyze how mood disorders may be influenced by the immune system because
of the pro-inflammatory cytokines it releases. The article includes background on
depression and anxiety as well as stress. They then tie all these together and how
anxiety and stress with the influence of the immune system can lead to
depression. The authors also discuss the effect of immune and neuroendocrine
alterations on emotions. This article relates back to the information discussed in
the article by Farzi in the way it also includes information about stress. This
relates because it gives a more in-depth definition and look on depression and
how there are other factors, like stress and anxiety, than can influence the
immune system leading to depression.
Kubesova, A., Tejkalova, H., Syslova, K., & Horacek, J. (n.d.). Biochemical,
Histopathological and Morphological Profiling of a Rat Model of Early Immune
Stimulation: Relation to Psychopathology. Plos One.
In this scholarly academic article, researchers from the Prague Psychiatric Center,
the National Institute of Mental Health, Charles University, and the Institute of
Chemical Technology describe the perinatal immune challenge and how it leads

to neurodevelopmental dysfunction, permanent immune dysregulation, and

abnormal behavior like those seen in various psychiatric disorders like mood and
anxiety disorders, for example. However, the purpose of this article is to
illuminate the effect on early immune stimulation that may reveal more on the
neurobiology of the human psychopathy. They studied adult male Wistar rats and
examined their brains, the plasma levels of certain neurotransmitters,
metabolites, and other things relating to the brain. The study found that immune
stimulation in adult animals can affect the levels of neurotransmitters and their
metabolites and lead to astrogliosis, a volume reduction in the hippocampus,
which supports the claim that immune stimulation has a very important role in
neuropsychiatric disorders. This article is especially important to my research
topic because it gives a more in depth look on the effects of immune stimulation
that the other articles did not.
Maes, M., Schiepers, O., & Wichers, M. (2005). Cytokines in major depression. Progress
in Neuro-Psychopharmacology and Biological Psychiatry, 29, 201-217.
The authors of this scholarly journal article, researchers/professors in the
Department of Psychiatry and Neuropsychology at Maastricht University,
explore the communication between the nervous, endocrine, and immune
systems and reflect on the increasing interest of the involvement of the immune
system in psychiatric disorders, mainly depression. They go into detail on how
pro-inflammatory cytokines can induce sickness behavior and consequently
can lead to changes in cognition, mood, and bring about depression. Also how
cytokines can reduce the ability of certain neurotransmitters that help keep

people from feeling depression. Even though it seems that cytokines can account
for the cause of many symptoms of depression, it remains to be established
whether cytokines play a causal role in depressive illness or represent
epiphenomena without major significance. This article is relevant to my topic
because is discusses the effects of cytokines on behavior, mood, and cognition
and what exactly cytokines do that can lead to depression.
Maier, S., & Watkins, L. (1998). Cytokines for Psychologists: Implications of
Bidirectional Immune-to-Brain Communication for Understanding Behavior,
Mood, and Cognition. American Psychological Association, 105(1), 83-107.
In this academic journal article, the authors, researchers at the University of
Colorado, discuss the brain, the immune system, and how they form a
bidirectional communication network where the immune system acts as a diffuse
sense organ that informs the brain about the happenings in the body. They also
discuss immune-brain pathway activation and how it may be important in
understanding certain occurrences that relate to like depression and suppression
of specific immunity, for example. In the article, the authors focused on articles
that delivered agents that stimulate immune cells, resulting in major changes in
behavior. They concluded by saying that the harmless protein giving to the
subjects in the experiments are often encountered by humans in everyday life and
question whether this immune stimulation could be a cause for the mood,
behavior, and cognition changes we experience from one day to the next. This
article is important in my researcher because it greatly discusses the bidirectional
communication between the brain and the immune system and immune

activation.
Myint, A., & Kim, Y. (n.d.). Network beyond IDO in psychiatric disorders: Revisiting
neurodegeneration hypothesis. Progress in Neuro-Psychopharmacology and
Biological Psychiatry, 304-313.
The authors of this academic article, who are researchers of various universities,
discuss how immune system activation has a well-documented involvement in
the pathophysiology in certain psychiatric disorders. They revel on how
cytokines can enhance the activity of an enzyme that can induce serotonin
depletion and a depressive mood, whereas the downstream metabolites can cause
changes in neuropsychiatric challenges. This article, however, focuses on the
involvement of the interaction between cytokines and IDO pathway in
depression, and the relationship between immune cells, other immune molecules,
and certain neurotransmitters and depression and other psychiatric disorders.
This article is important to my topic because it introduces how immune
activation has involvement in the pathophysiology of psychiatric disorders and
gives specific details on the role of cytokines in depression.
Pollak, Y., & Yirmiya, R. (n.d.). Cytokine-induced changes in mood and behaviour:
Implications for ???depression due to a general medical condition???,
immunotherapy and antidepressive treatment. The International Journal of
Neuropsychopharmacology, 389-399.
In this scholarly journal article, Yehuda Pollak and Raz Yirmiya, who are professors
at the Hebrew University of Jerusalem, evaluate the relationship between the
immune system and depression. They find through six major conclusions about

depression and medical conditions, like that cytokine immunotherapy in cancer

patients had brought about a major depressive episode in a huge number of
patients, that elevated levels of cytokines directly relates to depression and that
illnesses associated with depression should be treated with anti-depressant drugs.
This article shows relevance to my research conversation in its six conclusion
about depression and medical conditions.
Raison, C., Capuron, L., & Miller, A. (2006). Cytokines Sing The Blues: Inflammation
And The Pathogenesis Of Depression. Trends in Immunology, 27(1), 24-31.
Raison, Capuron, and Miller, researchers in the Department of Psychiatry and
Behavioral Sciences at Emory University School of Medicine, explore the role of
inflammatory responses caused by cytokines in the pathophysiology of
depression. It has been found that patients with depression have higher levels of
pro-inflammatory cytokines compared to those without depression. Also 50% of
patients taking therapy involving cytokines have shown depressive symptoms.
Cytokines also affect neurotransmitter metabolism, neuroendocrine function, and
behavior. Stress also plays a role in the increased amount of inflammatory
responses that lead to depression. The authors feel that depression might be a
behavioral byproduct of early adaptive advantages conferred by genes that
promote inflammation. They also feel that studying the signaling pathways of
pro-inflammatory cytokines can be an effective method to treat depression. This
article is relevant to my research in its discussion of the role of cytokines in the
pathophysiology of depression.
Sperner-Unterweger, B., Kohl, C., & Fuchs, D. (2012). Immune changes and

neurotransmitters: Possible interactions in depression? Progress in NeuroPsychopharmacology and Biological Psychiatry, 268-276.
In this academic journal article written by Barbara S-U, Claudia Kohl, and Dietmar
Fuchs, researchers at Innsbruck Medical University in Innsbruck Austria, the
authors discuss the role of neurotransmitters in neuropsychiatric symptoms, like
changes in mood and depression. These symptoms are common in patients with
inflammatory disorders but the pathogenesis of the symptoms is still elusive to
many researchers. The authors also discuss the role of immune activation in the
occurrence of these symptoms and the interactions between certain metabolic
pathways that may possibly be involved in depression and immune activation.
Considering these facts this hypothesis was made: Influenced by genetic an
epigenetic factors, the further development of depressive symptoms depends on
the onset, the duration, the intensity, and the characteristics of the immune
activating triggers. However, a link to neuropsychiatric symptoms in patients
that have inflammatory conditions has yet to be proven. This article shows
relevance to my topic because it discusses the role of neurotransmitters in
changes in mood and depression and the interaction between immune activation
and pathways that may be involved in depression.
Szabo, A., & Rajnavolgyi, E. (2013). The Brain-Immune-Gut Triangle: Innate Immunity
in Psychiatric and Neurological Disorders. Current Immunology Reviews, 9(4),
241-248.
The authors of this academic journal article start off the work by acknowledging that
it has been known for a while that there is communication between the immune

and nervous systems, but they also state how the biological rules and
complexity of the neuroimmune axis is yet to be clarified. The majority of the
article focuses on innate immune cells and the role they play in psychiatric and
neurological diseases. They also extensively look at monocytes, macrophages,
and dendritic cells and their role in inflammation. They feel that this research can
bring promising new innovations for therapeutic treatments in the future and
propose new perspectives for immune cell modification and their responses to
inflammatory signaling in the brain. This article has relevance to my research
topic in its exploration of immune cells and the role they play in psychiatric
diseases.
Yirmiya, R. (2000). Depression in medical illness: The role of the immune system.
Western Journal of Medicine, 333-336.
In this academic article, Raz Yirmiya defines Cytokines as nonantibody proteins
released by cells on contact with antigens and that act as intercellular mediators
and explains how during a physical sickness, the immune system communicates
with the brain through cytokine secretions. The author also discusses the
relationship between high levels of cytokines and psychological distresses like
depression, how immune activation can lead to depression, or at least a depressed
mood, and how depressive symptoms in patients that are physically sick could
actually possibly be because of immune activation and cytokine secretions and
not our brains psychological reaction to distress and incapacitation caused by the
sickness. This article is important to my research conversation because of its
definition of cytokines and its inclusion of the relationship between high levels of

cytokines and psychological distresses.

Ziemssen, T., & Kern, S. (2003). Psychoneuroimmunology Cross-talk between the
immune and nervous systems. Journal of Neurology, II8-II11.
The authors who wrote this academic journal article, researchers at the
Neuroimmunological Laboratory and Neurological Clinic in Dresden, Germany,
reflect on what the new field of Psychoneuroimmunology is and how it came to
be by the discovery of the communication between the immune and the nervous
system. They discuss how the brain modulates the immune system and vice versa
and how the nervous and endocrine system communicate as well. Also, they
explore the bidirectional communication between the central nervous system and
the immune system and how cytokines within the immune system can have an
effect on mood, behavior, and cognition. At the conclusion of the article, the
authors analyze how behavioral interventions can be effective in improving
mood, health behavior, and in altering neuroendocrine and immune functions.
However, researchers are not at the stage where a certain behavioral intervention
can be picked based on its ability to change parameters of physiological
function that are relevant to the progression of specific disease processes. This
article is important to my research topic because it talks about the bidirectional
communication between the immune and nervous systems, how exactly this
communication takes place, and the effects of cytokines on mood, behavior, and
cognition.