Angela Clayborne

Professor Wolcott
ENC 1102

The Immune and Nervous Systems and Psychiatric

Disorders: Where We Are Now and What Else There Is To
Know
The field of Psychoneuroimmunology, the study of the interaction between
the nervous and immune systems and psychological processes, has
discovered some great findings over the past 20 years concerning the
relationship between the immune system and the nervous system. Some of
these findings include the bidirectional communication between the nervous
and immune systems and how cytokines, small proteins found in the immune
system that are important in cell signaling, can affect mood (leading to mood
disorders), behavior, and cognition, particularly in patients with autoimmune
diseases (Jones; Maes et al., 2005; Maier & Watkins, 1998; Yirmiya, 2000;
Ziemssen & Kern, 2003; Irwin et al., 2007; Dantzer et al., 2008; Jones;
Kiecolt-Glaser et al., 2002; Maes et al., 2005; Myint & Kim; Pollak & Yirmiya;
Raison et al., 2006; Ziemssen & Kern, 2003). More recent research has been
focused on the effects of immune activation on behavior, mood, and
cognition (Irwin et al., 2007; Jones; Kiecolt-Glaser et al., 2002; Kubesova et
al.; Maier & Watkins, 1998; Myint & Kim; Kohl et al., 2012). Also, it is believed
that further study of this topic can provide new and improved treatments for

depression (Irwin et al., 2007; Jones; Raison et al., 2006; Szabo &
Rajnavolgyi, 2013). This literature review is intended to discuss key points on
the topic of the relationship between the immune system and the nervous
system and how the components of this relationship can affect behavior,
cognition, and mood leading to psychiatric disorders; however, in this review,
there is a focus on clinical depression and not so much on other psychiatric
disorders like bipolar disorder and schizophrenia, for example.

Bidirectional Communication Between the Immune and Nervous

Systems
One revolutionary discovery to psychiatrists and neuroscientists is that
there is a bidirectional communication between the immune system and the
nervous system. (Jones; Maes et al., 2005; Maier & Watkins, 1998; Yirmiya,
2000; Ziemssen & Kern, 2003) For a while, it was thought that the immune
system was autonomous, but research has shown that the Central Nervous
System (CNS) receives messages from the immune system and vice versa.
(Ziemssen & Kern, 2003; Yirmya, 2000) These two systems engage in
communication with each other for one vital reason: to maintain
homeostasis. This communication is enabled through the use of various
chemical messengers like neuroendocrine peptides, various hormones, and
cytokines. (Ziemssen & Kern, 2003).

Pro-inflammatory Cytokines and Depression

Pro-inflammatory cytokines can play a role in depression in patients with

autoimmune diseases and can lead to changes in behavior, mood, and
cognition (Irwin et al., 2007; Dantzer et al., 2008; Jones; Kiecolt-Glaser et al.,
2002; Maes et al., 2005; Myint & Kim; Pollak & Yirmiya; Raison et al., 2006;
Ziemssen & Kern, 2003). Cytokines are major communication molecules in
the immune system, and they play a key role in the regulation of the immune
response (Dantzer et al., 2008). It wasnt discovered that cytokines can
induce depressive symptoms in patients until clinicians, who were treating
cancer patients with purified or recombinant cytokines, noticed the
appearance of major depressive systems in a significant majority of the
patients. (Dantzer et al., 2008; Myint & Kim) Clinicians also noted that
cytokines administered exogenously induce a large set of symptoms,
referred to as sickness behavior, including malaise, weakness, fatigue,
sleepiness, and disinterest for usual activities, including feeding, drinking,
and social interaction (Dantzer, 2001; Dantzer et al., 2008; Maes et al.,
2005). Cytokines are believed to carry out these effects on mood and
behavior through distinct mechanisms, but this explanation needs more
investigation (Kiecolt-Glaser et al., Dantzer et al., 2008; Ziemssen & Kern,
2003)

Immune Activation and Mood, Behavior, and Cognition

Immune activation has also been demonstrated to negatively affect
behavior, mood, and cognition in humans. (Irwin et al., 2007; Jones; Kiecolt-

Glaser et al., 2002; Kubesova et al.; Maier & Watkins, 1998; Myint & Kim;
Kohl et al., 2012) Immune activation is the activation of the immune
response through mechanisms that are not quite understood yet. Some
researchers believe that Neuropeptide Y can induce immune activation.
Immune activation has been associated with deficits in hippocampaldependent memory such as contextual fear conditioning (OConnor et al.,
2008) It has also seen to create a distressed mood in patients and bring
about major depression. (Yirmiya, 2000) Despite the fact that it is not quite
understood how immune activation causes depressive moods, evidence has
shown that immune activation and inflammatory cytokines may work
together to play a role in depression. (Yirmiya, 2000; Jones)

Stress and the Immune System

Stress can also have a negative impact on the immune system leading to
altered moods (Farzi, 2015; Kiecolt-Glaser et al., 2002; Raison et al., 2006).
Evidence has shown that the production of pro-inflammatory cytokines can
be stimulated by stress and stressful experiences (Kiecolt-Glaser et al.,
2002). Stress and distress-related immune dysregulation is also a main
mechanism behind negative emotions and anxiety (Kiecolt-Glaser et al.,
2002; Raison et al., 2006).

Cytokines, Depression, and Treatments

As research continues, researchers are confident that understanding the

relationship between pro-inflammatory cytokines and depression can

possibly lead to new treatments for depression (Irwin et al., 2007; Jones;
Raison et al., 2006; Szabo & Rajnavolgyi, 2013). They feel that this can be
achieved by the identification of the intracellular molecular mechanisms
that are at the origin of the association between inflammation and
depression and only if cytokine signaling is the final pathway for the
conditions that lead to depression (OConnor et al., 2008; Irwin, 2008).

Conclusion/Gap
There is significant evidence that there is a relationship between the
immune system and the nervous system and that cytokines levels and
immune activation can affect cognition, behavior, and mood bringing about
depression in patients with autoimmune diseases. There has been light
discussion on possible treatments to depression that can arise from studying
these relationships; however very little research has been put forth to
discover these new treatments and therefore merits further research and
discussion. Also, there has been no discussion on if the antidepressants used
today reduce the amount of cytokines in patients. If new treatments for
battling depression were attained, then some of the problems facing
antidepressant use today, like an increased risk for suicide, increased
duration of chronic depression, agitation, and anxiety could possibly be
resolved or significantly reduced.

Project Proposal
Objective: The objective of this study, if it was actually carried out, would
be to determine the cytokine levels in clinically depressed patients and to
determine if current antidepressants can reduce the amount of cytokines
found in the patients.
Participants: The participants of the study would be comprised of 200
people: 100 clinically depressed patients between the ages of 18-65 who are
currently not being medicated for depression and 100 volunteers to act as
the control group between the ages of 18-65 who are not clinically depressed
and are not currently taking any other medications.
Procedure: First, the 100 patients with depression would be examined to
determine the extent of their depression. Then all 200 participants would
have a sample of blood extracted to determine the number of cytokines
present. Once this data was recorded, all participants would be given a
dosage of a common antidepressant drug (any common antidepressant
could suffice as long as every participant received the same antidepressant)
as recommended on the label for a month. At the end of the month, each
participant would have a blood sample taken again and analyzed to
determine the number of cytokines present.

Results and Discussion: If there was a significant difference in the amount

of cytokines in clinically depressed patients compared to people without
depression (where the people with depression show higher numbers of

cytokines than people without depression) and if, between the patients with
depression, patients with chronic depression showed higher amounts of
cytokines than patients that have had depression for shorter periods of time,
then that would show that cytokines can influence the occurrence and
duration of clinical depression. Also if the data showed that the
antidepressant drugs didnt significantly reduce the amount of cytokines,
then more research would need to be conducted to come up with an
antidepressant or other treatment that could reduce the number of cytokines
and possibly regulate the production of cytokines, thus treating depression
more effectively and for longer periods with less relapses.

Works Cited

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paradigm. Brain, Behavior, and Immunity, 17, 119-124.
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.
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.
Irwin, M., & Miller, A. (2007). Depressive Disorders And Immunity: 20 Years Of Progress And
Discovery. Brain, Behavior, and Immunity, 21, 374-383.
Irwin, M. (2008). Human psychoneuroimmunology: 20 Years of discovery. Brain, Behavior, and
Immunity, 22, 129-139.
Jones, K., & Thomsen, C. (n.d.). The role of the innate immune system in psychiatric disorders.
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Maier, S., & Watkins, L. (1998). Cytokines for Psychologists: Implications of Bidirectional
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