Download Schizophrenia an Autoimmune Disorder

IMMUNOLOGY
1
Schizophrenia: an Autoimmune Disorder
By Jennifer Kitchen
March 4, 2013
IMMUNOLOGY
2
Schizophrenia is a mental disorder that can impair a person’s ability to function.
A schizophrenic person may suffer from a wide array of pathological and behavioral
issues. These symptoms, considered either positive or negative manifestations, can
make daily living difficult. A schizophrenic person may suffer from positive
manifestations, such as delusions, hallucinations, disorganized speech, and grossly
disorganized or catatonic behavior (Frazier and Dryzmkowski, 2009). These symptoms
make dealing with reality much harder but along with a loss of many main functions
living can be a struggle. Negative manifestations of schizophrenia include affective
flattening, (a disturbance of feeling and emotion), alogia (loss of language or the ability
to communicate), and avolition (lack of motivation or drive) (Frazier and Dryzmkowski,
2009). Feelings of no purpose and no desire, along with the inability to convey these
disturbances to others are daily struggles a schizophrenic person must deal with.
Research into the underlying causes of these symptoms has come to some amazing
discoveries in immunology and genetics.
Relatives of a schizophrenic person have a greater risk, ten to one, of becoming
schizophrenic than people who do not have a relative with schizophrenia, as this
disorder is hereditary (Frazier and Dryzmkowski, 2009). Researchers have looked into
the genetic link and found an association. Different gene loci have been located on
chromosome 6p22.1 and researchers are considering them the most probable genes for
schizophrenia (Müller and Schwarz, 2010). This region, 6p22, contains genes involved
in immune regulation and the immune response is what “turns on” the schizophrenic
genes. For decades, viruses have been seen as the promoter of this disorder but
recently new findings show that it is not the virus or infectious agent, but the immune
IMMUNOLOGY
3
response, which determines the risk for schizophrenia (Müller and Schwarz, 2010).
This mental disorder is actually acquired through infection stimulating the immune
response, which in turn affects a genetic aspect that “turns on” schizophrenia.
The Immune Response and Schizophrenia
Inflammation is usually the protective response tissues have to injury, which
serves to destroy, dilute, or wall off both the injurious agent and the injured tissues.
Inflammation may be caused by infectious injury due to a bacterium or virus. The
reaction often helps protect the body. Research found signs of chronic inflammation of
the brain (encephalitis) were seen in schizophrenics, which produces
neurodegeneration (Müller and Schwarz, 2010). The neurodegenerative effects of this
chronic immune response explain some of the symptoms seen in patients with
schizophrenia.
Cytokines are small proteins released by cells that have specific effects on the
interactions between cells, communications between cells, or the behavior of cells. The
cytokines includes the interleukins, lymphokines, and cell signal molecules, such as
tumor necrosis factor and interferons. It can be shown that the cytokine, Interleukin-8,
increases the risk for schizophrenia in offspring of mothers who had increased levels of
this IL-8 during pregnancy (Müller and Schwarz, 2010). Interleukin-8 (IL-8) is a cytokine
derived from endothelial cells, fibroblasts, keratinocytes, macrophages, and monocytes
that causes chemotaxis of neutrophils and T-cell lymphocytes. Chemotaxis is a
response leukocytes have to products, such as IL-8, formed by immunological
reactions. In chemotaxis, leukocytes are attracted to and accumulate at the site of the
IMMUNOLOGY
4
reaction as part of the inflammatory response. Other cytokines have also been shown
to express neuropsychiatric side effects (depression, anxiety, hypomanic mood, etc.) in
patients treated with, interferon-gamma and Interleukin-2 (IL-2) (Schwartz and
Shechter, 2010). The proinflammatory response, when occurring in the central nervous
system (CNS), can be mentally impairing if the reaction goes on for too long.
The immune response is not made to stay active for long periods. The cytokines
calling forth leukocytes to the site of infection or trauma and causing chronic
inflammation is seen to increase risk for schizophrenia. Many studies are proposing a
link between systemic inflammation and this disorder, viewing inflammation in the CNS
as leukocytes attacking the brain (Schwartz and Shechter, 2010). When the immune
system prolongs inflammation, abnormal behavior may ensue and long-term damage to
the brain incurs. Schizophrenia can be seen as a degenerative disease, as the immune
system attacks cells in the CNS, oligodendrocyte cell loss, impaired synaptic
connectivity, and pyramidal cell dendrite shrinkage occur (Carter, C. J., 2011). The
autoimmune response in actuality is killing the brain cells.
Schizophrenia is a mental disorder brought about by an infection causing the
immune system to over-react and causes a genetic “switch” to be turned on. There is
no knowing if an individual has the precursor gene for schizophrenia without having a
genetic test done to see if there is an abnormal sequence in chromosome 6p22.1. Still,
more studies need to be done to confirm if this different gene loci is the culprit. Since
schizophrenia is genetic, there is no vaccine to prevent it and the best anyone can do is
comply with treatment if they are diagnosed with this disorder (Frazier and
Dryzmkowski, 2009). Living life with the schizophrenia is an experience not everyone
IMMUNOLOGY
5
can understand. Day to day living can be difficult, as well as simple daily tasks. The
symptoms are often controlled by the use of anti-psychotic drugs, psychotherapy, and
family support (Frazier and Dryzmkowski, 2009). With support and a plan, a person can
avoid many psychotic breaks or episodes.
Research into the causes of schizophrenic symptoms is leading to new
discoveries in immunology and genetics. Chromosome 6p22 and the inflammatory
response are going to need looked at further but may open up new doors to treatment
someday soon. Not only may this research benefit schizophrenia patients, it may also
lead to new interventions in other neuropathological disorders, such as bipolar disorder.
Only time will tell what great discoveries come from the genetics and immunological
fields.
IMMUNOLOGY
References
Carter, C. J., (2011), Schizophrenia: a pathogenetic autoimmune disease caused by
viruses and pathogens and dependent on genes. Journal of Pathogens; 2011.
doi:10.4061/2011/128318. http://www.hindawi.com/journals/jpath/2011/128318/ .
Frazier, M. S., and Dryzmkowski, J. W. (2009). Essentials of Human Diseases and
Conditions (4th Ed.). St. Louis, MO: Saunders Elsevier Inc.
Müller, N., and Schwarz, M.J., (2010). Immune System and Schizophrenia.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2971548/ .
Schwartz, M. and Shechter, R., (April 2010). Protective autoimmunity functions by
intracranial immunosurveillance to support the mind: the missing link between health
and disease. Molecular Psychiatry 15: 342-354. doi:10.1038/mp.2010.31.
http://www.nature.com/mp/journal/v15/n4/full/mp201031a.html .
6