Pathogens are major risk factors causing oxidative/nitrosative stress, NMDA receptor hypofunction, pathological neurodevelopment, and symptoms in schizophrenia
Creators: name: Anderson, Frederick
Publisher: name: Figshare
Year: 2017
Subjects: subject: 110319 Psychiatry (incl. Psychotherapy)
subject: FOS: Clinical medicine
subject: 111799 Public Health and Health Services not elsewhere classified
subject: FOS: Health sciences
subject: Diseases
subject: 111716 Preventive Medicine
subject: 111401 Foetal Development and Medicine
subject: 111706 Epidemiology
subject: 111504 Pharmaceutical Sciences
subject: Neuroscience
subject: 60502 Infectious Agents
subject: FOS: Biological sciences
subject: Mental Health

description: ABSTRACT

     There is now evidence that pathogens are a
major environmental trigger of pathologically elevated nitric oxide and/or oxidative/nitrosative
stress, which causes pathological neurodevelopment, N-methyl-D-aspartate
(NMDA) receptor hypofunction, a hyperdopaminergic state, and the symptoms of
schizophrenia, in the majority of cases. 
Factors which cause elevated nitric oxide, such as Chlamydiaceae have
been found in 40%–50% of schizophrenics tested, elevated human endogenous  retrovirus type W (HERV-W) elements found in
~65%, a schizophrenia antigen identified as <i>Mycobacterium
tuberculosis </i>found in ~65% of schizophrenics tested, and other pathogens
have been found in schizophrenics, but rarely in controls.  There is evidence that elevated nitric oxide/oxidative
stress is involved in the symptoms of schizophrenia:  A 3.8-fold average elevation of red blood
cell nitric oxide, a five-fold average elevation of oxidative stress, a 21%
average elevation in serum nitric oxide, and nitric oxide levels which
correlate with delusional states, are all evident in schizophrenia versus
controls.  Furthermore, on the same day that
serum nitric oxide reached ten-fold normal levels, neuropsychiatric symptoms
emerged in 70% of patients, including paranoia/delusions in 29%, in cancer
treatment with interleukin-2 (IL2). 
Fifty percent met criteria for delirium. 
Also, evidence demonstrates that sodium nitroprusside causes NMDA receptor
hypofunction and schizophrenia-like symptoms  in some humans.  Evidence indicates that nitric oxide is a
normal, feedback regulator of NMDA neurotransmission, but that pathologically
elevated nitric oxide, such as from pathogens, causes NMDA receptor
hypofunction and hyperdopaminergic activity, recognized factors in the
hallucinations, delusions, and cognitive symptoms of schizophrenia.  There is evidence that astroglial cells in
proximity to NMDA receptors are activated in 40%–50% of schizophrenics to
produce high-level nitric oxide, thus causing NMDA receptor hypofunction and a hyperdopaminergic state, and thus, in a similar way as phencyclidine (PCP) and ketamine, the symptoms of schizophrenia.  Pathogens
even limited to the blood can cause elevated inflammatory cytokines and elevated
nitric oxide which cross the blood brain barrier (BBB) into the brain to cause
NMDA receptor hypofunction and the symptoms of schizophrenia.  Since there is evidence of pathogens in the
majority of cases of schizophrenia and rarely in controls, detection and treatment of pathogens and
other risk factors in the prodromal stage and first-episode needs research, since adjunctive treatment of pathogens along with standard neuroleptic treatment may prevent further disease deterioration and allow improvement or
elimination of symptoms in schizophrenia.  Since there is evidence of pathogens in the majority of cases of schizophrenia, testing and treatment of pathogens and other risk factors before
conception and at various stages during development needs research as a method
to prevent schizophrenia.