Pathogens are major risk factors causing the disease and symptoms of schizophrenia through oxidative/nitrosative stress, NMDA receptor hypofunction, and pathological neurodevelopment: Treatment and prevention proposals for discussion
Creators: name: Anderson, Frederick
Publisher: name: figshare
Year: 2020
Subjects: subject: 110319 Psychiatry (incl. Psychotherapy)
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 111799 Public Health and Health Services not elsewhere classified
subject: FOS: Health sciences
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: FOS: Biological sciences
subject: 111714 Mental Health

description: ABSTRACT There is now evidence that specific pathogens are present in the majority of individuals with schizophrenia, and only rarely in healthy individuals. There is 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 brain 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.