If hyperstimulation is present in a patient with schizophrenia, it is understandable to suggest that hyperstimulation may have caused psychotic symptoms (alongside no pathological alterations or changeable reactions). If these levels of hyperstimulation are excessive, then it could cause many physical psychotic effects (detectable through brain imaging or even undetectable changes). 

NRHpo hyperstimulation in patients

The image below displays the distribution of degenerating neurons at eight different levels of an adult rat brain. These results show how the brain looks 4 days following treatment when exposed to a high dosage of an NMDAThis shows which neuronal populations are most at risk of degeneration when the NMDA receptor system is hypofunctional. 

University of Illinois at Chicago

Many researchers agree that similarities in many major symptom classifications is astounding, and a PCP diagnoses is difficult to separate from schizophrenia. PCP also is known for triggering a prolonged state of acute psychotic symptoms in chronic schizophrenia patients, while other drugs (like LSD) do not cause this scenario. Furthermore, many NMDA antagonists are able to trigger a florrid psychotic reaction similar to PCP psychosis. Since all of these drugs induce an NRHypo state, this article suggests that an NRHypo state (if present in a schizophrenic patient) could explain elements that characterize that illness. 

Evidence supporting hypothesis of NRHypo model

Corso, T. D., & Farber, N. B., et al., (1999, November 29). NMDA receptor hypofunction model of schizophrenia. Journal of Psychiatric Research. https://www.sciencedirect.com/science/article/abs/pii/S0022395699000291#:~:text=When%20the%20NMDA%20receptors%20in,hyperstimulate%20the%20primary%20corticolimbic%20neurons.

NMDA receptor hypofunction model of schizophrenia

As the defect in schizophrenia is developmentally related, this may cause certain treatment approaches to be sabotaged. If this study is correct in its assumption that specific excitatory receptors that lay on the surface of cerebrocortical neurons are being hyperstimulated, then this is a contribution to neurodegenerative or psychotic manifestations of schizophrenia. 

Pharmacological Approaches for this model

Representation of the distribution of degenerating neurons

Classes of drugs that abort the mechanism by which the NRHypo state damages the brain
- GABAa agonists
- muscarinic antagonists
- nonNMDA Glu antagonists
- sigma agents
- a2-adrenergic agonists
- 5HT2a agonists
- novel antipsychotics (such as olanzapine and clozapine)

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