Wednesday, May 1, 2019

Differing Hypotheses on the Neuropathology of Schizophrenia

Schizophrenia is a psychiatric condition that nearly 1% of the population experiences. This debilitating condition is associated with both negative and positive symptoms, both of which can be extremely debilitating and distressful. The positive symptoms of schizophrenia can be defined as the addition of a sensation while negative symptoms are related to deficits in preexisting experiences. Examples of positive symptoms include hallucinations across all sensual modalities as well as delusional thoughts which may elicit feelings such as being chased by someone, having something physically wrong with them as the result of some outrageous event, or even the sense of being superior to everyone else around them. Positive symptoms are typically present in addition to various negative symptoms such as alogia, affective flattening, social withdrawal, and deficits in following a daily routine. Generally speaking, individuals with schizophrenia typically experience psychosis as individuals with this disorder experience a distorted reality relative to the one neurotypical individuals experience. While the exact pathology of schizophrenia is highly debatable, various approaches to understanding it have lead researchers to gain some insight as to what may be happening in the brain to elicit these symptoms.

Dr. Monsheel Sodhi’s research explores what many in the field refer to as the glutamate hypothesis of schizophrenia. Dr. Sodhi discusses the pressing evidence suggesting that abnormalities within the glutamatergic system, an essential chemical pathway for proper neurological functioning, may be involved in the neuropathology of schizophrenia. While Dr. Sodhi’s research focuses specifically on the genetic expression of transporters and receptors within the glutamatergic system, she emphasized the importance of her research by showing that current psychotropic medications are only significantly effective in thirty percent of patients. Most of these medications work to modulate levels of dopamine and serotonin, two important chemicals in the brain heavily associated with mood and cognitive functioning. Given the significant findings in Dr. Sodhi’s research and the additional literature that supports her hypothesis on the pathology of schizophrenia, it’s interesting to see that the media continues to favor therapies and research still targeted towards understanding serotonin and dopamine’s role in schizophrenia.

An article in the Scientific American revisits a perspective on psychosis as it relates to schizophrenia. Any well-read scientist in the field of neuroscience or psychology is likely to be well aware of the focus on psychedelic and hallucinogenic substances in the late 1960’s. Drugs such as LSD, magic mushrooms, and peyote were thought to have been the key that unlocked the door to understanding multiple elements to sensation, perception, introspection, and cognitive function. Recently, research on these substances has made a comeback with the idea that their ability to mimic the symptoms of schizophrenia-related psychosis can provide a way to develop more effective treatments, specially for the negative symptoms of schizophrenia which current medications fail to relieve. Imaging of schizophrenic brains compared to healthy brains on psychedelics show that the neural networks involved in introspection and external attention mesh together abnormally in an identical way. Scientists hope that by finding a way to block this “boundary-blurring effect” in hallucinogen-induced psychosis, the pharmacology can be further tailored to fix the apparently similar phenomena present in the brains of individuals with schizophrenia-related psychosis.

Scientists invested in exploring the relationship between pathological psychosis and substance-induced psychosis have a solid basis from which they defend their research on. Given their focus on understanding the specific symptoms of auditory hallucinations, cognitive deficits, and social disengagement, it’s clear why hallucinations seem like the perfect solution to exploring the mechanisms behind these experiences. Hallucinogens have a seemingly unique ability to mimic these symptoms with enough similarity to identify the bases of the neuropathology involved with schizophrenia. The article in the Scientific American explained one study that showed one drug commonly used to treat anxiety, buspirone, was effective in preventing visual hallucinations, flooding of memories, and imaginative thinking specifically in those who were given psilocybin, the substance in magic mushrooms. The idea researchers have is that buspirone likely acted similarly to an early drug used to treat psychosis in Parkinson’s. Additionally, buspirone appeared to treat the same specific symptoms individuals in the early stages of schizophrenia experience, therefore offering some support in favor of the researchers hypothesis: that hallucinogen-induced psychosis can accurately model schizophrenia-related psychosis to provide a basis from which treatments for specific symptoms can be created.

The argument that hallucinogenic substances such as psilocybin, specially, are likely to provide information on how to effectively treat schizophrenia is interesting as these substances act on serotonin primarily. As Dr. Sodhi stated, current antipsychotic drugs that target the same chemical have proven to be less than effective for most individuals with schizophrenia in treating various symptoms. Regardless, the push for further research on a hallucinogenic substance that acts on that same chemical system is increasing in the the media. It’s important to remember that these chemical systems are extremely complex and highly intertwined with one another. There still may be a good chance that hallucinogenic substances could help us better understand these pathways especially considering the apparent similarities between psychosis and hallucinogen-induced psychosis in a healthy brain. Perhaps one of the greatest wonders of neuroscience, and perhaps one of the most frustrating, is that there is still much to be discovered about the highly complicated system that oversees everything we do, every experience we have, and every thought we conjure.

Scientific American article: “A Trip inside the Schizophrenic Mind” by Taylor Beck
https://www.scientificamerican.com/article/a-trip-inside-the-schizophrenic-mind/

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