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Neuroscience

Schizophrenia and highly educated guesses: Exploring common practices in treating this psychotic disorder

The article contains a review into the history of schizophrenia along with the treatment. This is done in order to understand exactly where schizophrenia is now as a disorder today. We then take a look at the neurobiology to understand a little about neurobiology on a chemical level ending with comparative treatments of schizophrenia worldwide.

By Will Onubogu

Published 11:55 EST, Sat December 4th, 2021

Introduction
The danger of the unknown. The medical world’s ability to not account for the unknown. These concepts are what Michael Focault’s “Madness and Civilization” emphasized; ideas lost in history. It is this very concept that allows us to formulate schizophrenia as a diverse disease under one helm. Schizophrenia is a psychotic disorder classified by positive symptoms: hallucinations and delusions, and an array of negative symptoms such as loss of will and loss of feelings, among many others (Shultz et al., 2007). Schizophrenia occurs most commonly among men in their early 20s and women in their late 20s (Patel et al., 2014). Data on 16,423 Americans from the U.S. National Library of Medicine National Institutes of Health indicate higher rates of diagnosis among Latino Americans (13%) and African Americans (15%) compared to Euro-Americans (9%) and Asians (9%; Schwartz & Blankenship, 2014). From the idea of dementia praecox to modern schizophrenia, we have yet to grasp the disease truly. Thus, in schizophrenia, one must wonder, how should schizophrenia be treated globally? This paper aims to review the history of schizophrenia and the development of past and current treatments, both in the United States and worldwide.

History of Schizophrenia
Benedict Augustine Morel (1809–1873) used the term dementia praecox as an early label of schizophrenia (Lavretsky, 2008). Morel thought of schizophrenia as an early form of dementia. It does make sense as there are intersecting traits such as worsened cognitive functions, which may contribute to his belief that schizophrenia was a form of dementia (Lavretsky, 2008). However, Emil Kraepelin’s description of catatonia, hebephrenia, along with his dementia paranoia, created the foundation for further interest in what schizophrenia was (Lavretsky, 2008). Beur then revolutionized schizophrenia by bringing the disease under one helm. Kraepelin had several different forms of what he called dementia praecox (Lavretsky, 2008). He believed there were fundamental symptoms all people with schizophrenia had accessory symptoms that changed person to person (Lavretsky, 2008). Psychic schisis or split, ambivalence, cognitive features of “loose associations,” avolition, inattention, autism, and incongruent features signified primary deficits for Bleuler (Lavretsky, 2008). In comparison, delusions and hallucinations were treated as accessory features of schizophrenia (Lavretsky, 2008). With the pioneers of schizophrenia allowing the development of ideas into more concrete symptoms and clear definitions, along with this came treatment.

History of Treatment for Schizophrenia
Early treatment was prolonged barbiturate-induced sleep therapy, insulin coma, or psychosurgery. Sleep therapy would induce unnaturally long sleep, sometimes leading to comas and death (Lopez-Munoz et al., 2005). Insulin comas were induced by giving the patients large amounts of insulin, putting the patient into a coma, which often did not help and sometimes led to death (Wright-Mendoza, 2018). With psychosurgery, the idea was to alter the brain, an idea created by António Egas Moniz (Toler, 2021). The most popular form of psychosurgery is a lobotomy, which tries to change the brain’s frontal lobe, which controls personality and behavior. However, some worrying result was brain damage and death (Toler, 2021). Terrier et al. cite that schizophrenia is found in 84% of the 771 lobotomized patients. The postoperative mortality was 7.4% (57 deaths)” (Ögren & Sandlund, 2007) and another saying, “When complications were reported, seizures represented the most common sequelae (1%–23%), followed by chronic headache (15%)…The death rate could have reached 5%.” (Terrier et al., 2019). Furthermore, for those with multiple lobotomies, seizures were more frequent, saying that 25.6% of patients had convulsions in prefrontal lobotomy. In comparison, convulsive seizures stood at 7 % for a simple operation and 47% for several operations (Freeman, 1953).
The first half of the 20th century saw the hospitalization (or jailing) of people with schizophrenia (Lavretsky, 2008). Because the disease was seen as untreatable, patients were essentially checked into the hospital for long periods of time, where they were abused and treated terribly (Lavretsky, 2000). Patients acting in ways deemed socially unacceptable were given what was known as a “chemical cosh” (Lavretsky, 2008). Cosh is derived from British slang, which means to bludgeon. Patients were heavily sedated to calm them, but it served no benefit in reducing symptoms (Lavretsky, 2008). The only effect was a temporary peace (Lavretsky, 2008. Another issue with treating people with schizophrenia in the asylums was that the treatment did not include any preparation for patients to enter the real world (Lavretsky, 2008). Patients’ symptoms would improve but in a context isolated from daily life (Lavretsky, 2008). There was not much improvement. In the 1930s, the Third Reich of Nazi Germany wished to eliminate schizophrenia (Lavretsky, 2008). It was done by euthanasia, which consisted of firstly lethal injection and later gas chambers (Lavretsky, 2008).
The middle of the 20th century brought typical antipsychotics through trying to create antihistamine drugs (Tandon, 2011). Typical antipsychotics are also known as neuroleptics (Tandon, 2011). The neuroleptics cause neurolepsis, a syndrome with the intended effect of psychomotor slowing, emotional quieting, and affective indifference (Tandon, 2011). Paul Charpentier, who experimented with phenothiazine derivatives, hoped to find properties in the compounds that helped with allergies (Ramachandraiah et al., 2009). Then in 1949, Henri-Marie Laborit, a French army surgeon, used promethazine, a phenothiazine derivative, on patients and saw that patients were much calmer and more cooperative (Ramachandraiah et al., 2009). Later on, a chlorinated derivative of phenothiazine was discovered by Laborit called chlorpromazine (Ramachandraiah et al., 2009). He claimed that this substance would be great therapy for patients with mental illnesses (Ramachandraiah et al., 2009). However, his colleagues met him with skepticism, and chlorpromazine was never introduced (Ramachandraiah et al., 2009). Jean Delay and Deniker’s study on 38 patients proved chlorpromazine an effective treatment, after which typical antipsychotics were introduced to the market (Ramachandraiah et al., 2009). Fast forward, and now atypical antipsychotics are dominating the medical world. Starting from the 1980s, they began a further diversification of treatment for people with schizophrenia (Abou-Setta et al., 2012). Second-generation antipsychotics include one of the most effective treatments for schizophrenia which is clozapine (Lieberman, 1996; Nuera, 2020). Clozapine, while being very effective, has a dangerous risk of Agranulocytosis. This disease means the body does not make enough of neutrophils, a type of white blood cell (Clevelandclinic, 2020). These days, even more, great atypical drugs such as risperidone, olanzapine, sertindole, quetiapine, and ziprasidone have shown up-and-coming prospects (Nuera, 2020). The advances made from the late 1800s to the 21st century have been incredible, but one must understand the neurobiology behind schizophrenia when trying to decipher the most globally effective treatment.

Neurobiology of Schizophrenia
Schizophrenia deals with chemical imbalances that influence the functioning of a person who is susceptible to schizophrenia. Imbalances of dopamine, glutamate, GABA, acetylcholine, and serotonin are believed to be essential contributors to schizophrenia (Brisch et al., 2014). These all are neurotransmitters that essentially control our physical nature. Dopamine is a neurotransmitter that regulates movement and emotion and is essential for the normal functioning of a person. If one’s dopamine is hypoactive or hyperactive, it can be detrimental to one’s health. What has been said about dopamine pertaining to schizophrenia is hyperactive dopamine transmission in the mesolimbic areas and hypoactive dopamine transmission in the prefrontal cortex in schizophrenia patients (Brisch et al., 2014). In addition to the mesolimbic brain areas, dopamine dysregulation is also seen in brain regions, including the amygdala and prefrontal cortex, necessary for emotional processing (Brisch et al., 2014). To put this more simply, the mesolimbic areas are our reward pathway activated by things like sugar we ingest (Adinoff, 2004). The region allows the processing of what is real or not as well. Hyperactive dopamine transmission in this region results in positive symptoms, such as hallucinations and delusions (Brisch et al., 2014). The prefrontal cortex (PFC) at this time is said to develop memory, perception, and many cognitive functions such as attention, impulse inhibition, prospective memory, and cognitive flexibility (Pryor & Veselis, 2006). Parts of our PFC help us perform tasks while other parts help us to take in information. The PFC, when it has hypoactive dopamine transmission, leads to negative symptoms, which means it lacks something that should be present (e.g., ability to communicate) (Shultz et al., 2007; Siddiqui & Goyal, 2008 ). We currently know this about schizophrenia from a chemical standpoint and what has been used to prescribe people with schizophrenia best.

Schizophrenia Treatment Globally
Treatment that is just as diverse worldwide as our understanding of the disease itself. Different medicinal regulations and different practices formed different treatments across regions. Nigeria’s residents have been more inclined to use more traditional medication to treat schizophrenia (Ayonrinde et al., 2004). Herbalists, traditional healers, and spiritual healings are all commonly sought out to treat schizophrenia (Adewuya, 2015). In contrast to Canada, Bermuda and the United States prefer antipsychotics (Crockford & Addington, 2017). A research paper notes on a study that included Nigeria that a systematic review of the effectiveness of traditional healers in treating mental disorders concluded that people with acute relapses improve. In contrast, in the care of traditional healers, improvements could not be established, however, as any different than the regular illness route (Endale, 2020). They are illustrating the effective properties herbs may have while also highlighting their ineffectiveness as a mainline treatment. Through my background on schizophrenia, one can see the advancement of antipsychotics and how it has helped people with schizophrenia the most out of all treatments. Looking into herbs for treating schizophrenia, the US National Library of Medicine National Institutes of Health has said herbs to be beneficial with regular antipsychotics, and this belief is not synonymous with this organization (Chengappa, 2018). K.N. Roy Chengappa, M.D. A professor of psychiatry remarks similar thoughts stating herbs can reduce worsening symptoms but should be taken along with antipsychotics (Chengappa, 2018).

Conclusion
This paper aimed to review the literature on the history of schizophrenia and the development of the most effective treatment. Schizophrenia is classified by positive and negative symptoms and is affected by the lack of or overabundance of dopamine transmission. It took many years and will take more to discover a more effective treatment for schizophrenia. Schizophrenia is a complicated disease that has stumped a generation and left us in mystery. We entertain the fruits of life in hopes of striking a discovery and coming one step closer to curing schizophrenia. Although more definitive answers would have been preferable, we are left with a scramble of highly educated guesses in science’s beginning and forward-moving end.

Will Onubogu, Youth Medical Journal 2021

References 

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(Siddiqui, 2008)

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By William Onubogu

Currently a 4-year senior at Berkshire School.

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