Schizophrenia is a heterogeneous psychiatric disorder whose pathogenesis involves various neurotransmitter systems. The authors conducted their study with the Ministry of Science and Technology of Taiwan and received a grant from Taipei Veterans General Hospital. In recent years, scientists have made notable progress in understanding the neurobiochemistry of schizophrenia. “…with varied symptoms and non – predictability of outcome schizophrenia needs the psychiatrist to be prepared for any form of the disorder” (Shrivastava & De Sousa, 2020, p. 4). The article’s primary goal is to review the dopamine hypothesis and study and analyze new targets invented in recent years. The authors note that this study analyzes the latest treatment strategies beyond the dopamine hypothesis. (Yang & Tsai, 2017, p. 1). Such studies are in demand because the treatment of the dopamine hypothesis does not explain the psychopathology of schizophrenia. The researchers came to these conclusions after going through several stages of the study. In this study, stages include:
- data collection, preliminary data review, assessment of factors;
- data analysis;
- interpretation of the analysis results.
In the article, the authors use such medical research methods as cross-sectional studies and randomized clinical trials. A cross-sectional study means that the authors evaluated the whitening, its prevalence, disease course, and its outcomes. Randomized clinical trials mean that the authors conducted a study on which drug is more effective concerning the disease, which is the article’s main topic.
Many papers have been analyzed on dopamine dysfunction, the explanation of multiple symptoms of schizophrenia, the role of glutamate in treating schizophrenia, the effects of serotonin and its transmission, and cigarette smoking in schizophrenic patients. The authors described such approaches to treating schizophrenia as special treatment for negative symptoms, treatment of cognitive deficiency, and treatment of individual stages of the disease have been studied.
Having studied the topic of the problem, the authors came to certain conclusions in their work. Most proposed treatments for schizophrenia have targeted the dopamine receptor. The dopamine hypothesis has partially succeeded in coping with positive symptoms but has difficulty with negative symptoms (Correll & Schooler, 2020, p. 519). The article also concludes that including functional magnetic resonance imaging in research may bring results and open up new strategies for treating schizophrenia. The authors reached these conclusions through their study, comparing the treatments for schizophrenia and the targets of schizophrenia for which the medications listed in the article are directed.
However, some questions regarding the treatment of schizophrenia emerge from the results of this study. For example, it was not said what targets of schizophrenia would be covered by the newest drugs. In addition, a deeper study requires the hypotheses mentioned in the article, except for dopamine. They could answer many questions in treating schizophrenia but are considered very quickly and in passing. It was also not indicated that AMPA receptor modulators may become alternatives to glycine. These substances enhance glutamatergic activity in the cortex, stimulate memory-dependent processes in animal experiments, and drastically improve memory without serious side effects.
Alternatively, this study could have been conducted using a cohort study. Then, it would be necessary to select a specific group of individuals suffering from this disease and trace their condition from the beginning of the experiment to the end. Thus, study could better consider the differences in the impact of treatments and side effects of different drugs to draw conclusions about which ones have the best effect on patients.
The article should also pay more attention to cannabinoid type-2 CB2, which plays a significant role in several processes related to schizophrenia. “CB2 receptors are expressed in the brain at lower levels than CB1 receptors, being present in glial cells, namely microglia and astrocytes, and specific subpopulations of neurons” (Cortez et al., 2020, p. 2). CB2 receptors cause modulation of various critical processes associated with schizophrenia. The endogenous cannabinoid system, including G-protein, associated with cannabinoid receptors of the first and second types, may be engaged in the etiopathogenesis of schizophrenia. This thought is to be supported by detecting elevated levels of anandamide in the cerebrospinal fluid (an endogenous cannabinoid) in patients with schizophrenia.
The research conducted by the authors in this article has much in common with the researchers mentioned in the textbook. In both works, scientists relied on gene research and attempted to find the genes responsible for the onset of schizophrenia. Many genome-wide studies have been cited that have confirmed the presence of genes responsible for producing schizophrenia. Both studies also looked at various internal and external factors influencing the development of schizophrenia. For example, the textbook mentions difficult working conditions, intransigence with loss, changes in growing up, infections, and toxic substances. In the article, the authors consider bad habits such as smoking and the effect of nicotine on the development of the disease. In addition, in both studies, much attention is paid to the different symptoms of schizophrenia, both negative and positive. Their differences and what consequences they lead to are indicated. Also, considerable attention is paid to the topic of the dopamine hypothesis, an explanation of the principle of its impact and an analysis of what its disadvantages are “…the drugs did not help 30% to 40% of patients with schizophrenia…” (Garrett & Hough, 2021, p. 464), and what methods of treatment it can be replaced in the future. Both studies analyze the side effects of dopamine-blocking drugs in treating schizophrenia. As alternatives, the scientists in both papers are looking at drugs that act on 5-HT2A receptors and drugs like phencyclidine and ketamine that act on the NMDA subtype of the glutamate receptor. These chemicals are said to have a much better effect on the body and do not bring such significant side effects as blocking the D2 subtype of dopamine.
In the article in question, it was said that treating the targets of schizophrenia has not yet been thoroughly studied and has many aspects that should be improved. For example, blocking the D2 receptor brings the desired result only in half of the cases. Therefore, it is necessary to study other methods of influencing the disease and its pathogens. The article provides several examples of which direction researchers should move in developing treatments for schizophrenia. For example, the authors report that metabotropic receptor 1 receptor antagonists are potential targets for positive symptoms in schizophrenia. The article pays little attention to the disruption of cytokine metabolism in schizophrenia. However, enough has been written about serotonin, and their interaction leads to competition between neurodegenerative quinolines and neuroprotective kynurenines in the brain. It can partially explain the neurodegenerative processes in schizophrenia. These data indicate that elevated levels of kynurenic acid in schizophrenia may cause hyperactivity of the mesocorticolimbic dopaminergic system.
This paper describes many of the weaknesses of the dopamine hypothesis and how they tried to deal with them. Stahl claims, “…there is much more to the treatment of psychosis than D2 antagonists, as recently demonstrated by pimavanserin, a new treatment for Parkinson’s disease psychosis and an agent with serotonin 2A antagonist properties but no D2 antagonist properties at all” (2018, p. 187). The article notes that at this stage of the development of the dopamine hypothesis, there was no description of the causes of the violation of the dopamine system, and it was not established which element of the dopaminergic transmission was impaired.
References
Correll C. & Schooler N. (2020). Negative symptoms in schizophrenia: A review and clinical guide for recognition, assessment, and treatment. Neuropsychiatric Disease and Treatment, 16, Article 519-534. Web.
Cortez L. Rodrigues da Silva N. Guimarães S. & Gomes V. (2020). Are CB2 receptors a new target for schizophrenia treatment? Frontiers in Psychiatry, 11, 587154. Web.
Garrett B. & Hough G. (2021). Brain & Behavior: An Introduction to Behavioral Neuroscience (6th Edition). SAGE Publications, Inc. (US). Web.
Shrivastava A. De Sousa A. (Eds.). (2020). Schizophrenia treatment outcomes: an evidence-based approach to recovery. Springer International Publishing
Stahl, M. (2018). Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate. CNS Spectrums, 23(3), 187-191. Web.
Yang A. Tsai S. (2017). New targets for schizophrenia treatment beyond the dopamine hypothesis. International Journal of Molecular Sciences, 18(8). Web.