Compare and contrast the NMDA hypofunction hypothesis of schizophrenia with the dopamine hypothesis of schizophrenia. Include how the hypotheses account for positive and negative symptoms in schizophrenia.
Positive and negative symptoms and cognitive deficits are present in schizophrenia patients, which often begin in early adolescence and deteriorate over time. A dysregulated dopamine system, according to the dopamine hypothesis of schizophrenia, makes a significant contribution to the disease’s proactive, negative, and cognitive symptoms. It also suggests that hyperactivity of dopamine D2 receptor neurotransmission in subcortical and limbic brain regions is linked to positive symptoms of schizophrenia. Negative and cognitive symptoms, on the other hand, are linked to hip dopamine D1 receptor neurotransmission in the prefrontal brain. Molecular imaging techniques allow for susceptible measurements of neuroreceptor binding in the human brain. In the last three decades, these techniques have been widely used to investigate dopaminergic abnormalities in schizophrenia patients’ brains.
The NMDA hypofunction hypothesis has been formulated to help understand the etiology and pathophysiology of schizophrenia (Lee & Zhou, 2019). Clinicians and pharmacologists recognize the NMDA hypofunction as a pathophysiological mechanism for schizophrenia. NMDA modulates memory, cognition, and higher-order brain functions. On the other hand, the dopamine hypothesis of schizophrenia is responsible for the positive symptoms such as hallucinations and delusions, as seen in this disorder. The strong connection between the ability to block dopamine D2 receptors and its clinical effectiveness is further supported by the hypothesis.
Stahl (2018) provides a classical theory of dopamine hyperactivity in the dopamine pathway where all antipsychotics block the D2 receptors. Here, hyperactivity is one of the causes of positive symptoms of schizophrenia. On the other hand, the NMDA hypofunction hypothesis recognizes that the hypofunctional NMDA receptors on the GABA interneurons could result in overactive downstream glutamate signaling. Stahl (2018) further acknowledges that the psychosis theories include the idea that dopamine hyperactivity results from glutamate imbalance in the prefrontal cortex. However, the dopamine hypothesis demonstrates that a lack of activation of D1 (D1R) receptors and a loss in dopamine transmission in the prefrontal cortex causes cognitive deficits similar to those seen in schizophrenia patients. Because of their physical relationship, these two receptors appear to be significant (Grunder & Cumming, 2016).
Several of the oldest and most influential explanations about the molecular basis of schizophrenia is the dopamine hypothesis. However, the revised dopamine hypothesis argues that dopamine dysregulation is seen in the prefrontal cortex and the amygdala, which are helpful in emotional processing. There are still substantial doubts about the role of dopamine in schizophrenia. Some say that it isn’t apparent whether schizophrenic patients’ brains have dopaminergic anomalies. Still, even if we accept the premise that they do, it’s unclear whether these changes in dopamine activity are the primary source of the symptoms of schizophrenia. Even though antipsychotic medications diminish dopamine receptor activation, around one-third of schizophrenic patients do not respond to them. On the other hand, the NMDA hypofunction hypothesis of schizophrenia, the NMDA hypofunction theory of schizophrenia, is based on the finding that NMDAR antagonists such phencyclidine, ketamine, and MK801 can cause both desirable and undesirable psychotic symptoms in healthy people and aggravate these abnormalities in schizophrenia. Increasing evidence shows that disruption of glutamate neurotransmission mediated by the N-methyl-D-aspartate receptor (NMDAR) may have a role in the pathogenesis of schizophrenia. Widespread acceptance of a concept might lead to fewer challenges, and rival ideas are generally overlooked.
Gründer, G., & Cumming, P. (2016). The dopamine hypothesis of schizophrenia: Current status. In The neurobiology of schizophrenia (pp. 109-124). Academic Press. Retrieved from https://www.sciencedirect.com/science/article/pii/B978012801829300015X
Lee, G., & Zhou, Y. (2019). NMDAR hypofunction animal models of schizophrenia. Frontiers in molecular neuroscience, 185. Retrieved from https://www.frontiersin.org/articles/10.3389/fnmol.2019.00185/full#:~:text=The%20N%2Dmethyl%2Dd%2D,schizophrenia%20in%20normal%20human%20subjects.
Stahl, S. M. (2018). Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate. CNS spectrums, 23(3), 187-191. Retrieved from https://www.cambridge.org/core/journals/cns-spectrums/article/beyond-the-dopamine-hypothesis-of-schizophrenia-to-three-neural-networks-of-psychosis-dopamine-serotonin-and-glutamate/3E9E50ED717219011DD1B570365010E8