A Critical Analysis of “All Roads to Schizophrenia Lead to Dopamine Supersensitivity and Elevated Dopamine D2High Receptors.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493870/
Adobe Stock.
Hypothesis
D2 is a central target for antipsychotic action and anti-Parkinson action, whether any particular property of D2 may be related to dopamine supersensitivity and schizophrenia.
Risk factors or altered genes that lead to dopamine supersensitivity can also increase the risk for psychosis or schizophrenia. Antipsychotics and agonists target the dopamine D2 receptor.
Antipsychotic clinical doses correlate with their affinities for the dopamine receptor in a state of high affinity (D2High) or low affinity (D2Low).
D2High receptors are consistently elevated in the animal models of the various human psychoses.
Thus, it is reasonable to consider and test whether D2High is a common target for the convergence of the various psychosis pathways (Seeman, 2011).
Dr. Greg Dunn.
Critical Methods
Review why schizophrenics are super sensitive to dopamine-like drugs.
Review if D2High state is a basis for dopamine hypersensitivity in animal models of schizophrenia.
Review Common Biomarkers:
Dopamine Supersensitivity.
Common Target for antipsychotics.
Supersensitivity is related to D2 density and D2High receptors.
Deletion of genes.
Environmental factors.
Birth Injury by cesarean section.
Critical Results
The results conclude that all animal models of schizophrenia exhibit:
Elevations in D2High receptors.
Brain lesions.
Drug-induced hypersensitivity.
Birth injury.
Social isolation.
Gene deletions in neural pathways for:
NMDA.
Dopamine.
GABA.
Acetylcholine.
Norepinephrine.
Conclusion
Multiple abnormal pathways align through a common pathway of dopamine hypersensitivity and elevated D2High receptors, triggering psychosis.
Antipsychotics alleviate psychosis and reverse the elevation of D2High. They remain attached for days, preventing relapse; accumulation induces tardive dyskinesia.
Clozapine and quetiapine are released from D2 within 12 to 24 hours and do not elicit parkinsonism or tardive dyskinesia.
Long-term use of antipsychotics drives ongoing dopamine hypersensitivity.
Switching from a traditional antipsychotic to an agonist (aripiprazole) can result in psychosis.
“Many risk factors lead to elevated D2High receptors and dopamine supersensitivity that underlie signs and symptoms of schizophrenia” (Seeman, 2011).
Future goals include imaging D2High receptors and desensitizing them in early-stage psychosis.
My Conclusion
The dissociation constant of a particular antipsychotic often differs among laboratories; while the results may have a somewhat similar outcome, the variables at play will alter the results from lab to lab.
Dopamine supersensitivity may be a basis for the positive signs and symptoms of psychosis, the underlying biology and hit’s relation to negative aspects of psychosis, such as cognition, is still unknown.
D2 receptor remains the central location and target for antipsychotics and antiparkinson drugs. It is best to avoid all psychostimulants in conjunction with antipsychotics due to the uptick in psychosis and drives supersensitivity within the individual.
The development of additional symptoms such as tardive dyskinesia depends on the long-term accumulation of antipsychotics on D2 receptors.
“Many risk factors lead to elevated D2High receptors and dopamine supersensitivity that underlie signs and symptoms of schizophrenia” (Seeman, 2011).
The hypothesis has been proven that multiple abnormal pathways align through a common pathway of dopamine hypersensitivity and elevated D2High receptors, triggering psychosis.
adobe stock.
References
Seeman, P. (2011). All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2(high) receptors. CNS Neuroscience & Therapeutics, 17(2), 118–132. https://doi.org/10.1111/j.1755-5949.2010.00162.x
About the author:
Melanie began attending Harvard in 2020 to complete a Graduate Certificate in Human Behavior with a specialization in Neuropsychology. Boling’s research has examined extreme environments and how they can have a potential negative impact on humans operating in the extreme environment. During her time at Harvard, she has built a mental wellness tool called a psychological field kit. Implementing these tools will allow an individual to thrive in an extreme environment while mitigating negative variables such as abnormal human behavior which can play a role in team degradation.
Melanie Boling, Extreme Environments Neuroscientist, Founder of Boling Expeditionary Research Group; and Neuropsychology Graduate Student, Harvard University.