Neurons in schizophrenia patients secrete greater amounts of dopamine, norepinephrine, and epinephrine — three neurotransmitters commonly linked to a range of psychiatric disorders. The findings, published in the journal Stem Cell Reports, confirms and enhances the theory of a chemical basis for schizophrenia.
“The study provides new insights into neurotransmitter mechanisms in schizophrenia that can lead to new drug targets and therapeutics,” said senior author Vivian Hook, Ph.D., a professor with Skaggs School of Pharmacy and the University of California, San Diego School of Medicine.
For the study, researchers created functioning neurons derived from pluripotent stem cells (hiPSCs), which were reprogrammed from skin cells of schizophrenia patients. This method allowed scientists to observe and stimulate human neurons in ways not possible in animal models or human subjects.
Researchers activated these neurons so that they would secrete neurotransmitters — chemicals that excite or inhibit the transmission of electrical signals through the brain. The process was also performed on stem cell lines from healthy adults.
The findings showed that neurons taken from schizophrenia patients secreted significantly greater amounts of the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine.
Catecholamine neurotransmitters are synthesized from the amino acid tyrosine, and the regulation of these neurotransmitters is known to be altered in several mental disorders. Many psychotropic drugs selectively target the activity of these neurotransmitters in the brain.
Not only did researchers observe abnormal neurotransmitter secretion in schizophrenia neurons, but they also found that more neurons were producing tyrosine hydroxylase, the first enzyme in the creation of dopamine, from which both norepinephrine and epinephrine are made.
This discovery is significant because it offers a reason for why schizophrenia patients have abnormal neurotransmitter levels: They are preprogrammed to have more of the neurons that make these neurotransmitters.
“All behavior has a neurochemical basis in the brain,” Hook said. “This study shows that it is possible to look at precise chemical changes in neurons of people with schizophrenia.”
Future treatments might involve being able to evaluate the severity of a patient’s disease, identify different subtypes of the disease, and pre-screen patients for drugs that would most likely help them. It also offers a way to test the effectiveness of new drugs.
“It is very powerful to be able to see differences in neurons derived from individual patients — and a big accomplishment in the field to develop a method that allows this,” Hook said.