While we frequently speak of mental illness as “a chemical imbalance,” the fact is it's difficult to find hard evidence of abnormal brain chemistry in those who suffer from psychiatric disorders. Now, UC San Diego researchers may have found a way to prove this commonly-held theory of imbalance. Using a model derived from stem cells, the researchers showed how the brain cells of patients with schizophrenia secrete higher amounts of three neurotransmitters.

"All behavior has a neurochemical basis in the brain," said Dr. Vivian Hook, a professor at UC San Diego School of Medicine. "This study shows that it is possible to look at precise chemical changes in neurons of people with schizophrenia." A chronic and severe brain disorder, schizophrenia affects an estimated one percent of Americans. Despite how disabling the illness is, schizophrenia leaves no tell-tale physical marks in brain tissue. As a result, scientists have not yet identified a definitive cause or cure, though they believe schizophrenia has a genetic basis.

For the current study, the researchers made a "brain in a petri dish." They created a model of functioning brain cells derived from human induced pluripotent stem cells (hiPSCs), which had been reprogrammed from skin cells of schizophrenia patients. The researchers constructed this model as a way to observe and stimulate human neurons in ways impossible in animal models or human subjects. They activated the cells so that they would secrete neurotransmitters — chemicals that excite or inhibit the transmission of electrical signals through the brain. Next, the researchers replicated this process on stem cell lines derived from healthy adults and compared the results.

The cultured "brain in a dish" neurons from schizophrenia patients secreted significantly greater amounts of the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine than did the neurons from healthy patients. Catecholamine neurotransmitters are synthesized from the amino acid tyrosine. In the schizophrenia neurons, the researchers also observed more neurons dedicated to the production of tyrosine hydroxylase, the first enzyme in the biosynthetic pathway for the synthesis of dopamine, from which both norepinephrine and epinephrine are made.

"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," said Hook. Once refined and applied, this research should allow scientists to evaluate the severity of a patient’s disease and to identify different sub-types of the disease. Best of all, scientists should be able to create new drugs to help patients based on this research.

Source: Hook V, et al. Stem Cell Reports. 2014.