Stem Cells reveal neurochemical flood in schizophrenics

Schizophrenia may be tripped off by an overabundance of chemical signals pumped out by neurons in the brain. The University of California, San Diego, announced Sept. 11 that researchers from the Skaggs School of Pharmacy and Pharmaceutical Sciences are using stem cells to see the flood of neurotransmitters first-hand.

Researchers including Vivian Hook, PhD, a professor in the UCSD Skaggs School and colleagues at the used stem cells called human induced pluripotent stem cells (hiPSCs) to learn more about the biochemistry behind schizophrenia. The results of the study were recently published in Stem Cell Reports.

"The study provides new insights into neurotransmitter mechanisms in schizophrenia that can lead to new drug targets and therapeutics,” Hook said in the UCSD release. Investigators from The Salk Institute for Biological Studies and the Icahn School of Medicine at Mount Sinai in New York City, also contributed to the research.

The scientists in Hook’s team found neurons in schizophrenics that produce larger quantities of catecholamine neurotransmitters involved in a range of psychiatric diseases, not just schizophrenia, which is estimated to affect one in 100 patients.

The hiPSCs were cultivated into neurons from the skin cells of schizophrenics and were observed in vitro as they secreted these neurotransmitters. A comparison between these “brain-in-a-dish” neurons and controls showed higher amounts of three catecholamine neurotransmitters in particular: dopamine, epinephrine and norepinephrine.

“All behavior has a neurochemical basis in the brain,” said Hook. “This study shows that it is possible to look at precise chemical changes in neurons of people with schizophrenia.”

These neurochemicals are synthesized from tyrosine, a biomarker for pharmaceutical studies. The researchers also found that more neurons were set to produce tyrosine hydroxylase, the initial phase in the pathway to produce dopamine, which then produces the other two neurotransmitters. Drugs that follow this pathway can target the over-production of neurotransmitters in psychiatric patients and tamp it down.