Comparing the brains of schizophrenia patients to healthy siblings may reveal significant clues to the debilitating disease, according to a new study at Michigan State University.
The research is the first to look at the neurotransmitters glutamate and gamma-aminobutyric acidergic (GABA) with a noninvasive imaging test called magnetic resonance spectroscopy in both schizophrenia patients and the healthy siblings of schizophrenia patients.
Glutamate promotes the firing of brain cells, and GABA inhibits this neural firing. They work hand in hand to regulate brain function.
At this time, most schizophrenia drugs regulate dopamine, another neurotransmitter in the brain; however, these medications do not work for everyone. Many researchers believe there are multiple risk factors for the illness, including imbalances in both dopamine and glutamate/GABA, and this has been confirmed by several studies. However, the exact relationship has remained unclear.
Currently there is no medication for schizophrenia that targets the glutamate/GABA system. In fact, medication for schizophrenia has changed very little in the past 50 years and remains somewhat limited in its effectiveness.
The study involved 21 patients with chronic schizophrenia, 23 healthy relatives (the relatives were siblings of other patients with schizophrenia, not the patients in the study) and a control group of 24 healthy subjects. It was performed in collaboration with researchers at the University Medical Center Utrecht in the Netherlands, where Thakkar served as a postdoctoral fellow.
According to the findings, both schizophrenia patients and healthy relatives show reduced levels of glutamate. But while the patients also showed reduced levels of GABA, the relatives had normal amounts of the inhibitory neurotransmitter.
This prompted the researchers to ask two questions: First, if glutamate is altered, why do these relatives not show symptoms of the illness? And, second, how did healthy relatives maintain normal levels of GABA even though they, like the patients, were genetically predisposed to schizophrenia and had altered glutamate levels?
“This finding is what’s most exciting about our study,” said lead investigator Dr. Katharine Thakkar, Michigan State University assistant professor of clinical psychology. “It hints at what kinds of things have to go wrong for someone to express this vulnerability toward schizophrenia.”
“The study gives us more specific clues into what kinds of systems we want to tackle when we’re developing new treatments for this very devastating illness.”
The brain scan used in the study — which is conducted on a conventional MRI machine — could eventually help clinicians target more specific treatments.
“There are likely different causes of the different symptoms and possibly different mechanisms of the illness across individuals,” Thakkar said.
“In the future, as this imaging technique becomes more refined, it could conceivably be used to guide individual treatment recommendations. That is, this technique might indicate that one individual would benefit more from treatment A and another individual would benefit more from treatment B, when these different treatments have different mechanisms of action.”
The findings are published online in the journal Biological Psychiatry.