Researchers Discover The Genomic Mechanism Behind Schizophrenia
Brett Smith for redOrbit.com – Your Universe Online
According to the scientists’ report in the journal Schizophrenia Research, problems with the Integrative Nuclear FGFR 1 Signaling (INFS) pathway during gestation leads to brain changes, ultimately causing behavioral problems, or schizophrenia, later in life. Previous research has shown that the pathway includes as many as 160 different genes.
“We believe this is the first model that explains schizophrenia from genes to development to brain structure and finally to behavior,” said lead author Michal Stachowiak, professor at the UB School of Medicine and Biomedical Sciences.
Previous research has shown that around 100 different genetic mutations are linked to the disorder. Stachowiak said his team set out to learn why this is the case and suspected INFS could be the culprit.
“It’s possible because INFS integrates diverse neurological signals that control the development of embryonic stem cell and neural progenitor cells, and links pathways involving schizophrenia-linked genes,” he said in a statement.
“INFS functions like the conductor of an orchestra,” Stachowiak explained. “It doesn’t matter which musician is playing the wrong note, it brings down the conductor and the whole orchestra. With INFS, we propose that when there is an alteration or mutation in a single schizophrenia-linked gene, the INFS system that controls development of the whole brain becomes untuned. That’s how schizophrenia develops.”
Using embryonic stem cells, the team from UB and collaborators from other institutions found that some of the key genes identified by previous schizophrenia researcher bind the fibroblast growth factor receptor protein (FGFR1). The result is a cascading effect on the entire INFS pathway.
“We believe that FGFR1 is the conductor that physically interacts with all genes that affect schizophrenia,” Stachowiak said. “We think that schizophrenia occurs when there is a malfunction in the transition from stem cell to neuron, particularly with dopamine neurons.”
To test their hypothesis, the research team engineered an FGFR1 mutation in mice. These mice then produced symptoms of the disease found in humans, including abnormal brain anatomy, irregular behavioral impacts and sensory overload.
According to the researchers, if a generalized genomic pathway is causing the disease, then a generalized approach might be the key to treating it.
“We may even be able to devise ways to arrest development of the disease before it presents fully in adolescence or adulthood,” Stachowiak said.
The UB work adds to recent schizophrenia research that showed nicotinic agonists, typically used to help with smoking cessation, can facilitate improved cognitive function in schizophrenics through their effect on the INFS. These studies show that schizophrenics smoke at a dramatically higher rate and this behavior could be a form of self-medication.
Some mental health observers note the proliferation of smoking bans in treatment facilities and how this could impact the patients being treated there. One study showed that in the first few hours after patients with schizophrenia enter a smoke-free psychiatric emergency setting, over 50 percent become agitated. The same study noted that giving patients who smoked a nicotine patch resulted in an average marked improvement in behavior.