Scientists Take Major Step Toward Understanding Schizophrenia

A landmark new study sheds some light on how certain genes may influence the development of schizophrenia, a complex psychiatric condition that scientists have long struggled to make sense of and to treat.

The findings, published Wednesday in the journal Nature, point toward possible causes underlying the psychiatric disorder that affects roughly 3.5 million Americans, or about 1 percent of the general population. Schizophrenia is characterized by symptoms including delusions, hallucinations, cognitive difficulties and abnormal social behavior.

Psychiatrists know little, however, about its origins and biological underpinnings.

“The fundamental scientific predicament in schizophrenia and in all mental illness is that we haven’t known even the most basic things about how these diseases start,” Dr. Steve McCarroll, a geneticist at Harvard University and one of the study’s authors, told The Huffington Post. “Any steps toward understanding the root causes of the disease is potentially really helpful.”

For the new study, researchers from across the U.S. collaborated to investigate how genetics influence an individual’s chance of developing the disease, isolating one particular gene that seems to drive that risk.

They found that people who carry a gene that speeds up or strengthens the normal developmental process of “synaptic pruning” in the brain are at a higher risk for developing schizophrenia. Typically, the brain uses this process to shed weak or unneeded neural connections as it matures. This happens primarily during adolescence and young adulthood, and is concentrated in the prefrontal cortex of the brain, which is associated with high-level thinking, planning and decision-making.

But in people with schizophrenia, the synaptic pruning process goes into overdrive. This may explain why those individuals have been shown to have fewer neural connections in their prefrontal cortex, and why the disorder almost always shows up during adolescence or young adulthood.

“The great majority of schizophrenia cases present between the ages of 16 and 25, which has always been one of the mysteries of the illness,” McCarroll said. “Why would it strike at this particular time in life?”

The researchers found that the gene associated with aggressive tagging of weak neural connections — meaning that more of these connections are eaten away by proteins than they are in a healthy brain — also carries the protein C4. The C4 protein tells another protein to attach to synapses, or neural connectors, in the brain.

“C4 is essentially placing the Post-it note on synapses that says ‘eat me,'” McCarroll said.

We think it’s incredibly important to understand the biological changes that are taking place during the period of adolescence that establishes human vulnerability to this illness.”Dr. Steve McCarroll, a co-author of the new research

While the findings are preliminary, scientists say they represent a step in the right direction.

“This paper gives us a foothold, something we can work on, and that’s what we’ve been looking for now, for a long, long time,” Dr. David Goldstein, a professor of genetics at Columbia University who was not involved in the study, told The New York Times.

The new findings hopefully will one day pave the way for more effective treatments and screening protocols for the disease, such as a test or drug that could target runaway synaptic pruning.

“Drugs today don’t treat schizophrenia — they treat a single symptom of schizophrenia, which is psychosis,” McCarroll said. “They don’t treat the cognitive decline and the emotional withdrawal that patients endure, because they don’t address the root causes. And the reason is that we haven’t figured out very basic things about what those root causes are.”

More research needs to be done to confirm the findings, as well as to devise new treatment options.

“We’re going to work very hard to try to understand what exactly is changing in the adolescent brain at this particular time of life,” McCarroll said. “We think it’s incredibly important to understand the biological changes that are taking place during the period of adolescence that establishes human vulnerability to this illness.”

source: by Carolyn Gregoire

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