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The Schizophrenia Gene: Brain Development and Disorder Tightly Linked

April 5, 2016

A recent issue of The New Yorker explored the personal side of a major scientific advance concerning schizophrenia. In the middle of Siddhartha Mukherjee’s touching narrative of severe mental illness across generations of his family in India, he describes the present state of genetic research into schizophrenia, and the revelation that the disorder appears intimately linked to the processes of normal and necessary brain development.

Specifically, scientists have implicated a group of proteins responsible for the consolidation stage of brain development, known as “pruning,” in the development of schizophrenia. The theory, as one of the researchers tells Mukherjee, is that schizophrenia “may be a disease of overpruning.”

Normally, pruning (which takes place from adolescence to early adulthood) is a way for the brain to get rid of unused neural pathways and connections, and strengthen and optimize the ones we do use. It “hardwires” what we’ve learned in childhood and adolescence. Although researchers don’t fully understand it, schizophrenia may be pruning gone awry. They have found higher levels of these pruning-related proteins in schizophrenic brains — in exactly the regions responsible for functions affected by schizophrenia, like planning and cognition. The onset of schizophrenia matches up closely with when pruning is occurring in the brain. And adults with schizophrenia have been shown to have fewer connections between neurons than typical people—what you might expect if pruning had gotten out of hand.

This Scientific American article explains the study in detail. The whole story of discovery is fascinating—including the revelation that proteins that usually function as part of our immune defense against foreign invaders do double-duty as the mechanisms of neural pruning. Perhaps most exciting is that as researchers get closer to understanding the mechanism and development of schizophrenia, treatments could be developed to address the cause, and not just the symptoms — and perhaps even prevent onset in young people who are at risk. That’s the holy grail for all health care, including mental health care, and particularly for devastating diseases like schizophrenia.

The possibility of changing these outcomes gets Mukherjee thinking about his family, about uncles whose blazing genius or preternatural empathy tipped into disaster — mania, death, lifelong dysfunction. “Our unique selves must live in some balanced state,” he writes, “between overedited and underedited brain circuits, between overpruned and underpruned synapses.”

Tagged with: In The News, Schizophrenia and Psychosis, Science and Research