Brain Cell Growth And Mental Disorders
A new study in “Cell” connects the mechanism that produces new brain cells in adults with the incidence of schizophrenia and other neuropsychiatric disorders. The study, supports a controversial theory linking diseases such as schizophrenia and depression to neurogenesis and provides new avenues for the possible treatment of such conditions.
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| Image: flicker/Staurland |
“This is the first time anybody has ever shown that this protein [coded by the gene] directly regulates the number of neural progenitors,” said Li-Huei Tsai, the study’s main author and a neuroscientist at the Picower Institute of Learning and Memory at the Massachusetts Institute of Technology.
Prior studies linked disturbances in neurogenesis in a brain region called the hippocampus to schizophrenia and suggested that anti-depressant medications such as Prozac work by stimulating hippocampal neurogenesis. The new findings link the gene, DISC1, to a signal pathway that controls neurogenesis and the development of the nervous system.
“It really fits in with a lot of background information to suggest that hippocampal neurogenesis in particular is potentially a process which is going wrong in psychiatric illness,” said Ben Pickard, a medical geneticist at the University of Edinburgh (not involved in the study).
Researchers first connected DISC1 and psychiatric disorders in 2001 — a large Scottish family with a high incidence of schizophrenia and bipolar disorder had a significant disruption in the gene’s sequence. Tsai and others have since linked other mutations in the gene to psychiatric disorders.
Tsai and her colleagues showed that the DISC1 protein “inhibits the inhibition” of neurogenesis. A mutation in the gene therefore can lead to the undisturbed inhibition neuronal growth. In adult mice, blocking the action of the DISC1 protein resulted in the display of symptoms associated with schizophrenia and depression.
GSK3-beta is the molecular target of lithium, the most effective treatment available for bipolar disorder. Although the compound has been used for decades, how it works is largely unknown. Tsai’s findings suggest that lithium’s mechanism may involve stimulating neurogenesis. “One of the most exciting aspects of the study is the parallel between this one function and lithium,” said Tsai.
It may also provide a genetic means of predicting which patients will respond to lithium. This is “giving us clues as to why the medications might work in some people and not in others,” said David Porteous, a molecular geneticist also at the University of Edinburgh (also not involved in the present work, but coauthor of the original DISC1 family study). “It’s not just a very good piece of science; it’s also giving us a roadmap to what we should be doing next.”
“We’re starting to develop a kind of genetic network around the DISC1 pathway,” he said, which points to “targets for intervention in a much more rational fashion than what’s been possible.”
I’d add that it might also provide an interesting avenue for non-drug therapy using brain exercises that promote neurogenesis.
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