A steady stream of nicotine
normalizes genetically-induced impairments in brain activity associated with
schizophrenia, according to new research involving the University of Colorado
Boulder. The finding sheds light on what causes the disease and why those who
have it tend to smoke heavily. Researchers envision their work could lead to
new non-addictive, nicotine-based treatments for some of the 51 million people
worldwide who suffer from the disease. The study found that when mice with
schizophrenic characteristics were given nicotine daily, their sluggish brain
activity increased within two days. Within one week it had normalized. The
international team of scientists set out to explore the underlying causes of
'hypofrontality' (a reduction of neuronal firing in the prefrontal cortex of
the brain). Hypofrontality is believed to be the root cause of many of the
signature cognitive problems experienced by schizophrenics, including trouble
paying attention, remembering things, making decisions and understanding verbal
explanations. Previous genome-wide association studies have suggested that
people with a variation in a gene called CHRNA5 are more likely to have
schizophrenia, but the mechanism for that association has remained unclear.
People with that variant are also more likely to smoke.
Eighty to 90 percent of people
with schizophrenia smoke and most are very heavy smokers, a fact that has long
led researchers to suspect they are self-medicating. For the study, the
researchers set out to answer several questions: Does a variant in the CHRNA5
gene lead to hypofrontality. If so, how? And does nicotine somehow interrupt
this effect? Eighty to 90 percent of people with schizophrenia smoke and most
are very heavy smokers, a fact that has long led researchers to suspect they
are self-medicating. To do so, the research team first took mice with the
CHRNA5 gene variant and used state-of-the-art brain imaging technologies to see
if they had hypofrontality. Then researchers, conducted behavioral tests to see
if the mice shared key characteristics of schizophrenics, like being unable to
suppress a startle response and being averse to social interaction. The results
validated that the gene variant likely plays a role in schizophrenia by causing
hypofrontality. Nicotine appeared to reverse this in the mice, normalizing
brain activity by acting on nicotinic receptors in regions of the brain key to
healthy cognitive function. Because hypofrontality is also associated with
addiction and other psychiatric conditions, the research could ultimately have
broad applications for drug development in the mental health field.
More information: