New research suggests that nicotine may help to treat schizophrenia patients.
A significant number of studies have shown the condition to be a brain disorder, with brain imaging techniques revealing that neurological impairment often accompanies schizophrenia.
One of the neurological abnormalities that former research has linked to schizophrenia is a decreased activity in the prefrontal cortex (PFC). This area hosts the brain's executive functions, such as judgment, decision-making, and problem-solving. The PFC also helps us to stay in control during stressful events, and deals with short-term and long-term memory.
A new study, published in the journal Nature Medicine, suggests that nicotine may be able to help schizophrenia patients.
Examining the link between smoking, schizophrenia, and genetics
Researchers from University of Colorado (CU) Boulder - led by Uwe Maskos, a researcher at the Institut Pasteur in Paris, France - set out to understand the causes of "hypofrontality," a decreased neuronal activation of the PFC when the task requires it.
Hypofrontality is thought to cause many of the cognitive problems associated with schizophrenia, including difficulty making decisions, focusing, or remembering things.
Additionally, former research has linked schizophrenia to a mutation in the CHRNA5 gene.
Many previous studies have also found a link between schizophrenia, the CHRNA5 gene, and smoking. Nearly 90 percent of people with schizophrenia smoke, most of them being heavy smokers, and 60 to 70 percent of people with bipolar disorder also smoke.
Additionally, research has shown an association between the number of cigarettes smoked per day and a polymorphic variation of the CHRNA5 gene.
In this context, Maskos and team asked the question: does a variation in the CHRNA5 gene trigger hypofrontality? If so, how does that happen, and can nicotine do anything to stop this process?
Nicotine found to correct hypofrontality
To begin, Maskos and team examined mice that had the CHRNA5 gene and displayed neurocognitive behavioral impairment in social interaction and sensorimotor tasks.
Specifically, they examined these mice that had a single-nucleotide polymorphism in the CHRNA5 gene - the alpha 5 nAChR subunit - which has been found to increase the risk for both smoking and schizophrenia.
Using brain imaging techniques, they found that these mice also had hypofrontality. The mice had decreased neural activity in a way that is similar to the hypofrontality found in patients with schizophrenia and addiction.
Finally, researchers administered nicotine to these mice, which reversed the hypofrontality. By acting on nicotinic receptors in brain areas related to healthy cognitive function, chronic nicotine administration reversed the cognitive impairment.
"Basically the nicotine is compensating for a genetically determined impairment," says Jerry Stitzel, a researcher at the Institute for Behavioral Genetics and one of the CU Boulder researchers. "No one has ever shown that before."
Implications for schizophrenia treatment
The authors conclude that their findings reveal a physiological basis for why schizophrenia patients tend to self-medicate by smoking.
The authors hope that their findings will ultimately lead to non-addictive, nicotine-based therapies for patients with schizophrenia.
"Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect, and validates that nicotine improves that deficit."
The treatment applications of their findings may be even broader, given that people living with attention deficit hyperactivity disorder, PTSD, or bipolar disorder have all been found to have decreased activity in the PFC.
"This defines a completely novel strategy for medication development," says lead author Maskos. "Identifying behavioral deficits associated with this mutation can be used for diagnostic or predictive work in schizophrenia," adds co-author Charles Hoeffer.