Schizophrenia is a common
mental illness with a high prevalence of smoking. More than 80% of schizophrenics
smoke compared to 25% of the general population. Both
schizophrenia and tobacco use have strong genetic components, which may overlap. It has been suggested that smoking in
schizophrenia may be a form of
self-medication in an attempt to treat an underlying
biological pathology. Smoking normalizes auditory evoked potential and eye tracking deficits in
schizophrenia, as well as improving cognitive function.
Nicotine acts through a family of
nicotinic receptors with either high or low affinity for
nicotine. The loci for several of these receptors have been genetically linked to both smoking and to
schizophrenia. Smoking changes gene expression for more than 200 genes in human hippocampus, and differentially normalizes aberrant gene expression in
schizophrenia. The α7*
nicotinic receptor, linked to
schizophrenia and smoking, has been implicated in sensory processing deficits and is important for cognition and protection from neurotoxicity.
Nicotine, however, has multiple health risks and desensitizes the receptor. A Phase I trial of DMXB-A, an α7* agonist, shows improvement in both P50 gating and in cognition, suggesting that further development of nicotinic
cholinergic drugs is a promising direction in
schizophrenia research.