Nicotinic mechanisms in the treatment of psychotic disorders: a focus on the α7 nicotinic receptor.

Nicotine is heavily abused by persons with schizophrenia. Nicotine better enables people with schizophrenia to filter out extraneous auditory stimuli. Nicotine also improves prepulse inhibition when compared to placebo. Nicotine similarly increases the amplitude of patients' duration mismatch negativity. The 15q13-14 region of the genome coding for the α7 nicotinic receptor is linked to schizophrenia. Multiple single nucleotide polymorphisms have been identified in this 15q13-14 gene promoter region that are more frequently present in people with schizophrenia than in normal controls. Abnormalities in expression and regulation of central nicotinic cholinoceptors with decreased α7 binding in multiple brain regions are also present. Nicotine enhances cognition in schizophrenia. Alternative agents that activate the nicotinic receptor have been tested including 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB-A). This compound improved attention, working memory, and negative symptoms in an add-on study in nonsmoking patients with schizophrenia. There are multiple other nicotinic agents, including positive allosteric modulators, in the preclinical stages of development. Finally, the effects of varenicline and clozapine and their relation to smoking cessation are discussed.