Nicotine effects on endophenotypes of schizophrenia

• Applicant: Professor Michael Wagner, Ph.D.
• Subject Area: Biological Psychiatry
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 24654226

Epidemiological and genetic data suggest an important pathophysiological role of nicotinic receptors for schizophrenia, and particularly for cognitive functions impaired in schizophrenia and their relatives. Studies employing medicated patients to further examine this role have inherent limitations, because they cannot disentangle whether effects of nicotine are related to (1) schizophrenic disease, (2) to its antipsychotic treatment, (3) to the genetic vulnerability for schizophrenia, or (4) to long-term nicotine use. In each of two separate experiments, one with smokers and one with non-smokers, we will study the effect of nicotine on four physiological and cognitive endophenotypes (sensory gating, antisaccades, sustained attention, working memory) in (a) patients with schizophrenia, (b) adult first-degree relatives of schizophrenic patients, and (c) controls. Stronger nicotine effects in relatives than in controls would support a genetic explanation. In a third study we test whether a known functional polymorphism in the promoter region of the nicotinic Alpha-7 ACh Receptor, strongly associated with sensory gating in one study (Leonard et al. 2002) is related to our endophenotypes, and their sensitivity to acute nicotine administration.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1226: Nicotine: Molecular and Physiological Effects in the Central Nervous System (CNS)
• Participating Person: Dr. Christian G. Schütz