Translating Neurobiology to the Treatment of Dual Diagnosis: The Example of Nicotinic Receptors and Neurocognitive Endophenotypes in Schizophrenia

Abstract

Endophenotypes are heritable traits associated with psychiatric illness. Certain endophenotypes associated with schizophrenia such as working memory and sensory gating may be linked to the high tobacco smoking prevalence in patients with schizophrenia. Evidence suggests a critical role for the nicotinic acetylcholine receptor system (nAChR) in the underlying pathophysiology of schizophrenia. Despite the negative consequences associated with tobacco use, patients with schizophrenia have a much more difficult time quitting smoking and remaining abstinent compared with their non-psychiatric counterparts. Deficits in nAChR function may contribute to the cognitive deficits that are seen with the illness, such as deficits in working memory and sensory gating, and to co-morbid tobacco use disorders. Accordingly, treatments for tobacco use disorder in this population should focus on remediation of the disease-related endophenotypes that restore neurocognitive function and reduce the risk of smoking relapse.