Smoking and double dissociation of prefrontal cognition in schizophrenia

Smoking prevalence is elevated in schizophrenia compared to the general population. Evidence suggests that smoking may lead to improvements of illness-related attention deficits. Departing from the notions that a) prefrontal dopaminergic deficits are associated with schizophrenia, b) that dopamine and nicotine interact in the ventral tegmental area, and that c) the dopaminergic effects on D1 follow a non-linear, inverted U-function, we hypothesized that prefrontal dopamine-mediated attention processes are differentially modulated by long-term nicotine consumption in schizophrenia and healthy controls. 104 schizophrenia patients and 104 carefully matched controls performed a cognitive test battery including CPT-IP, Attention Network Test, and WCST to cross-sectionally assess sustained, selective and executive attention, respectively. A significant interaction of ‘smoking status' x ’diagnostic group' was obtained for selective attention, i.e., conflict processing. In controls, smoking was significantly associated with an increased conflict effect, while the opposite effect was revealed for schizophrenia. We found a positive correlation between a cumulative measure of nicotine consumption and conflict effect in controls and a negative correlation in patients. These results provide evidence for specific directional effects of smoking on conflict processing that critically dissociate with diagnosis. Together, these findings support the self-medication hypothesis of schizophrenia.