Cigarette smoking and schizophrenia independently and reversibly altered intrinsic brain activity

Schizophrenia patients are at high risk for cigarette smoking, but the neurobiological mechanisms of this comorbid association are relatively unknown. Long-term nicotine intake may impact brain that are independently and additively associated with schizophrenia. We investigated whether altered intrinsic brain activity (iBA) related to schizophrenia pathology is also associated with nicotine addiction. Forty-two schizophrenia patients (21 smokers and 21 nonsmokers) and 21 sex- and age-matched healthy nonsmokers underwent task-free functional MRI. Whole brain iBA was measured by the amplitude of spontaneous low frequency fluctuation. Furthermore, correlation analyses between iBA, symptom severity and nicotine addiction severity were performed. We found that prefrontal cortex, right caudate, and right postcentral gyrus were related to both disease and nicotine addiction effects. More importantly, schizophrenia smokers, compared to schizophrenia nonsmokers showed reversed iBA in the above brain regions. In addition, schizophrenia smokers, relative to nonsmokers, altered iBA in the left striatal and motor cortices. The iBA of the right caudate was negatively correlated with symptom severity. The iBA of the right postcentral gyrus negatively correlated with nicotine addiction severity. The striatal and motor cortices could potentially increase the vulnerability of smoking in schizophrenia. More importantly, smoking reversed iBA in the right striatal and prefrontal cortices, consistent with the self-medication theory in schizophrenia. Smoking altered left striatal and motor cortices activity, suggesting that the nicotine addiction effect was independent of disease. These results provide a local property of intrinsic brain activity mechanism that contributes to cigarette smoking and schizophrenia.