Nicotine in action: cigarette smoking modulated homotopic functional connectivity in schizophrenia
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Cigarette smoking is intimately associated with both early onset and increased severity of schizophrenia. The self-medication hypothesis suggests that nicotine can relieve or restore neurocognitive deficits and symptoms associated with schizophrenia. Schizophrenia patients and healthy subjects who smoked showed deficits in communication between their hemispheres. These homotopic connectivity mechanisms associated with both schizophrenia and smoking comorbidity were largely unknown until now. A mixed sample including patients with schizophrenia (22 smokers and 27 non-smokers) and healthy controls (22 smokers and 21 non-smokers) based on clinical diagnoses and cigarette dependence were recruited for the current study. All subjects underwent resting-state functional magnetic resonance imaging to determine possible interactions between schizophrenia and smoking, and to determine the main effects of schizophrenia and smoking on homotopic functional connectivity. Decreased homotopic functional connectivity of the subgenual anterior cingulate cortex suggested a main effect of schizophrenia and smoking—an additive effect. Furthermore, we found an antagonistic interaction effect between schizophrenia and smoking located in the ventrolateral prefrontal cortex (VLPFC). In addition, the connectivity strength of the bilateral VLPFC was negatively correlated with the Positive and Negative Syndrome Scale Negative scores and positively correlated with lifetime smoking. These results suggest that smoking has multiple effects on the modulation of interhemispheric connectivity in schizophrenia. Our findings provide valuable information underlying the pathophysiological mechanisms of schizophrenia and offer a potential target for future clinical treatment of schizophrenia and smoking comorbidity.
KeywordsCigarette smoking Homotopic functional connectivity Schizophrenia Self-medication Ventrolateral prefrontal cortex Subgenual anterior cingulate cortex
This study was funded by the National Natural Science Foundation of China (61533006, 81471653, 81771919 and 61673089), China Postdoctoral Science Foundation (2013 M532229), Sichuan Science and Technology Program (2018TJPT0016), and the “111” project (B12027).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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