Preservation Effect: Cigarette Smoking Acts on the Dynamic of Influences Among Unifying Neuropsychiatric Triple Networks in Schizophrenia

Objective: The high prevalence of cigarette smoking in schizophrenia (SZ) is generally explained by the self-medication theory. However, its neurobiological mechanism remains unclear. The impaired dynamic of influences among unifying neuropsychiatric triple networks in SZ, including the central executive network (CEN), the default mode network (DMN), and the salience network (SN), might explain the nature of their syndromes, whereas smoking could regulate the dynamics within networks. Therefore, this study examined whether cigarette smoking could elicit a distinct improvement in the dynamics of triple networks in SZ and associated with the alleviation of symptoms.

Methods: Four groups were recruited, namely, SZ smoking (n = 22)/nonsmoking (n = 25), and healthy controls smoking (n = 22)/nonsmoking (n = 21). All participants underwent a resting-state functional magnetic resonance imaging (fMRI). The dynamics among unifying neuropsychiatric triple networks were measured using Granger causality analysis on the resting-sate fMRI signal. Interaction effects between SZ and smoking on dynamics were detected using 2-way analysis of covariance, correcting for sex, age, and education level.

Results: Whereas smoking reduced SN→DMN dynamic in healthy controls, it preserved the dynamic in SZ, thus suggesting a preservation effect. Moreover, smoking additionally increased DMN→CEN dynamic in SZ.

Conclusions: This finding from neural pathways shed new insights into the prevailing self-medication hypothesis in SZ. More broadly, this study elaborates on the neurobiological dynamics that may assist in the treatment of the symptomatology of SZ.