Tobacco Smoking and Gray Matter Volume in Individuals at Clinical High Risk for Psychosis: A Longitudinal Magnetic Resonance Imaging Study.

Background: Smoking is pervasive in young adults before psychosis onset and has been linked to worse clinical outcomes. Research suggests that smoking may play a role in psychosis pathogenesis, as increased smoking and gray matter reductions are associated with psychosis risk. However, a direct relationship in people at clinical high risk for psychosis (CHR-P) has not been established. Methods: 3T structural magnetic resonance imaging scans from the NAPLS-3 (North American Prodrome Longitudinal Study 3) were used. At baseline, 432 CHR-P nonsmokers and 110 CHR-P smokers were included, totaling 1617 scans across 2-, 4-, 6-, and 8-month follow-ups. Baseline gray matter volume differences between smoking and nonsmoking CHR-P were assessed with voxel-based morphometry. Linear mixed-effects models were used to examine association between smoking and gray matter volume across age in the superior frontal gyrus, anterior cingulate cortex, and insula. CHR-P individuals were categorized by tobacco use (no, low, high) to explore dose-response associations. Results: At baseline, no significant differences in gray matter volume were observed between smoking and nonsmoking CHR-P individuals, regardless of the tobacco use level. Longitudinal analyses showed no significant group or group × age associations with gray matter volume between the 2 groups. Conclusions: We observed no cross-sectional or longitudinal associations over 8 months between smoking and gray matter volume in CHR-P individuals. This suggests that no tobacco-related associations with gray matter volume reductions are evident yet in this vulnerable group, both in terms of psychosis and addiction risk. However, low smoking frequency and intensity in the current sample warrant further research with CHR-P individuals who are heavier smokers.