Evaluating the impact of cannabis use on thalamic connectivity in youth at clinical high risk of psychosis

Lisa Buchy, Tyrone D. Cannon, Alan Anticevic, Kristina Lyngberg, Kristin S. Cadenhead, Barbara A. Cornblatt, Thomas H. McGlashan, Diana O. Perkins, Larry J. Seidman, Ming T. Tsuang, Elaine F. Walker, Scott W. Woods, Carrie E. Bearden, Daniel H. Mathalon, Jean Addington

Disruptions in thalamic functional connectivity have been observed in people with schizophrenia and in youth at clinical high risk (CHR) of psychosis. However, the impact of environmental risk factors for psychosis on thalamic dysconnectivity is poorly understood. We tested whether thalamic dysconnectivity is related to patterns of cannabis use in a CHR sample. 162 CHR and 105 control participants were assessed on cannabis use severity, frequency, and age at onset of first use as part of the North American Prodrome Longitudinal Study and completed resting-state fMRI scans. Whole-brain thalamic functional connectivity maps were generated using individual subjects' anatomically defined thalamic seeds. Thalamic connectivity did not significantly correlate with current cannabis use severity or frequency in either CHR or controls. In CHR cannabis users, a significant correlation emerged between attenuated thalamic connectivity with left sensory/motor cortex and a younger age at onset of cannabis use. CHR who used cannabis before age 15 did not differ on thalamic connectivity as compared to CHR who used after age 15 or CHR who were cannabis naïve. No group differences in thalamic connectivity emerged when comparing CHR separated by moderate/high use frequency, low-frequency or cannabis naïve. Although a younger age at onset of cannabis use may be associated with disrupted thalamo-cortical coupling, cannabis use does not appear to be an identifying characteristic for thalamic connectivity in CHR with moderate/high use frequency compared to low-frequency users or CHR who are cannabis naïve.