Increased cortical inhibition deficits in first-episode schizophrenia with comorbid cannabis abuse

There is a high prevalence of substance use disorder (SUD) in first-episode schizophrenia (SZ), but its contribution to the underlying SZ pathophysiology remains unclear. Several studies using transcranial magnetic stimulation (TMS) have observed abnormalities in human motor cortex (M1) excitability in SZ. Studies on cortical excitability comparing SZ patients with and without comorbid substance abuse are lacking. A total of 29 first-episode SZ patients participated in this study; 12 had a history of comorbid cannabis abuse (SZ-SUD) and 17 did not (SZ-NSUD). We applied TMS to right and left M1 areas to assess the resting motor threshold (RMT), short-interval cortical inhibition (SICI), intracortical facilitation (ICF), and the contralateral cortical silent period (CSP). In SICI and ICF conditions, right M1 stimulation led to significantly higher motor evoked potential ratios in SZ-SUD compared to SZ-NSUD. This suggests lower cortical inhibition and increased ICF in first-episode SZ with previous cannabis abuse. There were no group differences in RMT and CSP duration. Neither were there any significant correlations between psychopathology (as indexed by Positive and Negative Syndrome Scale), disease characteristics, the extent of cannabis abuse, and TMS parameters (SICI, ICF, and CSP). Comorbid cannabis abuse may potentiate the reduced intracortical inhibition and enhanced ICF observed in first-episode SZ patients in some previous studies. This finding suggests an increased alteration of GABA(A) and NMDA receptor activity in cannabis-abusing first-episode patients as compared to schizophrenia patients with no history of substance abuse. This may constitute a distinct vulnerability factor in this special population.