Althou
gh altered
gamma-aminobutyric acid (GABA) neurotransmission has been implicated in the pathophysiolo
gy of schizophrenia, it is unclear whether the influence of GABA on workin
g memory processes is confounded by nicotine use in this population. It is therefore crucial to evaluate workin
g memory and its underlyin
g mechanisms in non-smokers with schizophrenia to eliminate the confoundin
g effects of nicotine on behavior and neurophysiolo
gy.
Methods
In this cross-sectional study, working memory was assessed using the verbal N-back task, while GABAergic function was assessed through motor cortical inhibition using single and paired-pulse transcranial magnetic stimulation (TMS) to the left primary motor cortex in 11 non-smokers with schizophrenia and 13 non-smoker healthy subjects.
Results
Similar to previously published studies, working memory performance was significantly impaired in the 3-back condition in patients with schizophrenia compared to healthy subjects (p = 0.036). In addition, GABAA receptor function was significantly reduced in schizophrenia as assessed by short interval cortical inhibition (SICI) (p = 0.005). A positive correlation was found between GABAA inhibition and working memory performance on the 3-back task (r(23) = 0.55, p = 0.006), suggesting that greater GABAA inhibition is associated with better performance on tasks of working memory.
Conclusions
Our findings highlight the role of GABAA receptor dysfunction in working memory and the pathophysiology of schizophrenia, and may represent a selective characteristic of schizophrenia. Moreover, these findings suggest a potential therapeutic role for targeting GABA receptor activity to improve cognition and quality of life in patients with schizophrenia.