Deficits in GABA_A receptor function and working memory in non-smokers with schizophrenia

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• 作者：Alanna C. Bridgman^a ; ^d ; Mera S. Barr^a ; ^b ; ^d ; ^{mera.barr@camh.ca" class="auth_mail" title="E-mail the corresponding author} ; Michelle S. Goodman^a ; ^d ; Robert Chen^c ; Tarek K. Rajji^d ; ^e ; Zafiris J. Daskalakis^b ; ^d ; Tony P. George^a ; ^b
• 关键词：Cortical inhibition ; N-back task ; Gamma-aminobutyric acid ; Transcranial magnetic stimulation
• 刊名：Schizophrenia Research
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：171
• 期：1-3
• 页码：125-130
• 全文大小：405 K

文摘

Although altered gamma-aminobutyric acid (GABA) neurotransmission has been implicated in the pathophysiology of schizophrenia, it is unclear whether the influence of GABA on working memory processes is confounded by nicotine use in this population. It is therefore crucial to evaluate working memory and its underlying mechanisms in non-smokers with schizophrenia to eliminate the confounding effects of nicotine on behavior and neurophysiology.

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, GABA_A receptor function was significantly reduced in schizophrenia as assessed by short interval cortical inhibition (SICI) (p = 0.005). A positive correlation was found between GABA_A inhibition and working memory performance on the 3-back task (r₍₂₃₎ = 0.55, p = 0.006), suggesting that greater GABA_A inhibition is associated with better performance on tasks of working memory.

Conclusions

Our findings highlight the role of GABA_A 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.