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

Abstract:

BACKGROUND: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, 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.

journal_name

Schizophr Res

journal_title

Schizophrenia research

authors

Bridgman AC,Barr MS,Goodman MS,Chen R,Rajji TK,Daskalakis ZJ,George TP

doi

10.1016/j.schres.2016.01.008

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

125-30

issue

1-3

eissn

0920-9964

issn

1573-2509

pii

S0920-9964(16)30008-1

journal_volume

171

pub_type

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