10779/rcsi.10794725.v1
Grant McQueen
Grant
McQueen
John Lally
John
Lally
Tracy Collier
Tracy
Collier
Fernando Zelaya
Fernando
Zelaya
David J. Lythgoe
David J.
Lythgoe
Gareth J. Barker
Gareth J.
Barker
James M. Stone
James M.
Stone
Philip McGuire
Philip
McGuire
James H. MacCabe
James H.
MacCabe
Alice Egerton
Alice
Egerton
Effects of N-acetylcysteine on brain glutamate levels and resting perfusion in schizophrenia.
Royal College of Surgeons in Ireland
2019
Schizophrenia
Glutamate
N-Acetylcysteine
Magnetic resonance spectroscopy
Arterial spin labelling
Anterior cingulate cortex.
Psychiatry (incl. Psychotherapy)
2019-11-22 17:10:30
Journal contribution
https://repository.rcsi.com/articles/journal_contribution/Effects_of_N-acetylcysteine_on_brain_glutamate_levels_and_resting_perfusion_in_schizophrenia_/10794725
<p><strong>RATIONALE:</strong> N-Acetylcysteine (NAC) is currently under investigation as an adjunctive treatment for schizophrenia. The therapeutic potential of NAC may involve modulation of brain glutamate function, but its effects on brain glutamate levels in schizophrenia have not been evaluated.</p>
<p><strong>OBJECTIVES:</strong> The aim of this study was to examine whether a single dose of NAC can alter brain glutamate levels. A secondary aim was to characterise its effects on regional brain perfusion.</p>
<p><strong>METHODS:</strong> In a double-blind placebo-controlled crossover study, 19 patients with a diagnosis of schizophrenia underwent two MRI scans, following oral administration of 2400 mg NAC or matching placebo. Proton magnetic resonance spectroscopy was used to investigate the effect of NAC on glutamate and Glx (glutamate plus glutamine) levels scaled to creatine (Cr) in the anterior cingulate cortex (ACC) and in the right caudate nucleus. Pulsed continuous arterial spin labelling was used to assess the effects of NAC on resting cerebral blood flow (rCBF) in the same regions.</p>
<p><strong>RESULTS:</strong> Relative to the placebo condition, the NAC condition was associated with lower levels of Glx/Cr, in the ACC (Pā<ā0.05), but not in the caudate nucleus. There were no significant differences in CBF in the NAC compared to placebo condition.</p>
<p><strong>CONCLUSIONS:</strong> These data provide preliminary evidence that NAC can modulate ACC glutamate in patients with schizophrenia. In contrast, physiological effects of NAC on the brain were not detectable as between session changes in rCBF. Future studies assessing the effects of a course of treatment with NAC on glutamate metabolites in schizophrenia are indicated.</p>