Peer Reviewed

1

Document Type

Article

Publication Date

23-8-2018

Keywords

Schizophrenia, Glutamate, N-Acetylcysteine, Magnetic resonance spectroscopy, Arterial spin labelling, Anterior cingulate cortex.

Funder/Sponsor

General Electric Healthcare. IXICO. Sunovion and Takeda.

Abstract

RATIONALE: 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.

OBJECTIVES: 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.

METHODS: 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.

RESULTS: Relative to the placebo condition, the NAC condition was associated with lower levels of Glx/Cr, in the ACC (P < 0.05), but not in the caudate nucleus. There were no significant differences in CBF in the NAC compared to placebo condition.

CONCLUSIONS: 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.

Disciplines

Medicine and Health Sciences | Psychiatry and Psychology

Citation

McQueen G, Lally J, Collier T, Zelaya F, Lythgoe DJ, Barker GJ, Stone JM, McGuire P, MacCabe JH, Egerton A. Effects of N-acetylcysteine on brain glutamate levels and resting perfusion in schizophrenia. Psychopharmacology. 2018;

PubMed ID

30141055

DOI Link

10.1007/s00213-018-4997-2

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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