¹Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Correspondence: Professor RG Steen, Department of Psychiatry, Campus Box #7160, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7160, USA. Tel: +1 919 966 8382, E-mail: Grant_Steen@med.unc.edu

Received 15 March 2005; Revised 29 April 2005; Accepted 17 June 2005; Published online 10 August 2005.

Abstract

A systematic review of the literature identified 64 published English-language papers that used proton (¹H) magnetic resonance spectroscopy to measure N-acetylaspartate (NAA) concurrently in healthy controls and in patients with a diagnosis of schizophrenia (SZ). A total of 1209 controls and 1256 patients have been evaluated, with 88% of studies carried out at 1.5 T field strength, and 77% of studies focused on patients with chronic SZ. There is consistent evidence that NAA is reduced in a broad range of tissues in the SZ brain. Broad consensus (10 studies) is emerging that NAA levels are reduced 5% in hippocampus and in both cortical gray matter (GM) and white matter (WM) of the frontal lobe. There is no evidence to support a hypothesis that relative NAA levels are reduced to a different degree in frontal lobe GM and WM, nor is there robust evidence of a difference in NAA levels between patients with first-episode and chronic SZ. Study reliability may be a problem, as most studies appear to be underpowered. With simple assumptions about the inherent difference in NAA levels between patients and controls, it can be calculated that a minimum sample size of approximately 39 patients and 39 controls is required for acceptable statistical power. Only three of 64 studies included enough subjects to have 80% power to detect a 10% NAA reduction in patients, and no studies were adequately powered to detect a 5% NAA reduction with 80% power.