Elevated brain lactate in schizophrenia: a 7 T magnetic resonance spectroscopy study

Abstract

Various lines of evidence suggest that brain bioenergetics and mitochondrial function may be altered in schizophrenia. On the basis of prior phosphorus-31 (³¹P)-magnetic resonance spectroscopy (MRS), post-mortem and preclinical studies, this study was designed to test the hypothesis that abnormal glycolysis leads to elevated lactate concentrations in subjects with schizophrenia. The high sensitivity of 7 Tesla proton (¹H)-MRS was used to measure brain lactate levels in vivo. Twenty-nine controls and 27 participants with schizophrenia completed the study. MRS scanning was conducted on a Philips 'Achieva' 7T scanner, and spectra were acquired from a voxel in the anterior cingulate cortex. Patients were assessed for psychiatric symptom severity, and all participants completed the MATRICS Consensus Cognitive Battery (MCCB) and University of California, San Diego Performance-Based Skills Assessment (UPSA). The relationship between lactate, psychiatric symptom severity, MCCB and UPSA was examined. Lactate was significantly higher in patients compared with controls (P=0.013). Higher lactate was associated with lower MCCB (r=-0.36, P=0.01) and UPSA total scores (r=-0.43, P=0.001). We believe this is the first study to report elevated in vivo cerebral lactate levels in schizophrenia. Elevated lactate levels in schizophrenia may reflect increased anaerobic glycolysis possibly because of mitochondrial dysfunction. This study also suggests that altered cerebral bioenergetics contribute to cognitive and functional impairments in schizophrenia.

Figure 1

(a) Representative anterior cingulate voxel location illustrated in red. (b) Representative in vivo spectrum (black line), LCModel fit (red line), residual (black line at top) and individual metabolite fits below. Asp, aspartate; Cr, creatine; GABA, gamma-aminobutyric acid; Gln, glutamine; Glu, glutamate; Lac, lactate; MM, macromolecules; ml, myo-inositol; NAA, n-acetylaspartate; NAAG, n-acetylaspartylglutamate; PCr, phosphocreatine; Ser, serine; Tau, taurine; tCho, phosphocholine+glycerophosphocholine.

Figure 2

The mean (s.d. bars) lactate levels by diagnostic group. Lactate levels were significantly higher in schizophrenia compared with the control group (P<0.05).

Figure 3

(a) A correlation scatter plot illustrating the negative relationship between lactate levels and general cognition function assess with the MCCB (total score). Schizophrenia group, gray circles, dashed trend line with r=−0.18, P>0.05. Control group, white squares, solid trend line with r=−0.10, P>0.05. Both groups combined, r=−0.36, P=0.01. (b) A correlation scatter plot illustrating the negative relationship between lactate levels and functional capacity assessed with the UPSA (total score). Schizophrenia group, gray circles, dashed trend line with r=−0.40, P<0.05. Control group, white squares, solid trend line with r=−0.008, P>0.05. Both groups combined, r=−0.43, P=0.001. MCCB, MATRICS Consensus Cognitive Battery; UPSA, University of California, San Diego Performance-Based Skills Assessment.