Functional magnetic resonance spectroscopy in patients with schizophrenia and bipolar affective disorder: Glutamate dynamics in the anterior cingulate cortex during a working memory task

Abstract

The glutamate system is implicated in the pathophysiology of schizophrenia and mood disorders. Using functional magnetic resonance spectroscopy (1H-fMRS), it is possible to monitor glutamate dynamically in activated brain areas and may give a closer estimate of glutamatergic neurotransmission than standard magnetic resonance spectroscopy. 14 patients with schizophrenia, 15 patients with bipolar disorder II (BPII) and 14 healthy volunteers underwent a 15 min N-back task in a 48s block design during 1H-fMRS acquisition. Data from the first, second and third 16s group of 8 spectra for each block were analysed to measure levels of glutamate and Glx (glutamate + glutamine), scaled to total creatine (TCr), across averaged 0-back and 2-back conditions. A 6 × 3 repeated-measures analysis of variance (rmANOVA) demonstrated a significant main effect of time for Glx/TCr (P = 0.022). There was a significant increase in Glu/TCr (P = 0.004) and Glx/TCr (P < 0.001) between the final spectra of the 0-back and first spectra of the 2-back condition in the healthy control group only. 2 × 2 rmANOVA revealed a significant time by group interaction for Glx/TCr (P = 0.019) across the 0-back condition, with levels reducing in healthy controls and increasing in the schizophrenia group. While healthy volunteers showed significant increases in glutamatergic measures between task conditions, the lack of such a response in patients with schizophrenia and BPII may reflect deficits in glutamatergic neurotransmission. Abnormal increases during periods of relatively low executive load, without the same dynamic modulation as healthy volunteers with increasing task difficulty, further suggests underlying abnormalities of glutamatergic neurotransmission in schizophrenia.