Table 1:
Glutamate metabolites and cognition in schizophrenia
| Author Year of publication | n (control/ patient) | Illness stage | Medication status | Cognitive domain | Region | Tesla | Metabolite | Acquisition | MRS Sequence | TE (ms) | Reference | Metabolite level group difference | Associations between metabolites and cognition |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (Chang et al., 2007) | 22/23 | Chronic (elderly) | mixed | MMSE | Frontal, temporal, and occipital WM | 4 | Glx | SV | PRESS | 30 | W | ↑Glx in all regions | No associations |
| (Ohrmann et al., 2007) | 20/35 | mixed | mixed | Broad neuropsychological battery | Left DLPFC | 1.5 | Glx | SV | STEAM | 20 | W | ↓Glx in SZ vs FEP and HC | DLPFC Glx was positively associated with the AVLT immediate in chronic medicated patients, but not FEP or HC |
| (Purdon et al., 2008) | 14/15 | Genetic HR (siblings) | Un-medicated | CPT | Frontal cortex | 3 | Glu | SV | STEAM | 20 | Cr | - | Higher frontal Glu was associated with lower score on the CPT in high risk subjects, but not HC |
| (Rusch et al., 2008) | 31/29 | mixed | Medicated | WCST | Left hippocampus and DLPFC | 2 | Glu, Gln | SV | PRESS | 30 | W | ↑DLPFC Glu/ Gln | Hippocampal Glu was negatively associated with better performance on the WCST in SZ, but not HC |
| (Rowland et al., 2009) | 11/20 | Chronic (10 deficit/ 10 non-deficit) | Medicated | RBANS | Middle frontal, inferior parietal cortex | 3 | Glx | SV | PRESS | 35 | W | - | No associations |
| (Shirayama et al., 2010) | 18/19 | Chronic | mixed | WCST, TMT, DSDT, Verbal fluency test, Stroop, Iowa gambling test | MPFC | 3 | Gln, Glu | SV | PRESS | 30 | W | ↑Gln/ Glu | MPFC Gln/Glu was negatively associated with the WCST and DSDT in the combined SZ and HC group |
| (Reid et al., 2010) | 23/26 | Chronic | Medicated | RBANS | ACC | 3 | Glx | SV | PRESS | 80 | Cr | - | No associations |
| (Yoon et al., 2010) | 13/13 | mixed | mixed | OSSS | Calcarine sulci | 3 | Glx | SV | MEGA- PRESS | 68 | Cr | - | No associations |
| (Bustillo et al., 2011) | 28/30 | Chronic Young: 10/12; Old: 18/18 | Medicated | Broad neuropsychological battery | frontal lobe and parietal lobe | 4 | Glx | MRSI | PEPSI | 15 | W | - | WM Glx was positively associated with cognitive performance in SZ, but not HC |
| (Seese et al., 2011) | 34/28 | Chronic (Children) | NR | K-FTDS | DLPFC, inferior frontal and superior temporal cortex | 1.5 | Glx | MRSI | PRESS | 30 | Cr | - | No associations |
| (Kegeles et al., 2012) | 22/32 | Chronic | Mixed | N-Back | MPFC, DLPFC | 3 | Glx | SV | MEGA-PRESS | 68 | Cr, W | ↑ MPFC Glx in un-medicated SZ | No associations |
| (Szulc et al., 2012) | 0/47 | Chronic | Un-medicated | WCST, TMT, Verbal fluency test | Frontal,temporal cortex, thalamus | 1.5 | Glx | SV | PRESS | 35 | Cr, W | N/A | No associations |
| (Reid et al., 2013) | 22/35 | Chronic | Medicated | RBANS | SN | 3 | Glx | SV | PRESS | 80 | Cr | - | SN Glx positively associated with RBANS total score in HC, but not SZ. |
| (Kraguljac et al., 2013) | 27/22 | Chronic | Un-medicated | RBANS | Hippocampus | 3 | Glx | SV | PRESS | 80 | Cr | ↑Glx | No associations |
| (Rowland et al., 2013b) | 20/21 | Chronic Young (11/10); old (10/10) | Medicated | RBANS | ACC, CSO | 3 | Glx | SV | MEGA- PRESS/ PRESS | 68/ 35 | W | ↓Glx in ACC and CSO | No associations |
| (Rowland et al., 2016b) | 53/45 | Chronic | mixed | DST, Digit symbol coding test, auditory MMN (EEG) | ACC | 3 | Glu, Gln, | SV | PR- STEAM/ | 6.5 | W | ↓Glu | No associations Higher Glu was associated with more negative MMN amplitude in SZ, but not in HC |
| (Bustillo et al., 2017) | 97/104 | Chronic | Medicated | MCCB | Axial supraventricular slab | 3 | Glx | MRSI | ↑Glx in GM and WM | No associations | |||
| (Huang et al., 2017) | 43/58 | FEP | naïve | MCCB | Left DLPFC | 3 | Glx | SV | Stimulated echo pulse | 9.2 | Cr | ↑Glx | No associations |
| (Reid et al., 2018) | 21/21 | FEP | Medicated | RBANS | ACC | 7 | Glu, Gln | SV | STEAM | 5 | W | ↓Glu | Negative association between Gln and RBANS immediate memory in HC, but not in SZ |
↑ Metabolite level is higher in patients than controls; ↓ Metabolite level is lower in patients than controls; - no group differences in metabolite levels
Abbreviations:
n: number of subjects; N/A: not applicable; NR: not reported; FEP: first episode psychosis patients; SZ: patients with schizophrenia; HR: high risk patients; HC: healthy controls
TE: Echo Time; SV: single voxel spectroscopy; MRSI: MR spectroscopic imaging; PRESS: Point Resolved Spectroscopy; MEGA-PRESS: Meshcher-Garwood Point Resolved Spectroscopy; STEAM: STimulated Echo Acquisition Mode; PEPSI: Proton Echoplanar spectroscopic Imaging; W: water; Cr: creatine; Glu: glutamate; Gln: glutamine; Glu/Gln: ratio between glutamate and glutamine; Glx: glutamate+ glutamine
ACC: anterior cingulate cortex; CSO: centrum semiovale; DLPFC: dorsolateral prefrontal cortex; GM: grey matter; MPFC: medial prefrontal cortex; SN: substantia nigra; WM: white matter
AVLT: auditory-verbal learning test, CPT: continuous performance test; DSDT: digit span distraction test; DST: digit sequencing task; EEG: Electroencephalogram; K-FTDS: kiddie formal thought disorder rating scale; MCCB: MATRICS consensus cognitive battery; MMSE: mini-mental state examination; MMN – Mismatch Negativity; OSSS: orientation specific surround suppression; RBANS: repeatable battery for the assessment of neuropsychological status; TMT: trail making test; WCST: wisconsin card sorting test