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. Author manuscript; available in PMC: 2015 Jun 17.
Published in final edited form as: Eur Neuropsychopharmacol. 2014 Aug 1;24(10):1591–1605. doi: 10.1016/j.euroneuro.2014.07.015

Table 1.

Summary of studies that met inclusion criteria (n=7).

Authors, year,
journal		 n Mean age,
(SD)		 Study
design		 Phase of
illness		 Antipsychotic
status		 Glutamatergic
marker(s)a 		Structural
measure(s)a 		Key findings
Kraguljac et al. (2013), JAMA Psychiatry 27 SCZ; 27 HC SCZ: 32.63 (9.28); HC: 32.85 (9.39) CS Mixed Unmedicated at assessment Glx in hippocampus. Assessed by 1H-MRS Hippocampal GM volume. Assessed by MRI In SCZ:

  • Negative correlation between hippocampal Glx and GM volume in two hippocampal clusters


In HC:

  • No significant correlation between hippocampal Glx and GM volume in hippocampus
Tandon et al. (2013), Schizophr. Res. 23 HR; 24 HC HR: 15.92 (4.21); HC: 15.57 (3.99) CS At risk Unmedicated at assessment Glx in thalamus and caudate. Assessed by 1H-MRS Thalamic and caudate volume. Assessed by MRI In HR:

  • Non-significant negative correlation between thalamic Glx and thalamic volume

  • Non-significant negative correlation between caudate Glx and caudate volume
Aoyama et al. (2011), Br. J. Psychiatry 17 SCZ; 17 HC SCZ: 25 (7); HC: 29 (10) L; 80 months FES Unmedicated at initial assessment; medicated at 10- and 80-month assessments Glutamine in thalamus and anterior cingulate; tGL in thalamus and anterior cingulate. Assessed by 1H-MRS Whole brain GM volume. Assessed by MRI In SCZ:

  • Positive correlation between thalamic glutamine loss and GM volume reduction in frontal, temporal, parietal and limbic lobes

  • No significant correlation between anterior cingulate glutamine and GM volume loss

  • No significant correlation between thalamic or anterior cingulate tGL and GM volume loss

  • Study involved introduction of medication


In HC:

  • No significant correlation between loss of thalamic glutamine and GM volume reduction
Klar et al. (2010), NeuroImage 29 SCZ; 44 HC SCZ: 27.6 (6.8); HC: 30.9 (7.9) CS Mixed Medicated at assessment Glutamate in hippocampus. Assessed by 1H-MRS Hippocampal volume. Assessed by MRI In SCZ:

  • Non-significant negative correlation between hippocampal glutamate and volume in hippocampus


In HC:

  • Non-significant negative correlation between hippocampal glutamate and volume in hippocampus
Stone et al. (2009), Biol. Psychiatry 27 ARMS; 27 HC ARMS: 25 (5); HC: 25 (4) CS At risk Unmedicated at assessment Glutamate in thalamus; glutamine in anterior cingulate. Assessed by 1H-MRS Whole brain GM volume. Assessed by MRI In ARMS:

  • Positive correlation between thalamic glutamate and GM volume in left prefrontal cortex, left insula, left cingulate, left superior temporal gyrus, left temporal pole and bilaterally in cerebellum and lingual gyrus

  • Negative correlation between thalamic glutamate and GM volume in dorsal anterior cingulate extending to posterior cingulate gyrus

  • Positive correlation between anterior cingulate glutamine and GM volume in posterior cingulate gyrus

  • Negative correlation between anterior cingulate glutamine and GM volume in left cerebellum


In HC:

  • No significant correlation between thalamic glutamate and GM volume

  • Positive correlation between anterior cingulate glutamine and GM volume in right temporal cortex

  • Negative correlation between anterior cingulate glutamine and GM volume in medial frontal and orbitofrontal cortex
Thebergeetal.(2007), Br. J. Psychiatry 16 SCZ; 16 HC SCZ: 25 (8); HC: 29 (12) L; 30 months FES Unmedicated at initial assessment; medicated at 10- and 30-month assessments Glutamine in thalamus and anterior cingulate. Assessed by 1H-MRS Whole brain GM volume and 1H-MRS voxel GM volume. Assessed by MRI In SCZ:

  • Positive correlation between thalamic glutamine loss and GM volume reduction in left angular gyrus, right precuneus and left superior and inferior temporal gyrus

  • Non-significant correlations between voxel glutamine loss and voxel GM volume loss

  • Study involved introduction of medication


In HC:

  • Non-significant correlations between voxel glutamine loss and voxel GM volume loss
Tsai et al. (1998), Biol. Psychiatry 61 SCZb; 23 HC SCZ: 37.7 (7.1); HC: 35.8 (10.1) CS Chronic Unmedicated at assessment CSF glutamate VBR; prefrontal atrophy. Assessed by CT In SCZ:

  • Negative correlation between CSF glutamate and VBR

  • Non-significant negative correlation between CSF glutamate and prefrontal atrophy

ARMS: at risk mental state; CS: cross-sectional; CT: computed tomography; FES: first episode schizophrenia; Glx: Glutamate+Glutamine; GM: grey matter; HC: healthy controls;1H-MRS: proton magnetic resonance spectroscopy; HR: high-risk; L: longitudinal; MRI: magnetic resonance imaging; SCZ: schizophrenia; SD: standard deviation; tGL: Glutamate+Glutamine; VBR: ventricle–brain ratio.

a

Only measures that were utilized for the investigation of the relationship between glutamatergic markers and brain structure, and were subsequently reported upon, are included in this table.

b

Included schizoaffective patients.