Metabolite markers of glutamatergic activity and neuro-inflammation in the superior temporal gyrus in patients with schizophrenia.
Sai Krishna Merugumala1, M. A. Niznikiewicz2, E. Del Re2, K. Spencer2, H. Liao1, P. G. Nestor3, R. W. McCarley3, N. Bolo4, and A. P. Lin1

1Radiology, Brigham and Women's Hospital, Boston, MA, United States, 2Laboratory of Neuroscience, Veterans Affairs Boston Healthcare System, Boston, MA, United States, 3Harvard Medical School, Boston, MA, United States, 4Beth Isreal Deaconess Medical Center, Boston, MA, United States


Many studies have shown that the superior temporal gyrus undergoes many changes in schizophrenia. Magnetic resonance spectroscopy studies of the brain have also shown brain metabolite levels are altered in schizophrenia however the superior temporal gyrus has not been examined in detail. The aim of this study was to compare brain metabolite levels in patients with schizophrenia and controls as well as examine their correlation with electrophysiology measures.


Schizophrenia (SZ) and schizophrenia spectrum disorders are prevalent in nearly 1% of the population throughout the world. The superior temporal gyrus (STG) has been implicated in several studies of SZ that show reductions in grey matter volume in that region as well as gamma band oscillation abnormalities originating in the STG (Spencer 2008). MRS studies have also shown abnormalities in brain metabolites associated with schizophrenia however most studies have focused on the prefrontal cortex or anterior cingulate. Due to the involvement of the STG in schizophrenia pathology and the insight that can be provided with MRS, the aim of our study was to examine neurometabolic differences in the STG in patients with schizophrenia when compared with control.


Fourteen Chronic SZ (CSZ) patients and 14 healthy controls (HC) matched for age and gender were recruited for this study. Estimates of Myo-inositol (mI), Choline (Cho), Glutamate (Glu), Glutamate+Glutamine (Glx) and Glutathione (GSH) levels were made utilizing short echo, single voxel spectroscopy (TR/TE=2000/30, PRESS, 128 averages, 24cm3). Gamma-Aminobutyric acid (GABA) was measured using MEGAPRESS (TE = 68 ms, TR = 2s, bandwidth = 2 kHz, 1024 complex data points, and 128 averaged acquisitions acquired both on and off resonance) in the same volume. All data was collected on a 3 Tesla (Siemens MAGNETOM Skyra) with a32 channel head coil. Partial volume fractions of gray matter, white matter, and cerebrospinal fluid were calculated for each voxel (right STG, left STG, and ACC). Metabolite concentrations were estimated from the spectra with LCModel and then corrected with the partial volume fractions. The uncertainty of the estimate is represented by the CRLB and a threshold of <20% was established as cutoff for reliable data. ANOVA was used to examine myo-inositol, choline, and glutathione in the left and right STG with group as a between factor, and region (left and right STG) as a within factor. One-way ANOVA was used to quantify the changes in metabolites in the ACC. In addition, correlations between white matter volume for each voxel and each metabolite in both subject groups were conducted. All analyses were corrected for age. Electrophysiological data, including oddball P300 and novel P300, and mismatch negativity were also measured. Correlational analyses were also done between MRS metabolite estimates and ERP components.


Group differences were observed in the right and left STG but not in the ACC for glutamate (p=0.031), glutathione (p=0.037), myo-inositol (p=0.035) choline (p=0.006). The estimated concentrations of these 4 metabolites were all higher in the CSZ group relative to HC group. Both mI and Cho in the left STG were negatively correlated with the white matter volume in the left STG in HC but not in the CSZ group (myo-inositol: HC: r=-0.62, p=0.018; CSZ: r=-0.29, p=0.36; choline: HC: r=-0.65, p=0.012; CSZ: r=-0.3, p=0.32). No significant differences between the groups were found for GABA. The measurement of the P300 novel amplitude showed a negative correlation with right STG glutamate levels (z scores) in HC (p=0.015), whereas the measurement showed a positive correlation with the right STG glutamate levels CSZ group (p=0.05). In addition, MMN amplitude showed significant positive correlation with left STG glutamate levels (z scores) in the CSZ group (p=0.01). In the HC group, the correlation between these measurements was not statistically significant.


Given that there were no significant group differences between the STG volume, the cause of the group differences in glutamatergic activity is unlikely to be due to volume losses in this region. Abnormalities in markers detected by MRS associated with neurotransmission (Glu), neuro-inflammation (GSH), glial proliferation (mI), and demyelination (Cho) in the STG but not ACC demonstrate that the STG voxel region is sensitive to changes in metabolites associated with SZ. The regional distribution of the abnormal biomarkers in the brain may provide insight on the underlying pathophysiology of schizophrenia.


No acknowledgement found.


[1] Spencer, K. M., Niznikiewicz, M. A., Shenton, M. E. & McCarley, R. W. Sensory-evoked gamma oscillations in chronic schizophrenia. Biological psychiatry 63, 744-747 (2008)

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)