164. Association Between Glutamate + Glutamine in the Left Temporoparietal Junction and Mismatch Negativity (MMN) in Antipsychotic-Naive/Free Schizophrenia Patients With Auditory Hallucinations

Abstract

Abstract Background: Mismatch negativity (MMN), a biomarker for schizophrenia, is understood to be dependent on glutamatergic neurotransmission. Although both glutamate and MMN are considered to be of high relevance to schizophrenia pathophysiology, only one study to date has examined this relationship directly. Moreover, this relationship has not been examined in unmedicated patients. We report findings from a study examining the association between in-vivo glutamate + glutamine (Glx) concentration in the left temporoparietal junction (TPJ), a region understood to be important in the pathophysiology of auditory hallucinations, and MMN amplitude in antipsychotic-naive/free patients. Methods: Right-handed schizophrenia patients (SCZ) with active auditory hallucinations (N = 23; 19 antipsychotic-naive; age = 31.8 ± 7.0 years, 12 males) and age- and sex-matched healthy controls (HC; N = 31, age = 29.3 ± 4.4 years, 23 males) underwent 1H magnetic resonance spectroscopy (MRS) in a 3 T scanner. Spectra were acquired from a single-voxel (2 × 2 × 2 cm) placed on the left TPJ. Immediately after the scan, auditory MMN in response to frequency deviants was assessed over the midline fronto-central region (Fz, FCz, and Cz) using gold plated electrodes in 17 SCZ and 18 HC. LCModel was used to estimate the absolute amount of Glx in subjects’ spectra. The Cramer-Rao lower bound (CRLB) for Glx was set at 10%. No subjects’ data exceeded the CRLB. Signal to noise ratio (SNR) was ≥25 and FWHM was <0.13 for all sprectra. Glx levels were corrected for the gray matter and CSF content of the voxel and expressed in institutional units. EEG data was analyzed using Curry7, and MMN values from the lead showing the maximum difference between the two groups was used for the correlation. Results: Significantly greater Glx was found in SCZ compared to HC (F = 6.3, P = .016). MMN amplitude was significantly lower in SCZ (t = 3.2, P = .003), the difference was greatest over Fz. Greater Glx level was significantly associated with lesser Fz MMN amplitude in SCZ (r = −.54, P = .039) but not in HC. Findings remained the same if only antipsychotic-naive patients were included in the analysis. Conclusion: This is the first report of an association between Glx and frequency MMN in antipsychotic-naive/free SCZ. Our findings show a direct link between MMN and glutamatergic neurotransmitter system and demonstrate that abnormal excitability of the TPJ (as revealed by higher Glx) is associated with aberrant sensory processing (as revealed by lower MMN amplitude) in schizophrenia patients with auditory hallucinations. Funding: SMA, AB, ACA, and SVK are supported by the Wellcome-DBT India Alliance (500236/Z/11/Z). VS is supported by ICMR (DHR/HRD/Young Scientist/Type-VI(2)/2015). HC is supported by DBT, Govt of India (DBT/2015/NIMHANS/345). This research work is supported by DST Grant (SB/YS/LS-37/2014) to SMA, and DST-SJF Grant (DST/SJF/LSA-02/2014–15) and DBT-CEIB Grant (BT/PR5322/COE/34/8/2012) to GV.