Higher levels of glutamate in the associative-striatum of subjects with prodromal symptoms of schizophrenia and patients with first-episode psychosis

Abstract

The glutamatergic and dopaminergic systems are thought to be involved in the pathophysiology of schizophrenia. Their interaction has been widely documented and may have a role in the neurobiological basis of the disease. The aim of this study was to compare, using proton magnetic resonance spectroscopy ((1)H-MRS), glutamate levels in the precommissural dorsal-caudate (a dopamine-rich region) and the cerebellar cortex (negligible for dopamine) in the following: (1) 18 antipsychotic-naïve subjects with prodromal symptoms and considered to be at ultra high-risk for schizophrenia (UHR), (2) 18 antipsychotic-naïve first- episode psychosis patients (FEP), and (3) 40 age- and sex- matched healthy controls. All subjects underwent a (1)H-MRS study using a 3Tesla scanner. Glutamate levels were quantified and corrected for the proportion of cerebrospinal fluid and percentage of gray matter in the voxel. The UHR and FEP groups showed higher levels of glutamate than controls, without differences between UHR and FEP. In the cerebellum, no differences were seen between the three groups. The higher glutamate level in the precommissural dorsal-caudate and not in the cerebellum of UHR and FEP suggests that a high glutamate level (a) precedes the onset of schizophrenia, and (b) is present in a dopamine-rich region previously implicated in the pathophysiology of schizophrenia.

Figure 1

Spectroscopic voxel placement in right dorsal caudate and right cerebellum and representative spectra for each region. Glu, glutamate; Gln, glutamine; NAA, N-acetylaspartate.

Figure 2

Glutamate (Glu) levels of each participant in the dorsal caudate and cerebellum of controls, ultra high-risk for schizophrenia (UHR), and first episode-psychosis patients (FEP). Bars represent the mean for that group. ^*vs control, p<0.05.

Figure 3

Correlation between glutamate (Glu) and N-acetylaspartate (NAA) in the dorsal caudate and cerebellum of the participants. Dorsal caudate: Pearson's r=0.70, p⩽0.001 in controls, Pearson's r=0.74, p⩽0.001 in ultra high-risk for schizophrenia (UHR), Pearson's r=0.78, p⩽0.001 in first episode-psychosis patients (FEP). Cerebellum: Pearson's r=0.81, p⩽0.001 in controls, Pearson's r=0.56, p=0.01 in UHR, Pearson's r=0.64, p=0.002 in FEP.