Six-month treatment with atypical antipsychotic drugs decreased frontal-lobe levels of glutamate plus glutamine in early-stage first-episode schizophrenia

Gotō, Naoki; Yoshimura, Reiji; Kakeda, Shingo; Nishimura, Joji; Moriya, Junji; Hayashi, Kenji; Katsuki, Asuka; Hori, Hikaru; Umene-Nakano, Wakako; Ikenouchi-Sugita, Atsuko; Korogi, Yukunori; Nakamura, Jun

doi:10.2147/ndt.s25582

Cited by 34 publications

(44 citation statements)

References 15 publications

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“…Two studies were performed at 3-T, one of which reported Glx (39) and one of which reported both glutamate and Glx (37). The remaining two studies, performed at 4-T, reported glutamate, glutamine (10, 31), and Glx (31).…”

Section: Resultsmentioning

confidence: 99%

Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia: A Systematic Review of Longitudinal 1H-MRS Studies

et al. 2017

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Schizophrenia is associated with brain glutamate dysfunction, but it is currently unclear whether antipsychotic administration can reduce the extent of glutamatergic abnormality. We conducted a systematic review of proton magnetic resonance spectroscopy (1H-MRS) studies examining the effects of antipsychotic treatment on brain glutamate levels in schizophrenia. The Medline database was searched to identify relevant articles published until December 2016. Inclusion required that studies examined longitudinal changes in brain glutamate metabolites in patients with schizophrenia before and after initiation of first antipsychotic treatment or a switch in antipsychotic treatment. The searches identified eight eligible articles, with baseline and follow-up measures in a total of 168 patients. The majority of articles reported a numerical reduction in brain glutamate metabolites with antipsychotic treatment, and the estimated overall mean reduction of 6.5% in Glx (the combined signal from glutamate and glutamine) across brain regions. Significant reductions in glutamate metabolites in at least one brain region were reported in four of the eight studies, and none of the studies reported a significant glutamatergic increase after antipsychotic administration. Relationships between the degree of change in glutamate and the degree of improvement in symptoms have been inconsistent but may provide limited evidence that antipsychotic response may be associated with lower glutamate levels before treatment and a greater extent of glutamatergic reduction during treatment. Further longitudinal, prospective studies of glutamate and antipsychotic response are required to confirm these findings.

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Section: Resultsmentioning

confidence: 99%

Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia: A Systematic Review of Longitudinal 1H-MRS Studies

et al. 2017

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“…Absolute GABA and Glx concentrations were quantified using scaling correction, the correction for relaxation, and partial volume effects based on the LCModel package and LCMgui, respectively. The edited spectra were fit using LCM-basis functions that were generated from phantom measurements using the MEGA-PRESS sequence with the appropriate acquisition parameters [54]. The GABA peak arose at 3.01 ppm and the Glx peak at 3.74 ppm [22].…”

Section: Methodsmentioning

confidence: 99%

Reducedγ-Aminobutyric Acid and Glutamate+Glutamine Levels in Drug-Naïve Patients with First-Episode Schizophrenia but Not in Those at Ultrahigh Risk

et al. 2016

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Altered γ-aminobutyric acid (GABA), glutamate (Glu) levels, and an imbalance between GABAergic and glutamatergic neurotransmissions have been involved in the pathophysiology of schizophrenia. However, it remains unclear how these abnormalities impact the onset and course of psychosis. In the present study, 21 drug-naïve subjects at ultrahigh risk for psychosis (UHR), 16 drug-naïve patients with first-episode schizophrenia (FES), and 23 healthy controls (HC) were enrolled. In vivo GABA and glutamate+glutamine (Glx) levels in the medial prefrontal cortex were measured using proton magnetic resonance spectroscopy. Medial prefrontal GABA and Glx levels in FES patients were significantly lower than those in HC and UHR, respectively. GABA and Glx levels in UHR were comparable with those in HC. In each group, there was a positive correlation between GABA and Glx levels. Reduced medial prefrontal GABA and Glx levels thus may play an important role in the early stages of schizophrenia.

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“…In the right cerebellum, these studies reported either elevated glutamate and Glx levels (de la Fuente-Sandoval et al, 2013b) or no differences (de la Fuente-Sandoval et al, 2011) between first episode participants and controls. Goto et al (2012) found no differences in Glx/Cr in the frontal or parieto-occipital lobe and elevated Glx/Cr in the basal ganglia (Goto et al, 2012). Overall, these data suggest higher glutamatergic metabolites in unmedicated, first-episode schizophrenia but caution is warranted since there is discrepancy among the specific glutamatergic metabolites quantified (glutamate, glutamine, or Glx) and brain regions.…”

Section: 1h-mrs In Schizophreniamentioning

confidence: 96%

“…Since glutamine is a precursor of glutamate, Gln/Glu ratio may be a good measure of glutamatergic neurotransmission turnover (Bustillo et al, 2010; Ongur et al, 2008; Shirayama et al, 2010). Another study reported elevated Glx/tCr in the left basal ganglia of 16 first episode schizophrenia participants, and no differences in the frontal lobe or parieto-occipital lobe compared to controls (Goto et al, 2012). This study did not provide detailed information regarding the medication status of participants with these results or size and placement of the frontal lobe voxel so it is unclear if the frontal lobe voxel incorporated the anterior cingulate cortex.…”

Section: 1h-mrs In Schizophreniamentioning

confidence: 99%

In vivo assessment of neurotransmitters and modulators with magnetic resonance spectroscopy: Application to schizophrenia

Wijtenburg

Yang

Fischer

et al. 2015

Neuroscience & Biobehavioral Reviews

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In vivo measurement of neurotransmitters and modulators is now feasible with advanced proton magnetic resonance spectroscopy (1H-MRS) techniques. This review provides a basic tutorial of MRS, describes the methods available to measure brain glutamate, glutamine, γ-aminobutyric acid, glutathione, N-acetylaspartylglutamate, glycine, and serine at magnetic field strengths of 3Tesla or higher, and summarizes the neurochemical findings in schizophrenia. Overall, 1H-MRS holds great promise for producing biomarkers that can serve as treatment targets, prediction of disease onset, or illness exacerbation in schizophrenia and other brain diseases.

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Six-month treatment with atypical antipsychotic drugs decreased frontal-lobe levels of glutamate plus glutamine in early-stage first-episode schizophrenia

Cited by 34 publications

References 15 publications

Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia: A Systematic Review of Longitudinal 1H-MRS Studies

Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia: A Systematic Review of Longitudinal 1H-MRS Studies

Reducedγ-Aminobutyric Acid and Glutamate+Glutamine Levels in Drug-Naïve Patients with First-Episode Schizophrenia but Not in Those at Ultrahigh Risk

In vivo assessment of neurotransmitters and modulators with magnetic resonance spectroscopy: Application to schizophrenia

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