Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Controlled Clinical Trial
. 2013 Oct;70(10):1057-66.
doi: 10.1001/jamapsychiatry.2013.289.

Glutamate levels in the associative striatum before and after 4 weeks of antipsychotic treatment in first-episode psychosis: a longitudinal proton magnetic resonance spectroscopy study

Camilo de la Fuente-Sandoval  1 , Pablo León-Ortiz, Mariana Azcárraga, Sylvana Stephano, Rafael Favila, Leonardo Díaz-Galvis, Patricia Alvarado-Alanis, Jesús Ramírez-Bermúdez, Ariel Graff-Guerrero
Affiliations
Controlled Clinical Trial

Glutamate levels in the associative striatum before and after 4 weeks of antipsychotic treatment in first-episode psychosis: a longitudinal proton magnetic resonance spectroscopy study

Camilo de la Fuente-Sandoval et al. JAMA Psychiatry. 2013 Oct.

Abstract

Importance: Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis. Whether this increase would persist after effective antipsychotic treatment is unknown.

Objectives: To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects.

Design, setting, and participants: Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age, sex, handedness, and cigarette smoking.

Interventions: Participants underwent 2 proton magnetic resonance spectroscopy studies: patients were imaged at baseline and after 4 weeks of antipsychotic treatment, while controls were imaged at baseline and at 4 weeks after the baseline measurement. Patients were treated with oral risperidone (open label) for 4 weeks with dosages that were titrated on the basis of clinical judgment.

Main outcomes and measures: Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel.

Results: Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls. After clinically effective antipsychotic treatment, glutamate levels significantly decreased in the associative striatum, with no significant change in the cerebellum. No differences in glutamate levels were observed between groups at 4 weeks.

Conclusions and relevance: Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinically effective antipsychotic treatment. These results provide support for the hypothesis that improvement in clinical symptoms might be related to a decrease in glutamate levels.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr de la Fuente-Sandoval has received grant support from Consejo Nacional de Ciencia y Technología, Instituto de Ciencia y Tecnología del Distrito Federal, and Janssen (Johnson & Johnson) and has served as a consultant or speaker for IMS Health, Carnot Laboratories, Eli Lilly, and Janssen. Dr Graff-Guerrero has received grant support from the National Institutes of Health, National Institute of Mental Health, Canadian Institutes of Health Research, Ontario Mental Health Foundation, Consejo Nacional de Ciencia y Technología, and Janssen (Johnson & Johnson) and has served as consultant or speaker for Abbott Laboratories, Gedeon Richter Plc, and Eli Lilly.

Figures

Figure 1
Figure 1. Voxel Placement in 2 Regions of Interest: the Right Associative Striatum and the Right Cerebellar Cortex
Representative spectra with the raw data (in black) and fitted data (in red) are shown for each region. Cr + PCr indicates creatine-containing compounds; Gln, glutamine; Glu, glutamate; Glx, glutamate + glutamine; GPC + PCh, choline-containing compounds; Ins, myo-inositol; and NAA, N-acetylaspartate.
Figure 2
Figure 2. Glutamate Levels in the Right Associative Striatum of Patients With First-Episode Psychosis (FEP) and Healthy Control Subjects at Baseline and at 4 Weeks
Horizontal bars represent the mean for the groups. *P < .05 after the removal of 2 outlying participants indicated within the circles.
See this image and copyright information in PMC

References

    1. Belforte JE, Zsiros V, Sklar ER, et al. Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat Neurosci. 2010;13(1):76–83. - PMC - PubMed
    1. Sharp FR, Tomitaka M, Bernaudin M, Tomitaka S. Psychosis: pathological activation of limbic thalamocortical circuits by psychomimetics and schizophrenia? Trends Neurosci. 2001;24(6):330–334. - PubMed
    1. Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry. 1995;52(12):998–1007. - PubMed
    1. Bartha R, Williamson PC, Drost DJ, et al. Measurement of glutamate and glutamine in the medial prefrontal cortex of never-treated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 1997;54(10):959–965. - PubMed
    1. Théberge J, Bartha R, Drost DJ, et al. Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry. 2002;159(11):1944–1946. - PubMed

Publication types