Glutamatergic Metabolites, Volume and Cortical Thickness in Antipsychotic-Naive Patients with First-Episode Psychosis: Implications for Excitotoxicity.
Neuroimaging studies investigating patients with schizophrenia often report appreciable volumetric reductions and cortical thinning, yet the cause of these deficits is unknown. The association between subcortical and cortical structural alterations, and glutamatergic neurometabolites is of particular interest due to glutamate's capacity for neurotoxicity; elevated levels may be related to neuroanatomical compromise through an excitotoxic process. To this end, we explored the relationships between glutamatergic neurometabolites and structural measures in antipsychotic-naive patients experiencing their first non-affective episode of psychosis (FEP). Sixty antipsychotic-naive patients with FEP and 60 age- and sex-matched healthy controls underwent a magnetic resonance imaging session, which included a T1-weighted volumetric image and proton magnetic resonance spectroscopy in the precommissural dorsal caudate. Group differences in precommissural caudate volume (PCV) and cortical thickness (CT), and the relationships between glutamatergic neurometabolites (ie, glutamate+glutamine (Glx) and glutamate) and these structural measures, were examined. PCV was decreased in the FEP group (p<0.001), yet did not differ when controlling for total brain volume. Cortical thinning existed in the FEP group within frontal, parietal, temporal, occipital, and limbic regions at a 5% false discovery rate. Glx levels were negatively associated with PCV only in the FEP group (p=0.018). The observed relationship between Glx and PCV in the FEP group is supportive of a focal excitotoxic mechanism whereby increased levels of glutamatergic markers are related to local structural losses. This process may be related to the prominent structural deficits that exist in patients with schizophrenia.
Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Eric
E
Plitman
Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.|Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, QC, Canada.
Raihaan
R
Patel
Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Jun Ku
JK
Chung
Kimel Family Translational Imaging-Genetics Research Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
Jon
J
Pipitone
Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Sofia
S
Chavez
Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
Francisco
F
Reyes-Madrigal
Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
Gladys
G
Gómez-Cruz
Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.|Department of Education, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
Pablo
P
León-Ortiz
Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.|Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, QC, Canada.
M Mallar
MM
Chakravarty
Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.|Neuropsychiatry Department, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
Camilo
C
de la Fuente-Sandoval
Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.|Campbell Institute Research Program, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
Ariel
A
Graff-Guerrero
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D018709:Statistics, Nonparametric; D015898:Tomography Scanners, X-Ray Computed
D014150:Antipsychotic Agents; D018698:Glutamic Acid