Format

Send to

Choose Destination
Int J Neuropsychopharmacol. 2015 Sep 12;19(3):pyv105. doi: 10.1093/ijnp/pyv105.

Cortico-Striatal GABAergic and Glutamatergic Dysregulations in Subjects at Ultra-High Risk for Psychosis Investigated with Proton Magnetic Resonance Spectroscopy.

Author information

1
Laboratory of Experimental Psychiatry (Drs de la Fuente-Sandoval, Reyes-Madrigal, and León-Ortiz), Neuropsychiatry Department (Dr de la Fuente-Sandoval), Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico; Department of Radiology, Weill Cornell Medical College, New York, NY (Ms Mao and Dr Shungu); Department of Education, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico (Dr León-Ortiz); Early Psychosis Intervention Department, Hospital Fray Bernardino Alvarez, Mexico City, Mexico (Dr Rodríguez-Mayoral); Palliative Care Unit, Instituto Nacional de Cancerología, Mexico City, Mexico (Dr Rodríguez-Mayoral); Laboratory of Neuropsychology, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico (Dr Solís-Vivanco); MR Advanced Applications, GE Healthcare, Mexico City, Mexico (Mr Favila); Multimodal Neuroimaging Schizophrenia Group, Research Imaging Centre, and Geriatric Mental Health Program at Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Canada (Dr Graff-Guerrero). fcamilo@unam.mx.
2
Laboratory of Experimental Psychiatry (Drs de la Fuente-Sandoval, Reyes-Madrigal, and León-Ortiz), Neuropsychiatry Department (Dr de la Fuente-Sandoval), Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico; Department of Radiology, Weill Cornell Medical College, New York, NY (Ms Mao and Dr Shungu); Department of Education, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico (Dr León-Ortiz); Early Psychosis Intervention Department, Hospital Fray Bernardino Alvarez, Mexico City, Mexico (Dr Rodríguez-Mayoral); Palliative Care Unit, Instituto Nacional de Cancerología, Mexico City, Mexico (Dr Rodríguez-Mayoral); Laboratory of Neuropsychology, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico (Dr Solís-Vivanco); MR Advanced Applications, GE Healthcare, Mexico City, Mexico (Mr Favila); Multimodal Neuroimaging Schizophrenia Group, Research Imaging Centre, and Geriatric Mental Health Program at Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Canada (Dr Graff-Guerrero).

Abstract

BACKGROUND:

Dysregulations of the major inhibitory and excitatory amino neurotransmitter systems of γ-aminobutyric acid and glutamate, respectively, have been described in patients with schizophrenia. However, it is unclear whether these abnormalities are present in subjects at ultra-high risk for psychosis.

METHODS:

Twenty-three antipsychotic naïve subjects at ultra-high risk and 24 healthy control subjects, matched for age, sex, handedness, cigarette smoking, and parental education, underwent proton magnetic resonance spectroscopy scans in the dorsal caudate bilaterally and the medial prefrontal cortex at 3T. Levels of γ-aminobutyric acid and of the combined resonance of glutamate and glutamine (Glx) were obtained using the standard J-editing technique and expressed as peak area ratios relative to the synchronously acquired unsuppressed voxel water signal.

RESULTS:

Higher levels of γ-aminobutyric acid (P<.001) and Glx (P=.007) were found in the dorsal caudate of the subjects at ultra-high risk than in the healthy controls. In the medial prefrontal cortex, likewise, both γ-aminobutyric acid (P=.03) and Glx (P=.006) levels were higher in the ultra-high risk group than in the healthy controls. No group differences were found for any of the other metabolites (N-acetylaspartate, total choline, or total creatine) in the 2 regions of interest.

CONCLUSIONS:

This study presents the first evidence of abnormal elevations, in subjects at ultra-high risk, of γ-aminobutyric acid and Glx in 2 brain regions that have been implicated in the pathophysiology of psychosis, warranting longitudinal studies to assess whether these neurotransmitter abnormalities can serve as noninvasive biomarkers of conversion risk to psychosis as well as of illness progression and treatment response.

KEYWORDS:

1H MRS; GABA; glutamate; psychosis; schizophrenia; ultra-high risk

PMID:
26364273
PMCID:
PMC4815472
DOI:
10.1093/ijnp/pyv105
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center