title: Cortico-Striatal GABAergic and Glutamatergic Dysregulations in Subjects at Ultra-High Risk for Psychosis Investigated with Proton Magnetic Resonance Spectroscopy.
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.
authors.affiliation: 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.
authors.forename: Camilo
authors.initials: C
authors.lastname: de la Fuente-Sandoval
authors.affiliation: 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).
authors.forename: Francisco
authors.initials: F
authors.lastname: Reyes-Madrigal
authors.affiliation: 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).
authors.forename: Xiangling
authors.initials: X
authors.lastname: Mao
authors.affiliation: 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).
authors.forename: Pablo
authors.initials: P
authors.lastname: León-Ortiz
authors.affiliation: 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).
authors.forename: Oscar
authors.initials: O
authors.lastname: Rodríguez-Mayoral
authors.affiliation: 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).
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Solís-Vivanco
authors.affiliation: 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).
authors.forename: Rafael
authors.initials: R
authors.lastname: Favila
authors.affiliation: 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).
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.affiliation: 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).
authors.forename: Dikoma C
authors.initials: DC
authors.lastname: Shungu
mesh_terms: D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007406:Interview, Psychological; D016014:Linear Models; D008297:Male; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D062706:Prodromal Symptoms; D066244:Proton Magnetic Resonance Spectroscopy; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D012306:Risk; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: 1H MRS; GABA; glutamate; psychosis; schizophrenia; ultra-high risk