1H MRSI evidence of metabolic abnormalities in childhood-onset schizophrenia

In adult schizophrenia, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have revealed volumetric and metabolic defects in multiple brain regions, among them the anterior cingulate, frontal cortex, striatum, thalamus, parietal cortex, and frontal and parietal white matter. This study used proton magnetic resonance spectroscopic imaging ((1)H MRSI) to identify potential metabolic abnormalities in these regions in childhood-onset schizophrenia. (1)H MRSI was acquired at 1.5 T and 272 ms echo time in 11 children and adolescents with schizophrenia (aged 7-18 years; seven boys, four girls; all but two medicated) and 20 age-matched healthy controls (10 boys, 10 girls). Absolute levels of N-acetyl compounds (NAA), creatine plus phosphocreatine (Cr), and choline compounds (Cho) were compared among groups in each region. In schizophrenic patients relative to controls, Cr was 14.3% higher in superior anterior cingulate (mean of left and right hemispheres). Cho was higher in superior anterior cingulate (30.3%), frontal cortex (13.3%), and caudate head (13.5%). In the thalamus, there was also a diagnosis-by-gender interaction, whereby NAA was lower in patients for male but not for female subjects. Elevated Cr suggests abnormal local cell-energy demand and elevated Cho is consistent with a prior proposal that patients with early age-of-onset schizophrenia exhibit phospholipid membrane disturbances. Low NAA may reflect diminished neuronal integrity.

[1]  B. Siesjö,et al.  Brain energy metabolism , 1978 .

[2]  W. Honer,et al.  An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone. , 2001, The American journal of psychiatry.

[3]  D. Braus,et al.  Lower concentration of thalamic n-acetylaspartate in patients with schizophrenia: a replication study. , 2001, The American journal of psychiatry.

[4]  D Matthaei,et al.  1H NMR chemical shift selective (CHESS) imaging. , 1985, Physics in medicine and biology.

[5]  Dorothee P. Auer,et al.  Reduced NAA in the thalamus and altered membrane and glial metabolism in schizophrenic patients detected by 1H-MRS and tissue segmentation , 2001, Schizophrenia Research.

[6]  K H Nuechterlein,et al.  Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study. , 2001, Archives of general psychiatry.

[7]  J. Mazziotta,et al.  MRI‐PET Registration with Automated Algorithm , 1993, Journal of computer assisted tomography.

[8]  M S Buchsbaum,et al.  Striatal size and relative glucose metabolic rate in schizotypal personality disorder and schizophrenia. , 2001, Archives of general psychiatry.

[9]  Tetsuya Takano,et al.  Proton magnetic resonance spectroscopy of basal ganglia in chronic schizophrenia , 1994, Biological Psychiatry.

[10]  J L Rapoport,et al.  Childhood-Onset Schizophrenia: Progressive Ventricular Change During Adolescence , 1997 .

[11]  R. Gillies,et al.  Phosphomonoester metabolism as a function of cell proliferative status and exogenous precursors. , 1996, Anticancer research.

[12]  Cynthia G. Wible,et al.  Caudate, putamen, and globus pallidus volume in schizophrenia: A quantitative MRI study , 1995, Psychiatry Research: Neuroimaging.

[13]  John Suckling,et al.  A computational morphometric MRI study of schizophrenia: effects of hallucinations. , 2002, Cerebral cortex.

[14]  William H. Oldendorf,et al.  N-Acetyl-L-Aspartic acid: A literature review of a compound prominent in 1H-NMR spectroscopic studies of brain , 1989, Neuroscience & Biobehavioral Reviews.

[15]  Ir W. De Backer,et al.  Review of neuroimaging studies of child and adolescent psychiatric disorders from the past 10 years. , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[16]  Corey C. Ford,et al.  Frontal lobe of children with schizophrenia spectrum disorders: A proton magnetic resonance spectroscopic study , 1998, Biological Psychiatry.

[17]  M Takigawa,et al.  Changes in levels of phosphorus metabolites in temporal lobes of drug-naive schizophrenic patients. , 1999, The American journal of psychiatry.

[18]  J H Duyn,et al.  Multisection proton MR spectroscopic imaging of the brain. , 1993, Radiology.

[19]  David G. Gadian,et al.  Proton MR Spectroscopy of Intracranial Tumours: In Vivo and In Vitro Studies , 1990, Journal of computer assisted tomography.

[20]  S. Lawrie,et al.  Brain abnormality in schizophrenia , 1998, British Journal of Psychiatry.

[21]  J. Sweeney,et al.  Thalamic volumes in patients with first-episode schizophrenia. , 2001, The American journal of psychiatry.

[22]  Usha Sinha,et al.  Relationships Between Choline Magnetic Resonance Spectroscopy, Apparent Diffusion Coefficient and Quantitative Histopathology in Human Glioma , 2000, Journal of Neuro-Oncology.

[23]  A W Toga,et al.  Brain abnormalities observed in childhood-onset schizophrenia: a review of the structural magnetic resonance imaging literature. , 2000, Mental retardation and developmental disabilities research reviews.

[24]  R. McCarley,et al.  MRI anatomy of schizophrenia , 1999, Biological Psychiatry.

[25]  David F. Horrobin,et al.  The membrane hypothesis of schizophrenia , 1994, Schizophrenia Research.

[26]  R. Murray,et al.  Which characteristics of schizophrenia predate psychosis? , 1998, Journal of psychiatric research.

[27]  Andrew Simmons,et al.  Structural magnetic imaging of the hippocampus in early onset schizophrenia , 2001, Biological Psychiatry.

[28]  Heinrich Sauer,et al.  31Phosphorus magnetic resonance spectroscopy of the dorsolateral prefrontal region in schizophrenics—a study including 50 patients and 36 controls , 1998, Biological Psychiatry.

[29]  Toshiro Fujimoto,et al.  Proton magnetic resonance spectroscopy of the left medial temporal and frontal lobes in chronic schizophrenia: preliminary report , 1995, Psychiatry Research: Neuroimaging.

[30]  D. Gadian,et al.  Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  Thomas G Schulze,et al.  Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial schizophrenia: a proton magnetic resonance spectroscopy study , 2000, Neuroscience Letters.

[32]  N Schuff,et al.  Reduced concentrations of thalamic N-acetylaspartate in male patients with schizophrenia. , 2000, The American journal of psychiatry.

[33]  Christian Gaser,et al.  Supporting evidence for the model of cognitive dysmetria in schizophrenia — a structural magnetic resonance imaging study using deformation-based morphometry , 2000, Schizophrenia Research.

[34]  Patrick R Hof,et al.  Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia , 2003, Biological Psychiatry.

[35]  Raquel E Gur,et al.  Proton Magnetic Resonance Spectroscopy in the Frontal and Temporal Lobes of Neuroleptic Naive Patients with Schizophrenia , 1999, Neuropsychopharmacology.

[36]  J N Giedd,et al.  Childhood-onset psychotic disorders: magnetic resonance imaging of volumetric differences in brain structure. , 2000, The American journal of psychiatry.

[37]  Matcheri S Keshavan,et al.  Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings–part I , 2000, Biological Psychiatry.

[38]  Richard A. Komoroski,et al.  In vitro 1H-magnetic resonance spectroscopy of postmortem brains with schizophrenia , 1997, Biological Psychiatry.

[39]  W H Wong,et al.  Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[40]  S. Bluml,et al.  Quantitative proton-decoupled 31P MRS of the schizophrenic brain in vivo. , 1999, Journal of computer assisted tomography.

[41]  Thomas Kammer,et al.  Frontal-subkortikale neuronale Schaltkreise , 1997 .

[42]  R. Murray,et al.  Meta-analysis of regional brain volumes in schizophrenia. , 2000, The American journal of psychiatry.

[43]  A. Toga,et al.  Localizing Age-Related Changes in Brain Structure between Childhood and Adolescence Using Statistical Parametric Mapping , 1999, NeuroImage.

[44]  John Lauriello,et al.  Effects of chronic haloperidol and clozapine treatments on frontal and caudate neurochemistry in schizophrenia , 2001, Psychiatry Research: Neuroimaging.

[45]  J. Levitt,et al.  Preliminary study of frontal lobe 1H MR spectroscopy in childhood‐onset schizophrenia , 1998, Journal of magnetic resonance imaging : JMRI.

[46]  J Hennig,et al.  Grading and therapy monitoring of astrocytomas with 1H-spectroscopy: preliminary study. , 1996, Anticancer research.

[47]  Patrick R. Hof,et al.  Molecular and Cellular Evidence for an Oligodendrocyte Abnormality in Schizophrenia , 2002, Neurochemical Research.

[48]  R. Murray,et al.  What risk factors tell us about the causes of schizophrenia and related psychoses , 2000, Current psychiatry reports.

[49]  G. Rajkowska,et al.  Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral prefrontal cortex in schizophrenia , 2002, Schizophrenia Research.

[50]  Richard S. J. Frackowiak,et al.  Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry. , 2002, The American journal of psychiatry.

[51]  I. Zs.-Nagy,et al.  A membrane hypothesis of aging. , 1978, Journal of theoretical biology.

[52]  Ron Kikinis,et al.  Volumetric Evaluation of the Thalamus in Schizophrenic Male Patients Using Magnetic Resonance Imaging , 1998, Biological Psychiatry.

[53]  Hirohiko Kimura,et al.  Thalamic abnormalities in patients with schizophrenia revealed by proton magnetic resonance spectroscopy , 2000, Psychiatry Research: Neuroimaging.

[54]  Jean-Marc Constans,et al.  Proton magnetic resonance spectroscopy (1H MRS) in schizophrenia: investigation of the right and left hippocampus, thalamus, and prefrontal cortex. , 2002, Schizophrenia bulletin.

[55]  John P. Stack,et al.  1H-magnetic resonance spectroscopy of the left temporal and frontal lobes in schizophrenia: Clinical, neurodevelopmental, and cognitive correlates , 1994, Biological Psychiatry.

[56]  M Noble,et al.  Specific Expression of N‐Acetylaspartate in Neurons, Oligodendrocyte‐Type‐2 Astrocyte Progenitors, and Immature Oligodendrocytes In Vitro , 1992, Journal of neurochemistry.

[57]  J. John Mann,et al.  In vivo neurochemistry of the brain in schizophrenia as revealed by magnetic resonance spectroscopy , 1998, Biological Psychiatry.

[58]  D J Jenden,et al.  In vivo 1H MRS choline: correlation with in vitro chemistry/histology. , 1996, Life sciences.

[59]  H. Yamasue,et al.  1H-MR spectroscopy and gray matter volume of the anterior cingulate cortex in schizophrenia , 2002, Neuroreport.

[60]  Stephen Ashwal,et al.  Proton Magnetic Resonance Spectroscopy: An Emerging Technology in Pediatric Neurology Research , 1998, Pediatric Research.

[61]  N C Andreasen,et al.  Change in basal ganglia volume over 2 years in patients with schizophrenia: typical versus atypical neuroleptics. , 1999, The American journal of psychiatry.

[62]  M. Davidson,et al.  Early diagnosis of schizophrenia — the first step towards secondary prevention , 2000, Acta psychiatrica Scandinavica. Supplementum.

[63]  Dennis D. Spencer,et al.  N-acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus , 2003, Neurology.

[64]  A. Toga,et al.  Mapping cortical asymmetry and complexity patterns in normal children , 2001, Psychiatry Research: Neuroimaging.

[65]  A. Warnke,et al.  Structural brain abnormalities specific to childhood-onset schizophrenia identified by neuroimaging techniques , 2002, Journal of Neural Transmission.

[66]  R. Murray,et al.  Superior temporal gyrus abnormalities in early-onset schizophrenia: similarities and differences with adult-onset schizophrenia. , 2001, The American journal of psychiatry.

[67]  A Bertolino,et al.  Proton magnetic resonance spectroscopy in schizophrenia. , 1999, European journal of radiology.

[68]  E. Walker,et al.  Intelligence in schizophrenia: meta-analysis of the research. , 1984, Schizophrenia bulletin.

[69]  Arthur W Toga,et al.  Medial temporal lobe in childhood-onset schizophrenia , 2001, Psychiatry Research: Neuroimaging.

[70]  J. Sweeney,et al.  Decreased caudate volume in neuroleptic-naive psychotic patients. , 1998, The American journal of psychiatry.

[71]  R. Asarnow,et al.  Childhood-onset schizophrenia: editors' introduction. , 1994, Schizophrenia bulletin.

[72]  J. Cummings,et al.  Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. , 2002, Journal of psychosomatic research.

[73]  Toshiro Inubushi,et al.  Proton magnetic resonance spectroscopy of the basal ganglia in patients with schizophrenia: a preliminary report , 1996, Schizophrenia Research.

[74]  D. Leibfritz,et al.  Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. , 1993, Developmental neuroscience.

[75]  Jean-Marc Constans,et al.  Apport de la spectroscopie par résonance magnétique dans la schizophrénie , 2000 .

[76]  J A Frank,et al.  Common pattern of cortical pathology in childhood-onset and adult-onset schizophrenia as identified by proton magnetic resonance spectroscopic imaging. , 1998, The American journal of psychiatry.

[77]  C. Frith,et al.  The cognitive abnormalities underlying the symptomatology and the disability of patients with schizophrenia. , 1995 .

[78]  R. Deicken,et al.  Proton Magnetic Resonance Spectroscopy of the Human Brain in Schizophrenia , 2000, Reviews in the neurosciences.

[79]  H WILSON,et al.  Early Diagnosis of Schizophrenia , 1951, British medical journal.

[80]  W. Fenton,et al.  Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia , 2000, Biological Psychiatry.

[81]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[82]  E. Aaes-Jørgensen,et al.  Essential fatty acids. , 1961, Physiological reviews.