TY - JOUR
T1 - Brain Metabolite Abnormalities in the White Matter of Elderly Schizophrenic Subjects
T2 - Implication for Glial Dysfunction
AU - Chang, Linda
AU - Friedman, Joseph
AU - Ernst, Thomas
AU - Zhong, Kai
AU - Tsopelas, Nicholas D.
AU - Davis, Kenneth
N1 - Funding Information:
This work was supported in part by funds from the National Institute of Health (Grant No. P50 MH 66392, a Conte Center Grant awarded to KD, Grant No. K24-DA16170 to LC; Grant No. K02-DA16991 to TE), VISN3 Mental Illness Research Education Clinical Center, US Department of Veteran Affairs, and Department of Energy (Office of Biological and Environmental Research). None of the authors have biomedical financial interests or potential conflicts of interest. We thank the research subjects who participated in this study. We also thank Dr. Michael Sanders for his participation in subject evaluation, and Drs. Dardo Tomasi and Elisabeth Caparelli for some of the magnetic resonance spectroscopy data acquisition and Renat Yakupov for technical assistance.
PY - 2007/12/15
Y1 - 2007/12/15
N2 - Background: Abnormalities in the white matter of the brain may occur in individuals with schizophrenia as well as with normal aging. Therefore, elderly schizophrenic patients may suffer further cognitive decline as they age. This study determined whether elderly schizophrenia participants, especially those with declined cognitive function (Clinical Dementia Rating score > 1), show white matter metabolite abnormalities on proton magnetic resonance spectroscopy and whether there are group differences in age-dependent changes in these brain metabolites. Method: Twenty-three elderly schizophrenia and twenty-two comparison participants fulfilling study criteria were enrolled. Localized, short echo-time 1H MRS at 4 Tesla was used to assess neurometabolite concentrations in several white matter regions. Results: Compared with healthy subjects, schizophrenia participants had lower N-acetyl compounds (-12.6%, p = .0008), lower myo-inositol (-16.4%, p = .026), and higher glutamate + glutamine (+28.7%, p = .0016) concentrations across brain regions. Schizophrenia participants with Clinical Dementia Rating ≥ 1 showed the lowest NA in the frontal and temporal regions compared with control subjects. Interactions between age and schizophrenia status on total creatine and choline-containing compounds were observed; only schizophrenia participants showed age-related decreases of these metabolites in the right frontal region. Conclusions: Decreased NA in these white matter brain regions likely reflects reduced neuronal content associated with decreased synapses and neuronal cell volumes. The elevated glutamate + glutamine, if reflecting elevated glutamate, could result from excess neuronal glutamate release or glial dysfunction in glutamate reuptake. The decreased myo-inositol in participants with schizophrenia suggests decreased glial content or dysfunctional glia, which might result from glutamate-mediated toxicity.
AB - Background: Abnormalities in the white matter of the brain may occur in individuals with schizophrenia as well as with normal aging. Therefore, elderly schizophrenic patients may suffer further cognitive decline as they age. This study determined whether elderly schizophrenia participants, especially those with declined cognitive function (Clinical Dementia Rating score > 1), show white matter metabolite abnormalities on proton magnetic resonance spectroscopy and whether there are group differences in age-dependent changes in these brain metabolites. Method: Twenty-three elderly schizophrenia and twenty-two comparison participants fulfilling study criteria were enrolled. Localized, short echo-time 1H MRS at 4 Tesla was used to assess neurometabolite concentrations in several white matter regions. Results: Compared with healthy subjects, schizophrenia participants had lower N-acetyl compounds (-12.6%, p = .0008), lower myo-inositol (-16.4%, p = .026), and higher glutamate + glutamine (+28.7%, p = .0016) concentrations across brain regions. Schizophrenia participants with Clinical Dementia Rating ≥ 1 showed the lowest NA in the frontal and temporal regions compared with control subjects. Interactions between age and schizophrenia status on total creatine and choline-containing compounds were observed; only schizophrenia participants showed age-related decreases of these metabolites in the right frontal region. Conclusions: Decreased NA in these white matter brain regions likely reflects reduced neuronal content associated with decreased synapses and neuronal cell volumes. The elevated glutamate + glutamine, if reflecting elevated glutamate, could result from excess neuronal glutamate release or glial dysfunction in glutamate reuptake. The decreased myo-inositol in participants with schizophrenia suggests decreased glial content or dysfunctional glia, which might result from glutamate-mediated toxicity.
KW - Glutamate
KW - myoinositol
KW - schizophrenia
KW - spectroscopy
KW - white matter
UR - http://www.scopus.com/inward/record.url?scp=36549069306&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2007.05.025
DO - 10.1016/j.biopsych.2007.05.025
M3 - Article
C2 - 17693392
AN - SCOPUS:36549069306
SN - 0006-3223
VL - 62
SP - 1396
EP - 1404
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 12
ER -