Regionally specific neuronal pathology in untreated patients with schizophrenia

A proton magnetic resonance spectroscopic imaging study

Alessandro Bertolino, Joseph H. Callicott, Igor Elman, Venkata Mattay, Gioacchino Tedeschi, Joseph A. Frank, Alan Breier, Daniel Weinberger

Research output: Contribution to journalArticle

Abstract

Background: Proton magnetic resonance spectroscopic imaging (1H-MRSI) studies have reported reductions of N-acetyl aspartate (NAA), a marker of neuronal integrity, in the hippocampal region (HIPPO) and dorsolateral prefrontal cortex (DLPFC) of pharmacologically treated patients with schizophrenia. The purpose of the present study was twofold: to exclude drug treatment as a source of the previous findings and to examine NAA relative concentrations in a unique sample of chronically untreated patients. Methods: We studied 12 medication-free patients, 5 of whom were 'drug naive' and symptomatic for a mean of 12 years, and 12 control subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined [i.e., NAA/creatine (CRE), NAA/choline (CHO), CHO/CRE] for multiple cortical and subcortical regions. Hippocampal formation and frontal lobe volumes were also measured to test for correlations with 1H-MRSI data. Results: Significant reductions of NAA/CRE and NAA/CHO were found bilaterally in HlIPPO and DLPFC. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios, length of illness, and volumes of the hippocampal region and frontal lobe. Mean ratios and effect sizes were not different in chronically ill but still medication-naive patients in comparison with subacute patients and previously studied chronic patients receiving medications. Conclusions: Bilateral reductions of NAA ratios in HIPPO and DLPFC are reliable findings. The findings implicate a relatively localized pattern of neurochemical pathology that does not appear to change with prolonged illness whether medicated or unmedicated.

Original languageEnglish (US)
Pages (from-to)641-648
Number of pages8
JournalBiological Psychiatry
Volume43
Issue number9
DOIs
StatePublished - May 1 1998
Externally publishedYes

Fingerprint

Protons
Schizophrenia
Magnetic Resonance Imaging
Pathology
Creatine
Choline
Prefrontal Cortex
Frontal Lobe
N-acetylaspartate
Pharmaceutical Preparations
Hippocampus
Chronic Disease

Keywords

  • H magnetic resonance spectroscopic imaging
  • Drug treatment
  • Hipocampal area
  • N-acetyl-aspartate
  • Prefrontal cortex
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Regionally specific neuronal pathology in untreated patients with schizophrenia : A proton magnetic resonance spectroscopic imaging study. / Bertolino, Alessandro; Callicott, Joseph H.; Elman, Igor; Mattay, Venkata; Tedeschi, Gioacchino; Frank, Joseph A.; Breier, Alan; Weinberger, Daniel.

In: Biological Psychiatry, Vol. 43, No. 9, 01.05.1998, p. 641-648.

Research output: Contribution to journalArticle

Bertolino, Alessandro ; Callicott, Joseph H. ; Elman, Igor ; Mattay, Venkata ; Tedeschi, Gioacchino ; Frank, Joseph A. ; Breier, Alan ; Weinberger, Daniel. / Regionally specific neuronal pathology in untreated patients with schizophrenia : A proton magnetic resonance spectroscopic imaging study. In: Biological Psychiatry. 1998 ; Vol. 43, No. 9. pp. 641-648.
@article{a19cc696056a4cf29116285675b2dbee,
title = "Regionally specific neuronal pathology in untreated patients with schizophrenia: A proton magnetic resonance spectroscopic imaging study",
abstract = "Background: Proton magnetic resonance spectroscopic imaging (1H-MRSI) studies have reported reductions of N-acetyl aspartate (NAA), a marker of neuronal integrity, in the hippocampal region (HIPPO) and dorsolateral prefrontal cortex (DLPFC) of pharmacologically treated patients with schizophrenia. The purpose of the present study was twofold: to exclude drug treatment as a source of the previous findings and to examine NAA relative concentrations in a unique sample of chronically untreated patients. Methods: We studied 12 medication-free patients, 5 of whom were 'drug naive' and symptomatic for a mean of 12 years, and 12 control subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined [i.e., NAA/creatine (CRE), NAA/choline (CHO), CHO/CRE] for multiple cortical and subcortical regions. Hippocampal formation and frontal lobe volumes were also measured to test for correlations with 1H-MRSI data. Results: Significant reductions of NAA/CRE and NAA/CHO were found bilaterally in HlIPPO and DLPFC. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios, length of illness, and volumes of the hippocampal region and frontal lobe. Mean ratios and effect sizes were not different in chronically ill but still medication-naive patients in comparison with subacute patients and previously studied chronic patients receiving medications. Conclusions: Bilateral reductions of NAA ratios in HIPPO and DLPFC are reliable findings. The findings implicate a relatively localized pattern of neurochemical pathology that does not appear to change with prolonged illness whether medicated or unmedicated.",
keywords = "H magnetic resonance spectroscopic imaging, Drug treatment, Hipocampal area, N-acetyl-aspartate, Prefrontal cortex, Schizophrenia",
author = "Alessandro Bertolino and Callicott, {Joseph H.} and Igor Elman and Venkata Mattay and Gioacchino Tedeschi and Frank, {Joseph A.} and Alan Breier and Daniel Weinberger",
year = "1998",
month = "5",
day = "1",
doi = "10.1016/S0006-3223(97)00555-6",
language = "English (US)",
volume = "43",
pages = "641--648",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "9",

}

TY - JOUR

T1 - Regionally specific neuronal pathology in untreated patients with schizophrenia

T2 - A proton magnetic resonance spectroscopic imaging study

AU - Bertolino, Alessandro

AU - Callicott, Joseph H.

AU - Elman, Igor

AU - Mattay, Venkata

AU - Tedeschi, Gioacchino

AU - Frank, Joseph A.

AU - Breier, Alan

AU - Weinberger, Daniel

PY - 1998/5/1

Y1 - 1998/5/1

N2 - Background: Proton magnetic resonance spectroscopic imaging (1H-MRSI) studies have reported reductions of N-acetyl aspartate (NAA), a marker of neuronal integrity, in the hippocampal region (HIPPO) and dorsolateral prefrontal cortex (DLPFC) of pharmacologically treated patients with schizophrenia. The purpose of the present study was twofold: to exclude drug treatment as a source of the previous findings and to examine NAA relative concentrations in a unique sample of chronically untreated patients. Methods: We studied 12 medication-free patients, 5 of whom were 'drug naive' and symptomatic for a mean of 12 years, and 12 control subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined [i.e., NAA/creatine (CRE), NAA/choline (CHO), CHO/CRE] for multiple cortical and subcortical regions. Hippocampal formation and frontal lobe volumes were also measured to test for correlations with 1H-MRSI data. Results: Significant reductions of NAA/CRE and NAA/CHO were found bilaterally in HlIPPO and DLPFC. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios, length of illness, and volumes of the hippocampal region and frontal lobe. Mean ratios and effect sizes were not different in chronically ill but still medication-naive patients in comparison with subacute patients and previously studied chronic patients receiving medications. Conclusions: Bilateral reductions of NAA ratios in HIPPO and DLPFC are reliable findings. The findings implicate a relatively localized pattern of neurochemical pathology that does not appear to change with prolonged illness whether medicated or unmedicated.

AB - Background: Proton magnetic resonance spectroscopic imaging (1H-MRSI) studies have reported reductions of N-acetyl aspartate (NAA), a marker of neuronal integrity, in the hippocampal region (HIPPO) and dorsolateral prefrontal cortex (DLPFC) of pharmacologically treated patients with schizophrenia. The purpose of the present study was twofold: to exclude drug treatment as a source of the previous findings and to examine NAA relative concentrations in a unique sample of chronically untreated patients. Methods: We studied 12 medication-free patients, 5 of whom were 'drug naive' and symptomatic for a mean of 12 years, and 12 control subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined [i.e., NAA/creatine (CRE), NAA/choline (CHO), CHO/CRE] for multiple cortical and subcortical regions. Hippocampal formation and frontal lobe volumes were also measured to test for correlations with 1H-MRSI data. Results: Significant reductions of NAA/CRE and NAA/CHO were found bilaterally in HlIPPO and DLPFC. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios, length of illness, and volumes of the hippocampal region and frontal lobe. Mean ratios and effect sizes were not different in chronically ill but still medication-naive patients in comparison with subacute patients and previously studied chronic patients receiving medications. Conclusions: Bilateral reductions of NAA ratios in HIPPO and DLPFC are reliable findings. The findings implicate a relatively localized pattern of neurochemical pathology that does not appear to change with prolonged illness whether medicated or unmedicated.

KW - H magnetic resonance spectroscopic imaging

KW - Drug treatment

KW - Hipocampal area

KW - N-acetyl-aspartate

KW - Prefrontal cortex

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=0032079453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032079453&partnerID=8YFLogxK

U2 - 10.1016/S0006-3223(97)00555-6

DO - 10.1016/S0006-3223(97)00555-6

M3 - Article

VL - 43

SP - 641

EP - 648

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 9

ER -