Biochemical markers of intelligence: a proton MR spectroscopy study of normal human brain

Jung, Rex E.; Brooks, William M.; Yeo, Ronald A.; Chiulli, Stephen J.; Weers, David C.; Sibbitt, Wilmer L.

doi:10.1098/rspb.1999.0790

Cited by 140 publications

(94 citation statements)

References 30 publications

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“…This reduction was not related to length of untreated psychosis, symptom severity or whether subjects were or were not antipsychotic naive. However, global NAA was directly correlated to general cognitive function for the whole study sample (schizophrenia and healthy subjects), consistent with previous observations in normals (Jung et al, 1999a;Valenzuela et al, 2000) as well across a wide range of neurological and psychiatric disorders (Ross and Sachdev, 2004). Randomized, prospective treatment with haloperidol and quetiapine, did not result in changes in NAA levels.…”

Section: Discussionsupporting

confidence: 89%

“…Similar cognitive-NAA relationships have been described in various neurological conditions (Ross and Sachdev, 2004) and in healthy subjects (Jung et al, 1999a). Our results with relatively short follow-up do not support further NAA reductions or normalizations with treatment.…”

Section: Discussionsupporting

confidence: 72%

“…Spectroscopic voxels were selected in the left caudate (volume ¼ 6 cc), left frontal and occipital lobes (12.6 cc), and right cerebellum (12.6 cc) using the T1-weighted imaging series (Figure 1). To control for head tilt, a standardized method of left frontal and occipital voxels prescription was implemented to select the inferiorsuperior plane (see Jung et al, 2002). The anterior-posterior and lateral placement varied individually to maximize white matter and minimize CSF inclusion as determined by visual inspection.…”

Section: Magnetic Resonance Studiesmentioning

confidence: 99%

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Proton Magnetic Resonance Spectroscopy During Initial Treatment With Antipsychotic Medication in Schizophrenia

Bustillo

Rowland

Jung

et al. 2007

Neuropsychopharmacol

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Reduced brain N-acetyl-aspartate (NAA) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction. However, the potential confounding effect of antipsychotic drugs on NAA has not been resolved. We studied 32 minimally treated schizophrenia patients and 21 healthy subjects with single-voxel proton magnetic resonance spectroscopy ( 1 H-MRS) of the frontal and occipital lobes, caudate nucleus, and cerebellum. Concentrations of NAA, Choline, and Cre were determined and corrected for the proportion of cerebrospinal fluid (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind manner with either haloperidol or quetiapine. 1 H-MRS was repeated every 6 months for up to 2 years. There was a group main effect for baseline NAA with lower global NAA in schizophrenia subjects before treatment compared to healthy controls. Global NAA was directly related to measures of global cognitive performance in the whole subject sample. Following treatment with haloperidol or quetiapine, there were no changes in NAA in any of the regions studied. Early in the illness, schizophrenia patients already demonstrate subtle reductions in NAA. Treatment with typical or atypical antipsychotic medications for several months does not result in NAA changes.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 72%

Section: Magnetic Resonance Studiesmentioning

confidence: 99%

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Proton Magnetic Resonance Spectroscopy During Initial Treatment With Antipsychotic Medication in Schizophrenia

Bustillo

Rowland

Jung

et al. 2007

Neuropsychopharmacol

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“…Decreased NAA may serve as a reversible marker of neuronal injury (e.g., Kalra et al 1998;de Stefano et al 1995). Levels of NAA have been demonstrated to correlate with overall neuropsychological performance, suggesting that NAA has a global role in neuronal function (Jung et al 1999). Like MI levels, NAA levels in MDMA users could theoretically be altered due to direct MDMA actions, or other glial, neuronal, or metabolic effects.…”

Section: Brain Metabolites: Myoinositol and N-acetylaspartatementioning

confidence: 99%

Neuroimaging research in human MDMA users: a review

Cowan

2006

Psychopharmacology

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Rationale Determining whether, under what circumstances, and to what extent 3,4-methylenedioxymethamphetamine (MDMA) exposure produces chronic changes in human brain function is a critical public health issue. MDMA is a widely used recreational drug commonly sold as "Ecstasy". Because findings from the animal literature have indicated that specific dosage regimens of MDMA can produce longlasting alterations in serotonergic function, existing studies of MDMA effects in humans have examined brain serotonin (5-HT) transporters (5-HTT) and receptors or have examined brain structures or functions potentially affected by MDMA. Objectives The objectives of this review are to provide a background for interpreting human MDMA neuroimaging research, to examine existing neuroimaging data regarding the rationale for and limitations to human MDMA research, and to provide suggestions for improving the design and interpretation of future neuroimaging approaches. Results Of the existing neuroimaging studies in human MDMA users, few experimental designs have been replicated across different research groups. Only investigations employing nuclear imaging methods to assay brain 5-HTT levels have been replicated across methods and research laboratories. These studies have found reduced levels of the 5-HTT in recently abstinent MDMA users with some evidence for normalization of 5-HTT levels with prolonged abstinence. However, the sensitivity of these methods is unknown.Conclusions The current state of neuroimaging in human MDMA users does not permit conclusions regarding the long-term effects of MDMA exposure. Future study designs might benefit from improved sample homogeneity, increased length of MDMA abstinence, longitudinal study design, test-retest measures, serotonergic specificity, and multimodal approaches.

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“…The metabolite N-acetyl-aspartate (NAA) is considered a marker of neuronal viability and/or integrity. NAA concentrations are reduced in affected areas in neurodegenerative diseases [18] and correlate with cognitive performance [19]. With respect to schizophrenia, MRS may allow to disentangle the meaning of white matter and gray matter volume reductions which may stand for neuronal loss or dysfunction [20].…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

et al. 2014

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Background: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). Methods: Schizophrenia patients with (AH; n=12) and without hallucinations (NH; n=8) and healthy controls (HC; n=11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyrus were defined anatomically. Results: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4±6.1 mm (range: 2.7-36.1 mm) for Broca's area and 16.8±6.2 mm (range:4.5-26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p = 0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p = 0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p = 0.03) and negative (p = 0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p = 0.008). Conclusion: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci. Highlights

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Biochemical markers of intelligence: a proton MR spectroscopy study of normal human brain

Cited by 140 publications

References 30 publications

Proton Magnetic Resonance Spectroscopy During Initial Treatment With Antipsychotic Medication in Schizophrenia

Proton Magnetic Resonance Spectroscopy During Initial Treatment With Antipsychotic Medication in Schizophrenia

Neuroimaging research in human MDMA users: a review

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

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