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MR Spectroscopic Studies of the Brain in Psychiatric Disorders

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Brain Imaging in Behavioral Neuroscience

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 11))

Abstract

The measurement of brain metabolites with magnetic resonance spectroscopy (MRS) provides a unique perspective on the brain bases of neuropsychiatric disorders. As a context for interpreting MRS studies of neuropsychiatric disorders, we review the characteristic MRS signals, the metabolic dynamics, and the neurobiological significance of the major brain metabolites that can be measured using clinical MRS systems. These metabolites include N-acetylaspartate (NAA), creatine, choline-containing compounds, myo-inositol, glutamate and glutamine, lactate, and gamma-amino butyric acid (GABA). For the major adult neuropsychiatric disorders (schizophrenia, bipolar disorder, major depression, and the anxiety disorders), we highlight the most consistent MRS findings, with an emphasis on those with potential clinical or translational significance. Reduced NAA in specific brain regions in schizophrenia, bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder corroborate findings of reduced brain volumes in the same regions. Future MRS studies may help determine the extent to which the neuronal dysfunction suggested by these findings is reversible in these disorders. Elevated glutamate and glutamine (Glx) in patients with bipolar disorder and reduced Glx in patients with unipolar major depression support models of increased and decreased glutamatergic function, respectively, in those conditions. Reduced phosphomonoesters and intracellular pH in bipolar disorder and elevated dynamic lactate responses in panic disorder are consistent with metabolic models of pathogenesis in those disorders. Preliminary findings of an increased glutamine/glutamate ratio and decreased GABA in patients with schizophrenia are consistent with a model of NMDA hypofunction in that disorder. As MRS methods continue to improve, future studies may further advance our understanding of the natural history of psychiatric illnesses, improve our ability to test translational models of pathogenesis, clarify therapeutic mechanisms of action, and allow clinical monitoring of the effects of interventions on brain metabolic markers.

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Abbreviations

1H-MRS:

Proton magnetic resonance spectroscopy

2D:

Two dimensional

31P-MRS:

Phosphorous magnetic resonance spectroscopy

ADP:

Adenosine diphosphate

AGAT:

Arginine-glycine aminotransferase

ASICs:

Acid sensing ion channels

ASPA:

Aspartoacylase

Asp-NAT:

Aspartate N-acetyltransferase

ATP:

Adenosine triphosphate

CK:

Creatine kinase

CNS:

Central nervous system

CO2:

Carbon dioxide

CSF:

Cerebrospinal fluid

CSI:

Chemical shift imaging

EAAT1:

Excitatory amino acid transporter 1

EAAT2:

Excitatory amino acid transporter 2

ECF:

Extracellular fluid

EEG:

Electroencephalogram

GAA:

Guanidinoacetate

GABA:

Gamma aminobutyric acid

GABA-T:

Gamma aminobutyric acid transaminase

GAD:

Glutamic acid decarboxylase

GAD65:

65 kilodalton form of GAD

GAD67:

67 kilodalton form of GAD

GAMT:

Guanidinoacetate methyltransferase

GAT:

GABA transporter

Glx:

The combined signal from glutamate and glutamine

GPCho:

Glycerophosphorylcholine

H+:

Hydrogen ions

Hz:

Hertz, or cycles per second

Km:

Michaelis-Menten constant

MCT:

Monocarboxylate transporter

MEGA:

Mescher-Garwood

mM:

Millimoles

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

mRNA:

Messenger ribonucleic acid

MRS:

Magnetic resonance spectroscopy

MRSI:

Magnetic resonance spectroscopic imaging

MRUI:

Magnetic Resonance User Interface

ms:

Milliseconds

NAA:

N-acetylaspartate

NAAG:

N-acetylaspartylglutamate

NMDA:

N-methyl-D-aspartic acid

OCD:

Obsessive compulsive disorder

PCho:

Phosphorylcholine

PEPSI:

Proton echoplanar spectroscopic imaging

pH:

Negative logarithm of hydrogen ion concentration

PMEs:

Phosphomonoesters

ppm:

Parts per million

PRESS:

Point resolved spectroscopic sequence

PTSD:

Post traumatic stress disorder

SSRI:

Selective serotonin reuptake inhibitor

TCA:

Tricarboxylic acid

TE:

Echo time

VGluT:

Vesicular glutamate transporter

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Authors and Affiliations

  1. University of California Davis Medical Center, Sacramento, CA, USA

    Richard J. Maddock & Michael H. Buonocore

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  1. Richard J. Maddock
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  2. Michael H. Buonocore
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Correspondence to Richard J. Maddock .

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Editors and Affiliations

  1. , UC Davis Imaging Center, University of California at Davis, X Street 4701, Sacramento, 95817, California, USA

    Cameron S. Carter

  2. , Dep of Experimental Psychology/Dep of Ps, University of Cambridge, Downing Site, Cambridge, CB2 3EB, United Kingdom

    Jeffrey W. Dalley

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Maddock, R.J., Buonocore, M.H. (2011). MR Spectroscopic Studies of the Brain in Psychiatric Disorders. In: Carter, C., Dalley, J. (eds) Brain Imaging in Behavioral Neuroscience. Current Topics in Behavioral Neurosciences, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2011_197

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