Abstract
Background
A recent magnetic resonance spectroscopy (MRS) study revealed low γ-aminobutyric acid
(GABA) levels in the occipital cortex of depressed patients. No in vivo study has
been reported to measure postsynaptic GABA receptors in the patients.
Methods
Cortical benzodiazepine (BZ) binding to GABAA receptors was measured with [123I]iomazenil and single photon emission computed tomography in unmedicated patients
with unipolar major depression (n = 13) and healthy subjects (n = 19). Group differences were evaluated by means of statistical parametric mapping
(SPM) with partial volume correction for gray matter. Occipital GABA levels were determined
by proton MRS in a subgroup (n = 6) of the patients.
Results
No evidence of altered BZ binding was found in patients with depression compared with
healthy control subjects in the SPM analysis. Although reduction in gray matter volume
was observed in the frontal cortex and amygdala of the patients, partial volume correction
of the atrophy did not change the result of unaltered BZ binding. GABA levels were
found lower in the occipital cortex; however, BZ binding did not show significant
relationship to GABA levels.
Conclusions
GABAA receptor binding measured in vivo with BZ radioligand binding are not altered in
patients with depression.
Keywords
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References
- Reproducibility of SPECT measurement of benzodiazepine receptors in human brain with iodine-123-iomazenil.J Nucl Med. 1995; 36: 167-175
- Alterations of benzodiazepine receptors in type II alcoholics measured with SPECT and iomazenil.Am J Psychiatry. 1998; 11 ([123I]): 1550-1555
- No evidence of altered in vivo benzodiazepine receptor binding in schizophrenia.Neuropsychopharmacology. 1999; 20: 650-661
- SPECT measurement of benzodiazepine receptors in human brain with [123I]iomazenil.J Nucl Med. 1994; 35: 228-238
- Use-dependent regulation of GABAA receptors.International Rev Neurobiol. 1996; 39: 53-76
- Effect of neuroactive steroids on flumazenil binding to the GABAA receptor complex in vitro.Neuropharmacology. 1995; 34 ([3H]): 1169-1175
- Hippocampal volume reduction in major depression.Am J Psychiatry. 2000; 157: 115-118
- SPECT [123I]iomazenil measurement of benzodiazepine receptors in panic disorder.Biol Psychiatry. 2000; 47: 96-106
- Brain GABAA/benzodiazepine binding sites and glutamic acid decarboxylase activity in depressed suicide victims.Brain Res. 1988; 460: 114-123
- Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study.Arch Gen Psychiatry. 1993; 50: 7-16
- GABA receptors, lipids, and gangliosides in cobalt epileptic focus.Adv Neurol. 1986; 44: 379-391
- Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides.Neuropharmacology. 1984; 23: 1561-1569
- Subgenual prefrontal cortex abnormalities in mood disorders.Nature. 1997; 386: 824-827
- Stress-induced behavioral depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy.Brain Res. 1989; 487: 45-51
- Structured Clinical Interview for DSM-IV Axis I Disorders. Patient Edition. Biometric Research Department, New York State Psychiatric Institute, New York1995
- Assessing the significance of focal activations using their spatial extent.Hum Brain Mapping. 1994; 1: 210-220
- Statistical parametric maps in functional imaging.Hum Brain Mapping. 1995; 2: 189-210
- Changes of benzodiazepine receptors during chronic benzodiazepine administration in humans.Eur J Pharmacol. 1999; 368: 161-172
- CSF neurochemistry in depressed, manic and schizophrenic patients compared with normal controls.Am J Psychiatry. 1984; 141: 1540-1553
- CSF GABA in normal subjects and patients with depression, schizophrenia, mania, and anorexia nervosa.Am J Psychiatry. 1981; 138: 1098-1101
- GABA levels in CSF of patients with psychiatric disorders.Am J Psychiatry. 1980; 137: 362-364
- Low plasma gamma-aminobutyric acid levels during the late luteal phase of women with premenstrual dysphoric disorders.Am J Psychiatry. 1996; 153: 718-720
- Characterization of the benzodiazepine radioligand 125I-Ro16–0154.Life Sci. 1990; 47: 1535-1546
- Cerebrospinal fluid gamma-aminobutyric acid and homovanillic acid in depressive disorders.Biol Psychiatry. 1982; 17: 877-883
- Effects of learned helplessness on brain GABA receptors.Neurosci Res. 2000; 38: 193-198
- Magentic resonance imaging of the caudate nuclei in depression.Arch Gen Psychiatry. 1992; 49: 553-557
- Benzodiazepine receptor and neurotransmitter studies in the brain of suicides.Life Sci. 1987; 41: 2623-2630
- Benzodiazepine antagonist Ro 15–1788.J Neurochem. 1981; 37: 714-722
- Molecular biology of GABAA receptors.FASEB J. 1990; 4: 1469-1480
- Benzodiazepine receptors in the post-mortem brain of suicide victims and schizophrenic subjects.Psychiatry Res. 1997; 71: 137-149
- Plasma GABA in mood disorders.Psychopharmacol Bull. 1990; 26: 157-161
- Significance of nonuniform attenuation correction in quantitative brain SPECT imaging.J Nucl Med. 1998; 39: 1719-1726
- Cortical grey matter and benzodiazepine receptors in malformation of cortical development. A voxel-based comparison of structural and functional imaging data.Brain. 1997; 120: 1961-1973
- Benzodiazepine binding sites and their modulators in hippocampus of violent suicide victims.Biol Psychiatry. 1992; 32: 922-931
- 1H Observe/13C-decouple spectroscopic measurements of lactate and glutamate in the rat brain in vivo.Proc Natl Acad Sci U S A. 1985; 82: 1633-1637
- Reduced cortical γ-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy.Arch Gen Psychiatry. 1999; 56: 1043-1047
- Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression.Br J Psychiatry. 1998; 172: 527-532
- 3D MRI studies of neuroanatomic changes in unipolar major depression.Biol Psychiatry. 2000; 48: 791-800
- Amygdala core nuclei volumes are decreased in recurrent major depression.Neuroreport. 1998; 22: 2023-2028
- Hippocampal atrophy in recurrent major depression.Proc Natl Acad Sci U S A. 1996; 93: 3908-3913
- Widespread cerebral structural changes in patients with cortical dysgenesis and epilepsy.Brain. 1995; 118: 1039-1050
- The anatomy of mood disorders—review of structural neuroimaging studies.Biol Psychiatry. 1997; 41: 86-106
- Structured Clinical Interview for DSM-III-R-Non-Patient Edition (SCID-NP, Ver 1.0). American Psychiatric Press, Washington, DC1990
- Benzodiazepine binding sites in amygdala and hippocampus of depressed suicide victims.J Affective Disorder. 1990; 18: 11-15
- GABAergic modulation of benzodiazepine binding site sensitivity.Nature. 1978; 274: 383-385
- The GABA-ergic system.Ann Rev Neurosci. 1985; 8: 21-44
- Effects of Vigabatrin on the GABAergic system as determined by [123I]iomazenil SPECT and GABA MRS.Epilepsia. 1999; 40: 1433-1438
- [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia.Psychiatry Res Neuroimaging. 1999; 91: 163-173
- Adrenalectomy prevents the stress-induced decrease in in vivo [3H]Ro 15–1788 binding to GABAA benzodiazepine receptors in the mouse.Brain Res. 1990; 519: 347-350
- A voxel-based method for the statistical analysis of gray and white matter density applied to schizophrenia.Neuroimage. 1995; 2: 244-252
- Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and nonhuman primates.Nucl Med Biol. 1992; 19: 881-888
Article info
Publication history
Accepted:
October 14,
2002
Received in revised form:
September 23,
2002
Received:
June 13,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
