Cortical Gamma-Aminobutyric Acid Levels and the Recovery from Ethanol Dependence: Preliminary Evidence of Modification by Cigarette Smoking

Mason, Graeme F.; Petrakis, Ismene L.; Graaf, Robin A. de; Gueorguieva, Ralitza; Guidone, Elizabeth; Coric, Vladimir; Epperson, C. Neill; Rothman, Douglas L.; Krystal, John H.

doi:10.1016/j.biopsych.2005.06.009

Cited by 71 publications

(69 citation statements)

References 65 publications

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“…A number of these MRS studies, however, used metabolite ratios rather than absolute concentrations, typically relative to creatine (Cr), to quantify target metabolites, assuming that Cr is robust to CNS aging or insult and therefore remains stable. Indeed, several MRS studies report lack of significant deficits in uncomplicated alcoholics when regional measures of NAA were expressed as a function of the amount of underlying tissue (Mason et al, 2006;Meyerhoff et al, 2004;O'Neill et al, 2001;Pfefferbaum et al, 2005;Schweinsburg et al, 2000). In the Pfefferbaum et al study (2005), where NAA was expressed as a ratio of Cr, an apparent NAA deficit was present, but, it was as much attributable to a lower NAA peak as it was to a higher Cr peak in the alcoholics than controls.…”

Section: Introductionmentioning

confidence: 99%

Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

Pfefferbaum

Adalsteinsson

Bell

et al. 2006

Neuropsychopharmacol

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Wernicke's encephalopathy (WE) is characterized by lesions in thalamus, hypothalamus (including mammillary nuclei), and inferior colliculi, results in serious disabilities, has an etiology of thiamine deficiency, is treatable with thiamine, and occurs most commonly with alcoholism. Despite decades of study, whether alcohol exposure exacerbates the neuropathology or retards its resolution remains controversial. To examine patterns of brain damage and recovery resulting from thiamine deprivation with and without alcohol exposure, we conducted in vivo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3 T in alcohol-preferring (P) rats, which had voluntarily consumed large amounts of alcohol before thiamine manipulation. A total of 18 adult male P rats (nine alcohol-exposed) received a thiamine-deficient diet for 2 weeks: 10 (five alcohol-exposed) received intraperitoneal (i.p.) pyrithiamine (PT) and eight (four alcohol-exposed) received i.p. thiamine supplementation. Neurological signs developed by day 14. Rats were scanned before thiamine depletion and 18 and 35 days after thiamine repletion. Two-dimensional J-resolved MRS single-voxel spectra with water reference were collected in a voxel subtending the thalamus; metabolite quantification was corrected for voxel tissue content. MRI identified significant enlargement of dorsal ventricles and increase in signal intensities in thalamus, inferior colliculi, and mammillary nuclei of PT compared with thiamine-treated (TT) groups from MRI 1-2, followed by significant normalization from MRI 2-3 in thalamus and colliculi, but not mammillary nuclei and lateral ventricles. Voxel-by-voxel analysis revealed additional hyperintense signal clusters in the dorsal and ventral hippocampus and enlargement of the fourth ventricle. MRS showed a significant decline and then partial recovery in thalamic N-acetylaspartate, a marker of neuronal integrity, in PT compared with TT rats, with no change detected in creatine, choline, or glutamate. PT rats with prior alcohol exposure exhibited attenuated recovery in the thalamus and arrested growth of the corpus callosum; further, two of the five alcohol-exposed PT rats died prematurely. Parenchymal and ventricular changes with thiamine manipulation concur with human radiological signs of WE. The enduring macrostructural and neurochemical abnormalities involving critical nodes of Papez circuit carry liabilities for development of amnesia and incomplete recovery from other cognitive and motor functions subserved by the affected neural systems.

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Section: Introductionmentioning

confidence: 99%

Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

Pfefferbaum

Adalsteinsson

Bell

et al. 2006

Neuropsychopharmacol

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“…Previous comparisons of alcoholic versus healthy subjects or non-heavily drinking controls by proton magnetic resonance spectroscopy ( 1 H-MRS) have revealed reduced levels of brain N-acetylaspartate (NAA) in most (Fein et al, 1994;Jagannathan et al, 1996;Seitz et al, 1999;Bendszus et al, 2001;Schweinsburg et al, 2001;Bloomer et al, 2004;Durazzo et al, 2004;Meyerhoff et al, 2004;Viola et al, 2004) but not all investigations and brain regions studied (Schweinsburg et al, 2000;Parks et al, 2002;Ende et al, 2005;Mason et al, 2006). Similarly, lowered levels of choline have been detected (Jagannathan et al, 1996;Seitz et al, 1999;Bloomer et al, 2004;Viola et al, 2004;Ende et al, 2005;Mason et al, 2006), although this finding seems even more ambiguous (Schweinsburg et al, 2000(Schweinsburg et al, , 2001(Schweinsburg et al, , 2003 and dependent on localization (Bendszus et al, 2001;Parks et al, 2002).…”

mentioning

confidence: 99%

Manifestations of early brain recovery associated with abstinence from alcoholism

Bartsch¹,

Homola²,

Biller³

et al. 2006

Brain

175

142

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Chronic alcohol abuse results in morphological, metabolic, and functional brain damage which may, to some extent, be reversible with early effects upon abstinence. Although morphometric, spectroscopic, and neuropsychological indicators of cerebral regeneration have been described previously, the overall amount and spatial preference of early brain recovery attained by abstinence and its associations with other indicators of regeneration are not well established. We investigated global and local brain volume changes in a longitudinal two-timepoint study with T 1 -weighted MRI at admission and after short-term (6-7 weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics. Volumetric brain gain was related to metabolic and neuropsychological recovery. On admission and after short-term abstinence, structural image evaluation using normalization of atrophy (SIENA), its voxelwise statistical extension to multiple subjects, proton MR spectroscopy ( 1 H-MRS), and neuropsychological tests were applied. Upon short-term sobriety, 1 H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically detected global brain volume gain amounted to nearly two per cent on average and was spatially significant around the superior vermis, perimesencephalic, periventricular and frontal brain edges. It correlated positively with the percentages of cerebellar and frontomesial choline increase, as detected by 1 H-MRS. Moreover, frontomesial NAA gains were associated with improved performance on the d2-test of attention. In 10 ageand gender-matched healthy control subjects, no significant brain volume or metabolite changes were observed. Although cerebral osmotic regulations may occur initially upon sobriety, significant increases of cerebellar choline and frontomesial NAA levels detected at stable brain water integrals and creatine concentrations, serum electrolytes and red blood cell indices in our patient sample suggest that early brain recovery through abstinence does not simply reflect rehydration. Instead, even the adult human brain and particularly its white matter seems to possess genuine capabilities for regrowth. Our findings emphasize metabolic as well as regionally distinct morphological capacities for partial brain recovery from toxic insults of chronic alcoholism and substantiate early measurable benefits of therapeutic sobriety. Further understanding of the precise mechanisms of this recovery may become a valuable model of brain regeneration with relevance for other disorders.Keywords: alcoholism; morphometry; MR spectroscopy; SIENA; voxelwise SIENA statistics Abbreviations:1 H-MRS = proton MR spectroscopy; NAA = N-acetylaspartate; PBVC = percentage brain volume change; SIENA = structural image evaluation using normalization of atrophy

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“…More recently, GABA levels measured by 1 H MRS have been found to be normal or slightly elevated after one week of sobriety but fall by approximately 12% after 4 weeks of sobriety (87), which is in agreement with a significant decline in plasma GABA levels between 1 day and 3 weeks of sobriety (88). Within the field of alcoholism research, there is growing prescription of anticonvulsant medications to facilitate detoxification and to prevent relapse (89-91).…”

Section: Glutamate Glutamine and Gabamentioning

confidence: 82%

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

Mason

Krystal

2006

NMR Biomed.

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Magnetic resonance spectroscopy (MRS) is likely in the near future to play a key role in the process of drug discovery and evaluation. As the pharmaceutical industry seeks biochemical markers of drug delivery, efficacy and toxicity, this non-invasive technique offers numerous ways to study adults and children repeatedly and without ionizing radiation. In this article, we survey an array of the information that MRS offers about neurochemistry in general and psychiatric disorders and their treatment in particular. We also present growing evidence of glial abnormalities in neuropsychiatric disorders and discuss what MRS is contributing to that line of investigation. The third major direction of this article is the discussion of where MRS techniques are headed and how those new techniques can contribute to studies of mechanisms of psychiatric disease and drug discovery.

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Cortical Gamma-Aminobutyric Acid Levels and the Recovery from Ethanol Dependence: Preliminary Evidence of Modification by Cigarette Smoking

Cited by 71 publications

References 65 publications

Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

Development and Resolution of Brain Lesions Caused by Pyrithiamine- and Dietary-Induced Thiamine Deficiency and Alcohol Exposure in the Alcohol-Preferring Rat: A Longitudinal Magnetic Resonance Imaging and Spectroscopy Study

Manifestations of early brain recovery associated with abstinence from alcoholism

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

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