Effects of Heavy Drinking, Binge Drinking, and Family History of Alcoholism on Regional Brain Metabolites

Meyerhoff, Dieter J.; Blumenfeld, Rob; Truran, Diana; Lindgren, Joselyn; Flenniken, Derek; Cardenas, Valerie A.; Chao, Li-Lian; Rothlind, Johannes C.; Studholme, Colin; Weiner, Michael W.

doi:10.1097/01.alc.0000121805.12350.ca

Cited by 137 publications

(147 citation statements)

References 66 publications

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“…Schizophrenia-MRS is capable of detecting both endogenous compounds in the brain as well as consumed or administered drugs ranging from anti-cancer agents (Port and Wolf, 2003), to alcohol ingested in excess (Danielsen and Ross, 1999) to anti-epileptic medications (e.g., valproic acid) administered in therapeutic doses (Bluml et al, 2002). Chronic alcoholism is accompanied by loss of NAA (Jagannathan et al, 1996;Meyerhoff et al, 2004) which in some studies is reported to recover after prolonged abstinence (Parks et al, 2002).…”

Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,209

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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Section: Magnetic Resonance Spectroscopy and Imaging Of Naamentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,209

1,126

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“…Regional gray-matter, white-matter, and cerebrospinal-fl uid volumetry was performed using automated probabilistic segmentation, combined with automated atlas-based region labeling of the four lobes, cerebellum, and subcortical structures (Cardenas et al, 2005;Meyerhoff et al, 2004). Values obtained were normalized to intracranial volume for each participant.…”

Section: Magnetic Resonance Acquisition and Analysesmentioning

confidence: 99%

Metabolite Levels in the Brain Reward Pathway Discriminate Those Who Remain Abstinent From Those Who Resume Hazardous Alcohol Consumption After Treatment for Alcohol Dependence

Durazzo¹,

Pathak²,

Gaździński³

et al. 2010

J. Stud. Alcohol Drugs

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ABSTRACT. Objective:This study compared baseline metabolite levels in components of the brain reward system among individuals who remained abstinent and those who resumed hazardous alcohol consumption after treatment for alcohol dependence. Method: Fiftyone treatment-seeking alcohol-dependent individuals (abstinent for approximately 7 days [SD = 3]) and 26 light-drinking nonsmoking controls completed 1.5-T proton magnetic resonance spectroscopic imaging, yielding regional concentrations of N-acetylaspartate, cholinecontaining compounds, creatine-containing compounds, and myoinositol. Metabolite levels were obtained in the following component of the brain reward system: dorsolateral prefrontal cortex, anterior cingulate cortex, insula, superior corona radiata, and cerebellar vermis. Alcohol-dependent participants were followed over a 12-month period after baseline study (i.e., at 7 days of abstinence [SD = 3]) and were classifi ed as abstainers (no alcohol consumption; n = 18) and resumers (any alcohol consumption; n = 33) at follow-up. Baseline metabolite levels in abstainers and resumers and light-drinking nonsmoking controls were compared in the above regions of interest. Results: Resumers demonstrated signifi cantly lower baseline N-acetylaspartate concentrations than light-drinking nonsmoking controls and abstainers in all regions of interest. Resumers also exhibited lower creatine-containing-compound concentrations than abstainers in the dorsolateral prefrontal cortex, superior corona radiata, and cerebellar vermis. Abstainers did not differ from light-drinking nonsmoking controls on baseline metabolite concentrations in any region of interest. Conclusions: The signifi cantly decreased N-acetylaspartate and creatine-containing-compound concentrations in resumers suggest compromised neuronal integrity and abnormalities in cellular bioenergetics in major neocortical components and white-matter interconnectivity of the brain reward pathway. The lack of metabolite differences between abstainers and light-drinking nonsmoking controls suggests premorbid factors potentially contributed to the baseline brain metabolite abnormalities observed in resumers. A LCOHOL-USE DISORDERS (AUDs; i.e., alcohol dependence and abuse) are characterized by a chronically relapsing/remitting course over the lifetime (Dawson et al., 2007;Jin et al., 1998;Miller et al., 2001;Zywiak et al., 2006). The resumption of hazardous levels of alcohol consumption after treatment is common (Donovan, 1996;Maisto and Connors, 2006;Miller et al., 2001;Monahan and Finney, 1996), and appears to be mediated by a complex interplay among genetic, neurobiological, neurocognitive, psychological/psychiatric, and sociodemographic factors (Adinoff et al., 2005;Baler and Volkow, 2006;Bottlender and Soyka, 2005;Bradizza et al., 2006;Glenn and Parsons, 1991;Goodman, 2008;Heinz et al., 2003;Jin et al., 1998;Koob, 2003;Moos and Moos, 2006;Parsons et al., 1990;Sher et al., 2005;Weiss and Porrino, 2002;Zywiak et al., 2006). A considerable amount of research has inve...

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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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Effects of Heavy Drinking, Binge Drinking, and Family History of Alcoholism on Regional Brain Metabolites

Cited by 137 publications

References 66 publications

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Metabolite Levels in the Brain Reward Pathway Discriminate Those Who Remain Abstinent From Those Who Resume Hazardous Alcohol Consumption After Treatment for Alcohol Dependence

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

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