Loss of Control of Alcohol Use and Severity of Alcohol Dependence in Non‐Treatment‐Seeking Heavy Drinkers Are Related to Lower Glutamate in Frontal White Matter

Ende, Gabriele; Hermann, Derik; Demirakça, Traute; Hoerst, Mareen; Tunc-Skarka, Nuran; Weber‐Fahr, Wolfgang; Wichert, Svenja; Rabinstein, Juri; Frischknecht, Ulrich; Mann, Karl; Vollstädt‐Klein, Sabine

doi:10.1111/acer.12149

Cited by 46 publications

(33 citation statements)

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“…Moreover, FA, NAA, and tCho were each significantly correlated with FH density (number of parents and grandparents with substance use disorders), and these relationships were not affected by removing participants who had psychiatric conditions or had tried alcohol or other drugs. Our results parallel findings of reduced NAA and elevated tCho in frontal white matter of individuals with alcohol and other drug use disorders [Ende et al, ; Licata and Renshaw, ] and suggest this altered pattern may be present prior to the initiation of alcohol or other drug use in at risk individuals.…”

Section: Discussionsupporting

confidence: 89%

Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders

et al. 2014

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Individuals with a family history of substance use disorder (FH+) show impaired frontal white matter as indicated by diffusion tensor imaging (DTI). This impairment may be due to impaired or delayed development of myelin in frontal regions, potentially contributing to this population’s increased risk for developing substance use disorders. In this study, we examined high angular resolution DTI and proton magnetic resonance spectroscopy data from the anterior corona radiata were collected in 80 FH+ and 34 FH− youths (12.9 ±1.0 years old). White matter integrity indices included fractional anisotropy (FA), N-acetylaspartate (NAA), and total choline (tCho). Lower FA suggests decreased myelination. Decreased NAA coupled with higher tCho suggests impaired build-up and maintenance of cerebral myelin and consequently greater breakdown of cellular membranes. We found FH+ youths had lower FA (P <0.0001) and NAA (P =0.017) and higher tCho (P =0.04). FH density (number of parents and grandparents with substance use disorders) was negatively correlated with FA (P <0.0001) and NAA (P =0.011) and positively correlated with tCho (P =0.001). FA was independently predicted by both FH density (P =0.006) and NAA (P= 0.002), and NAA and tCho were both independent predictors of FH density (P <0.001). Our finding of lower frontal FA in FH+ youths corresponding to lower NAA and increased tCho is consistent with delayed or impaired development of frontal white matter in FH+ youths. Longitudinal studies are needed to determine how these differences relate to substance use outcomes.

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Section: Discussionsupporting

confidence: 89%

Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders

et al. 2014

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“…These lower occipital or ACC (into adjacent white matter) glutamate levels were correlated with greater drinking severity [e.g., more alcohol-related consequences (Thoma et al, 2011), loss of control over drinking (Ende et al, 2013)] or poorer neuropsychological functioning [e.g., more impaired visual-motor or attentional functioning (Bagga et al, 2014; Pennington et al, 2014)]. In contrast, other studies reported no differences between alcohol-addicted individuals and controls in glutamate or Glx in the cerebellar vermis (Seitz et al, 1999), dorsolateral PFC (DLPFC) (Nery et al, 2010), or dACC (Yeo et al, 2013).…”

Section: Glutamatergic Alterations In Drug Addiction (Table 1)mentioning

confidence: 99%

Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity

Moeller

London

Northoff³

2016

Neuroscience & Biobehavioral Reviews

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Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications.

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“…1 H‐MRS investigations of anterior cingulate glutamate in AD have produced seemingly conflicting results, with reports of increased (Lee et al., ), decreased (Thoma et al., ), and equivalent glutamate levels among AD relative to non‐AD individuals (Bauer et al., ; Yeo et al., ). However, when independent cross‐sectional 1 H‐MRS investigations of glutamate in AD are sorted by time since participants' last drink, the literature as a whole supports that brain glutamate levels in individuals with AD are abnormally low during active drinking (e.g., <24 hours from last alcohol consumption; Ende et al., ), abnormally high during acute withdrawal (e.g., 48 to 72 hours from last alcohol consumption; Hermann et al., ), and abnormally low once again 1 week from last alcohol consumption (Mon et al., ). Additional research suggests that anterior cingulate cortex (ACC) glutamate levels may normalize approximately 2 to 5 weeks from last alcohol consumption (Hermann et al., ; Mon et al., ).…”

mentioning

confidence: 99%

Associations Between Recent Heavy Drinking and Dorsal Anterior CingulateN-Acetylaspartate and Glutamate Concentrations in Non-Treatment-Seeking Individuals with Alcohol Dependence

Prisciandaro

Schacht

Prescot

et al. 2016

Alcohol Clin Exp Res

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Background Proton magnetic resonance spectroscopy (1H-MRS) studies have consistently found abnormal brain concentrations of N-acetylaspartate (NAA) and glutamate in individuals with alcohol use disorders (AUD) relative to light drinkers. However, most such studies have focused on individuals in treatment for severe alcohol dependence and few studies have investigated associations between neurochemical concentrations and recent alcohol consumption. The present study focused on associations between recent drinking and prefrontal neurometabolite concentrations in non-severe, non-treatment seeking individuals with AUD. Methods Nineteen treatment naïve alcohol-dependent individuals aged 21–40 completed a 1H-MRS scan. Single-voxel 1H-MRS spectra were acquired in dorsal anterior cingulate (dACC) using a Two-dimensional J-resolved Point Resolved Spectroscopy (2D J-PRESS) sequence. Associations between recent heavy drinking, assessed using the Timeline FollowBack, and dACC metabolite concentrations were estimated via regression controlling for within-voxel tissue composition. Results Participants provided a negative breathalyzer reading and reported between 1 and 5 days (M = 2.45, SD = 1.23) since their last drink. Number of heavy drinking days in the 14 days preceding the scan (M = 4.84, SD = 3.32) was significantly inversely associated with both glutamate/water (β = −0.63, t(17) = −3.37, p = 0.004) and NAA/water concentrations (β = −0.59, t(17) = −2.98, p = 0.008). Conclusions The present study extends the literature by demonstrating inverse associations between recent heavy drinking and dACC glutamate and NAA concentrations in a sample of non-severe, non-treatment seeking individuals with AD. These findings may support the hypothesis that amount of recent alcohol consumption may account for differences in neuronal metabolism, even in non-severe, non-treatment seeking alcoholics.

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Loss of Control of Alcohol Use and Severity of Alcohol Dependence in Non‐Treatment‐Seeking Heavy Drinkers Are Related to Lower Glutamate in Frontal White Matter

Abstract: In contrast to the rather unspecific rise in choline-containing compounds, low Glu in frontal WM may be specific for the shift from nondependent heavy drinking to dependence and does not reflect a simple effect of the amount of alcohol consumption alone.

Cited by 46 publications

References 46 publications

Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders

Combining diffusion tensor imaging and magnetic resonance spectroscopy to study reduced frontal white matter integrity in youths with family histories of substance use disorders

Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity

Associations Between Recent Heavy Drinking and Dorsal Anterior CingulateN-Acetylaspartate and Glutamate Concentrations in Non-Treatment-Seeking Individuals with Alcohol Dependence

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