Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence.
JAMA Psychiatry
; 76(7): 749-758, 2019 07 01.
Article
in En
| MEDLINE
| ID: mdl-30942831
ABSTRACT
Importance Although the detrimental effects of alcohol on the brain are widely acknowledged, observed structural changes are highly heterogeneous, and diagnostic markers for characterizing alcohol-induced brain damage, especially in early abstinence, are lacking. This heterogeneity, likely contributed to by comorbidity factors in patients with alcohol use disorder (AUD), challenges a direct link of brain alterations to the pathophysiology of alcohol misuse. Translational studies in animal models may help bridge this causal gap. Objective:
To compare microstructural properties extracted using advanced diffusion tensor imaging (DTI) in the brains of patients with AUD and a well-controlled rat model of excessive alcohol consumption and monitor the progression of these properties during early abstinence. Design, Setting, andParticipants:
This prospective observational study included 2 cohorts of hospitalized patients with AUD (n = 91) and Marchigian Sardinian alcohol-preferring (msP) rats (n = 27). In humans cross-sectional comparison were performed with control participants (healthy men [n = 36]) and longitudinal comparisons between different points after alcohol withdrawal. In rats, longitudinal comparisons were performed in alcohol-exposed (n = 27) and alcohol-naive msP rats (n = 9). Human data were collected from March 7, 2013, to August 3, 2016, and analyzed from June 14, 2017, to May 31, 2018; rat data were collected from January 15, 2017, to May 12, 2017, and analyzed from October 11, 2017, to May 28, 2018. Main Outcomes andMeasures:
Fractional anisotropy and other DTI measures of white matter properties after long-term alcohol exposure and during early abstinence in both species and clinical and demographic variables and time of abstinence after discharge from hospital in patients.Results:
The analysis included 91 men with AUD (mean [SD] age, 46.1 [9.6] years) and 27 male rats in the AUD groups and 36 male controls (mean [SD] age, 41.7 [9.3] years) and 9 male control rats. Comparable DTI alterations were found between alcohol and control groups in both species, with a preferential involvement of the corpus callosum (fractional anisotropy Cohen d = -0.84 [P < .01] corrected in humans and Cohen d = -1.17 [P < .001] corrected in rats) and the fornix/fimbria (fractional anisotropy Cohen d = -0.92 [P < .001] corrected in humans and d = -1.24 [P < .001] corrected in rats). Changes in DTI were associated with preadmission consumption patterns in patients and progress in humans and rats during 6 weeks of abstinence. Mathematical modeling shows this process to be compatible with a sustained demyelination and/or a glial reaction. Conclusions and Relevance Using a translational DTI approach, comparable white matter alterations were found in patients with AUD and rats with long-term alcohol consumption. In humans and rats, a progression of DTI alterations into early abstinence (2-6 weeks) suggests an underlying process that evolves soon after cessation of alcohol use.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
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Alcohol Drinking
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Alcoholism
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Alcohol Abstinence
/
White Matter
Type of study:
Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adult
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Animals
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Humans
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Male
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Middle aged
Language:
En
Journal:
JAMA Psychiatry
Year:
2019
Document type:
Article
Affiliation country: