HomeAbout the InstituteResearch UnitsPeopleLinksPh.D ProgramEnglish Language Idioma EspañolWeb SearchIntranet Access
 
 
Research highlights
Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence.

De Santis S, Bach P, Pérez-Cervera L, Cosa-Linan A, Weil G, Vollstädt-Klein S, Hermann D, Kiefer F, Kirsch P, Ciccocioppo R, Sommer WH, Canals S.

JAMA Psychiatry
Published: 2019 Apr 3


Press Release CSIC (spanish)

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, and Participants:
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 and Measures:
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 less .01] corrected in humans and Cohen d=-1.17 [P less .001] corrected in rats) and the fornix/fimbria (fractional anisotropy Cohen d=-0.92 [P less .001] corrected in humans and d=-1.24 [P less .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.


From left to right: Laura Pérez-Cervera, Santiago Canals, Silvia De Santis.

Research Highlights Archive

CSIC-UMH
 
 
Consejo Superior de Investigaciones Científicas
Universidad Miguel Hernández

Campus de San Juan | Sant Joan d’Alacant
Alicante | España

in@umh.es
direccion.in@umh.es
Tel. + 34 965 23 37 00
Fax + 34 965 91 95 61
© 2004-2016 Instituto de Neurociencias
Alicante | España | Legal Note | Mapa Web
Diseño web Digital Nature