Dataset Information

Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence.

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, 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?

SUBMITTER: De Santis S

PROVIDER: S-EPMC6583663 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence.

De Santis Silvia S Bach Patrick P Pérez-Cervera Laura L Cosa-Linan Alejandro A Weil Georg G Vollstädt-Klein Sabine S Hermann Derik D Kiefer Falk F Kirsch Peter P Ciccocioppo Roberto R Sommer Wolfgang H WH Canals Santiago S

JAMA psychiatry 20190701 7

<h4>Importance</h4>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 anima ...[more]

PMID: 30942831

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Project description:BackgroundAlcohol dependence exacts a toll on brain white matter microstructure, which has the potential of repair with prolonged sobriety. Diffusion tensor imaging (DTI) enables in-vivo quantification of tissue constituents and localisation of tracts potentially affected in alcohol dependence and its recovery. We did an extended longitudinal study of alcoholism's trajectory of effect on selective fibre bundles with sustained sobriety or decline with relapse.MethodsParticipants were drawn from a longitudinal, 1·5T DTI database of 841 scans of individuals with various medical or neuropsychiatric conditions and normal ageing. Participants diagnosed with alcohol dependence had to meet the criteria from DSM-IV for alcohol dependence. Controls were screened and free of any DSM-IV axis I diagnosis, including being without history of alcohol or drug abuse or dependence. Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcohol-dependent individuals and 56 controls examined 2-5 times over 1-8 year intervals. We identified regions showing group differences with a white matter atlas. For macrostructural comparison, we measured corpus callosum and centrum semiovale volumes on MRI.FindingsThis study took place in the USA, between June 23, 2000, and Sept 6, 2011. TBSS identified a large cluster (threshold p<0·001), where controls showed significant fractional anisotropy (FA) decrease with ageing and alcohol-dependent individuals had significantly lower FA than controls regardless of age. Over the examination interval, 27 (57%) alcohol-dependent individuals abstained, ten (21%) relapsed into light drinking, and ten (21%) relapsed into heavy drinking (>5 kg of alcohol/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcohol-dependent group; however, the abstainers' slopes paralleled those of controls, whereas the heavy-drinking relapsers' slopes showed accelerated ageing. Callosal genu and body microstructure but not macrostructure showed untoward alcohol-related effects. Affected projection and association tracts had an anterior and superior neuroanatomical distribution.InterpretationReturn to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcohol-dependent individuals maintaining sobriety over extended periods showed improvement in brain fibre tract integrity reflective of fibre reorganisation and myelin restoration, indicative of a neural mechanism explaining recovery.FundingUS National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA).

Project description:BackgroundNeuroimage literature of autism spectrum disorder (ASD) has a moderate-to-high risk of bias, partially because those combined with intellectual impairment (II) and/or minimally verbal (MV) status are generally ignored. We aimed to provide more comprehensive insights into white matter alterations of ASD, inclusive of individuals with II (ASD-II-Only) or MV expression (ASD-MV).MethodsSixty-five participants with ASD (ASD-Whole; 16.6 ± 5.9 years; comprising 34 intellectually able youth, ASD-IA, and 31 intellectually impaired youth, ASD-II, including 24 ASD-II-Only plus 7 ASD-MV) and 38 demographic-matched typically developing controls (TDC; 17.3 ± 5.6 years) were scanned in accelerated diffusion-weighted MRI. Fixel-based analysis was undertaken to investigate the categorical differences in fiber density (FD), fiber cross section (FC), and a combined index (FDC), and brain symptom/cognition associations.ResultsASD-Whole had reduced FD in the anterior and posterior corpus callosum and left cerebellum Crus I, and smaller FDC in right cerebellum Crus II, compared to TDC. ASD-IA, relative to TDC, had no significant discrepancies, while ASD-II showed almost identical alterations to those from ASD-Whole vs. TDC. ASD-II-Only had greater FD/FDC in the isthmus splenium of callosum than ASD-MV. Autistic severity negatively correlated with FC in right Crus I. Nonverbal full-scale IQ positively correlated with FC/FDC in cerebellum VI. FD/FDC of the right dorsolateral prefrontal cortex showed a diagnosis-by-executive function interaction.LimitationsWe could not preclude the potential effects of age and sex from the ASD cohort, although statistical tests suggested that these factors were not influential. Our results could be confounded by variable psychiatric comorbidities and psychotropic medication uses in our ASD participants recruited from outpatient clinics, which is nevertheless closer to a real-world presentation of ASD. The outcomes related to ASD-MV were considered preliminaries due to the small sample size within this subgroup. Finally, our study design did not include intellectual impairment-only participants without ASD to disentangle the mixture of autistic and intellectual symptoms.ConclusionsASD-associated white matter alterations appear driven by individuals with II and potentially further by MV. Results suggest that changes in the corpus callosum and cerebellum are key for psychopathology and cognition associated with ASD. Our work highlights an essential to include understudied subpopulations on the spectrum in research.

Dataset Information

Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence.

Publications

Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence.

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