Dataset Information

Causal Network Modeling of the Determinants of Drinking Behavior in Comorbid Alcohol Use and Anxiety Disorder.

ABSTRACT: BACKGROUND:Anxiety and depression disorders (internalizing psychopathology) occur in approximately 50% of patients with alcohol use disorder (AUD) and mark a 2-fold increase in the rate of relapse in the months following treatment. In a previous study using network modeling, we found that perceived stress and drinking to cope (DTC) with negative affect were central to maintaining network associations between internalizing psychopathology INTP and drinking in comorbid individuals. Here, we extend this approach to a causal framework. METHODS:Measures of INTP, drinking urges/behavior, abstinence self-efficacy, and DTC were obtained from 362 adult AUD treatment patients who had a co-occurring anxiety disorder. Data were analyzed using a machine-learning algorithm ("Greedy Fast Causal Inference"[ GFCI]) that infers paths of causal influence while identifying potential influences associated with unmeasured ("latent") variables. RESULTS:DTC with negative affect served as a central hub for 2 distinct causal paths leading to drinking behavior, (i) a direct syndromic pathway originating with social anxiety and (ii) an indirect stress pathway originating with perceived stress. CONCLUSIONS:Findings expand the field's knowledge of the paths of influence that lead from internalizing disorder to drinking in AUD as shown by the first application in psychopathology of a powerful network analysis algorithm (GFCI) to model these causal relationships.

SUBMITTER: Anker JJ

PROVIDER: S-EPMC6318065 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Causal Network Modeling of the Determinants of Drinking Behavior in Comorbid Alcohol Use and Anxiety Disorder.

Anker Justin J JJ Kummerfeld Erich E Rix Alexander A Burwell Scott J SJ Kushner Matt G MG

Alcoholism, clinical and experimental research 20181125 1

<h4>Background</h4>Anxiety and depression disorders (internalizing psychopathology) occur in approximately 50% of patients with alcohol use disorder (AUD) and mark a 2-fold increase in the rate of relapse in the months following treatment. In a previous study using network modeling, we found that perceived stress and drinking to cope (DTC) with negative affect were central to maintaining network associations between internalizing psychopathology INTP and drinking in comorbid individuals. Here, w ...[more]

PMID: 30371947

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Project description:Purpose: To determine whether previously observed behavioral differences in alcoholic human patients after fecal microbiota transplantation (FMT) could be transferred to mice. Methods: Fecal microbiota samples from a previously published phase 1, double-blind, randomized clinical trial of AUD-related cirrhosis patients were used to colonize germ-free mice. Fecal material was transferred to 10-15-week-old GF C57BL/6 male mice by daily gavage for 3 day. The mice were housed in sterile individually filtered cages for 15 days after which stool was collected and then they underwent the alcohol preference experiment using 2-bottle choice drinking (water and 20% ethanol v/v). Microbial DNA was isolated from stool samples by sequencing the V1 and V2 variable regions of the bacterial 16S rRNA gene were sequenced using Multitag fusion primers and sequenced on an Ion Torrent PGM next-generation sequencer. Intestinal mucosa, liver, and prefrontal cortex tissue was collected from mice at time of sacrifice. RNAseq was used to measure gene expression in pre-FMT and post-FMT samples. RNAseq data were aligned to the mouse genome (GRCm39) using STAR (version 2.7.9a) and counts were generated with HTSeq (version 0.13.5). Genes with very low counts across the study (defined as fewer than 10 counts in more than 2 samples) were eliminated before differential expression analysis. Low count genes were determined separately for each tissue type. The DESeq2 package for R was then used to measure differential expression between pre-FMT and post-FMT mice in the intestine, liver, and PFC. Benjamini and Hochberg False Discovery Rate (FDR) was used to correct for multiple testing with FDR ≤ 0.2 considered significant. Results: Mice colonized with post-FMT stool significantly reduced ethanol acceptance, intake and preference versus pre-FMT colonized mice. Microbial taxa that were higher in post-FMT humans were also associated with lower alcohol intake and preference in mice. RNAseq further showed that differential gene expression, post-FMT, occurred in the intestine rather than the liver and prefrontal cortex. Conclusions: FMT leads to significant change in gut microbiome population, which in turn alters gene expression in the intestine. FMT also significantly affects alcohol consumption. The microbiotal-intestinal interface may alter gut-liver-brain axis and reduce alcohol consumption in humans.

Dataset Information

Causal Network Modeling of the Determinants of Drinking Behavior in Comorbid Alcohol Use and Anxiety Disorder.

Publications

Causal Network Modeling of the Determinants of Drinking Behavior in Comorbid Alcohol Use and Anxiety Disorder.

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