Dataset Information

Neurofunctional Domains Derived From Deep Behavioral Phenotyping in Alcohol Use Disorder.

ABSTRACT: OBJECTIVE:The authors evaluated whether three neurofunctional domains proposed to be critical in the addiction cycle, namely, incentive salience, negative emotionality, and executive function, could be identified through factor analysis of a deeply phenotyped clinical sample. METHODS:Clinical, behavioral, and self-report measures of addiction, personality, cognition, behavior, and exposure to early-life stress were collected as part of a screening and natural history study of alcohol use disorders in 454 individuals representing the spectrum of alcohol use and use disorders. The multiple indicators, multiple causes (MIMIC) approach was used to identify significant predictors of the latent factors identified by the analysis. RESULTS:The results showed significant support for both three- and four-factor models to explain biobehavioral variation in this sample of participants with alcohol use disorder and control subjects, but the three-factor model had the best fit indices. With some nuances, including cross-correlation (lack of independence) between the three factors, the factors corresponded to incentive salience, negative emotionality, and executive function (executive control). The MIMIC model revealed that both exposure to early-life stress and sociodemographic variables predicted these factors. CONCLUSIONS:These findings suggest that three correlated neurofunctional domains are relevant for alcohol use disorder. More work is required to validate and standardize measures of neurofunctional domains in alcohol use disorder, to extend these findings to other addictive disorders, and to relate variations in them to predisposition, clinical course, treatment response, neuroimaging data, and other psychophysical indicators.

SUBMITTER: Kwako LE

PROVIDER: S-EPMC6609498 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Neurofunctional Domains Derived From Deep Behavioral Phenotyping in Alcohol Use Disorder.

Kwako Laura E LE Schwandt Melanie L ML Ramchandani Vijay A VA Diazgranados Nancy N Koob George F GF Volkow Nora D ND Blanco Carlos C Goldman David D

The American journal of psychiatry 20190104 9

<h4>Objective</h4>The authors evaluated whether three neurofunctional domains proposed to be critical in the addiction cycle, namely, incentive salience, negative emotionality, and executive function, could be identified through factor analysis of a deeply phenotyped clinical sample.<h4>Methods</h4>Clinical, behavioral, and self-report measures of addiction, personality, cognition, behavior, and exposure to early-life stress were collected as part of a screening and natural history study of alco ...[more]

PMID: 30606047

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Project description:RATIONALE:Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity. OBJECTIVES:In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task. METHODS:Out of 69 adult study participants, we included n?=?49 in our final analyses: Individuals had a diagnosis of either AUD (n?=?13), ADHD (n?=?14) or both (n?=?5), or were healthy controls (HC; n?=?17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. RESULTS:The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. CONCLUSIONS:Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Project description:This review summarizes the proceedings of a symposium presented at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference held in Volterra, Italy on May 9-12, 2017. Psychiatric diseases, including alcohol-use disorders (AUDs), are influenced through complex interactions of genes, neurobiological pathways, and environmental influences. A better understanding of the common neurobiological mechanisms underlying an AUD necessitates an integrative approach, involving a systematic assessment of diverse species and phenotype measures. As part of the World Congress on Stress and Alcoholism, this symposium provided a detailed account of current strategies to identify mechanisms underlying the development and progression of AUDs. Dr. Sean Farris discussed the integration and organization of transcriptome and postmortem human brain data to identify brain regional- and cell type-specific differences related to excessive alcohol consumption that are conserved across species. Dr. Brien Riley presented the results of a genome-wide association study of DSM-IV alcohol dependence; although replication of genetic associations with alcohol phenotypes in humans remains challenging, model organism studies show that COL6A3, KLF12, and RYR3 affect behavioral responses to ethanol, and provide substantial evidence for their role in human alcohol-related traits. Dr. Rob Williams expanded upon the systematic characterization of extensive genetic-genomic resources for quantifying and clarifying phenotypes across species that are relevant to precision medicine in human disease. The symposium concluded with Dr. Robert Hitzemann's description of transcriptome studies in a mouse model selectively bred for high alcohol ("binge-like") consumption and a non-human primate model of long-term alcohol consumption. Together, the different components of this session provided an overview of systems-based approaches that are pioneering the experimental prioritization and validation of novel genes and gene networks linked with a range of behavioral phenotypes associated with stress and AUDs.

Dataset Information

Neurofunctional Domains Derived From Deep Behavioral Phenotyping in Alcohol Use Disorder.

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Neurofunctional Domains Derived From Deep Behavioral Phenotyping in Alcohol Use Disorder.

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