Sleep as an Important Target or Modifier in Alcohol Use Disorder Clinical Treatment: Example From a Recent Gabapentin Randomized Clinical Trial.

Objectives: Alcohol consumption affects sleep both in healthy populations and in patients with alcohol use disorder (AUD). However, sleep has typically not been considered within AUD pharmacotherapy trials. We used data from a completed gabapentin clinical treatment trial to explore the medication's effect on patient-rated insomnia measured by a standard insomnia rating (Insomnia Severity Index [ISI]) and whether this influenced gabapentin's effects on alcohol consumption.

Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

Aims: Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems.

Methods: We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N = 346).

Predictors of symptom course in alcohol use disorder.

Background: Symptoms often play an important role in the scientific inquiry of psychological disorders and have been theorized to play a functional role in the disorders themselves. However, little is known about the course of specific symptoms and individual differences in course. Understanding the course of specific symptoms and factors influencing symptom course can inform psychological theory and future research on course and treatment.

Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone.

Alcohol Use Disorder (AUD) is characterized by loss of control over drinking. Behavioral control is mediated, in part, by cortical dopamine signaling. Inhibition of catechol-O-methyltransferase (COMT), the enzyme primarily responsible for cortical dopamine inactivation, may increase cortical dopamine, especially among individuals with genetically mediated lower dopaminergic tone, such as COMT rs4680 (val158met) val-allele homozygotes.

Cross-sectional and longitudinal AUD symptom networks: They tell different stories.

Modern theoretical models of Alcohol Use Disorder (AUD) highlight the different functional roles played by various mechanisms associated with different symptoms. Symptom network models (SNMs) offer one approach to modeling AUD symptomatology in a way that could reflect these processes and provide important information on the progression and persistence of disorder. However, much of the research conducted using SNMs relies on cross-sectional data, which has raised questions regarding the extent they reflect dynamic processes.

Epigenetic moderators of naltrexone efficacy in reducing heavy drinking in Alcohol Use Disorder: a randomized trial.

Polymorphisms in genes associated with opioid signaling and dopamine reuptake and inactivation may moderate naltrexone efficacy in Alcohol Use Disorder (AUD), but the effects of epigenetic modification of these genes on naltrexone response are largely unexplored. This study tested interactions between methylation in the μ-opioid receptor (OPRM1), dopamine transporter (SLC6A3), and catechol-O-methyltransferase (COMT) genes as predictors of naltrexone effects on heavy drinking in a 16-week randomized, placebo-controlled trial among 145 treatment-seeking AUD patients. OPRM1 methylation interacted with both SLC6A3 and COMT methylation to moderate naltrexone efficacy, such that naltrexone-treated individuals with lower methylation of the OPRM1 promoter and the SLC6A3 promoter (p = 0.

Effects of Gabapentin on Dorsal Anterior Cingulate Cortex GABA and Glutamate Levels and Their Associations With Abstinence in Alcohol Use Disorder: A Randomized Clinical Trial.

Objective: Although gabapentin has demonstrated efficacy in mitigating alcohol withdrawal symptoms and preventing relapse drinking in individuals with alcohol use disorder (AUD), the neurobiological mechanisms of action underlying these therapeutic effects remain unknown. The present study evaluated changes in GABA and glutamate levels in the dorsal anterior cingulate cortex (dACC) as candidate mechanisms of action.

Methods: In a 16-week randomized clinical trial, 68 adults with AUD, including a history of alcohol withdrawal syndrome, received 1,200 mg/day of gabapentin (N=37) or placebo (N=31) and nine medical management visits after ≥72 hours of abstinence.

Determining the optimal pulse number for theta burst induced change in cortical excitability.

Theta-burst stimulation (TBS) is a form of non-invasive neuromodulation which is delivered in an intermittent (iTBS) or continuous (cTBS) manner. Although 600 pulses is the most common dose, the goal of these experiments was to evaluate the effect of higher per-dose pulse numbers on cortical excitability. Sixty individuals were recruited for 2 experiments.

Opioid and Dopamine Genes Interact to Predict Naltrexone Response in a Randomized Alcohol Use Disorder Clinical Trial.

Background: While the opiate antagonist, naltrexone, is approved for treating alcohol use disorder (AUD), not everyone who receives the medication benefits from it. This study evaluated whether the OPRM1 SNP rs1799971 interacts with the dopamine transporter gene DAT1/SLC6A3 VNTR rs28363170 or the catechol-O-methyltransferase (COMT) gene SNP rs4680 in predicting naltrexone response.

Methods: Individuals who met DSM-IV alcohol dependence were randomly assigned to naltrexone (50 mg/d) or placebo based on their OPRM1 genotype (75 G-allele carriers and 77 A-allele homozygotes) and also genotyped for DAT1 VNTR (9 vs.

Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial.

Importance: Although an estimated 30 million people meet criteria for alcohol use disorder (AUD), few receive appropriate pharmacotherapy. A more personalized, symptom-specific, approach might improve efficacy and acceptance.

Objective: To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcohol withdrawal symptoms.

Systematic review and meta-analysis of the moderating effect of rs1799971 in OPRM1, the mu-opioid receptor gene, on response to naltrexone treatment of alcohol use disorder.

Background And Aims: There is wide inter-individual variability in response to the treatment of alcohol use disorder (AUD) with the opioid receptor antagonist naltrexone. To identify patients who may be most responsive to naltrexone treatment, studies have examined the moderating effect of rs1799971, a single nucleotide polymorphism (SNP) that encodes a non-synonymous substitution (Asn40Asp) in the mu-opioid receptor gene, OPRM1. The aims of this study were to: (1) conduct a systematic review of randomized clinical trials (RCTs); (2) assess the bias of the available studies and gauge publication bias; and (3) meta-analyze the interaction effect of the Asn40Asp SNP on the response to naltrexone treatment.

On Ising models and algorithms for the construction of symptom networks in psychopathological research.

During the past 5 to 10 years, an estimation method known as has been used extensively to produce symptom networks (or, more precisely, symptom dependence graphs) from binary data in psychopathological research. The method is based on a particular type of Ising model that corresponds to binary pairwise Markov random fields, and its popularity is due, in part, to an efficient estimation process that is based on a series of ₁-regularized logistic regressions. In this article, we offer an unprecedented critique of the Ising model and .

The Abused Inhalant Toluene Impairs Medial Prefrontal Cortex Activity and Risk/Reward Decision-Making during a Probabilistic Discounting Task.

Inhalant (e.g., toluene) misuse is linked to behavioral and cognitive deficits in humans, yet preclinical studies of the effect of inhalants on higher-order cognition are limited.

The influence of sample selection on the structure of psychopathology symptom networks: An example with alcohol use disorder.

Increasingly, the structure of mental disorders has been studied in the form of a network, characterizing how symptoms or criteria interact with and influence each other. Many studies of psychiatric symptoms and diagnostic criteria employ community or population-based surveys using co-occurrence of the symptoms/criteria to form the networks. However, given the overall low prevalence rates of mental disorders and their symptoms in the general population, most of those surveyed may not exhibit or endorse any symptoms and yet are often included in network analyses.

Criteria Definitions and Network Relations: The Importance of Criterion Thresholds.

Across various structured diagnostic instruments, the criteria used to diagnose alcohol use disorder (AUD) are not assessed consistently. For example, different instruments often pose questions that reflect different thresholds of the underlying symptoms. We consider the criteria for and to demonstrate the influence of using different thresholds for a positive symptom endorsement with respect to the estimated edges of a symptom network.

Cortical substrates of cue-reactivity in multiple substance dependent populations: transdiagnostic relevance of the medial prefrontal cortex.

Elevated drug-cue elicited brain activity is one of the most widely cited, transdiagnostically relevant traits of substance dependent populations. These populations, however, are typically studied in isolation. The goal of this study was to prospectively investigate the spatial topography of drug-cue reactivity in a large set of individuals dependent on either cocaine, alcohol, or nicotine.

Estimating transdiagnostic symptom networks: The problem of "skip outs" in diagnostic interviews.

Network models of the symptoms of psychological disorders provide a novel lens for examining comorbidity. Viewing symptoms as causal entities in their own right, researchers can attempt to identify specific symptoms that "bridge" diagnostic entities, providing a more granular perspective on comorbidity than the one provided by analysis at the syndromal level. Such analyses could help identify transdiagnostic targets for both research and clinical interventions.

Identification and validation of midbrain Kcnq4 regulation of heavy alcohol consumption in rodents.

Currently available pharmacotherapies for treating alcohol use disorder (AUD) suffer from deleterious side effects and are not efficacious in diverse populations. Clinical and preclinical studies provide evidence that the Kcnq family of genes that encode K7 channels influence alcohol intake and dependence. K7 channels are a class of slowly activating voltage-dependent K channels that regulate neuronal excitability.

Author Correction: Gray and white matter integrity influence TMS signal propagation: a multimodal evaluation in cocaine-dependent individuals.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Gray and white matter integrity influence TMS signal propagation: a multimodal evaluation in cocaine-dependent individuals.

Transcranial magnetic stimulation (TMS) can stimulate cortical and subcortical brain regions. However, in order to reach subcortical targets, intact monosynaptic connections are required. The goal of this investigation was to evaluate the contribution of white matter integrity and gray matter volume to frontal pole TMS-evoked striatal activity in a large cohort of chronic cocaine users.

Nicotine-Use/Smoking Is Associated with the Efficacy of Naltrexone in the Treatment of Alcohol Dependence.

Background: The opioid antagonist naltrexone is not efficacious for every alcohol treatment seeker. However, various individual factors, such as genetic differences and nicotine-use/smoking status, have been suggested as predictors of naltrexone response. In a randomized clinical trial, we previously reported that nicotine-use/smoking status might be a stronger predictor of naltrexone efficacy than OPRM1 A118G single nucleotide polymorphism (SNP) genotype.

Detecting Clusters/Communities in Social Networks.

Cohen's κ, a similarity measure for categorical data, has since been applied to problems in the data mining field such as cluster analysis and network link prediction. In this paper, a new application is examined: community detection in networks. A new algorithm is proposed that uses Cohen's κ as a similarity measure for each pair of nodes; subsequently, the κ values are then clustered to detect the communities.

A method for making inferences in network analysis: Comment on Forbes, Wright, Markon, and Krueger (2017).

Forbes, Wright, Markon, and Krueger (2017) make a compelling case for proceeding cautiously with respect to the overinterpretation and dissemination of results using the increasingly popular approach of creating "networks" from co-occurrences of psychopathology symptoms. We commend the authors on their initial investigation and their utilization of cross-validation techniques in an effort to capture the stability of a variety of network estimation methods. Such techniques get at the heart of establishing "reproducibility," an increasing focus of concern in both psychology (e.