Persistence Of Alcohol Use Disorders Research Articles

Ethanol-Induced Suppression of G Protein–Gated Inwardly Rectifying K+–Dependent Signaling in the Basal Amygdala

BackgroundThe basolateral amygdala (BLA) regulates mood and associative learning and has been linked to the development and persistence of alcohol use disorder. The GABABR (gamma-aminobutyric acid B receptor) is a promising therapeutic target for alcohol use disorder, and previous work suggests that exposure to ethanol and other drugs can alter neuronal GABABR-dependent signaling. The effect of ethanol on GABABR-dependent signaling in the BLA is unknown. MethodsGABABR-dependent signaling in the mouse BLA was examined using slice electrophysiology following repeated ethanol exposure. Neuron-specific viral genetic manipulations were then used to understand the relevance of ethanol-induced neuroadaptations in the basal amygdala subregion (BA) to mood-related behavior. ResultsThe somatodendritic inhibitory effect of GABABR activation on principal neurons in the basal but not the lateral subregion of the BLA was diminished following ethanol exposure. This adaptation was attributable to the suppression of GIRK (G protein–gated inwardly rectifying K+) channel activity and was mirrored by a redistribution of GABABR and GIRK channels from the surface membrane to internal sites. While GIRK1 and GIRK2 subunits are critical for GIRK channel formation in BA principal neurons, GIRK3 is necessary for the ethanol-induced neuroadaptation. Viral suppression of GIRK channel activity in BA principal neurons from ethanol-naïve mice recapitulated some mood-related behaviors observed in C57BL/6J mice during ethanol withdrawal. ConclusionsThe ethanol-induced suppression of GIRK-dependent signaling in BA principal neurons contributes to some of the mood-related behaviors associated with ethanol withdrawal in mice. Approaches designed to prevent this neuroadaptation and/or strengthen GIRK-dependent signaling may prove useful for the treatment of alcohol use disorder.

Chronic intermittent ethanol promotes ventral subiculum hyperexcitability via increases in extrinsic basolateral amygdala input and local network activity

The hippocampus, particularly its ventral domain, can promote negative affective states (i.e. stress and anxiety) that play an integral role in the development and persistence of alcohol use disorder (AUD). The ventral hippocampus (vHC) receives strong excitatory input from the basolateral amygdala (BLA) and the BLA-vHC projection bidirectionally modulates anxiety-like behaviors. However, no studies have examined the effects of chronic alcohol on the BLA-vHC circuit. In the present study, we used ex vivo electrophysiology in conjunction with optogenetic approaches to examine the effects of chronic intermittent ethanol exposure (CIE), a well-established rodent model of AUD, on the BLA-vHC projection and putative intrinsic vHC synaptic plasticity. We discovered prominent BLA innervation in the subicular region of the vHC (vSub). CIE led to an overall increase in the excitatory/inhibitory balance, an increase in AMPA/NMDA ratios but no change in paired-pulse ratios, consistent with a postsynaptic increase in excitability in the BLA-vSub circuit. CIE treatment also led to an increase in intrinsic network excitability in the vSub. Overall, our findings suggest a hyperexcitable state in BLA-vSub specific inputs as well as intrinsic inputs to vSub pyramidal neurons which may contribute to the negative affective behaviors associated with CIE.

Getting to the Heart of Low Sensitivity to Alcohol: Context Moderates Low Cardiovascular Response to Alcohol in Persons With a Family History of Alcohol Use Disorder.

BackgroundLow sensitivity to alcohol in persons with a family history of alcoholism (FH+), compared to those without (FH−), contributes to risk for alcohol use disorder (AUD). However, sensitivity of FH+ cardiovascular response to alcohol is not well understood. This gap is significant because cardiovascular processes contribute to emotional regulation and stress response problems theorized to be central to the development and persistence of AUD. This study compared changes in heart rate (HR) and HR variability (HRV) between FH groups after consuming alcohol and control beverages and examined how these changes were moderated by emotional and alcohol‐related contexts.MethodsYoung adults (N = 165) with FH+ (n = 110) or FH− (n = 55) each completed 2 sessions, separated by 1 week. They received one of 3 different beverages (alcohol, placebo, and told‐no‐alcohol) in each session. Electrocardiogram data were recorded during pre–beverage consumption and post–beverage consumption baselines, and then during 4 picture cue tasks (neutral, positive, negative, and alcohol‐related). Generalized estimating equations were used to examine differences in cardiovascular reactivity (changes in HR and HRV power at ~ 0.1 Hz) across FH groups, beverage conditions, and picture cue tasks.ResultsA significant beverage condition × cue task × FH interaction effect on HRV was observed. The FH+ group, compared to the FH− group, showed (a) significantly less HRV suppression in specific cue contexts following alcohol, (b) a mixed pattern of more and less HRV suppression across cue contexts following placebo, and (c) a similar HRV reactivity pattern in the told‐no‐alcohol condition across cue tasks. For HR, there were no significant effects involving FH.ConclusionsDiminished cardiovascular sensitivity to oral alcohol in FH+ persons varied within a given drinking episode depending on emotional and alcohol‐related features of the context, suggesting that environmental characteristics play a role in the expression of low sensitivity to alcohol among FH+ individuals.

The onset and progression of alcohol use disorders: A qualitative study from Goa, India

ABSTRACTQuantitative evidence about the burden of alcohol use disorders (AUDs) needs to be complemented with a nuanced qualitative understanding of explanatory models to help supplement public health strategies that are too often steeped uncritically in biomedical models. The aim of this study was to identify the role of various factors in the onset and persistence of AUD and recovery from AUD. This was a qualitative study nested in a population cohort from Goa, India. In-depth interviews of men with incident, recovered, and persistent AUD covered topics such as changes in drinking habits over time, perceptions and experiences about starting/stopping drinking, and so on. Data were analyzed using thematic analysis. Reasons to begin drinking included social drinking, functional use of alcohol, stress, and boredom. Progression to problematic drinking patterns was characterized by drinking alone, alternating between abstinent and heavy drinking periods, and drinking based on the availability of finances. Some enablers to reduce/stop drinking included consequences of drinking lifestyle and personal resolve; some barriers included availability of alcohol at social events and stress. Some reasons for persisting heavy use of alcohol included lack of family support, physical withdrawal symptoms, peer pressure, stress, and easy availability. This article offers a strong conceptualization and nuanced understanding of AUD across a spectrum of developmental courses. This adds to the limited literature on explanatory models of AUD in India and identifies potential targets for prevention and treatment strategies for AUD in low- and middle-income country settings.

Is cannabis use associated with an increased risk of onset and persistence of alcohol use disorders? A three-year prospective study among adults in the United States

In this chapter the basic approach toward optimum design problems is outlined. The general formulation of any optimum design problem has three steps, such as identification of the objective function, the constraints, and the design variables. The various possibilities in all these three steps are illustrated through a number of examples, ranging from water heating/cooling systems to integrated energy system for a village. Often only some of the components of a system are to be optimized and the designs of the rest of the components have to be kept unaltered. Additional constraints to be incorporated in such optimization problems are brought out through a few examples.

Is cannabis use associated with an increased risk of onset and persistence of alcohol use disorders? A three-year prospective study among adults in the United States

BackgroundThe relationship between cannabis use and alcohol use disorders (AUDs) over time remains unclear. The current study used longitudinal data from adults in the United States (U.S.) to investigate the association between cannabis use and risk of onset and persistence of AUDs three years later. MethodsThe study used data from respondents who completed both waves of the National Epidemiological Study of Alcohol Use and Related Disorders (NESARC; Wave 1, 2001–2001; Wave 2, 2004–2005) and for whom the age of first cannabis use preceded the age of any AUD. Incident AUDs were examined among respondents with no lifetime AUD diagnosis at Wave 1 (n=27,461). Persistent AUDs were examined among respondents with a lifetime AUD diagnosis at Wave 1 (n=2,121). ResultsAmong adults with no history of AUD, cannabis use at Wave 1 was associated with increased incidence of an AUD three years later relative to no cannabis use (Odds Ratio (OR)=5.43; 95% Confidence Interval (CI)=4.54–6.49). Among adults with a history of AUD, cannabis use at Wave 1 was associated with increased likelihood of AUD persistence three years later relative to no cannabis use (OR=1.74; 95% CI=1.56–1.95). These relationships remained significant after controlling for demographics, psychiatric disorders, and other substance use disorders. ConclusionsCannabis use is associated with increased risk of AUD onset and persistence over the course of three years among U.S. adults. Community-based and clinical programs aimed at preventing or treating problematic alcohol use may benefit from integrating information about cannabis use in order to improve outcomes.

Introduction to special section: ADHD, impulsivity, and alcohol abuse.

The goal of this special section is to highlight progress made and primary research reports on the relation between Attention Deficit Hyperactivity Disorder (ADHD), impulsivity, and alcohol use disorders (AUDs) utilizing a diverse range of methods. The four papers examine various psychological processes underlying the broad construct of impulsivity that are related largely to impairments in inhibitory control. The section addresses the influences of reward sensitivity, working memory/attention control, and social functioning in the development and persistence of AUDs among individuals with ADHD. These papers are important because they approach the relation between ADHD and AUDs, and the role of impulsivity, from varied perspectives.

Commentary on Tuithofet al. (2013): Implications of the DSM-5 revision for the analysis of persistence/remission of alcohol use disorder

The findings of Tuithof et al. [1] are consistent with studies of the course of DSM-IV [2] alcohol use disorder (AUD) in the general population, demonstrating that many episodes of AUD are of limited duration and many individuals who have experienced remission of AUD symptoms drink at levels that may increase the risk of relapse [3–7]. A prospective study based on just two data points is of limited utility for yielding valid inferences about a dynamic process such as persistence/remission of AUD, in that at least three data points are necessary to chart the chronic relapsing pattern that characterizes a substantial proportion of individuals with lifetime AUD in long-term prospective studies [8–11]. In fact, retrospective data, despite limitations related to recall error and selective survival, may actually tell us more about the recovery process than prospective data with single follow-up [3]. Despite the inherent limitations of its study design, this study nonetheless raises some interesting questions about how the persistence of AUD is related to remission, how has this changed under the DSM-5 and what new research opportunities may arise out of these changes. Under the DSM-IV, individuals who meet the criteria for alcohol dependence at t1 but do not satisfy the requirements for persistent dependence or full remission (cessation of all AUD symptoms) at t2 fall into the category of partial remission, comprising alcohol abuse and/or subclinical dependence symptoms. Individuals who do not satisfy the requirements for persistent abuse include both those who have progressed to dependence and those in full remission. Thus, the absence of persistence does not necessarily signify full remission. Retrospective studies of US population samples have shown that partial remission of dependence is common, peaking in prevalence at ≈40% 5–9 years after onset of dependence [4]. Individuals in partial remission drink more and have a lower quality of life than those in full remission, but drink less and have a higher quality of life than those with persistent dependence [12,13]. Because individuals in partial remission are distinct from those with persistent or fully remitted AUD, a clearer picture of the significance of factors associated with the course of DSM-IV AUD could be obtained by excluding partial remission cases from analyses or including them as a separate outcome category in multinomial models. The proposed DSM-5 revision [14] does not recognize partial remission as a course specifier for AUD [15]. Among individuals with AUD (2+ positive criteria) at t1, those with subclinical levels of AUD symptoms at t2 count as fully remitted, along with those who are asymptomatic. In addition, the newly added criterion of craving, which may persist even after discontinuation of drinking, does not preclude achievement of remission. Thus, full remission and persistent AUD are more complementary under the DSM-5 than they were under the DSM-IV; i.e., there are no longer any cases that fall between these categories. However, regardless of whether partial remission is formally recognized or subsumed under full remission, the residual presence of cases with a subclinical level of symptoms reduces the contrast between persistent and asymptomatic cases. Thus, challenges remain with dichotomous outcome measures when modeling correlates of remission or persistence. However, the DSM-5 definition of AUD as a unitary latent construct whose symptoms vary along a continuum of severity suggests new approaches to the study of persistence/remission that may overcome some of the limitations of a dichotomous outcome measure. One such approach is to examine correlates of increase/decrease in AUD severity, and to see whether a change of a given magnitude has different correlates depending on the base level of severity. That is, does a drop from 8 to 5 positive criteria between t1 and t2 have the same correlates as a drop from 4 to 1? Similarly, does the impact of a given decrease in severity on changes in consumption and quality of live vary based on initial severity level? Results of such an approach would at least be suggestive of factors that differentially affect the early versus later stages of recovery, and they would clearly distinguish factors associated with remission of AUD of varying severity levels. The addition of craving as a criterion for DSM-5 AUD also suggests new opportunities for analyses. Unlike most AUD criteria, which reflect or result from but do not cause heavy drinking, craving can reinforce excessive consumption, which may in turn lead to the persistence of other AUD symptoms. By studying the unique contribution of craving to the course of AUD, i.e., its impact net of the number of other AUD criteria, we may be able to draw valuable inferences related to the benefits of medical treatment for the alleviation of craving. In summary, the proposed DSM-5 criteria for AUD should facilitate multiple new analytic approaches that will enhance our understanding of factors associated with the course of AUD and implications for treatment.