Clock genes × stress × reward interactions in alcohol and substance use disorders.
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ABSTRACT:
SUBMITTER: Perreau-Lenz S
PROVIDER: S-EPMC4457607 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
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Project description:Substance dependence constitutes a profound societal burden. Although large numbers of individuals use licit or illicit substances, few transition to dependence. The specific factors influencing this transition are not well understood. Substance-dependent individuals tend to be swayed by the immediate rewards of drug taking, but are often insensitive to delayed negative consequences of their behavior. Dependence is consequently associated with impulsivity for reward and atypical learning from feedback. Behavioral impulsivity is indexed using tasks measuring spontaneous decision-making and capacity to control impulses. While evidence indicates drug taking exacerbates behavioral impulsivity for reward, animal and human studies of drug naïve populations demonstrate it might precede any drug-related problems. Research suggests dependent individuals are also more likely to learn from rewarding (relative to punishing) feedback. This may partly explain why substance-dependent individuals fail to modify their behavior in response to negative outcomes. This enhanced learning from reward may constitute a further pre-existing risk factor for substance dependence. Although impulsivity for reward and preferential learning from rewarding feedback are both underpinned by a compromised dopaminergic system, few studies have examined the relationship between these two mechanisms. The interplay of these processes may help enrich understanding of why some individuals transition to substance dependence.
| S-EPMC7657456 | biostudies-literature
Project description:BackgroundSocial norms regarding substance use predict substance use behaviors. In a sample of jailed women with alcohol use disorders (AUDs), we compared (i) jailed women's perceptions of the US women population's rates of substance use, with US women's actual rates of substance use; (ii) jailed women's perceived rates of substance use by US women, with their perceptions of use by their own friends; and (iii) US women's actual rates of substance use, with observed sample substance use rates.MethodsParticipants were 205 jailed women who met criteria for an AUD. We used the 1-sample or dependent-samples t-test to make the comparisons.ResultsParticipants overestimated US women's rates of substance use and incarceration rates. They perceived their friends' substance use as less common than US women's. The jailed women reported higher rates of their own substance use than actual rates by US women. In addition, jailed women self-reported less cannabis use, but more alcohol and cocaine use and cigarette smoking, than they perceived their friends to have used. The more women perceived their friends as drinking, the less they had a goal to drink less or abstain from drinking postincarceration; in contrast, perceptions of US women's drinking were not related to personal goals for drinking.ConclusionsInterventions that correct misperceptions about substance use norms may have utility for jailed women with AUDs.
| S-EPMC7722182 | biostudies-literature
Project description:Treatments for substance use and stress disorders are based on ameliorating behavioral symptoms, not on reversing the synaptic pathology that has the potential to cure disorders. This failing arises in part from a research focus on how pre- and postsynaptic physiology is changed even though key neuropathology exists in the perisynaptic neuropil that homeostatically regulates synaptic transmission. We explore recent findings from the substance use and stress disorder literature pointing to a key role for perisynaptic astroglia and signaling in the extracellular matrix (ECM) in regulating synaptic pathology. We conclude that drugs and stress initiate long-lasting changes in brain synapses via enduring neuroadaptations in astroglia and the ECM, and that modulating extrasynaptic regulators may be therapeutically useful.
| S-EPMC8688303 | biostudies-literature
Project description:BACKGROUND:Depression and alcohol abuse or dependence (AUD) co-occur in the general population more frequently than expected by chance. Alcohol use influences the circadian rhythms generated by the central pacemaker in the suprachiasmatic nucleus, and circadian rhythm alterations in turn are common in depressive disorders as well as among persons addicted to alcohol. METHODS:32 SNPs in 19 circadian clockwork related genes were analyzed using DNA from 76 individuals with comorbid depression and AUD, 446 individuals with AUD and 517 healthy controls with no psychiatric diagnosis. The individuals participated in a nationwide health examination study, representative of the general population aged 30 and over in Finland. RESULTS:The CLOCK haplotype TTGC formed by SNPs rs3805151, rs2412648, rs11240 and rs2412646, was associated with increased risk for comorbidity (OR = 1.65, 95% CI = 1.14-2.28, P = 0.0077). The SNPs of importance for this suggestive association were rs2412646 and rs11240 indicating location of the functional variation in the block downstream rs2412648. There was no indication for association between CLOCK and AUD. CONCLUSION:Our findings suggest an association between the CLOCK gene and the comorbid condition of alcohol use and depressive disorders. Together with previous reports it indicates that the CLOCK variations we found here may be a vulnerability factor to depression given the exposure to alcohol in individuals having AUD.
| S-EPMC2854106 | biostudies-literature
Project description:ObjectiveThe authors qualitatively examined how lesbian, gay, bisexual, transgender, and queer (LGBTQ) young adults with probable substance use disorders conceptualized their substance use vis-à-vis their LGBTQ identities.MethodsIndividual, in-depth, semistructured interviews were conducted with 59 LGBTQ young adults (ages 21-34) who were participants in a larger longitudinal cohort study and who met criteria for a probable substance use disorder. Data were analyzed via iterative, thematic analytic processes.ResultsParticipants' narratives highlighted processes related to minority stress that shape substance use, including proximal LGBTQ stressors (e.g., self-stigma and expectations of rejection) and distal LGBTQ stressors (e.g., interpersonal and structural discrimination) and associated coping. Participants also described sociocultural influences, including the ubiquitous availability of substances within LGBTQ social settings, as salient contributors to their substance use and development of substance use disorders. Participants who considered themselves transgender or other gender minorities, all of whom identified as sexual minorities, described unique stressors and coping at the intersection of their minority identities (e.g., coping with two identity development and disclosure periods), which shaped their substance use over time.ConclusionsMultilevel minority stressors and associated coping via substance use in adolescence and young adulthood, coupled with LGBTQ-specific sociocultural influences, contribute to the development of substance use disorders among some LGBTQ young adults. Treatment providers should address clients' substance use vis-à-vis their LGBTQ identities and experiences with related stressors and sociocultural contexts and adopt culturally humble and LGBTQ-affirming treatment approaches. Efforts to support LGBTQ youths and young adults should focus on identifying ways of socializing outside of substance-saturated environments.
| S-EPMC7002176 | biostudies-literature
Project description:OBJECTIVE:Bipolar disorder and substance use disorder frequently co-occur. However, little is known about the near-term effects of substance use on bipolar disorder. Thus, the present study tests whether alcohol use precipitates depression among patients with co-occurring bipolar disorder and substance use disorder. METHOD:This study uses data collected as part of 2 clinical trials (the first study was conducted from March 1999 through March 2004 and the second study was conducted from August 2003 through May 2007) of a manualized group therapy for patients with co-occurring bipolar disorder and substance dependence. One hundred fifteen participants were assessed at baseline and each month through month 8. Baseline diagnoses were made using the Structured Clinical Interview for DSM-IV, and monthly substance use and mood data were collected using the Longitudinal Interval Follow-Up Evaluation and the Addiction Severity Index. Generalized estimating equation methodology was used to analyze these longitudinal data. RESULTS:Our primary hypotheses were supported: days of alcohol use and an increase in days of alcohol use each significantly predicted the presence of a depressive episode in the subsequent month when controlling for current depression and current drug use. CONCLUSION:These data suggest that alcohol use in patients with bipolar disorder and substance dependence increases the risk of a depressive episode in the near term. TRIAL REGISTRATION:This study draws on data generated during 2 clinical trials. One was exempt from trial registration; clinicaltrials.gov Identifier for other trial: NCT00227838.
| S-EPMC2713748 | biostudies-literature
Project description:While there is broad recognition of the high societal costs of substance use disorders (SUD), treatment rates are low. We examined whether, in the United States, participants with substance or alcohol use disorder would report a greater willingness to enter SUD treatment located in a primary care setting (primary care) or more commonly found specialty care setting in the United States (usual care).Randomized survey-embedded experiment.US web-based research panel in which participants were randomized to read one-paragraph vignettes describing treatment in usual care (specialty drug or alcohol treatment center), primary care or collaborative care within a primary care setting.A total of 42 451 panelists aged 18+ were screened for substance or alcohol use disorder using validated diagnostic criteria. Participants included 344 with a substance use disorder and 634 with an alcohol use disorder not in treatment with no prior treatment history.Willingness to enter treatment across vignettes by condition.Among participants with a substance use disorder, 24.6% of those randomized to usual care reported being willing to enter drug treatment compared with 37.2% for primary care [12.6 percentage point difference; 95% confidence interval (CI) = 0.8, 24.4) and 34.0% for collaborative care (9.4 percentage point difference; 95% CI = -2.0, 20.8). Among participants with an alcohol use disorder, 17.6% of those randomized to usual care reported being willing to enter alcohol treatment compared with 20.3% for primary care (2.6 percentage point difference; 95% CI = -4.9, 10.1) and 20.8% for collaborative care (3.1 percentage point difference; 95% CI = -4.3, 10.6). The most common reason for not being willing to enter drug (63%) and alcohol (78%) treatment was the belief that treatment was not needed.In the United States, people diagnosed with substance or alcohol use disorders appear to be more willing to enter treatment in a primary care setting than in a specialty drug treatment center. Expanding availability of primary care-based substance use disorder treatment could increase treatment rates in the United States.
| S-EPMC4940268 | biostudies-literature
Project description:Impulsive delayed reward discounting (DRD) is an important behavioral process in alcohol use disorders (AUDs), reflecting incapacity to delay gratification. Recent work in neuroeconomics has begun to unravel the neural mechanisms supporting DRD, but applications of neuroeconomics in relation to AUDs have been limited. This study examined the neural mechanisms of DRD preferences in AUDs, with emphasis on dissociating activation patterns based on DRD choice type and level of cognitive conflict. Heavy drinking adult men with (n?=?13) and without (n?=?12) a diagnosis of an AUD completed a monetary DRD task during a functional magnetic resonance imaging scan. Participant responses were coded based on choice type (impulsive versus restrained) and level of cognitive conflict (easy versus hard). AUD+ participants exhibited significantly more impulsive DRD decision-making. Significant activation during DRD was found in several decision-making regions, including dorsolateral prefrontal cortex (DLPFC), insula, posterior parietal cortex (PPC), and posterior cingulate. An axis of cognitive conflict was also observed, with hard choices associated with anterior cingulate cortex and easy choices associated with activation in supplementary motor area. AUD+ individuals exhibited significant hyperactivity in regions associated with cognitive control (DLPFC) and prospective thought (PPC) and exhibited less task-related deactivation of areas associated with the brain's default network during DRD decisions. This study provides further clarification of the brain systems supporting DRD in general and in relation to AUDs.
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Project description:Bipolar spectrum disorders (BSDs) and substance use disorders (SUDs) are associated with neural reward dysfunction. However, it is unclear what pattern of neural reward function underlies pre-existing vulnerability to BSDs and SUDs, or whether neural reward function explains their high co-occurrence. The current paper provides an overview of the separate literatures on neural reward sensitivity in BSDs and SUDs. We provide a systematic review of 35 studies relevant to identifying neural reward function vulnerability to BSDs and SUDs. These studies include those examining neural reward processing on a monetary reward task with prospective designs predicting initial onset of SUDs, familial risk studies that examine unaffected offspring or first-degree relatives of family members with BSDs or SUDs, and studies that examine individuals with BSDs or SUDs who are not currently in an episode of the disorder. Findings from the review highlight that aberrant responding and connectivity across neural regions associated with reward and cognitive control confers risk for the development of BSDs and SUDs. Discussion focuses on limitations of the extant literature. We conclude with an integration and theoretical model for understanding how aberrant neural reward responding may constitute a vulnerability to the development of both BSDs and SUDs.
| S-EPMC8206019 | biostudies-literature
Project description:Stress is a major driving force in alcohol use disorders (AUDs). It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual's brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc) following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs) play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.
| S-EPMC4588139 | biostudies-literature