Dataset Information

Effects of an opioid (proenkephalin) polymorphism on neural response to errors in health and cocaine use disorder.

ABSTRACT: Chronic exposure to drugs of abuse perturbs the endogenous opioid system, which plays a critical role in the development and maintenance of addictive disorders. Opioid genetics may therefore play an important modulatory role in the expression of substance use disorders, but these genes have not been extensively characterized, especially in humans. In the current imaging genetics study, we investigated a single nucleotide polymorphism (SNP) of the protein-coding proenkephalin gene (PENK: rs2609997, recently shown to be associated with cannabis dependence) in 55 individuals with cocaine use disorder and 37 healthy controls. Analyses tested for PENK associations with fMRI response to error (during a classical color-word Stroop task) and gray matter volume (voxel-based morphometry) as a function of Diagnosis (cocaine, control). Results revealed whole-brain Diagnosis×PENK interactions on the neural response to errors (fMRI error>correct contrast) in the right putamen, left rostral anterior cingulate cortex/medial orbitofrontal cortex, and right inferior frontal gyrus; there was also a significant Diagnosis×PENK interaction on right inferior frontal gyrus gray matter volume. These interactions were driven by differences between individuals with cocaine use disorders and controls that were accentuated in individuals carrying the higher-risk PENK C-allele. Taken together, the PENK polymorphism-and potentially opioid neurotransmission more generally-modulates functioning and structural integrity of brain regions previously implicated in error-related processing. PENK could potentially render a subgroup of individuals with cocaine use disorder (i.e., C-allele carriers) more sensitive to mistakes or other related challenges; in future studies, these results could contribute to the development of individualized genetics-informed treatments.

SUBMITTER: Moeller SJ

PROVIDER: S-EPMC4567394 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of an opioid (proenkephalin) polymorphism on neural response to errors in health and cocaine use disorder.

Moeller Scott J SJ Beebe-Wang Nicasia N Schneider Kristin E KE Konova Anna B AB Parvaz Muhammad A MA Alia-Klein Nelly N Hurd Yasmin L YL Goldstein Rita Z RZ

Behavioural brain research 20150708

Chronic exposure to drugs of abuse perturbs the endogenous opioid system, which plays a critical role in the development and maintenance of addictive disorders. Opioid genetics may therefore play an important modulatory role in the expression of substance use disorders, but these genes have not been extensively characterized, especially in humans. In the current imaging genetics study, we investigated a single nucleotide polymorphism (SNP) of the protein-coding proenkephalin gene (PENK: rs260999 ...[more]

PMID: 26164485

Similar Datasets

Project description:BackgroundIn substance-dependent individuals, drug deprivation and drug use trigger divergent behavioral responses to environmental cues. These divergent responses are consonant with data showing that short- and long-term adaptations in dopamine signaling are similarly sensitive to state of drug use. The literature suggests a drug state-dependent role of learning in maintaining substance use; evidence linking dopamine to both reinforcement learning and addiction provides a framework to test this possibility.MethodsIn a randomized crossover design, 22 participants with current cocaine use disorder completed a probabilistic loss-learning task during functional magnetic resonance imaging while on and off cocaine (44 sessions). Another 54 participants without Axis I psychopathology served as a secondary reference group. Within-drug state and paired-subjects' learning effects were assessed with computational model-derived individual learning parameters. Model-based neuroimaging analyses evaluated effects of drug use state on neural learning signals. Relationships among model-derived behavioral learning rates (α+, α-), neural prediction error signals (δ+, δ-), cocaine use, and desire to use were assessed.ResultsDuring cocaine deprivation, cocaine-dependent individuals exhibited heightened positive learning rates (α+), heightened neural positive prediction error (δ+) responses, and heightened association of α+ with neural δ+ responses. The deprivation-enhanced neural learning signals were specific to successful loss avoidance, comparable to participants without psychiatric conditions, and mediated a relationship between chronicity of drug use and desire to use cocaine.ConclusionsNeurocomputational learning signals are sensitive to drug use status and suggest that heightened reinforcement by successful avoidance of negative outcomes may contribute to drug seeking during deprivation. More generally, attention to drug use state is important for delineating substrates of addiction.

Project description:Opioid use disorder is a major public health crisis. While effective treatments are available, outcomes vary widely across individuals and relapse rates remain high. Understanding neural mechanisms of treatment response may facilitate the development of personalized and/or novel treatment approaches. Methadone-maintained, polysubstance-using individuals (n = 53) participated in fMRI scanning before and after substance-use treatment. Connectome-based predictive modeling (CPM)-a recently developed, whole-brain approach-was used to identify pretreatment connections associated with abstinence during the 3-month treatment. Follow-up analyses were conducted to determine the specificity of the identified opioid abstinence network across different brain states (cognitive vs. reward task vs. resting-state) and different substance use outcomes (opioid vs. cocaine abstinence). Posttreatment fMRI data were used to assess network changes over time and within-subject replication. To determine further clinical relevance, opioid abstinence network strength was compared with healthy subjects (n = 38). CPM identified an opioid abstinence network (p = 0.018), characterized by stronger within-network motor/sensory connectivity, and reduced connectivity between the motor/sensory network and medial frontal, default mode, and frontoparietal networks. This opioid abstinence network was anatomically distinct from a previously identified cocaine abstinence network. Relationships between abstinence and opioid and cocaine abstinence networks replicated across multiple brain states but did not generalize across substances. Network connectivity measured at posttreatment related to abstinence at 6-month follow-up (p < 0.009). Healthy comparison subjects displayed intermediate network strengths relative to treatment responders and nonresponders. These data indicate dissociable anatomical substrates of opioid vs. cocaine abstinence. Results may inform the development of novel opioid-specific treatment approaches to combat the opioid epidemic.

Project description:ImportanceOpioid-stimulant co-use is a common problem with few evidence-based treatments.ObjectiveTo examine bupropion slow release (SR) enhancement of a tailored abstinence incentive program for stimulant use in persons with opioid use disorder.Design, setting, and participantsThis 26-week, double-blind, placebo-controlled randomized clinical trial with a 4-week follow-up period was conducted at 4 methadone treatment programs in Baltimore, Maryland. Included participants were persons receiving methadone for the treatment of opioid use disorder with past 3-month cocaine use and current cocaine use disorder between March 2015 and September 2019. Data were analyzed from November 2020 through August 2022.InterventionsA 6-week incentive induction period with monetary incentives for evidence of cocaine abstinence during thrice-weekly urine testing was conducted. Persons achieving 2 weeks of consecutive abstinence during induction were assigned to the relapse prevention group (20 individuals); otherwise, individuals were assigned to the abstinence initiation group (60 individuals). Participants were randomized within incentive groups to bupropion SR (150 mg oral twice daily; 40 participants) or placebo (40 participants). Incentives were available until week 26, and study medication ended week 30.Main outcomes and measuresThe mean percentage of participants with cocaine abstinence (by negative urinalysis or self-report) during weeks 7 to 26 (ie, the incentive intervention period) and 27 to 30 (ie, the follow-up period) and the percentage of participants testing negative for cocaine at weeks 26 and 30 were assessed. Main effects of medication collapsed across incentive conditions and sensitivity analyses of medications within incentive conditions were assessed. Analyses were conducted in the modified intention-to-treat sample (ie, 80 individuals who received ≥1 dose of study medication) and completers (ie, 52 individuals who completed ≥1 visit during week 30).ResultsAmong 80 participants (42 Black [52.5% ] and 35 White [43.8%]; mean [SD] age, 45.7 (9.4) years; 52 males [65.0%]) receiving methadone for opioid use disorder, 40 participants were randomized to receive bupropion SR and 40 participants to receive placebo. No significant difference on urinalysis or self-reported cocaine use was observed between medication groups. Sensitivity analyses revealed differential patterns for incentive subgroups. Participants in the relapse prevention group had high abstinence (>80%; eg, during weeks 7-26 in the modified intention-to-treat analysis, 410 of 456 samples [89.9%] from participants in the bupropion SR group tested negative for cocaine) throughout the trial regardless of whether they were randomized to bupropion SR or placebo. Participants in the abstinence initiation group had better outcomes with bupropion SR than placebo throughout the trial (mean [SD] total number of samples testing negative for cocaine, 30.3 [21.6] samples for bupropion SR vs 17.1 [14.9] samples for placebo; P = .05) and more participants receiving bupropion SR than placebo were abstinent at the end of the study (20 of 30 participants [66.7%] vs 9 of 30 participants [30.0%]; P = .04).Conclusions and relevanceIn this randomized clinical trial, an overall benefit for bupropion SR vs placebo when combined with a financial abstinence incentive program was not observed. Results among incentive subgroups suggest that continued evaluation of medications, including bupropion SR, for stimulant treatment using a tailored approach that factors early abstinence into study design and interpretation may be needed.Trial registrationClinicalTrials.gov Identifier: NCT02111798.

Dataset Information

Effects of an opioid (proenkephalin) polymorphism on neural response to errors in health and cocaine use disorder.

Publications

Effects of an opioid (proenkephalin) polymorphism on neural response to errors in health and cocaine use disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets