Brain tract structure predicts relapse to stimulant drug use.
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ABSTRACT:
SUBMITTER: Tisdall L
PROVIDER: S-EPMC9245633 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Brain tract structure predicts relapse to stimulant drug use.
Tisdall Loreen L MacNiven Kelly H KH Padula Claudia B CB Leong Josiah K JK Knutson Brian B
Proceedings of the National Academy of Sciences of the United States of America 20220621 26
Diffusion tractography allows identification and measurement of structural tracts in the human brain previously associated with motivated behavior in animal models. Recent findings indicate that the structural properties of a tract connecting the midbrain to nucleus accumbens (NAcc) are associated with a diagnosis of stimulant use disorder (SUD), but not relapse. In this preregistered study, we used diffusion tractography in a sample of patients treated for SUD (<i>n</i> = 60) to determine wheth ...[more]
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Project description:BackgroundPatients with stimulant use disorder experience high rates of relapse. While neurobehavioral mechanisms involved in initiating drug use have been studied extensively, less research has focused on relapse.MethodsTo assess motivational processes involved in relapse and diagnosis, we acquired functional magnetic resonance imaging responses to nondrug (monetary) gains and losses in detoxified patients with stimulant use disorder (n = 68) and community control participants (n = 42). In a prospective multimodal design, we combined imaging of brain function, brain structure, and behavior to longitudinally track subsequent risk for relapse.ResultsAt the 6-month follow-up assessment, 27 patients remained abstinent, but 33 had relapsed. Patients with blunted anterior insula (AIns) activity during loss anticipation were more likely to relapse, an association that remained robust after controlling for potential confounds (i.e., craving, negative mood, years of use, age, and gender). Lower AIns activity during loss anticipation was associated with lower self-reported negative arousal to loss cues and slower behavioral responses to avoid losses, which also independently predicted relapse. Furthermore, AIns activity during loss anticipation was associated with the structural coherence of a tract connecting the AIns and the nucleus accumbens, as was functional connectivity between the AIns and nucleus accumbens during loss processing. However, these neurobehavioral responses did not differ between patients and control participants.ConclusionsTaken together, the results of the current study show that neurobehavioral markers predicted relapse above and beyond conventional self-report measures, with a cross-validated accuracy of 72.7%. These findings offer convergent multimodal evidence that implicates blunted avoidance motivation in relapse to stimulant use and may therefore guide interventions targeting individuals who are most vulnerable to relapse.
| S-EPMC10840879 | biostudies-literature
Project description:ImportanceAlthough chronic relapse is a characteristic of addiction to stimulants, conventional measures (eg, clinical, demographic, and self-report) do not robustly identify which individuals are most vulnerable to relapse.ObjectivesTo test whether drug cues are associated with increased mesolimbic neural activity in patients undergoing treatment for stimulant use disorder and whether this activity is associated with risk for subsequent relapse.Design, setting, and participantsThis prospective cohort study of 76 participants included a control group for baseline group comparisons. Veteran patients (n = 36) with stimulant use disorders were recruited from a 28-day residential treatment program at the Veterans Affairs Palo Alto Health Care System. Healthy controls (n = 40) were recruited from the surrounding community. Baseline data were collected between September 21, 2015, and January 26, 2018, from patients and healthy controls using functional magnetic resonance imaging during a performance of a reward cue task. Patients' stimulant use was subsequently assessed after treatment discharge (at approximately 1, 3, and 6 months) to assess relapse outcomes.Main outcomes and measuresPrimary measures included neural responses to drug and food cues in estimated mesolimbic volumes of interest, including the medial prefrontal cortex, nucleus accumbens (NAcc), and ventral tegmental area. The primary outcome variable was relapse (defined as any stimulant use), assessed both dichotomously (3 months after discharge) and continuously (days to relapse). Brain activity measures were contrasted between groups to validate neural measures of drug cue reactivity, which were then used to estimate relapse outcomes of patients.ResultsRelative to controls (n = 40; 16 women and 24 men; mean [SD] age, 32.0 [11.6] years), patients (n = 36; 2 women and 34 men; mean [SD] age, 43.4 [13.3] years) showed increased mesolimbic activity in response to drug cues (medial prefrontal cortex, t74 = 2.90, P = .005, Cohen d = 0.66; NAcc, t74 = 2.39, P = .02, Cohen d = 0.54; and ventral tegmental area, t74 = 4.04, P < .001, Cohen d = 0.92). In patients, increased drug cue response in the NAcc (but not other volumes of interest) was associated with time to relapse months later (Cox proportional hazards regression hazard ratio, 2.30; 95% CI, 1.40-3.79). After controlling for age, NAcc response to drug cues classified relapsers (12 patients; 1 woman and 11 men; mean [SD] age, 49.3 [14.1] years) and abstainers (21 patients; 1 woman and 20 men; mean [SD] age, 39.3 [12.3] years) at 3 months with 75.8% classification accuracy. Model comparison further indicated that NAcc responses to drug cues were associated with relapse above and beyond estimations of relapse according to conventional measures.Conclusions and relevanceResponses in the NAcc to stimulant cues appear to be associated with relapse in humans. Identification of neural markers may eventually help target interventions to the most vulnerable individuals.
| S-EPMC6324538 | biostudies-literature
Project description:Error-monitoring abnormalities in stimulant-dependent individuals (SDIs) may be due to reduced awareness of committed errors, or to reduced sensitivity upon such awareness. The distinction between these alternatives remains largely undifferentiated, but may have substantial clinical relevance. We sought to better characterize the nature, and clinical relevance, of SDIs' error-monitoring processes by comparing carefully isolated neural responses during the presentation of negative feedback to a) stimulant dependence status and b) lifetime stimulant use. Forty-eight SDIs and twenty-three non-SDIs performed an fMRI-based time-estimation task specifically designed to isolate neural responses associated with the presentation (versus expectation) of contingent negative feedback. SDIs showed reduced dACC response compared to non-SDIs following the presentation of negative feedback, but only when error expectancies were controlled. Moreover, lifetime stimulant use correlated negatively with magnitude of expectancy-controlled dACC attenuation. While this finding was minimized after controlling for age, these results suggest that SDIs may be characterized by a core reduction in neural activity following error feedback, in the context of intact feedback expectancies. Correlations with lifetime stimulant use suggest that this neural attenuation may hold clinical significance.
| S-EPMC6034587 | biostudies-literature
Project description:BackgroundDecision-making processes have been posited to affect treatment outcome in addicted patients.ObjectiveThe present multi-site study assessed whether two measures of decision-making predicted relapse and subsequent use in stimulant-dependent patients.MethodsA total of 160 methamphetamine- or cocaine-dependent patients participating in a multi-site clinical trial evaluating a modified 12-step facilitation intervention for stimulant-dependent patients (STAGE-12) were assessed. Decision-making processes of risk and delay (Iowa Gambling Task [IGT]) and response reversal (Wisconsin Card Sorting Task [WCST]) were obtained shortly after treatment admission followed by assessment of stimulant use over the next six months. The relationships of the IGT and WCST (Perseverative Errors) with relapse (yes/no) and days of stimulant use during the 6-month period following post-randomization were evaluated.ResultsPerformance on the IGT and WCST did not significantly predict relapse status or time to relapse. Unexpectedly, worse performance on the IGT was associated with a fewer number of stimulant use days (p = 0.001). In contrast, worse performance on the WCST (more perseverative errors) was associated with a greater number of stimulant use days (p = 0.0003). The predictive effects of perseverative errors on subsequent use were confined to methamphetamine-dependent and Minority participants.ConclusionsDecision-making processes, as measured in the current study, do not uniformly predict relapse or subsequent use. A decrease in the salience attribution of non-drug reinforcers may explain the positive relationship between IGT performance and post-relapse use. More comprehensive and global measures of impulsiveness may better assess relapse risk and use.
| S-EPMC4817850 | biostudies-literature
Project description:BackgroundStimulant drugs such as cocaine and amphetamine have a high abuse liability, but not everyone who uses them develops dependence. However, the risk for dependence is increased for individuals with a family history of addiction. We hypothesized that individuals without a family history of dependence who have been using cocaine recreationally for several years but have not made the transition to dependence will differ in terms of personality traits and brain structure from individuals who are either dependent on stimulants or at risk for dependence.MethodsWe compared 27 individuals without a familial risk of dependence who had been using cocaine recreationally with 50 adults with stimulant dependence, their nondependent siblings (n = 50), and unrelated healthy volunteers (n = 52) who had neither a personal nor a family history of dependence. All participants underwent a magnetic resonance imaging brain scan and completed a selection of personality measures that have been associated with substance abuse.ResultsIncreased sensation-seeking traits and abnormal orbitofrontal and parahippocampal volume were shared by individuals who were dependent on stimulant drugs or used cocaine recreationally. By contrast, increased levels of impulsive and compulsive personality traits and limbic-striatal enlargement were shared by stimulant-dependent individuals and their unaffected siblings.ConclusionsWe provide evidence for distinct neurobiological phenotypes that are either associated with familial vulnerability for dependence or with regular stimulant drug use. Our findings further suggest that some individuals with high sensation-seeking traits but no familial vulnerability for dependence are likely to use cocaine but may have relatively low risk for developing dependence.
| S-EPMC3705207 | biostudies-literature
Project description:BackgroundWhile the mandate to check patients' prescription history in Prescription Drug Monitoring Program (PDMP) database before prescribing/dispensing controlled drugs has been shown to be an important tool to curb opioid abuse, less is known about whether the mandate can reduce the misuse of other commonly abused prescription drugs. We examined whether PDMP use mandates were associated with changes in prescription stimulant and depressant quantities.MethodsUsing data from Automated Reports and Consolidate Ordering System (ARCOS), we employed difference-in-differences design to estimate the association between PDMP use mandates and prescription stimulant and depressant quantities in 50 U.S. states and the District of Columbia from 2006 to 2020. Limited PDMP use mandate was specific only to opioids or benzodiazepines. Expansive PDMP use mandate was non-specific to opioid or benzodiazepine and required prescribers/dispensers to check PDMP when prescribing/dispensing targeted controlled substances in Schedule II-V. The main outcomes were population-adjusted prescription stimulant (amphetamine, methylphenidate, lisdexamfetamine) and depressant (amobarbital, butalbital, pentobarbital, secobarbital) quantities in grams.ResultsThere was no evidence that limited PDMP use mandate was associated with a reduction in the prescription stimulant and depressant quantities. However, expansive PDMP use mandate that was non-specific to opioid or benzodiazepine and required prescribers/dispensers to check PDMP when prescribing/dispensing targeted controlled substances in Schedule II-V was associated with 6.2% (95% CI: -10.06%, -2.08%) decline in prescription amphetamine quantity.ConclusionExpansive PDMP use mandate was associated with a decline in prescription amphetamine quantity. Limited PDMP use mandate did not appear to change prescription stimulant and depressant quantities.
| S-EPMC10334646 | biostudies-literature
Project description:Chronic drug use negatively impacts ageing, resulting in diminished health and quality of life. However, little is known about biomarkers of abnormal ageing in stimulant drug users. Using morphometric similarity network mapping, a novel approach to structural connectomics, we first mapped cross-sectional morphometric similarity trajectories of ageing in the publicly available Rockland Sample (20-80 years of age, n = 665). We then compared morphometric similarity and neuropsychological function between non-treatment-seeking, actively using patients with stimulant use disorder (n = 183, mean age: 35.6 years) and healthy control participants (n = 148, mean age: 36.0 years). The significantly altered mean regional morphometric similarity was found in 43 cortical regions including the inferior and orbital frontal gyri, pre/postcentral gyri and anterior temporal, superior parietal and occipital areas. Deviations from normative morphometric similarity trajectories in patients with stimulant use disorder suggested abnormal brain ageing. Furthermore, deficits in paired associates learning were consistent with neuropathology associated with both ageing and stimulant use disorder. Morphometric similarity mapping provides a promising biomarker for ageing in health and disease and may complement existing neuropsychological markers of age-related cognitive decline. Neuropathological ageing mechanisms in stimulant use disorder warrant further investigation to develop more age-appropriate treatments for older people addicted to stimulant drugs.
| S-EPMC9178962 | biostudies-literature
Project description:BackgroundEvaluating the risk of relapse is a pivotal step in the treatment of patients with methamphetamine use disorder (MUD). The 30-item Stimulant Relapse Risk Scale (SRRS) was originally developed in Japan to meet the demand. This study examined the reliability, validity, and factor structure of the Chinese version of the SRRS for patients with MUD.Methods247 patients with MUD self-rated the Chinese version of the SRRS. Cronbach's alpha coefficients and inter-item correlation analysis were used to assess the internal consistency reliability. Construct validity was determined through confirmatory factor analysis (CFA), and concurrent validity was examined using the visual analogue scale (VAS) for drug craving and the severity of dependence scale (SDS). We followed the participants for 1 year and assessed the predictive validity based on the correlation of the scores of the Chinese version of the SRRS with the relapse rate within 3, 6, and 12 months of follow-up.ResultsCFA revealed satisfactory model fit estimates for the 22-item Chinese version of the SRRS that consisted of four subscales. The four-factored 22-item Chinese version of the SRRS had adequate internal consistency with Cronbach's alphas ranging from 0.76 to 0.92. The 22-item Chinese version of the SRRS scores were significantly correlated with the VAS and SDS scores as well as the relapse rate within 3, 6, and 12 months, indicating good concurrent and predictive validity of this scale. The receiver operating characteristic curve revealed a cutoff score of 40 could discriminate between participants with (SDS score ≥ 4) and without (SDS score < 4) methamphetamine dependence (area under the curve = 0.71, p < 0.01).ConclusionsThe 22-item Chinese version of the SRRS that consists of four subscales is a valid and reliable instrument to assess the relapse risk in patients with MUD.
| S-EPMC11232344 | biostudies-literature
Project description:PurposeThe aim of this study was to assess the impact of pre-injury stimulant use (amphetamine, cocaine, methamphetamine and/or ecstasy) on outcomes after isolated severe traumatic brain injury (TBI).MethodsRetrospective 2017 TQIP study, including adult trauma patients (≥16 years old) who underwent drug and alcohol screening on admission and sustained an isolated severe TBI (head AIS ≥3). Patients with significant extracranial trauma (AIS ≥3) were excluded. Epidemiological and clinical characteristics, procedures and outcome variables were collected. Patients with isolated stimulant use were matched 1:1 for age, gender, mechanism of injury, head AIS and overall comorbidities, with patients with negative toxicology and alcohol screen. Outcomes in the two groups were compared with univariable and multivariable regression analysis.Results681 patients with isolated TBI and stimulant use were matched with 681 patients with negative toxicology and alcohol screen. The incidence of hypotension and CGS <9 was similar in the two groups. In multivariable regression analysis, stimulant use was not independently associated with mortality (OR 0.95, 95% CI 0.61-1.49). However, stimulant use was associated with longer hospital length of stay (HLOS) (RC 1.13, 95%CI 1.03-1.24).ConclusionPre-injury stimulant use is common in patients admitted for severe TBI, but was not independently associated with mortality when compared to patients with negative toxicology. However, stimulant use was associated with a significant longer HLOS.
| S-EPMC9446589 | biostudies-literature
Project description:BackgroundPatients with stimulant use disorder (SUD) show impairments when making value-based choices that are associated with disruptions in neural processing across brain networks. Making optimal choices requires learning from outcomes to update knowledge and further optimise ongoing behaviour. The optimal functioning of neural systems that underpin the ability to make favourable choices is an essential component for life functioning, and successful recovery in patients with SUD. Therefore, we sought to investigate the neural processes that underpin value-based choices in SUD patients. We hypothesise that patients with SUD have reduced functional connectivity while making financial choices during a probabilistic reinforcement learning task.MethodsWe investigated connectivity associated with loss and reward value-based choices and their outcomes in patients with SUD and healthy control participants during a pharmacological magnetic resonance imaging study. Participants received a single dose of a dopamine receptor agonist, pramipexole, and a dopamine receptor antagonist, amisulpride, in a randomised, double-blind, placebo-controlled, balanced, crossover design. Functional task-related connectivity was analysed taking a whole brain connectomics approach to identify networks that are differentially modulated by dopaminergic receptor functioning.ResultsSUD patients showed widespread reductions in connectivity during both reward and loss value-based choices and outcomes, which were negatively correlated with the duration of stimulant drug use. Disturbances to functional brain connectivity in SUD patients during task performance were not modulated acutely by either amisulpride or pramipexole.ConclusionsReductions in brain connectivity, particularly when making value-based choices and processing outcomes, may underlie learning impairments in SUD patients. Given that acute dopaminergic modulation did not improve brain connectivity impairments in SUD patients, it is likely that alternative treatments are needed.
| S-EPMC11474215 | biostudies-literature