Selected Investigator Publications

@article{FAROKHNIA2021108835,

title = {A population-based investigation of the association between alcohol intake and serum total ghrelin concentrations among cigarette-smoking, non-alcohol-dependent male individuals},

author = {Mehdi Farokhnia and Gwen Murphy and Stephanie J. Weinstein and Navan N. Shah and Dominick Parisi and Demetrius Albanes and Lorenzo Leggio},

url = {https://pubmed.ncbi.nlm.nih.gov/34214881/},

doi = {https://doi.org/10.1016/j.drugalcdep.2021.108835},

issn = {0376-8716},

year  = {2021},

date = {2021-06-24},

urldate = {2021-06-24},

journal = {Drug and Alcohol Dependence},

volume = {226},

pages = {108835},

abstract = {Background 

Ghrelin plays significant roles in regulating appetite, food intake, and metabolism. Furthermore, the ghrelin system is increasingly being studied in relation to alcohol seeking behaviors. To this end, it is important to understand the possible effects of alcohol intake on the ghrelin system. The aim of the present study was to investigate the association between alcohol drinking and circulating ghrelin levels in a large sample of cigarette-smoking, non-alcohol-dependent male individuals. 

Methods We utilized data from two nested case-control studies (study A},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{https://doi.org/10.1111/adb.13033,

title = {A closer look at alcohol-induced changes in the ghrelin system: novel insights from preclinical and clinical data},

author = {Sara L. Deschaine and Mehdi Farokhnia and Adriana Gregory-Flores and Lia J. Zallar and Zhi-Bing You and Hui Sun and Deon M. Harvey and Renata C. N. Marchette and Brendan J. Tunstall and Bharath K. Mani and Jacob E. Moose and Mary R. Lee and Eliot Gardner and Fatemeh Akhlaghi and Marisa Roberto and James L. Hougland and Jeffrey M. Zigman and George F. Koob and Leandro F. Vendruscolo and Lorenzo Leggio},

url = {https://pubmed.ncbi.nlm.nih.gov/33908131/},

doi = {https://doi.org/10.1111/adb.13033},

year  = {2021},

date = {2021-04-07},

urldate = {2021-04-07},

journal = {Addiction Biology},

volume = {n/a},

number = {n/a},

pages = {e13033},

abstract = {Abstract Ghrelin is a gastric-derived peptide hormone with demonstrated impact on alcohol intake and craving, but the reverse side of this bidirectional link, that is, the effects of alcohol on the ghrelin system, remains to be fully established. To further characterize this relationship, we examined (1) ghrelin levels via secondary analysis of human laboratory alcohol administration experiments with heavy-drinking participants; (2) expression of ghrelin, ghrelin receptor, and ghrelin-O-acyltransferase (GOAT) genes (GHRL, GHSR, and MBOAT4, respectively) in post-mortem brain tissue from individuals with alcohol use disorder (AUD) versus controls; (3) ghrelin levels in Ghsr knockout and wild-type rats following intraperitoneal (i.p.) alcohol administration; (4) effect of alcohol on ghrelin secretion from gastric mucosa cells ex vivo and GOAT enzymatic activity in vitro; and (5) ghrelin levels in rats following i.p. alcohol administration versus a calorically equivalent non-alcoholic sucrose solution. Acyl- and total-ghrelin levels decreased following acute alcohol administration in humans, but AUD was not associated with changes in central expression of ghrelin system genes in post-mortem tissue. In rats, alcohol decreased acyl-ghrelin, but not des-acyl-ghrelin, in both Ghsr knockout and wild-type rats. No dose-dependent effects of alcohol were observed on acyl-ghrelin secretion from gastric mucosa cells or on GOAT acylation activity. Lastly, alcohol and sucrose produced distinct effects on ghrelin in rats despite equivalent caloric value. Our findings suggest that alcohol acutely decreases peripheral ghrelin concentrations in vivo, but not in proportion to alcohol's caloric value or through direct interaction with ghrelin-secreting gastric mucosal cells, the ghrelin receptor, or the GOAT enzyme.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{FAULKNER2021108638,

title = {A neuroimaging investigation into the role of peripheral metabolic biomarkers in the anticipation of reward in alcohol use},

author = {Monica L. Faulkner and Reza Momenan and Lorenzo Leggio},

url = {https://pubmed.ncbi.nlm.nih.gov/33667782/},

doi = {https://doi.org/10.1016/j.drugalcdep.2021.108638},

issn = {0376-8716},

year  = {2021},

date = {2021-04-01},

urldate = {2021-04-01},

journal = {Drug and Alcohol Dependence},

volume = {221},

pages = {108638},

abstract = {Background 

The relationship between alcohol use and metabolism has focused on the effects of alcohol use on metabolic factors. Metabolic factors, such as triglycerides, cholesterol, and glucose, have been shown to be associated with increased risk for heavy alcohol consumption and alcohol use disorder (AUD). It's been suggested that changes in metabolic factors may play a role in reward seeking behaviors and pathways. Studies on feeding behavior and obesity revealed the role of triglycerides in neural response to food cues in neurocircuitry regulating reward and feeding behaviors. This study aimed to explore the relationship of peripheral metabolism, alcohol use, and reward processing in individuals that use alcohol. 

Methods 

Ninety participants from a previously collected dataset were included in the analysis. Participants were treatment seeking, detoxified individuals with AUD and healthy individuals without AUD, with the following metabolic biomarkers: triglyceride, glucose, high- and low-density cholesterol, and HbA1c levels. Participants completed a neuroimaging version of the Monetary Incentive Delay task (MID). 

Results 

Correlations on peripheral metabolic biomarkers, alcohol use, and neural activity during reward anticipation and outcome during the MID task were not significant. Mediation models revealed triglycerides and high-density cholesterol had significant effects on left anterior insula during anticipation of potential monetary loss and this effect was not mediated by alcohol use. 

Conclusion 

Limbic recruitment by anticipation of monetary rewards revealed an independent relationship with peripheral metabolism and was not affected by individual differences in alcohol use, despite the effects of alcohol use on metabolic markers and reward processing neural circuitry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Panlilio:2021aa,

title = {Beyond abstinence and relapse II: momentary relationships between stress, craving, and lapse within clusters of patients with similar patterns of drug use},

author = {Leigh V Panlilio and Samuel W Stull and Jeremiah W Bertz and Albert J Burgess-Hull and Stephanie T Lanza and Brenda L Curtis and Karran A Phillips and David H Epstein and Kenzie L Preston},

url = {https://pubmed.ncbi.nlm.nih.gov/33558983/},

doi = {10.1007/s00213-021-05782-2},

isbn = {1432-2072},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Psychopharmacology},

abstract = {Rationale

Given that many patients being treated for opioid-use disorder continue to use drugs, identifying clusters of patients who share similar patterns of use might provide insight into the disorder, the processes that affect it, and ways that treatment can be personalized.



Objectives and methods

We applied hierarchical clustering to identify patterns of opioid and cocaine use in 309 participants being treated with methadone or buprenorphine (in a buprenorphine–naloxone formulation) for up to 16 weeks. A smartphone app was used to assess stress and craving at three random times per day over the course of the study.



Results

Five basic patterns of use were identified: frequent opioid use, frequent cocaine use, frequent dual use (opioids and cocaine), sporadic use, and infrequent use. These patterns were differentially associated with medication (methadone vs. buprenorphine), race, age, drug-use history, drug-related problems prior to the study, stress-coping strategies, specific triggers of use events, and levels of cue exposure, craving, and negative mood. Craving tended to increase before use in all except those who used sporadically. Craving was sharply higher during the 90 min following moderate-to-severe stress in those with frequent use, but only moderately higher in those with infrequent or sporadic use.



Conclusions

People who share similar patterns of drug-use during treatment also tend to share similarities with respect to psychological processes that surround instances of use, such as stress-induced craving. Cluster analysis combined with smartphone-based experience sampling provides an effective strategy for studying how drug use is related to personal and environmental factors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/ijnp/pyab004,

title = {Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study},

author = {Mehdi Farokhnia and Kelly M Abshire and Aaron Hammer and Sara L Deschaine and Anitha Saravanakumar and Enoch Cobbina and Zhi-Bing You and Carolina L Haass-Koffler and Mary R Lee and Fatemeh Akhlaghi and Lorenzo Leggio},

url = {https://pubmed.ncbi.nlm.nih.gov/33560411/},

doi = {10.1093/ijnp/pyab004},

issn = {1461-1457},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {International Journal of Neuropsychopharmacology},

abstract = {Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol-seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder. Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic, and stress-related hormones, which are particularly relevant in the context of alcohol use. The goal of the present study was to provide a comprehensive assessment of neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals. This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included 2 experimental alcohol administration paradigms: i.v. alcohol self-administration and i.v. alcohol clamp. Each paradigm consisted of 2 counterbalanced sessions of i.v. ghrelin or placebo administration. Repeated blood samples were collected during each session, and peripheral concentrations of the following hormones were measured: leptin, glucagon-like peptide-1, pancreatic polypeptide, gastric inhibitory peptide, insulin, insulin-like growth factor-1, cortisol, prolactin, and aldosterone. Despite some statistical differences, findings were consistent across the 2 alcohol administration paradigms: i.v. ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, cortisol, and prolactin, both acutely and during the whole session. Lower levels of leptin and higher levels of aldosterone were also found during the ghrelin vs placebo session. These findings, gathered from a clinically relevant sample of heavy-drinking individuals with alcohol use disorder, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use.},

note = {pyab004},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tsai:kq,

title = {Converging structural and functional evidence for a rat salience network},

author = {Pei-Jung Tsai and Robin J Keeley and Stephanie A Carmack and Janaina C M Vendruscolo and Hanbing Lu and Hong Gu and Leandro F Vendruscolo and George F Koob and Ching-Po Lin and Elliot A Stein and Yihong Yang},

url = {https://doi.org/10.1016/j.biopsych.2020.06.023},

isbn = {0006-3223},

year  = {2020},

date = {2020-06-24},

urldate = {2020-06-24},

booktitle = {Biological Psychiatry},

journal = {Biological Psychiatry},

publisher = {Elsevier},

abstract = {Background

The salience network (SN) is dysregulated in many neuropsychiatric disorders, including substance use disorder. Initially described in humans, identification of a rodent SN would provide the ability to mechanistically interrogate this network in preclinical models of neuropsychiatric disorders.



Methods

We used modularity analysis on resting-state functional MRI data of rats (n=32) to parcellate rat insula into functional subdivisions and to identify a potential rat SN based on functional connectivity patterns from the insular subdivisions. We then used mouse tract tracing data from the Allen brain atlas to confirm the network’s underlying structural connectivity. We next compared functional connectivity profiles of the SN across rat, marmoset (n=10) and humans (n=30). Finally, we assessed rat SN’s response to conditioned cues in rats (n=21) with a history of heroin self-administration.



Results

We identified a putative rat SN, which consists of primarily the ventral anterior insula and anterior cingulate cortex, based on functional connectivity patterns from the ventral anterior insular division. Functional connectivity architecture of the rat SN is supported by the mouse neuronal tracer data. Moreover, the anatomical profile of the identified rat SN is similar to that of non-human primates and humans. Finally, we demonstrate that the rat SN responds to conditioned cues and increases functional connectivity to the Default Mode Network during conditioned heroin withdrawal.



Conclusions

The neurobiological identification of a rat SN together with a demonstration of its functional relevance provides a novel platform with which to interrogate its functional significance in normative and neuropsychiatric disease models.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Giorgi:2020aa,

title = {Cultural Differences in Tweeting about Drinking Across the US.},

author = {Salvatore Giorgi and David B Yaden and Johannes C Eichstaedt and Robert D Ashford and Anneke E K Buffone and Andrew H Schwartz and Lyle H Ungar and Brenda Curtis},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32053866},

doi = {10.3390/ijerph17041125},

issn = {1660-4601 (Electronic); 1660-4601 (Linking)},

year  = {2020},

date = {2020-02-11},

urldate = {2020-02-11},

journal = {Int J Environ Res Public Health},

volume = {17},

number = {4},

address = {Computer and Information Science Department, University of Pennsylvania, Philadelphia, PA 19104, USA.},

abstract = {Excessive alcohol use in the US contributes to over 88,000 deaths per year and costs over $250 billion annually. While previous studies have shown that excessive alcohol use can be detected from general patterns of social media engagement, we characterized how drinking-specific language varies across regions and cultures in the US. From a database of 38 billion public tweets, we selected those mentioning "drunk", found the words and phrases distinctive of drinking posts, and then clustered these into topics and sets of semantically related words. We identified geolocated "drunk" tweets and correlated their language with the prevalence of self-reported excessive alcohol consumption (Behavioral Risk Factor Surveillance System; BRFSS). We then identified linguistic markers associated with excessive drinking in different regions and cultural communities as identified by the American Community Project. "Drunk" tweet frequency (of the 3.3 million geolocated "drunk" tweets) correlated with excessive alcohol consumption at both the county and state levels (r = 0.26 and 0.45, respectively, p < 0.01). Topic analyses revealed that excessive alcohol consumption was most correlated with references to drinking with friends (r = 0.20), family (r = 0.15), and driving under the influence (r = 0.14). Using the American Community Project classification, we found a number of cultural markers of drinking: religious communities had a high frequency of anti-drunk driving tweets, Hispanic centers discussed family members drinking, and college towns discussed sexual behavior. This study shows that Twitter can be used to explore the specific sociocultural contexts in which excessive alcohol use occurs within particular regions and communities. These findings can inform more targeted public health messaging and help to better understand cultural determinants of substance abuse.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{FISCHELL2020,

title = {Transcranial Direct Current Stimulation Applied to the Dorsolateral and Ventromedial Prefrontal Cortices in Smokers Modifies Cognitive Circuits Implicated in the Nicotine Withdrawal Syndrome},

author = {Sarah Aronson Fischell and Thomas J Ross and Zhi-De Deng and Betty Jo Salmeron and Elliot A Stein},

url = {http://www.sciencedirect.com/science/article/pii/S2451902220300173},

doi = {https://doi.org/10.1016/j.bpsc.2019.12.020},

issn = {2451-9022},

year  = {2020},

date = {2020-01-13},

urldate = {2020-01-13},

journal = {Biological Psychiatry: Cognitive Neuroscience and Neuroimaging},

abstract = {Background 

The Nicotine Withdrawal Syndrome remains a major impediment to smoking cessation. Cognitive and affective disturbances are associated with altered connectivity within and between the Executive Control Network (ECN), Default Mode Network (DMN), and Salience Network. We hypothesized that functional activity in cognitive control networks, and downstream amygdala circuits, would be modified by application of transcranial direct current stimulation (tDCS) to the left (L) dorsolateral prefrontal cortex (dlPFC, ECN) and right (R) ventromedial prefrontal cortex (vmPFC, DMN). 

Methods 

15 smokers (7 women) and 28 matched nonsmokers (14 women) participated in a randomized, sham-controlled, double-blind, exploratory crossover study of three tDCS conditions: Anodal-(L)dlPFC/Cathodal-(R)vmPFC, reversed polarity, and sham. Cognitive tasks probed withdrawal-related constructs (error monitoring; working memory; amygdala reactivity), while simultaneous fMRI measured brain activity. We assessed tDCS impact on trait (nonsmokers vs. sated-smokers) and state (sated vs abstinent) smoking aspects. 

Results 

Single-session, Anodal-(L)dlPFC/Cathodal-(R)vmPFC tDCS enhanced deactivation of DMN nodes during the working memory task and strengthened anterior cingulate cortex activity during the error monitoring task. Smokers were more responsive to tDCS-induced DMN deactivation when sated (vs. withdrawn), and displayed greater cingulate activity during error monitoring than nonsmokers. Nicotine withdrawal reduced task engagement and attention, and reduced suppression of DMN nodes. 

Conclusions 

Cognitive circuit dysregulation associated with nicotine withdrawal may be modifiable by anodal tDCS applied to L-dlPFC and cathodal tDCS applied to R-vmPFC. tDCS may have stronger effects as a complement to existing therapies, such as nicotine replacement, due to possible enhanced plasticity in the sated state. (NCT01511614, https://clinicaltrials.gov/).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Epstein:2020aa,

title = {Prediction of stress and drug craving ninety minutes in the future with passively collected GPS data},

author = {David H Epstein and Matthew Tyburski and William J Kowalczyk and Albert J Burgess-Hull and Karran A Phillips and Brenda L Curtis and Kenzie L Preston},

doi = {10.1038/s41746-020-0234-6},

isbn = {2398-6352},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {npj Digital Medicine},

volume = {3},

number = {1},

pages = {26},

abstract = {Just-in-time adaptive interventions (JITAIs), typically smartphone apps, learn to deliver therapeutic content when users need it. The challenge is to ``push''content at algorithmically chosen moments without making users trigger it with effortful input. We trained a randomForest algorithm to predict heroin craving, cocaine craving, or stress (reported via smartphone app 3x/day) 90 min into the future, using 16 weeks of field data from 189 outpatients being treated for opioid-use disorder. We used only one form of continuous input (along with person-level demographic data), collected passively: an indicator of environmental exposures along the past 5 h of movement, as assessed by GPS. Our models achieved excellent overall accuracy---as high as 0.93 by the end of 16 weeks of tailoring---but this was driven mostly by correct predictions of absence. For predictions of presence, ``believability''(positive predictive value, PPV) usually peaked in the high 0.70s toward the end of the 16 weeks. When the prediction target was more rare, PPV was lower. Our findings complement those of other investigators who use machine learning with more broadly based ``digital phenotyping''inputs to predict or detect mental and behavioral events. When target events are comparatively subtle, like stress or drug craving, accurate detection or prediction probably needs effortful input from users, not passive monitoring alone. We discuss ways in which accuracy is difficult to achieve or even assess, and warn that high overall accuracy (including high specificity) can mask the abundance of false alarms that low PPV reveals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{FEDOTA2020b,

title = {Time-Varying Functional Connectivity Decreases as a Function of Acute Nicotine Abstinence},

author = {John R Fedota and Thomas J Ross and Juan Castillo and Michael R McKenna and Allison L Matous and Betty Jo Salmeron and Vinod Menon and Elliot A Stein},

url = {https://pubmed.ncbi.nlm.nih.gov/33436331/},

doi = {https://doi.org/10.1016/j.bpsc.2020.10.004},

issn = {2451-9022},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Biological Psychiatry: Cognitive Neuroscience and Neuroimaging},

abstract = {\textbf{Background}

The nicotine withdrawal syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging uses static measures of resting-state functional connectivity and assumes time-invariance and is thus unable to capture dynamic brain-behavior relationships. Recent advances in resting-state functional connectivity signal processing allow characterization of time-varying functional connectivity (TVFC), which characterizes network communication between networks that reconfigure over the course of data collection. Therefore, TVFC may more fully describe network dysfunction related to the NWS. 



\textbf{Methods}

To isolate alterations in the frequency and diversity of communication across network boundaries during acute nicotine abstinence, we scanned 25 cigarette smokers in the nicotine-sated and abstinent states and applied a previously validated method to characterize TVFC at a network and a nodal level within the brain. 



\textbf{Results}

During abstinence, we found brain-wide decreases in the frequency of interactions between network nodes in different modular communities (i.e., temporal flexibility). In addition, within a subset of the networks examined, the variability of these interactions across community boundaries (i.e., spatiotemporal diversity) also decreased. Finally, within 2 of these networks, the decrease in spatiotemporal diversity was significantly related to NWS clinical symptoms. 



\textbf{Conclusions}

Using multiple measures of TVFC in a within-subjects design, we characterized a novel set of changes in network communication and linked these changes to specific behavioral symptoms of the NWS. These reductions in TVFC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks during acute abstinence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ashford:2020aa,

title = {Digital recovery networks: Characterizing user participation, engagement, and outcomes of a novel recovery social network smartphone application.},

author = {Robert D Ashford and Salvatore Giorgi and Beau Mann and Chris Pesce and Lon Sherritt and Lyle Ungar and Brenda Curtis},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31856951},

doi = {10.1016/j.jsat.2019.11.005},

issn = {1873-6483 (Electronic); 0740-5472 (Linking)},

year  = {2019},

date = {2019-11-15},

urldate = {2019-11-15},

journal = {J Subst Abuse Treat},

volume = {109},

pages = {50--55},

address = {University of the Sciences, Substance Use Disorders Institute, United States of America; University of Pennsylvania, Treatment Research Center, United States of America. Electronic address: rashford@mail.usciences.edu.},

abstract = {BACKGROUND: Recovery support services, including in vivo (i.e., face to face) peer-based supports and social networks, are associated with positive effects on substance use disorder recovery outcomes. The translation of in vivo supports to digital platforms is a recent development that is mostly unexamined. The types of users and their engagement patterns of digital recovery support services (D-RSS), and the utility of objective and self-report data in predicting future recovery outcomes require further study to move the recovery support field forward. METHODS: De-identified individual user data from Sober Grid, a recovery social network site (R-SNS) smartphone application, for the years 2015-2018 was analyzed to identify the demographics, engagement patterns, and recovery outcomes of active users. Analysis of variance (ANOVA) tests were used to examine between generational group differences on activity variables and recovery outcomes. Logistic and linear regressions were used to identify significant predictors of sobriety length and relapse among users. RESULTS: The most active tercile of users (n = 1273; mAge = 39 years; 62% male) had average sobriety lengths of 195.5 days and had experienced 4.4 relapses on average since sign-up. Users have over 33,000 unilateral and nearly 14,000 bilateral connections. Users generated over 120,000 unique posts, 507,000 comments, 1617,000 likes, 12,900 check-ins, and 593,000 chats during the period of analysis. Recovery outcomes did not vary between generations, though user activity was significantly different between Generations (Millennials, Generation X, and Baby Boomers), with baby boomers and generation X having higher levels of engagement and connection among all activity markers. Logistic regression results revealed gender (female) was associated with a lower likelihood of reporting loneliness or sexual feelings as an emotional trigger. Linear regressions revealed generation, number of unilateral connections, and number of check-ins was associated with sobriety length, while generation and number of check-ins was associated with number of relapses. CONCLUSIONS: Active users of Sober Grid engage in several platform features that provide objective data that can supplement self-report data for analysis of recovery outcomes. Most commonly uses features are those similar to features readily available in open-ecosystem social network sites (e.g., Facebook). Prediction model results suggest that demographic factors (e.g., age, gender) and activity factors (e.g., number of check-ins) may be useful in deploying just-in-time interventions to prevent relapse or offer additional social support. Further empirical examination is needed to identify the utility of such interventions, as well as the mechanisms of support that accompany feature use or engagement with the D-RSS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gardner:2019uv,

title = {Defining and Predicting Opioid and Cocaine Treatment Response},

author = {Robert A. Gardner and David H. Epstein and Kenzie L. Preston and Karran A. Phillips},

url = {https://pubmed.ncbi.nlm.nih.gov/31315479/},

doi = {10.1080/10826084.2019.1638405},

isbn = {1082-6084},

year  = {2019},

date = {2019-11-10},

urldate = {2019-11-10},

booktitle = {Substance Use & Misuse},

journal = {Substance Use & Misuse},

volume = {54},

number = {13},

pages = {2134--2143},

publisher = {Taylor & Francis},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bertz:2019vn,

title = {Sleep reductions associated with illicit opioid use and clinic-hour changes during opioid agonist treatment for opioid dependence: Measurement by electronic diary and actigraphy},

author = {Jeremiah W. Bertz and David H. Epstein and David Reamer and William J. Kowalczyk and Karran A. Phillips and Ashley P. Kennedy and Michelle L. Jobes and Greg Ward and Barbara A. Plitnick and Mariana G. Figueiro and Mark S. Rea and Kenzie L. Preston},

url = {https://pubmed.ncbi.nlm.nih.gov/31540611/},

doi = {10.1016/j.jsat.2019.08.011},

isbn = {0740-5472},

year  = {2019},

date = {2019-11-01},

urldate = {2019-11-01},

booktitle = {Journal of Substance Abuse Treatment},

journal = {Journal of Substance Abuse Treatment},

volume = {106},

pages = {43--57},

publisher = {Elsevier},

abstract = {Sleep problems are commonly reported during opioid agonist treatment (OAT) for opioid use disorders. Inpatient studies have found both sleep disturbances and improved sleep during OAT. Illicit opioids can also disrupt sleep, but it is unclear how they affect sleep in outpatients receiving OAT. Therefore, we used electronic diary entries and actigraphy to measure sleep duration and timing in opioid-dependent participants (n?=?37) treated with methadone (n?=?15) or buprenorphine (n?=?22). For 16?weeks, participants were assigned to attend our clinic under different operating hours in a crossover design: Early hours (07:00?09:00) vs. Late hours (12:00?13:00) for 4?weeks each in randomized order, followed for all participants by our Standard clinic hours (07:00?11:30) for 8?weeks. Throughout, participants made daily electronic diary self-reports of their sleep upon waking; they also wore a wrist actigraph for 6 nights in each of the three clinic-hour conditions. Drug use was assessed by thrice-weekly urinalysis. In linear mixed models controlling for other sleep-relevant factors, sleep duration and timing differed by drug use and by clinic hours. Compared to when non-using, participants slept less, went to bed later, and woke later when using illicit opioids and/or both illicit opioids and cocaine. Participants slept less and woke earlier when assigned to the Early hours. These findings highlight the role OAT clinic schedules can play in structuring the sleep/wake cycles of OAT patients and clarify some of the circumstances under which OAT patients experience sleep disruption in daily life.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hu:2019aa,

title = {Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals.},

author = {Yuzheng Hu and Betty Jo Salmeron and Irina N Krasnova and Hong Gu and Hanbing Lu and Antonello Bonci and Jean L Cadet and Elliot A Stein and Yihong Yang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30988198},

doi = {10.1073/pnas.1819978116},

issn = {1091-6490 (Electronic); 0027-8424 (Linking)},

year  = {2019},

date = {2019-04-30},

urldate = {2019-04-30},

journal = {Proc Natl Acad Sci U S A},

volume = {116},

number = {18},

pages = {9066--9071},

address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Programs, National Institutes of Health, Baltimore, MD 21224; yihongyang@intra.nida.nih.gov huyuzheng@zju.edu.cn.},

abstract = {Substance use disorders (SUDs) impose severe negative impacts upon individuals, their families, and society. Clinical studies demonstrate that some chronic stimulant users are able to curtail their drug use when faced with adverse consequences while others continue to compulsively use drugs. The mechanisms underlying this dichotomy are poorly understood, which hampers the development of effective individualized treatments of a disorder that currently has no Food and Drug Administration-approved pharmacological treatments. In the present study, using a rat model of methamphetamine self-administration (SA) in the presence of concomitant foot shocks, thought to parallel compulsive drug taking by humans, we found that SA behavior correlated with alterations in the balance between an increased orbitofrontal cortex-dorsomedial striatal "go" circuit and a decreased prelimbic cortex-ventrolateral striatal "stop" circuit. Critically, this correlation was seen only in rats who continued to self-administer at a relatively high rate despite receiving foot shocks of increasing intensity. While the stop circuit functional connectivity became negative after repeated SA in all rats, "shock-resistant" rats showed strengthening of this negative connectivity after shock exposure. In contrast, "shock-sensitive" rats showed a return toward their baseline levels after shock exposure. These results may help guide novel noninvasive brain stimulation therapies aimed at restoring the physiological balance between stop and go circuits in SUDs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{STULL2019183,

title = {The chippers, the quitters, and the highly symptomatic: A 12-month longitudinal study of DSM-5 opioid- and cocaine-use problems in a community sample},

author = {Samuel W. Stull and Leigh V. Panlilio and Landhing M. Moran and Jennifer R. Schroeder and Jeremiah W. Bertz and David H. Epstein and Kenzie L. Preston and Karran A. Phillips},

url = {https://pubmed.ncbi.nlm.nih.gov/31108264/},

doi = {https://doi.org/10.1016/j.addbeh.2019.04.030},

issn = {0306-4603},

year  = {2019},

date = {2019-04-29},

journal = {Addictive Behaviors},

volume = {96},

pages = {183-191},

abstract = {Background 

Individual trajectories of drug use and drug-related problems are highly heterogeneous. There is no standard taxonomy of these trajectories, but one could be developed by defining natural categories based on changes in symptoms of substance-use disorders over time. 

Methods Our study was conducted in a community sample in Baltimore, Maryland. At baseline, all participants were using opioids and/or cocaine, but none were in treatment. Drug use and symptomatology were assessed again at 12 months (N = 115). 

Results We defined Quitters as participants who had not used for at least 30 days at follow-up (17%). For the remaining participants, we performed longitudinal cluster analysis on DSM symptom-counts, identifying three trajectory clusters: newly or persistently Symptomatic (40%) participants, Chippers (21.5%) with few symptoms, and Converted Chippers (21.5%) with improved symptom counts. Logistic regression showed that profiles of Quitters did not resemble Chippers, but instead resembled Symptomatic participants, having high probability of disorderly home neighborhood, nonwhite race, and negative mood. Quitters tended to have two protective factors: initiating opioid-agonist treatment during the study (reffect = 0.25, CL95 0.02--0.48) and lack of polydrug use (reffect = 0.25, CL95 0.004--0.49). Converted Chippers tended to be white, with orderly home neighborhoods and less negative mood (reffects 0.24 to 0.31, CL95 0.01--0.54). 

Conclusions 

Changes in DSM symptomology provided a meaningful measure of individual trajectories. Quitters shared psychosocial characteristics with Symptomatic participants, but not with participants who continued to use with few symptoms. This suggests that Quitters abstained out of necessity, not because their problems were less severe.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ashford2019c,

title = {Biased labels: An experimental study of language and stigma among individuals in recovery and health professionals.},

author = {Ashford, Robert D and Brown, Austin M and McDaniel, Jessica and Curtis, Brenda},

url = {https://www.ncbi.nlm.nih.gov/pubmed/30945955/},

doi = {10.1080/10826084.2019.1581221},

issn = {1532-2491 (Electronic); 1082-6084 (Linking)},

year  = {2019},

date = {2019-04-04},

urldate = {2019-04-04},

journal = {Subst Use Misuse},

volume = {54},

number = {8},

pages = {1376--1384},

abstract = {BACKGROUND: Labels such as "addict" and "substance abuser" have been found to elicit implicit and explicit stigma among the general public previously. The difference in the levels of this bias among individuals in recovery and those employed in the health profession has not yet been identified, however. The current study seeks to answer this question using measures of implicit bias. 



METHODS: A subset sample (n = 299) from a previously completed study (n = 1288) was selected for analysis. Mixed-model ANOVA tests were completed to identify variance between d-prime automatic association scores with the terms "addict" and "substance abuser" among individuals in recovery and those identified as working in the health professions. 



RESULTS: Individuals in recovery did not have lower negative associations with either term, whereas individuals employed as health professionals had greater negative associations with the term "substance abuser" but did not have greater negative associations with the term "addict." 



CONCLUSIONS: Results provide further evidence that previously identified stigmatizing labels have the potential to influence medical care and medical practitioner perceptions of individuals with substance use disorders and should be avoided. Further exploration into the role negative associations derived from commonly used labels have in the individual recovery process is needed to draw appropriate recommendations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bertz:2018aa,

title = {Combining ecological momentary assessment with objective, ambulatory measures of behavior and physiology in substance-use research.},

author = {Jeremiah W Bertz and David H Epstein and Kenzie L Preston},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29174666},

doi = {10.1016/j.addbeh.2017.11.027},

issn = {1873-6327 (Electronic); 0306-4603 (Linking)},

year  = {2018},

date = {2018-08-01},

journal = {Addict Behav},

volume = {83},

pages = {5--17},

address = {Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., BRC Building, Suite 200, Baltimore, MD 21224, USA.},

abstract = {Whereas substance-use researchers have long combined self-report with objective measures of behavior and physiology inside the laboratory, developments in mobile/wearable electronic technology are increasingly allowing for the collection of both subjective and objective information in participants' daily lives. For self-report, ecological momentary assessment (EMA), as implemented on contemporary smartphones or personal digital assistants, can provide researchers with near-real-time information on participants' behavior and mood in their natural environments. Data from portable/wearable electronic sensors measuring participants' internal and external environments can be combined with EMA (e.g., by timestamps recorded on questionnaires) to provide objective information useful in determining the momentary context of behavior and mood and/or validating participants' self-reports. Here, we review three objective ambulatory monitoring techniques that have been combined with EMA, with a focus on detecting drug use and/or measuring the behavioral or physiological correlates of mental events (i.e., emotions, cognitions): (1) collection and processing of biological samples in the field to measure drug use or participants' physiological activity (e.g., hypothalamic-pituitary-adrenal axis activity); (2) global positioning system (GPS) location information to link environmental characteristics (disorder/disadvantage, retail drug outlets) to drug use and affect; (3) ambulatory electronic physiological monitoring (e.g., electrocardiography) to detect drug use and mental events, as advances in machine learning algorithms make it possible to distinguish target changes from confounds (e.g., physical activity). Finally, we consider several other mobile/wearable technologies that hold promise to be combined with EMA, as well as potential challenges faced by researchers working with multiple mobile/wearable technologies simultaneously in the field.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ding:2019aa,

title = {Evidence of subgroups in smokers as revealed in clinical measures and evaluated by neuroimaging data: a preliminary study.},

author = {Xiaoyu Ding and Betty Jo Salmeron and Jamei Wang and Yihong Yang and Elliot A Stein and Thomas J Ross},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29516603},

doi = {10.1111/adb.12620},

issn = {1369-1600 (Electronic); 1355-6215 (Linking)},

year  = {2018},

date = {2018-03-08},

urldate = {2018-03-08},

journal = {Addict Biol},

volume = {24},

number = {4},

pages = {777--786},

address = {Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.},

abstract = {To date, fractionation of the nicotine addiction phenotype has been limited to that based primarily on characteristics of cigarette use, although it is widely appreciated that a variety of individual factors are associated with tobacco use disorder. Identifying subtypes of tobacco use disorder based on such factors may lead to better understanding of potential treatment targets, individualize treatments and improve outcomes. In this preliminary study, to identify potential subgroups, we applied hierarchical clustering to a broad range of assessments measuring personality, IQ and psychiatric symptoms, as well as various environmental and experiential characteristics from 102 otherwise healthy cigarette smokers. The identified subgroups were further compared on various resting-state fMRI measures from a subset (N = 65) of individuals who also underwent resting-state fMRI scanning. The clustering dendrogram indicated that smokers can be divided into three subgroups. Each subgroup had unique clinical assessment characteristics. The division yielded imaging differences between subgroups in the supplementary motor area/middle cingulate cortex and the cuneus. Regression analyses showed that amplitude of low frequency fluctuations in the supplementary motor area/middle cingulate cortex differed between groups and were negatively correlated with the Toronto Alexithymia Scale subscale Difficulty Describing Feelings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sutherland:2018aa,

title = {Functional Neurocircuits and Neuroimaging Biomarkers of Tobacco Use Disorder.},

author = {Matthew T Sutherland and Elliot A Stein},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29398401},

doi = {10.1016/j.molmed.2017.12.002},

issn = {1471-499X (Electronic); 1471-4914 (Linking)},

year  = {2018},

date = {2018-02-01},

urldate = {2018-02-01},

journal = {Trends Mol Med},

volume = {24},

number = {2},

pages = {129--143},

address = {Department of Psychology, Florida International University, Miami, FL, USA.},

abstract = {Drug abuse and addiction remain major public health issues, exemplified by the opioid epidemic currently devastating the United States. Treatment outcomes across substance use disorders remain unacceptably poor, wherein drug discovery/development for this multifaceted neuropsychiatric disorder focuses on single molecular-level targets. Rather, our opinion is that a systems-level neuroimaging perspective is crucial for identifying novel therapeutic targets, biomarkers to stratify patients, and individualized treatment strategies. Focusing on tobacco use disorder, we advocate a brain systems-level perspective linking two abuse-related facets (i.e., statelike withdrawal and traitlike addiction severity) with specific neurocircuitry (insula- and striatum-centered networks). To the extent that precise neurocircuits mediate distinct facets of abuse, treatment development must adopt not only a systems-level perspective, but also multi-intervention rather than mono-intervention practices.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fedota:2018aa,

title = {Nicotine Abstinence Influences the Calculation of Salience in Discrete Insular Circuits.},

author = {John R Fedota and Xiaoyu Ding and Allison L Matous and Betty Jo Salmeron and Michael R McKenna and Hong Gu and Thomas J Ross and Elliot A Stein},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29529410},

doi = {10.1016/j.bpsc.2017.09.010},

issn = {2451-9030 (Electronic); 2451-9022 (Linking)},

year  = {2018},

date = {2018-02-01},

urldate = {2018-02-01},

journal = {Biol Psychiatry Cogn Neurosci Neuroimaging},

volume = {3},

number = {2},

pages = {150--159},

address = {Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland. Electronic address: john.fedota@nih.gov.},

abstract = {BACKGROUND: Insular subdivisions show distinct patterns of resting-state functional connectivity (rsFC) with specific brain regions, each with different functional significance. Seeds in these subdivisions are employed to characterize the effects of acute nicotine abstinence on rsFC between insula subdivisions and brain networks implicated in addiction and attentional control. METHODS: In a within-subjects design, resting-state blood oxygen level-dependent data were collected from treatment-seeking smokers (N= 20) following smoking satiety and again following 48 hours of nicotine abstinence. Three right hemisphere insular regions of interest (dorsal, ventral, and posterior) served as seeds for analyses. Indices of both static and dynamic rsFC were obtained and correlated with indices of subjective withdrawal and behavioral performance. RESULTS: Abstinence-induced physiological, subjective, and cognitive differences were observed. Overall dynamic rsFC was reduced during abstinence, and circuits containing each insular seed showed changes in rsFC as a function of nicotine abstinence. Specifically, dorsal and posterior insular connections to the default mode and salience networks were enhanced, while a previously undescribed ventral insular connection to the executive control network was reduced. Further, static rsFC was significantly correlated with subjective ratings of aversive affect and withdrawal in the modified ventral and posterior insular-seeded circuits. CONCLUSIONS: As predicted, divergent connections between insula subdivisions and anticorrelated resting brain networks were observed during abstinence. These changes reflect an attentional bias toward aversive affective processing and not directly away from exogenous cognitive processing, suggesting a coordinated modulation of circuits associated with interoceptive and affective processing that instantiates an aversive state during nicotine abstinence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hertzel:2017aa,

title = {Perceptions of Neighborhood Mediate the Relationship Between PTSD Symptoms and Coping in a Neighborhood-Matched Substance-Using Sample.},

author = {Sara K Hertzel and Jennifer Schroeder and Landhing M Moran and Anika A Alvanzo and William J Kowalczyk and David H Epstein and Kenzie L Preston and Karran A Phillips},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28885301},

doi = {10.1097/ADM.0000000000000343},

issn = {1935-3227 (Electronic); 1932-0620 (Linking)},

year  = {2017},

date = {2017-11-01},

urldate = {2017-11-01},

journal = {J Addict Med},

volume = {11},

number = {6},

pages = {440--448},

address = {Intramural Research Program, National Institute on Drug Abuse (SKH, JS, LMM, WJK, DHE, KLP, KAP), Division of General Internal Medicine, Johns Hopkins University, Baltimore, MD (AAA).},

abstract = {OBJECTIVES: People with substance use problems living in neighborhoods with high levels of disorder are disproportionately likely to experience trauma and develop PTSD symptoms. We sought to evaluate the relationships between objective neighborhood disorder, perceptions of neighborhood, and the use of maladaptive coping behaviors among both non-substance-using and substance-using participants with and without PTSD symptoms. METHODS: Participants (255 non-drug users [NDUs], 168 marijuana and/or alcohol users [MAUs], and 273 opioid and/or stimulant users) completed the Addiction Severity Index, PTSD Checklist-Civilian Version, The COPE Inventory, and the Perceived Neighborhood Scale. The Neighborhood Inventory for Environmental Typology (NIfETy) was used to objectively assess neighborhood disorder at participants' home addresses. Regression modeling was used to assess within-group predictors of PTSD and test for mediation in the relationships between PTSD, perceptions of neighborhood, and coping behaviors. RESULTS: In NDUs, lower sense of community partially mediated the relationship between PTSD symptoms and using mental disengagement to cope. In MAUs, higher levels of perceived crime partially mediated the individual relationships between PTSD symptoms and using mental disengagement, focusing on and venting emotions, and using substances to cope. Opioid and/or stimulant users with PTSD symptoms reported using higher levels of mental disengagement, focusing on and venting emotions, and substances to cope and perceived a higher degree of crime; no mediation was inferred. CONCLUSION: Perceptions of community and crime may be more predictive of PTSD symptoms than objectively measured neighborhood disorder. These perceptions partially mediate the relationship between maladaptive coping behaviors and PTSD symptoms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Moran:2017aa,

title = {Aripiprazole for cocaine abstinence: a randomized-controlled trial with ecological momentary assessment.},

author = {Landhing M Moran and Karran A Phillips and William J Kowalczyk and Udi E Ghitza and Daniel A Agage and David H Epstein and Kenzie L Preston},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27755017},

doi = {10.1097/FBP.0000000000000268},

issn = {1473-5849 (Electronic); 0955-8810 (Linking)},

year  = {2017},

date = {2017-02-01},

journal = {Behav Pharmacol},

volume = {28},

number = {1},

pages = {63--73},

address = {aClinical Pharmacology and Therapeutics Research Branch bCenter for Clinical Trials Network, National Institute on Drug Abuse, Bethesda, Maryland, USA.},

abstract = {Aripiprazole blocks psychostimulant seeking in a rat model of relapse. However, in humans, it may increase ongoing use. We tested aripiprazole specifically for relapse prevention. Methadone-maintained outpatients who were abstinent from cocaine in weeks 11-12 were randomized to double-blind aripiprazole (15 mg daily) or placebo in weeks 13-27 after 12 weeks of contingency management. Participants reported craving through ecological momentary assessment. We stopped the trial because very few (18/41) participants fulfilled the abstinence criterion. The results suggested that aripiprazole delayed lapse [hazard ratio (HR)=0.45, 95% confidence interval (CI)=0.14-1.42},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fedota2016,

title = {Insula Demonstrates a Non-Linear Response to Varying Demand for Cognitive Control and Weaker Resting Connectivity With the Executive Control Network in Smokers.},

author = {John R Fedota and Allison L Matous and Betty Jo Salmeron and Hong Gu and Thomas J Ross and Elliot A Stein},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27112116},

doi = {10.1038/npp.2016.62},

issn = {1740-634X (Electronic); 0893-133X (Linking)},

year  = {2016},

date = {2016-04-26},

journal = {Neuropsychopharmacology},

volume = {41},

number = {10},

pages = {2557--2565},

address = {Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.},

abstract = {Deficits in cognitive control processes are a primary characteristic of nicotine addiction. However, while network-based connectivity measures of dysfunction have frequently been observed, empirical evidence of task-based dysfunction in these processes has been inconsistent. Here, in a sample of smokers (n=35) and non-smokers (n=21), a previously validated parametric flanker task is employed to characterize addiction-related alterations in responses to varying (ie, high, intermediate, and low) demands for cognitive control. This approach yields a demand-response curve that aims to characterize potential non-linear responses to increased demand for control, including insensitivities or lags in fully activating the cognitive control network. We further used task-based differences in activation between groups as seeds for resting-state analysis of network dysfunction in an effort to more closely link prior inconsistencies in task-related activation with evidence of impaired network connectivity in smokers. For both smokers and non-smokers, neuroimaging results showed similar increases in activation in brain areas associated with cognitive control. However, reduced activation in right insula was seen only in smokers and only when processing intermediate demand for cognitive control. Further, in smokers, this task-modulated right insula showed weaker functional connectivity with the superior frontal gyrus, a component of the task-positive executive control network. These results demonstrate that the neural instantiation of salience attribution in smokers is both more effortful to fully activate and has more difficulty communicating with the exogenous, task-positive, executive control network. Together, these findings further articulate the cognitive control dysfunction associated with smoking and illustrate a specific brain circuit potentially responsible.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kennedy2015,

title = {Continuous in-the-field measurement of heart rate: Correlates of drug use, craving, stress, and mood in polydrug users.},

author = {Ashley P Kennedy and David H Epstein and Michelle L Jobes and Daniel Agage and Matthew Tyburski and Karran A Phillips and Amin Ahsan Ali and Rummana Bari and Syed Monowar Hossain and Karen Hovsepian and Md Mahbubur Rahman and Emre Ertin and Santosh Kumar and Kenzie L Preston},

url = {https://www.ncbi.nlm.nih.gov/pubmed/25920802},

doi = {10.1016/j.drugalcdep.2015.03.024},

issn = {1879-0046 (Electronic); 0376-8716 (Linking)},

year  = {2015},

date = {2015-06-01},

journal = {Drug Alcohol Depend},

volume = {151},

pages = {159--166},

address = {Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, United States.},

abstract = {BACKGROUND: Ambulatory physiological monitoring could clarify antecedents and consequences of drug use and could contribute to a sensor-triggered mobile intervention that automatically detects behaviorally risky situations. Our goal was to show that such monitoring is feasible and can produce meaningful data. METHODS: We assessed heart rate (HR) with AutoSense, a suite of biosensors that wirelessly transmits data to a smartphone, for up to 4 weeks in 40 polydrug users in opioid-agonist maintenance as they went about their daily lives. Participants also self-reported drug use, mood, and activities on electronic diaries. We compared HR with self-report using multilevel modeling (SAS Proc Mixed). RESULTS: Compliance with AutoSense was good; the data yield from the wireless electrocardiographs was 85.7%. HR was higher when participants reported cocaine use than when they reported heroin use (F(2,9)=250.3, p<.0001) and was also higher as a function of the dose of cocaine reported (F(1,8)=207.7, p<.0001). HR was higher when participants reported craving heroin (F(1,16)=230.9, p<.0001) or cocaine (F(1,14)=157.2, p<.0001) than when they reported of not craving. HR was lower (p<.05) in randomly prompted entries in which participants reported feeling relaxed, feeling happy, or watching TV, and was higher when they reported feeling stressed, being hassled, or walking. CONCLUSIONS: High-yield, high-quality heart-rate data can be obtained from drug users in their natural environment as they go about their daily lives, and the resultant data robustly reflect episodes of cocaine and heroin use and other mental and behavioral events of interest.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee:2014aa,

title = {Complexity of oxytocins effects in a chronic cocaine dependent population.},

author = {Mary R Lee and Matthew Glassman and Brooks King-Casas and Deanna L Kelly and Elliot A Stein and Jennifer Schroeder and Betty Jo Salmeron},

url = {https://www.ncbi.nlm.nih.gov/pubmed/25044050/},

doi = {10.1016/j.euroneuro.2014.06.005},

issn = {1873-7862 (Electronic); 0924-977X (Linking)},

year  = {2014},

date = {2014-09-01},

journal = {Eur Neuropsychopharmacol},

volume = {24},

number = {9},

pages = {1483--1491},

address = {National Institute on Alcohol Abuse and Alcoholism, Laboratory of Clinical and Translational Studies, Bethesda, MD, USA. Electronic address: leemary@mail.nih.gov.},

abstract = {Behavioral and neuroplastic changes occurring in the development of addiction parallel those that occur in social bonding. This has led to speculation that drugs of abuse co-opt systems that subserve social attachment to shift attachment to drugs of abuse. Oxytocin, a neuropeptide that is important in social bonding, has been shown in rodents to decrease psychostimulant self-administration, locomotor activity, and conditioned place preference, it is unclear what role it may play in human drug addiction. In this double-blind, placebo-controlled crossover study, 23 cocaine-dependent inpatients in court-ordered treatment completed 4 task sessions measuring desire to use cocaine, cue-induced craving, monetary reward decisions and social cognition. Before each session, subjects administered 24 IU of intranasal oxytocin or placebo. Oxytocin increased desire to use cocaine and cue-induced excitability with no effect on cue-induced desire to use. Oxytocin also removed the effect of state anger on several measures of cue reactivity. Response to monetary reward increased under oxytocin and measures of social cognition worsened. The significant increase in the desire for drug and monetary reward as well as the significant decrease in measures of social cognition was small but warrant further study of the effect of oxytocins effect in cocaine dependent subjects. The effect of oxytocin to modulate the relationship between state anger and cue reactivity should be explored further for potential therapeutic use of oxytocin in cocaine dependent patients. These findings are discussed in light of the human and rodent oxytocin literature.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}