Browse
Recent Submissions
Item Reorganization of Substance Use Treatment and Harm Reduction Services During the COVID-19 Pandemic: A Global Survey(Frontiers Media, 2021-04-29) Radfar, Seyed Ramin; De Jong, Cornelis A. J.; Farhoudian, Ali; Ebrahimi, Mohsen; Rafei, Parnian; Vahidi, Mehrnoosh; Yunesian, Masud; Kouimtsidis, Christos; Arunogiri, Shalini; Massah, Omid; Deylamizadeh, Abbas; Brady, Kathleen T.; Busse, Anja; ISAM-PPIG Global Survey Consortium; Potenza, Marc N.; Ekhtiari, Hamed; Baldacchino, Alexander Mario; Psychiatry, School of MedicineBackground: The coronavirus disease 2019 (COVID-19) pandemic has impacted people with substance use disorders (SUDs) worldwide, and healthcare systems have reorganized their services in response to the pandemic. Methods: One week after the announcement of the COVID-19 as a pandemic, in a global survey, 177 addiction medicine professionals described COVID-19-related health responses in their own 77 countries in terms of SUD treatment and harm reduction services. The health responses were categorized around (1) managerial measures and systems, (2) logistics, (3) service providers, and (4) vulnerable groups. Results: Respondents from over 88% of countries reported that core medical and psychiatric care for SUDs had continued; however, only 56% of countries reported having had any business continuity plan, and 37.5% of countries reported shortages of methadone or buprenorphine supplies. Participants of 41% of countries reported partial discontinuation of harm-reduction services such as needle and syringe programs and condom distribution. Fifty-seven percent of overdose prevention interventions and 81% of outreach services were also negatively impacted. Conclusions: Participants reported that SUD treatment and harm-reduction services had been significantly impacted globally early during the COVID-19 pandemic. Based on our findings, we highlight several issues and complications resulting from the pandemic concerning people with SUDs that should be tackled more efficiently during the future waves or similar pandemics. The issues and potential strategies comprise the following: (1) helping policymakers to generate business continuity plans, (2) maintaining the use of evidence-based interventions for people with SUDs, (3) being prepared for adequate medication supplies, (4) integrating harm reduction programs with other treatment modalities, and (5) having specific considerations for vulnerable groups such as immigrants and refugees.Item Recent Perceived Stress, Amygdala Reactivity to Acute Psychosocial Stress, and Alcohol and Cannabis Use in Adolescents and Young Adults With Bipolar Disorder(Frontiers Media, 2021-11-15) Le, Vanessa; Kirsch, Dylan E.; Tretyak, Valeria; Weber, Wade; Strakowski, Stephen M.; Lippard, Elizabeth T. C.; Psychiatry, School of MedicineBackground: Psychosocial stress negatively affects the clinical course of bipolar disorder. Studies primarily focused on adults with bipolar disorder suggest the impact of stress is progressive, i.e., stress response sensitizes with age. Neural mechanisms underlying stress sensitization are unknown. As stress-related mechanisms contribute to alcohol/substance use disorders, variation in stress response in youth with bipolar disorder may contribute to development of co-occurring alcohol/substance use disorders. This study investigated relations between psychosocial stress, amygdala reactivity, and alcohol and cannabis use in youth with bipolar disorder, compared to typically developing youth. Methods: Forty-two adolescents/young adults [19 with bipolar disorder, 23 typically developing, 71% female, agemean ± SD = 21 ± 2 years] completed the Perceived Stress Scale (PSS), Daily Drinking Questionnaire modified for heaviest drinking week, and a modified Montreal Imaging Stress functional MRI Task. Amygdala activation was measured for both the control and stress conditions. Main effects of group, condition, total PSS, and their interactions on amygdala activation were modeled. Relationships between amygdala response to acute stress with recent alcohol/cannabis use were investigated. Results: Greater perceived stress related to increased right amygdala activation in response to the stress, compared to control, condition in bipolar disorder, but not in typically developing youth (group × condition × PSS interaction, p = 0.02). Greater amygdala reactivity to acute stress correlated with greater quantity and frequency of alcohol use and frequency of cannabis use in bipolar disorder. Conclusion: Recent perceived stress is associated with changes in amygdala activation during acute stress with amygdala reactivity related to alcohol/cannabis use in youth with bipolar disorder.Item Reporting Essentials for DElirium bioMarker Studies (REDEEMS): Explanation and Elaboration(European Delirium Association, 2022-12-21) Amgarth-Duff, Ingrid; Hosie, Annemarie; Caplan, Gideon A.; Adamis, Dimitrios; Watne, Leiv Otto; Cunningham, Colm; Oh, Esther S.; Wang, Sophia; Lindroth, Heidi; Sanders, Robert D.; Olofsson, Birgitta; Girard, Timothy D.; Steiner, Luzius A.; Vasunilashorn, Sarinnapha M.; Agar, Meera; Psychiatry, School of MedicineDespite many studies of potential delirium biomarkers, delirium pathophysiology remains unclear. Evidence shows that the quality of reporting delirium biomarker studies is sub-optimal. Better reporting of delirium biomarker studies is needed to understand delirium pathophysiology better. To improve robustness, transparency and uniformity of delirium biomarker study reports, the REDEEMS (Reporting Essentials for DElirium bioMarker Studies) guideline was developed by an international group of delirium researchers through a three-stage process, including a systematic review, a three-round Delphi study, and a follow-up consensus meeting. This process resulted in a 9-item guideline to inform delirium fluid biomarker studies. To enhance implementation of the REDEEMS guideline, this Explanation and Elaboration paper provides a detailed explanation of each item. We anticipate that the REDEEMS guideline will help to accelerate our understanding of delirium pathophysiology by improving the reporting of delirium biomarker research and, consequently the capacity to synthesise results across studies.Item Clinical Characterization of Juvenile Fibromyalgia in a Multicenter Cohort of Adolescents Enrolled in a Randomized Clinical Trial(Wiley, 2023) Lynch-Jordan, Anne M.; Connelly, Mark; Guite, Jessica W.; King, Christopher; Goldstein-Leever, Alana; Logan, Deirdre E.; Nelson, Sarah; Stinson, Jennifer N.; Ting, Tracy V.; Wakefield, Emily O.; Williams, Amy E.; Williams, Sara E.; Kashikar-Zuck, Susmita; Fibromyalgia Integrative Training for Teens Clinical Trial Study Group; Childhood Arthritis and Rheumatology Research Alliance Pain Workgroup Investigators; Psychiatry, School of MedicineObjective: Juvenile fibromyalgia (JFM) is a complex chronic pain condition that remains poorly understood. The study aimed to expand the clinical characterization of JFM in a large representative sample of adolescents with JFM and identify psychological factors that predict pain interference. Methods: Participants were 203 adolescents (ages 12-17 years) who completed baseline assessments for the multisite Fibromyalgia Integrative Training for Teens (FIT Teens) randomized control trial. Participants completed the Pain and Symptom Assessment Tool, which includes a Widespread Pain Index (WPI; 0-18 pain locations) and Symptom Severity checklist of associated somatic symptoms (SS; 0-12) based on the 2010 American College of Rheumatology criteria for fibromyalgia. Participants also completed self-report measures of pain intensity, functional impairment, and psychological functioning. Results: Participants endorsed a median of 11 painful body sites (WPI score) and had a median SS score of 9. Fatigue and nonrestorative sleep were prominent features and rated as moderate to severe by 85% of participants. Additionally, neurologic, autonomic, gastroenterologic, and psychological symptoms were frequently endorsed. The WPI score was significantly correlated with pain intensity and catastrophizing, while SS scores were associated with pain intensity and all domains of physical and psychological functioning. Depressive symptoms, fatigue, and pain catastrophizing predicted severity of pain impairment. Conclusion: JFM is characterized by chronic widespread pain with fatigue, nonrestorative sleep, and other somatic symptoms. However, how diffusely pain is distributed appears less important to clinical outcomes and impairment than other somatic and psychological factors, highlighting the need for a broader approach to the assessment and treatment of JFM.Item Defining Suicidal Thought and Behavior Phenotypes for Genetic Studies(medRxiv, 2024-07-29) Monson, Eric T.; Colbert, Sarah M. C.; Andreassen, Ole A.; Ayinde, Olatunde O.; Bejan, Cosmin A.; Ceja, Zuriel; Coon, Hilary; DiBlasi, Emily; Izotova, Anastasia; Kaufman, Erin A.; Koromina, Maria; Myung, Woojae; Nurnberger, John I., Jr.; Serretti, Alessandro; Smoller, Jordan W.; Stein, Murray B.; Zai, Clement C.; Suicide Working Group of the Psychiatric Genomics Consortium; Aslan, Mihaela; Barr, Peter B.; Bigdeli, Tim B.; Harvey, Philip D.; Kimbrel, Nathan A.; Patel, Pujan R.; Cooperative Studies Program (CSP) #572; Ruderfer, Douglas; Docherty, Anna R.; Mullins, Niamh; Mann, J. John; Psychiatry, School of MedicineBackground: Standardized definitions of suicidality phenotypes, including suicidal ideation (SI), attempt (SA), and death (SD) are a critical step towards improving understanding and comparison of results in suicide research. The complexity of suicidality contributes to heterogeneity in phenotype definitions, impeding evaluation of clinical and genetic risk factors across studies and efforts to combine samples within consortia. Here, we present expert and data-supported recommendations for defining suicidality and control phenotypes to facilitate merging current/legacy samples with definition variability and aid future sample creation. Methods: A subgroup of clinician researchers and experts from the Suicide Workgroup of the Psychiatric Genomics Consortium (PGC) reviewed existing PGC definitions for SI, SA, SD, and control groups and generated preliminary consensus guidelines for instrument-derived and international classification of disease (ICD) data. ICD lists were validated in two independent datasets (N = 9,151 and 12,394). Results: Recommendations are provided for evaluated instruments for SA and SI, emphasizing selection of lifetime measures phenotype-specific wording. Recommendations are also provided for defining SI and SD from ICD data. As the SA ICD definition is complex, SA code list recommendations were validated against instrument results with sensitivity (range = 15.4% to 80.6%), specificity (range = 67.6% to 97.4%), and positive predictive values (range = 0.59-0.93) reported. Conclusions: Best-practice guidelines are presented for the use of existing information to define SI/SA/SD in consortia research. These proposed definitions are expected to facilitate more homogeneous data aggregation for genetic and multisite studies. Future research should involve refinement, improved generalizability, and validation in diverse populations.Item Diffusion tensor analysis of white matter tracts is prognostic of persisting post-concussion symptoms in collegiate athletes(Elsevier, 2024) Bertò, Giulia; Rooks, Lauren T.; Broglio, Steven P.; McAllister, Thomas A.; McCrea, Michael A.; Pasquina, Paul F.; Giza, Christopher; Brooks, Alison; Mihalik, Jason; Guskiewicz, Kevin; Goldman, Josh; Duma, Stefan; Rowson, Steven; Port, Nicholas L.; Pestilli, Franco; Psychiatry, School of MedicineBackground and objectives: After a concussion diagnosis, the most important issue for patients and loved ones is how long it will take them to recover. The main objective of this study is to develop a prognostic model of concussion recovery. This model would benefit many patients worldwide, allowing for early treatment intervention. Methods: The Concussion Assessment, Research and Education (CARE) consortium study enrolled collegiate athletes from 30 sites (NCAA athletic departments and US Department of Defense service academies), 4 of which participated in the Advanced Research Core, which included diffusion-weighted MRI (dMRI) data collection. We analyzed the dMRI data of 51 injuries of concussed athletes scanned within 48 h of injury. All athletes were cleared to return-to-play by the local medical staff following a standardized, graduated protocol. The primary outcome measure is days to clearance of unrestricted return-to-play. Injuries were divided into early (return-to-play < 28 days) and late (return-to-play >= 28 days) recovery based on the return-to-play clinical records. The late recovery group meets the standard definition of Persisting Post-Concussion Symptoms (PPCS). Data were processed using automated, state-of-the-art, rigorous methods for reproducible data processing using brainlife.io. All processed data derivatives are made available at https://brainlife.io/project/63b2ecb0daffe2c2407ee3c5/dataset. The microstructural properties of 47 major white matter tracts, 5 callosal, 15 subcortical, and 148 cortical structures were mapped. Fractional Anisotropy (FA) and Mean Diffusivity (MD) were estimated for each tract and structure. Correlation analysis and Receiver Operator Characteristic (ROC) analysis were then performed to assess the association between the microstructural properties and return-to-play. Finally, a Logistic Regression binary classifier (LR-BC) was used to classify the injuries between the two recovery groups. Results: The mean FA across all white matter volume was negatively correlated with return-to-play (r = -0.38, p = 0.00001). No significant association between mean MD and return-to-play was found, neither for FA nor MD for any other structure. The mean FA of 47 white matter tracts was negatively correlated with return-to-play (rμ = -0.27; rσ = 0.08; rmin = -0.1; rmax = -0.43). Across all tracts, a large mean ROC Area Under the Curve (AUCFA) of 0.71 ± 0.09 SD was found. The top classification performance of the LR-BC was AUC = 0.90 obtained using the 16 statistically significant white matter tracts. Discussion: Utilizing a free, open-source, and automated cloud-based neuroimaging pipeline and app (https://brainlife.io/docs/tutorial/using-clairvoy/), a prognostic model has been developed, which predicts athletes at risk for slow recovery (PPCS) with an AUC=0.90, balanced accuracy = 0.89, sensitivity = 1.0, and specificity = 0.79. The small number of participants in this study (51 injuries) is a significant limitation and supports the need for future large concussion dMRI studies and focused on recovery.Item Sitagliptin elevates plasma and CSF incretin levels following oral administration to nonhuman primates: relevance for neurodegenerative disorders(Springer, 2024) Li, Yazhou; Vaughan, Kelli L.; Wang, Yun; Yu, Seong‑Jin; Bae, Eun‑Kyung; Tamargo, Ian A.; Kopp, Katherine O.; Tweedie, David; Chiang, Cheng‑Chuan; Schmidt, Keith T.; Lahiri, Debomoy K.; Tones, Michael A.; Zaleska, Margaret M.; Hoffer, Barry J.; Mattison, Julie A.; Greig, Nigel H.; Psychiatry, School of MedicineThe endogenous incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) possess neurotrophic, neuroprotective, and anti-neuroinflammatory actions. The dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin reduces degradation of endogenous GLP-1 and GIP, and, thereby, extends the circulation of these protective peptides. The current nonhuman primate (NHP) study evaluates whether human translational sitagliptin doses can elevate systemic and central nervous system (CNS) levels of GLP-1/GIP in naive, non-lesioned NHPs, in line with our prior rodent studies that demonstrated sitagliptin efficacy in preclinical models of Parkinson's disease (PD). PD is an age-associated neurodegenerative disorder whose current treatment is inadequate. Repositioning of the well-tolerated and efficacious diabetes drug sitagliptin provides a rapid approach to add to the therapeutic armamentarium for PD. The pharmacokinetics and pharmacodynamics of 3 oral sitagliptin doses (5, 20, and 100 mg/kg), equivalent to the routine clinical dose, a tolerated higher clinical dose and a maximal dose in monkey, were evaluated. Peak plasma sitagliptin levels were aligned both with prior reports in humans administered equivalent doses and with those in rodents demonstrating reduction of PD associated neurodegeneration. Although CNS uptake of sitagliptin was low (cerebrospinal fluid (CSF)/plasma ratio 0.01), both plasma and CSF concentrations of GLP-1/GIP were elevated in line with efficacy in prior rodent PD studies. Additional cellular studies evaluating human SH-SY5Y and primary rat ventral mesencephalic cultures challenged with 6-hydroxydopamine, established cellular models of PD, demonstrated that joint treatment with GLP-1 + GIP mitigated cell death, particularly when combined with DPP-4 inhibition to maintain incretin levels. In conclusion, this study provides a supportive translational step towards the clinical evaluation of sitagliptin in PD and other neurodegenerative disorders for which aging, similarly, is the greatest risk factor.Item Neural Activity in the Anterior Insula at Drinking Onset and Licking Relates to Compulsion-Like Alcohol Consumption(Society for Neuroscience, 2024-02-28) Starski, Phillip; Morningstar, Mitch D.; Katner, Simon N.; Frasier, Raizel M.; De Oliveira Sergio, Thatiane; Wean, Sarah; Lapish, Christopher C.; Hopf, F. Woodward; Psychiatry, School of MedicineMuch remains unknown about the etiology of compulsion-like alcohol drinking, where consumption persists despite adverse consequences. The role of the anterior insula (AIC) in emotion, motivation, and interoception makes this brain region a likely candidate to drive challenge-resistant behavior, including compulsive drinking. Indeed, subcortical projections from the AIC promote compulsion-like intake in rats and are recruited in heavy-drinking humans during compulsion for alcohol, highlighting the importance of and need for more information about AIC activity patterns that support aversion-resistant responding. Single-unit activity was recorded in the AIC from 15 male rats during alcohol-only and compulsion-like consumption. We found three sustained firing phenotypes, sustained-increase, sustained-decrease, and drinking-onset cells, as well as several firing patterns synchronized with licking. While many AIC neurons had session-long activity changes, only neurons with firing increases at drinking onset had greater activity under compulsion-like conditions. Further, only cells with persistent firing increases maintained activity during pauses in licking, suggesting roles in maintaining drive for alcohol during breaks. AIC firing was not elevated during saccharin drinking, similar to lack of effect of AIC inhibition on sweet fluid intake in many studies. In addition, we observed subsecond changes in AIC neural activity tightly entrained to licking. One lick-synched firing pattern (determined for all licks in a session) predicted compulsion-like drinking, while a separate lick-associated pattern correlated with greater consumption across alcohol intake conditions. Collectively, these data provide a more integrated model for the role of AIC firing in compulsion-like drinking, with important relevance for how the AIC promotes sustained motivated responding more generally.Item The role of beta- and alpha-adrenergic receptors on alcohol drinking(Elsevier, 2023) De Oliveira Sergio, Thatiane; Wean, Sarah; Katner, Simon Nicholas; Hopf, Frederic W.; Psychiatry, School of MedicineAlcohol Use Disorders (AUD) is characterized by compulsion-like alcohol drinking (CLAD), where intake despite negative consequences can be a major clinical obstacle. With few treatment options available for AUD, there is a significant need for novel therapies. The noradrenergic system is an important hub for regulating stress responses and maladaptive drives for alcohol. Studies have shown that drugs targeting α1 adrenenergic receptors (ARs) may represent a pharmacological treatment for pathological drinking. However, the involvement of β ARs for treating human drinking has received scant investigation, and thus we sought to provide pre-clinical validation for possible AR utility for CLAD by analyzing whether β AR antagonists propranolol (β1/2), betaxolol (β1), and ICI, 118,551 (β2) impacted CLAD and alcohol-only drinking (AOD) in male Wistar rats. We found that the highest dose of propranolol tested systemically (10 mg/kg) reduced alcohol drinking, while 5 mg/kg propranolol reduced drinking with a trend to impact CLAD more than AOD, and with no effects of 2.5 mg/kg. Betaxolol (2.5 mg/kg) also decreased drinking, while ICI 118.551 had no effects. Also, while AR compounds might have utility for AUD, they can also lead to undesirable side effects. Here, a combination of ineffective doses of propranolol and prazosin reduced both CLAD and AOD. Finally, we investigated the effect of propranolol and betaxolol in two brain areas related to pathological drinking, the anterior insula (aINS) and medial prefrontal cortex (mPFC). Surprisingly, propranolol (1-10 μg) in aINS or mPFC did not affect CLAD or AOD. Together, our findings provide new pharmacological insights into noradrenergic regulation of alcohol consumption, which may inform AUD therapy.Item Interactive effects of drinking history and impulsivity on college drinking(Elsevier, 2013) Adams, Zachary W.; Milich, Richard; Lynam, Donald R.; Charnigo, Richard J.; Psychiatry, School of MedicineThe transition from adolescence into emerging adulthood is a critical developmental period for changes in alcohol use and drinking related problems. Prior research has identified a number of distinct developmental alcohol use trajectories, which appear to be differentially related to young adult drinking outcomes. Another correlate of alcohol use in early adulthood is impulsivity. The primary aim of this study was to examine the moderating role of impulsivity in the relation between patterns of past alcohol use and hazardous drinking during the first year of college. Participants (N=452; 49% male; mean age 18.5years; 82% Caucasian) completed self-report measures during the first year of college, including retrospective alcohol use calendars, current alcohol use and drinking problems, and personality. Group-based trajectory modeling was used to identify groups with similar adolescent drinking history from retrospective, self-report. Four groups were identified: abstainers/very light users, late/moderate users, early/moderate users, and steep increase/heavy users. The abstainer/very light user group reported the lowest levels of alcohol use and problematic drinking in college; the steep increase/heavy use group reported the highest levels of alcohol use and problematic drinking. As predicted, the role of personality-specifically urgency, or emotion-based rash action-was strongest among moderate use groups. These findings may be helpful in guiding targeted prevention and intervention programs for alcohol use and abuse.