Publications by authors named "Jennifer Stewart"

191 Publications

Amplification of Positivity Therapy for Co-occurring Alcohol Use Disorder with Depression and Anxiety Symptoms: Pilot Feasibility Study and Case Series.

Behav Modif 2021 Jul 12:1454455211030506. Epub 2021 Jul 12.

Laureate Institute for Brain Research, Tulsa, OK, USA.

Positive valence system dysregulation is a relatively unexplored transdiagnostic mechanism and potential treatment target underpinning alcohol use and anxiety and depression symptoms. The current study examined the feasibility and potential benefit of a behavioral intervention focused on amplification of positivity (AMP) with eight adults (five female) diagnosed with alcohol use disorder and clinically significant depression or anxiety (ClinicalTrials.gov: NCT04278365). AMP for alcohol use (AMP-A) was delivered in 11 individual sessions involving positive activity interventions integrated alongside psychoeducation and alcohol use monitoring. Case descriptions are provided to illustrate treatment implementation. Treatment credibility and acceptability, participant endorsement of the therapy, and homework compliance were rated moderate to high. Exploratory, intent-to-treat analyses suggested medium to large effect sizes for post-treatment improvements in alcohol use, depression, anxiety, and positive affect. Results provide initial evidence of feasibility and acceptability of AMP-A and will be useful for informing future randomized clinical trials to examine clinical efficacy.
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http://dx.doi.org/10.1177/01454455211030506DOI Listing
July 2021

The Impact of COVID-19 on Adolescent Mental Health: Preliminary Findings From a Longitudinal Sample of Healthy and At-Risk Adolescents.

Front Pediatr 2021 8;9:622608. Epub 2021 Jun 8.

Laureate Institute for Brain Research, Tulsa, OK, United States.

The COVID-19 pandemic has brought on far-reaching consequences for adolescents. Adolescents with early life stress (ELS) may be at particular risk. We sought to examine how COVID-19 impacted psychological functioning in a sample of healthy and ELS-exposed adolescents during the pandemic. A total of 24 adolescents (15 healthy, nine ELS) completed self-report measures prior to and during the COVID-19 pandemic. The effect of COVID-19 on symptoms of depression and anxiety were explored using linear mixed-effect analyses. With the onset of the pandemic, healthy but not ELS-exposed adolescents evidenced increased symptoms of depression and anxiety (s < 0.05). Coping by talking with friends and prioritizing sleep had a protective effect against anxiety for healthy adolescents ( = -3.76, = 0.002). On average, this study demonstrated large increases in depression and anxiety in adolescents who were healthy prior to the COVID-19 pandemic, while ELS-exposed adolescents evidenced high but stable symptoms over time.
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http://dx.doi.org/10.3389/fped.2021.622608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217763PMC
June 2021

Pathological findings in horses with lumbosacral region pain.

Equine Vet J 2021 Jun 12. Epub 2021 Jun 12.

Centre for Equine Studies, Animal Health Trust, Lanwades Park, Newmarket, Suffolk, CB8 7UU, UK.

Background: There is a lack of understanding of the pathological and/or physiological nature of lumbosacral region pain.

Objectives: To describe the gross variations of the osseous and soft tissues of the lumbosacral region and report the histological findings of sections of nerve tissue in affected and control horses.

Study Design: Descriptive post-mortem case series.

Methods: All horses had undergone full clinical and gait assessment, including ridden exercise. Horses with a substantial response to infiltration of local anaesthetic solution around the sacroiliac joint regions were included in the affected group (n=27). Horses for which the source(s) of pain was confirmed by diagnostic anaesthesia to be distant to the lumbosacral region were included in the control group (n=5). The pelvic regions were isolated and the soft tissues were assessed grossly. Sections of the lumbosacral plexus and cranial gluteal, sciatic and obturator nerves were examined histologically. The osseous specimens were evaluated for anatomical variants and abnormalities. Data were analysed using descriptive statistics.

Results: Gross discolouration of the sciatic or obturator nerves was observed in 7 (26%) affected and no control horses. Grade 3/3 histological abnormality scores were assigned in 22% of nerve sections from affected horses compared with 3% from control horses. Several osseous variants (bifid sacral spinous processes, straight-shaped sacroiliac joint surface, short arrow-shaped sacral alae, left-right asymmetry of sacral alae, sacral curvature, absence of the 4 -5 and ankylosis of the 5 -6 lumbar articular process joints, left-right asymmetry of caudocranial position of the 4 -5 and lumbar-sacral articular process joints) and abnormalities (sacroiliac enthesopathy, extra ventral sacroiliac joint surface, lumbosacral symphyseal periarticular modelling, lumbosacral intertransverse joint pitting-lesions) were more frequently observed in affected horses.

Main Limitations: Both control and affected horses may have had pre-clinical abnormalities.

Conclusions: Lumbosacral region pain may reflect the presence of a number of pathological changes. Neural pain may play an important role in some horses.
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http://dx.doi.org/10.1111/evj.13488DOI Listing
June 2021

Long-term stability of computational parameters during approach-avoidance conflict in a transdiagnostic psychiatric patient sample.

Sci Rep 2021 Jun 3;11(1):11783. Epub 2021 Jun 3.

Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, OK, 74136, USA.

Maladaptive behavior during approach-avoidance conflict (AAC) is common to multiple psychiatric disorders. Using computational modeling, we previously reported that individuals with depression, anxiety, and substance use disorders (DEP/ANX; SUDs) exhibited differences in decision uncertainty and sensitivity to negative outcomes versus reward (emotional conflict) relative to healthy controls (HCs). However, it remains unknown whether these computational parameters and group differences are stable over time. We analyzed 1-year follow-up data from a subset of the same participants (N = 325) to assess parameter stability and relationships to other clinical and task measures. We assessed group differences in the entire sample as well as a subset matched for age and IQ across HCs (N = 48), SUDs (N = 29), and DEP/ANX (N = 121). We also assessed 2-3 week reliability in a separate sample of 30 HCs. Emotional conflict and decision uncertainty parameters showed moderate 1-year intra-class correlations (.52 and .46, respectively) and moderate to excellent correlations over the shorter period (.84 and .54, respectively). Similar to previous baseline findings, parameters correlated with multiple response time measures (ps < .001) and self-reported anxiety (r = .30, p < .001) and decision difficulty (r = .44, p < .001). Linear mixed effects analyses revealed that patients remained higher in decision uncertainty (SUDs, p = .009) and lower in emotional conflict (SUDs, p = .004, DEP/ANX, p = .02) relative to HCs. This computational modelling approach may therefore offer relatively stable markers of transdiagnostic psychopathology.
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http://dx.doi.org/10.1038/s41598-021-91308-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175390PMC
June 2021

Erratum to "Sex differences in circulating inflammatory mediators as a function of substance use disorder" [Drug Alcohol Depend. 221 (2021) 108610].

Drug Alcohol Depend 2021 Jul 21;224:108743. Epub 2021 May 21.

Laureate Institute for Brain Research, Tulsa, OK, USA; Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK, USA.

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http://dx.doi.org/10.1016/j.drugalcdep.2021.108743DOI Listing
July 2021

COVID-19 vaccine willingness and cannabis use histories.

medRxiv 2021 Apr 28. Epub 2021 Apr 28.

Background: Cannabis use is associated with problematic health-behaviors such as excessive alcohol and tobacco use, and sedentary behavior. Here, we examined the association between cannabis use history and an especially topical health-behavior, willingness to receive a COVID-19 vaccine.

Methods: COVID-19 vaccine willingness was surveyed in a subset of participants from the Tulsa 1000 Study, which is a longitudinal study of psychiatric treatment-seeking and healthy control participants. We identified 45 participants who completed a COVID-19 vaccine questionnaire and reported more than 10 lifetime cannabis uses. Those participants were compared to a group of 45 individuals with very light (<10) cannabis use histories who were propensity score-matched on age, sex, income, and race. Two-group -tests and Bayes factor analysis on vaccine willingness were conducted between groups. Exploratory correlation analyses were conducted on vaccine willingness and lifetime cannabis use levels within the cannabis group only.

Results: Vaccine willingness did not differ between the two groups ( =0.33, =.74; BF =4.3). However, a negative correlation was identified within the cannabis group, such that higher lifetime cannabis use histories correlated with less willingness to receive a vaccine (rho = -.33, =.03).

Conclusions: Although vaccine willingness did not differ between the two matched groups, preliminary evidence suggests that heavy lifetime cannabis use might indicate a reluctance to engage in health-promoting behaviors like receiving a COVID-19 vaccine.
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http://dx.doi.org/10.1101/2021.04.26.21256109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095213PMC
April 2021

Evaluation of natural killer cell assay performance on shipped blood specimens.

J Immunol Methods 2021 Aug 2;495:113049. Epub 2021 Apr 2.

Chronic Viral Diseases Branch, DHCPP/NCEZID, Centers for Disease Control and Prevention, Atlanta, GA, United States of America.

Documenting the importance of NK cell function as a biomarker for diseases and physiologic conditions including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), will require assays amenable to clinical implementation and standardization. Research studies typically perform NK functional assays on the day of sample collection. This pilot study was conducted to compare assay formats and specimen processing to identify those that are most tolerant of conditions required for shipping and amenable to standardization as shown by inter-assay and inter-laboratory correlation of results. We compared performance within and between assays that measure NK cell function using direct cytotoxicity [chromium-51 release (CRCA) or fluorescence (Flow Cytometry Cytotoxicity Assay, FCCA)] or an indirect surrogate marker (CD107a surface expression)]. Additional variables for within/between assay comparisons included time of testing (same day as specimen collection or next day within 24 h), specimen types [whole blood or isolated peripheral blood mononuclear cells (PBMCs)], and processing method (fresh or cryopreserved). Statistical measures included number of samples tested in assay conditions (n), medians (x͂), interquartile range (IQR), Pearson correlation coefficient (R), and correlation p-value (p). Samples came from 3 clinics and included 31 participants. Same day testing was only available for the subset of participants enrolled from the site of the laboratory performing CRCA. Results from same day CRCA testing of whole blood were considered the gold standard [n = 10, x͂=10.0%, IQR = 7.2%], and correlated well with PBMCs isolated next day [n = 26, x͂= 15.6%, IQR = 13.1%] [R = 0.59, p = 0.03]. Next day CRCA results were compromised using whole blood or frozen PBMCs. Next day FCCA cytotoxicity in PBMC [n = 30, x͂=34.1%, IQR = 15.5%] correlated with same day CRCA PMBC [R = 0.8, p = 0.001] and next day CRCA PMBC [R = 0.5, p < 0.0001]. CD107a expression after induction by PMA and ionomycin did not correlate with other cytotoxicity measures. NK function can be measured in PBMCs isolated after overnight shipping/storage at ambient temperature and CRCA and FCCA results on this sample type are well correlated.
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http://dx.doi.org/10.1016/j.jim.2021.113049DOI Listing
August 2021

Sex differences in circulating inflammatory mediators as a function of substance use disorder.

Drug Alcohol Depend 2021 04 15;221:108610. Epub 2021 Feb 15.

Laureate Institute for Brain Research, Tulsa, OK, USA; Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK, USA.

Background: Substance use disorders (SUD) with comorbid depression and anxiety are linked to poor treatment outcome and relapse. Although some depressed individuals exhibit elevated blood-based inflammation (interleukin-6 [IL-6] and C reactive protein [CRP]), few studies have examined whether the presence of SUD exacerbates inflammation.

Methods: Treatment-seeking individuals with major depressive disorder (MDD), anxiety disorders, and/or SUD (N = 160; 80 % with MDD) recruited into the Tulsa 1000 study provided blood samples, participated in clinical interviews, and completed a questionnaire battery querying symptoms of current psychopathology and emotional processing. Analyses followed a multistep process. First, groups were created on the presence versus absence of 1+ lifetime SUD diagnoses: SUD+ (37 F, 43 M) and SUD- (60 F, 20 M). Second, a principal component analysis (PCA) of questionnaire data resulted in two factors, one indexing negative emotionality/withdrawal motivation and one measuring positive emotionality/approach motivation. Third, SUD groups, extracted PCA factors, and nuisance covariates (age, body mass index [BMI], nicotine use, psychotropic medication [and hormone/contraception use in females]) were entered as simultaneous predictors of blood-based inflammation (IL-6, IL-8, IL-10, tumor necrosis factor-α, and CRP).

Results: Within females, SUD + exhibited higher IL-8 and IL-10 but lower CRP levels than SUD-. In contrast, SUD was not associated with biomarker levels in males. Across sexes, higher BMI was linked to higher IL-6 and CRP levels, and within the five biomarkers, IL-6 and CRP shared the most variance.

Conclusion: These findings point to sex-specific inflammatory profiles as a function of SUD that may provide new targets for intervention.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026624PMC
April 2021

Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder.

Brain Behav Immun 2021 03 26;93:214-225. Epub 2021 Jan 26.

Laureate Institute for Brain Research, Tulsa, OK, United States; Department of Community Medicine, University of Tulsa, Tulsa, OK, United States.

Background: Major depressive disorder (MDD) is the leading cause of years lived with disability worldwide, and up to 40% of individuals with MDD do not respond to current treatments. Studies suggest that peripheral inflammation plays an important role in the striatal mesolimbic dopamine pathway and corticostriatal reward circuitry in MDD. Although MDD patients show blunted striatal responses to reward, the link between degree of inflammation and attenuation of reward processing is unclear. We investigated whether MDD patients with elevated peripheral inflammation exhibit attenuated reward responses to enhance our understanding of MDD pathophysiology and develop more effective treatments for current non-responders.

Methods: MDD subjects varying on serum C-reactive protein (CRP) concentrations (MDD-High CRP, >3 mg/L, n = 44; MDD-Low CRP, <3 mg/L, n = 44) and healthy comparisons (HC, n = 44) completed a monetary incentive delay (MID) task and provided blood samples to measure inflammation-related markers. MDD-High and MDD-Low were propensity score-matched on age, sex, body mass index (BMI), smoking status, exercise and MID task head motion. Percent change in blood oxygen level-dependent (BOLD) signal during anticipation of wins and losses was extracted from bilateral nucleus accumbens, dorsal caudate and dorsolateral putamen regions of interest (ROIs). A linear mixed-effects model was used to test group (MDD-High, MDD-Low and HC), condition (large-win, small-win and no win), and their interaction for these ROIs as well as whole-brain voxelwise data. Analyses also tested group differences in inflammatory mediators. Correlations were used to explore the relationship between inflammatory mediators and brain regions showing differences between MDD-High and MDD-Low.

Results: MDD-High exhibited: (a) lower BOLD signal change in dorsal caudate, thalamus, left insula and left precuneus during anticipation of small wins than MDD-Low; and (b) higher serum soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 6 (IL-6) concentrations than MDD-Low and HC. MDD as a whole, regardless of CRP-based inflammation, exhibited: (a) lower precuneus BOLD signal change to large wins than HC; and (b) higher Interleukin 1 receptor antagonist (IL-1ra), macrophage-derived chemokine (MDC) and macrophage inflammatory protein-1 alpha (MIP-1α) concentrations than HC. Higher serum sICAM-1 concentrations were associated with lower caudate BOLD signal change to small wins only within the MDD-High group.

Conclusion: Within MDD patients, high inflammation (CRP, sICAM-1) was linked to reduced striatal activation recruited to discriminate intermediate reward magnitudes. These findings support an association between levels of peripheral inflammation and the degree of reward-related activation in individuals with MDD.

Registration Of Clinical Trials: The ClinicalTrials.gov identifier for the clinical protocol associated with data published in this current paper is NCT02450240, "Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders."
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http://dx.doi.org/10.1016/j.bbi.2021.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979507PMC
March 2021

Latent variables for region of interest activation during the monetary incentive delay task.

Neuroimage 2021 04 24;230:117796. Epub 2021 Jan 24.

Laureate Institute for Brain Research, 6655 South Yale Avenue, Tulsa, OK 74136, USA; Department of Community Medicine, Oxley Health Sciences, University of Tulsa, 800 South Tucker Drive, Tulsa, OK 74104, USA.

Background: The Monetary Incentive Delay task (MID) has been used extensively to probe anticipatory reward processes. However, individual differences evident during this task may relate to other constructs such as general arousal or valence processing (i.e., anticipation of negative versus positive outcomes). This investigation used a latent variable approach to parse activation patterns during the MID within a transdiagnostic clinical sample.

Methods: Participants were drawn from the first 500 individuals recruited for the Tulsa-1000 (T1000), a naturalistic longitudinal study of 1000 participants aged 18-55 (n = 476 with MID data). We employed a multiview latent analysis method, group factor analysis, to characterize factors within and across variable sets consisting of: (1) region of interest (ROI)-based blood oxygenation level-dependent (BOLD) contrasts during reward and loss anticipation; and (2) self-report measures of positive and negative valence and related constructs.

Results: Three factors comprised of ROI indicators emerged to accounted for >43% of variance and loaded on variables representing: (1) general arousal or general activation; (2) valence, with dissociable responses to anticipation of win versus loss; and (3) region-specific activation, with dissociable activation in salience versus perceptual brain networks. Two additional factors were comprised of self-report variables, which appeared to represent arousal and valence.

Conclusions: Results indicate that multiview techniques to identify latent variables offer a novel approach for differentiating brain activation patterns during task engagement. Such approaches may offer insight into neural processing patterns through dimension reduction, be useful for probing individual differences, and aid in the development of optimal explanatory or predictive frameworks.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110176PMC
April 2021

Perceptual insensitivity to the modulation of interoceptive signals in depression, anxiety, and substance use disorders.

Sci Rep 2021 Jan 22;11(1):2108. Epub 2021 Jan 22.

Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, OK, 74136, USA.

This study employed a series of heartbeat perception tasks to assess the hypothesis that cardiac interoceptive processing in individuals with depression/anxiety (N = 221), and substance use disorders (N = 136) is less flexible than that of healthy individuals (N = 53) in the context of physiological perturbation. Cardiac interoception was assessed via heartbeat tapping when: (1) guessing was allowed; (2) guessing was not allowed; and (3) experiencing an interoceptive perturbation (inspiratory breath hold) expected to amplify cardiac sensation. Healthy participants showed performance improvements across the three conditions, whereas those with depression/anxiety and/or substance use disorder showed minimal improvement. Machine learning analyses suggested that individual differences in these improvements were negatively related to anxiety sensitivity, but explained relatively little variance in performance. These results reveal a perceptual insensitivity to the modulation of interoceptive signals that was evident across several common psychiatric disorders, suggesting that interoceptive deficits in the realm of psychopathology manifest most prominently during states of homeostatic perturbation.
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http://dx.doi.org/10.1038/s41598-021-81307-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822872PMC
January 2021

Best practices for the development, analytical validation and clinical implementation of flow cytometric methods for chimeric antigen receptor T cell analyses.

Cytometry B Clin Cytom 2021 01 29;100(1):79-91. Epub 2020 Dec 29.

Navigate BioPharma Services, Inc., a Novartis subsidiary, Carlsbad, California, USA.

Chimeric Antigen Receptor (CAR) T cells are recognized as efficacious therapies with demonstrated ability to produce durable responses in blood cancer patients. Regulatory approvals and acceptance of these unique therapies by patients and reimbursement agencies have led to a significant increase in the number of next generation CAR T clinical trials. Flow cytometry is a powerful tool for comprehensive profiling of individual CAR T cells at multiple stages of clinical development, from product characterization during manufacturing to longitudinal evaluation of the infused product in patients. There are unique challenges with regard to the development and validation of flow cytometric methods for CAR T cells; moreover, the assay requirements for manufacturing and clinical monitoring differ. Based on the collective experience of the authors, this recommendation paper aims to review these challenges and present approaches to address them. The discussion focuses on describing key considerations for the design, optimization, validation and implementation of flow cytometric methods during the clinical development of CAR T cell therapies.
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http://dx.doi.org/10.1002/cyto.b.21985DOI Listing
January 2021

A Bayesian computational model reveals a failure to adapt interoceptive precision estimates across depression, anxiety, eating, and substance use disorders.

PLoS Comput Biol 2020 12 14;16(12):e1008484. Epub 2020 Dec 14.

Laureate Institute for Brain Research, Tulsa, Oklahoma, United States of America.

Recent neurocomputational theories have hypothesized that abnormalities in prior beliefs and/or the precision-weighting of afferent interoceptive signals may facilitate the transdiagnostic emergence of psychopathology. Specifically, it has been suggested that, in certain psychiatric disorders, interoceptive processing mechanisms either over-weight prior beliefs or under-weight signals from the viscera (or both), leading to a failure to accurately update beliefs about the body. However, this has not been directly tested empirically. To evaluate the potential roles of prior beliefs and interoceptive precision in this context, we fit a Bayesian computational model to behavior in a transdiagnostic patient sample during an interoceptive awareness (heartbeat tapping) task. Modelling revealed that, during an interoceptive perturbation condition (inspiratory breath-holding during heartbeat tapping), healthy individuals (N = 52) assigned greater precision to ascending cardiac signals than individuals with symptoms of anxiety (N = 15), depression (N = 69), co-morbid depression/anxiety (N = 153), substance use disorders (N = 131), and eating disorders (N = 14)-who failed to increase their precision estimates from resting levels. In contrast, we did not find strong evidence for differences in prior beliefs. These results provide the first empirical computational modeling evidence of a selective dysfunction in adaptive interoceptive processing in psychiatric conditions, and lay the groundwork for future studies examining how reduced interoceptive precision influences visceral regulation and interoceptively-guided decision-making.
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http://dx.doi.org/10.1371/journal.pcbi.1008484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769623PMC
December 2020

Best practices for optimization and validation of flow cytometry-based receptor occupancy assays.

Cytometry B Clin Cytom 2021 01 1;100(1):63-71. Epub 2020 Dec 1.

Flow Contract Site Laboratory, Bothell, Washington, USA.

In the development of therapeutic compounds that bind cell surface molecules, it is critical to demonstrate the extent to which the drug engages its target. For cell-associated targets, flow cytometry is well-suited to monitor drug-to-target engagement through receptor occupancy assays (ROA). The technology allows for the identification of specific cell subsets within heterogeneous populations and the detection of nonabundant cellular antigens. There are numerous challenges in the design, development, and implementation of robust ROA. Among the most difficult challenges are situations where there is receptor modulation or when the target-antigen is expressed at low levels. When the therapeutic molecules are bi-specific and bind multiple targets, these challenges are increased. This manuscript discusses the challenges and proposes best practices for designing, optimizing, and validating ROA.
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http://dx.doi.org/10.1002/cyto.b.21970DOI Listing
January 2021

Flow cytometric method transfer: Recommendations for best practice.

Cytometry B Clin Cytom 2021 01 18;100(1):52-62. Epub 2020 Nov 18.

Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland.

As with many aspects of the validation and monitoring of flow cytometric methods, the method transfer processes and acceptance criteria described for other technologies are not fully applicable. This is due to the complexity of the highly configurable instrumentation, the complexity of cellular measurands, the lack of qualified reference materials for most assays, and limited specimen stability. There are multiple reasons for initiating a method transfer, multiple regulatory settings, and multiple context of use. All of these factors influence the specific requirements for the method transfer. This recommendation paper describes the considerations and best practices for the transfer of flow cytometric methods and provides individual case studies as examples. In addition, the manuscript emphasizes the importance of appropriately conducting a method transfer on data reliability.
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http://dx.doi.org/10.1002/cyto.b.21971DOI Listing
January 2021

Machine Learning Analysis of Electronic Nose in a Transdiagnostic Community Sample With a Streamlined Data Collection Approach: No Links Between Volatile Organic Compounds and Psychiatric Symptoms.

Front Psychiatry 2020 16;11:503248. Epub 2020 Sep 16.

Laureate Institute for Brain Research, Tulsa, OK, United States.

Non-intrusive, easy-to-use and pragmatic collection of biological processes is warranted to evaluate potential biomarkers of psychiatric symptoms. Prior work with relatively modest sample sizes suggests that under highly-controlled sampling conditions, volatile organic compounds extracted from the human breath (exhalome), often measured by an electronic nose ("e-nose"), may be related to physical and mental health. The present study utilized a streamlined data collection approach and attempted to replicate and extend prior e-nose links to mental health in a standard research setting within large transdiagnostic community dataset (N = 1207; 746 females; 18-61 years) who completed a screening visit at the Laureate Institute for Brain Research between 07/2016 and 05/2018. Factor analysis was used to obtain latent exhalome variables, and machine learning approaches were employed using these latent variables to predict three types of symptoms independent of each other (depression, anxiety, and substance use disorder) within separate training and a test sets. After adjusting for age, gender, body mass index, and smoking status, the best fitting algorithm produced by the training set accounted for nearly 0% of the test set's variance. In each case the standard error included the zero line, indicating that models were not predictive of clinical symptoms. Although some sample variance was predicted, findings did not generalize to out-of-sample data. Based on these findings, we conclude that the exhalome, as measured by the e-nose within a less-controlled environment than previously reported, is not able to provide clinically useful assessments of current depression, anxiety or substance use severity.
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http://dx.doi.org/10.3389/fpsyt.2020.503248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524957PMC
September 2020

Best Practices in Dementia Care: A Review of the Grey Literature on Guidelines for Staffing and Physical Environment in Long-Term Care.

Can J Aging 2020 Nov 16:1-16. Epub 2020 Nov 16.

Alzheimer Society of B.C., Vancouver, British Columbia.

In its first national strategy on dementia, the Government of Canada has highlighted the need to improve quality of care for individuals living with dementia, with emphasis on following best practices and evidence in care delivery and providing care staff access to education and training. It is also known that the design of the physical environment of care homes is integral to the care experience of individuals living with dementia. Therefore, this study aims to identify the best national and international practices implemented in care homes for people living with dementia in: (1) education, training, staffing, and care practices; and (2) environmental design and physical infrastructure, through the review of relevant grey literature. This article highlights key recommendations for improving the quality of care for residents living with dementia in care homes, such as: (1) facilitating translation of training into practice, (2) maintaining consistent staffing levels, and (3) designing care homes to facilitate wayfinding, accessibility, safety, comfort, appropriate sensory stimulation, familiarity, and homelikeness. The findings from this review are expected to inform the development of guidelines for a provincial dementia-friendly care home designation program and various advocacy efforts to help achieve the objectives of the national strategy on dementia.
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http://dx.doi.org/10.1017/S0714980820000392DOI Listing
November 2020

Greater decision uncertainty characterizes a transdiagnostic patient sample during approach-avoidance conflict: a computational modelling approach.

J Psychiatry Neurosci 2021 01 4;46(1):E74-E87. Epub 2021 Jan 4.

From the Laureate Institute for Brain Research, Tulsa, OK, USA (Smith, Kirlic, Stewart, Touthang, Kuplicki, Khalsa, Feinstein, Paulus, Aupperle); and the Oxley College of Health Sciences, University of Tulsa, Tulsa, OK, USA (Stewart, Khalsa, Paulus, Aupperle).

Background: Imbalances in approach-avoidance conflict (AAC) decision-making (e.g., sacrificing rewards to avoid negative outcomes) are considered central to multiple psychiatric disorders. We used computational modelling to examine 2 factors that are often not distinguished in descriptive analyses of AAC: decision uncertainty and sensitivity to negative outcomes versus rewards (emotional conflict).

Methods: A previously validated AAC task was completed by 478 participants, including healthy controls ( = 59), people with substance use disorders ( = 159) and people with depression and/or anxiety disorders who did not have substance use disorders ( = 260). Using an active inference model, we estimated individual-level values for a model parameter that reflected decision uncertainty and another that reflected emotional conflict. We also repeated analyses in a subsample (59 healthy controls, 161 people with depression and/or anxiety disorders, 56 people with substance use disorders) that was propensity-matched for age and general intelligence.

Results: The model showed high accuracy (72%). As further validation, parameters correlated with reaction times and self-reported task motivations in expected directions. The emotional conflict parameter further correlated with self-reported anxiety during the task ( = 0.32, < 0.001), and the decision uncertainty parameter correlated with self-reported difficulty making decisions ( = 0.45, < 0.001). Compared to healthy controls, people with depression and/or anxiety disorders and people with substance use disorders showed higher decision uncertainty in the propensity-matched sample ( = 2.16, = 0.03, and = 2.88, = 0.005, respectively), with analogous results in the full sample; people with substance use disorders also showed lower emotional conflict in the full sample ( = 3.17, = 0.002).

Limitations: This study was limited by heterogeneity of the clinical sample and an inability to examine learning.

Conclusion: These results suggest that reduced confidence in how to act, rather than increased emotional conflict, may explain maladaptive approach-avoidance behaviours in people with psychiatric disorders.
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http://dx.doi.org/10.1503/jpn.200032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955838PMC
January 2021

Integration of Simultaneous Resting-State Electroencephalography, Functional Magnetic Resonance Imaging, and Eye-Tracker Methods to Determine and Verify Electroencephalography Vigilance Measure.

Brain Connect 2020 12 28;10(10):535-546. Epub 2020 Oct 28.

Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.

Concurrent electroencephalography and resting-state functional magnetic resonance imaging (rsfMRI) have been widely used for studying the (presumably) awake and alert human brain with high temporal/spatial resolution. Although rsfMRI scans are typically collected while individuals are instructed to focus their eyes on a fixated cross, objective and verified experimental measures to quantify degree of vigilance are not readily available. Electroencephalography (EEG) is the modality extensively used for estimating vigilance, especially during eyes-closed resting state. However, pupil size measured using an eye-tracker device could provide an indirect index of vigilance. Three 12-min resting scans (eyes open, fixating on the cross) were collected from 10 healthy control participants. We simultaneously collected EEG, fMRI, physiological, and eye-tracker data and investigated the correlation between EEG features, pupil size, and heart rate. Furthermore, we used pupil size and EEG features as regressors to find their correlations with blood-oxygen-level-dependent fMRI measures. EEG frontal and occipital beta power (FOBP) correlates with pupil size changes, an indirect index for locus coeruleus activity implicated in vigilance regulation ( = 0.306,  < 0.001). Moreover, FOBP also correlated with heart rate ( = 0.255,  < 0.001), as well as several brain regions in the anticorrelated network, including the bilateral insula and inferior parietal lobule. In this study, we investigated whether simultaneous EEG-fMRI combined with eye-tracker measurements can be used to determine EEG signal feature associated with vigilance measures during eyes-open rsfMRI. Our results support the conclusion that FOBP is an objective measure of vigilance in healthy human subjects. Impact statement We revealed an association between electroencephalography frontal and occipital beta power (FOBP) and pupil size changes during an eyes-open resting state, which supports the conclusion that FOBP could serve as an objective measure of vigilance in healthy human subjects. The results were validated by using simultaneously recorded heart rate and functional magnetic resonance imaging (fMRI). Interestingly, independently verified heart rate changes can also provide an easy-to-determine measure of vigilance during resting-state fMRI. These findings have important implications for an analysis and interpretation of dynamic resting-state fMRI connectivity studies in health and disease.
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http://dx.doi.org/10.1089/brain.2019.0731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757617PMC
December 2020

Parsing impulsivity in individuals with anxiety and depression who use Cannabis.

Drug Alcohol Depend 2020 12 16;217:108289. Epub 2020 Sep 16.

Laureate Institute for Brain Research. 6655 S. Yale Ave., Tulsa, OK 74136. USA; University of Tulsa, Tulsa, OK, USA.

Background: Individuals with anxiety/depression may impulsively use cannabis to acutely induce positive affect and attenuate aversive mood states. However, few studies have attempted to parse impulsivity displayed by anxious/depressed cannabis users. This investigation examined what aspects of impulsivity characterize those individuals using self-report and functional MRI (fMRI) measures.

Methods: Individuals with any lifetime anxiety/depression diagnoses and problematic cannabis use ("Anx/Dep+CB"; n=42) were compared to a propensity score-matched group with very low cannabis use ("Anx/Dep-lowCB"; n=42), and a healthy control group (n=37). Impulsivity was measured using the UPPS-P Impulsivity Questionnaire and the Stop Signal Task (SST) during fMRI. For UPPS-P, regression models estimated group-by-impulsivity subscale interactions with post-hoc pairwise tests. For the SST, similar regression models were estimated with four a-priori regions of interest (ROIs; right opercularis, orbitalis, dorsal and ventral anterior insula) during stop-success and stop-failure processing. Null SST findings were followed up using Bayes factor analysis to quantify the evidence in support of the null hypothesis.

Results: For the UPPS-P, a significant group-by-subscale interaction indicated that the Anx/Dep+CB group exhibited higher levels of impulsivity on the negative- and positive-urgency subscales relative to both comparison groups. Higher negative-urgency correlated with heavier lifetime cannabis use across groups. For the SST, there were no ROI task activation differences. Bayes factor analysis determined the null findings were at least three times more likely than the alternative hypothesis for all ROIs.

Conclusions: Impulsivity under periods of heightened affect, but not motor response inhibitions, characterized anxious/depressed individuals who use cannabis.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736515PMC
December 2020

High-sensitivity flow cytometric assays: Considerations for design control and analytical validation for identification of Rare events.

Cytometry B Clin Cytom 2021 01 17;100(1):42-51. Epub 2020 Sep 17.

Caprion Biosciences, Montreal, Quebec, Canada.

The current consensus recommendation papers dealing with the unique requirements for the analytical validation of assays performed by flow cytometry address the validation of sensitivity (both analytical and functional) only in general terms. In this paper, a detailed approach for designing and validating the sensitivity of rare event methods is described. The impact of panel design and optimization on the lower limit of quantification (LLOQ) and suggestions for reporting data near, or below, the LLOQ are addressed. This paper serves to provide best practices for the development, optimization, and analytical validation of flow cytometric assays designed to assess rare events. Note that this paper does not discuss clinical sensitivity validation, which addresses the positive and negative predictive value of the test result.
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http://dx.doi.org/10.1002/cyto.b.21949DOI Listing
January 2021

Evaluating the resource allocation index as a potential fMRI-based biomarker for substance use disorder.

Drug Alcohol Depend 2020 11 9;216:108211. Epub 2020 Aug 9.

Laureate Institute for Brain Research, 6655 South Yale Ave., Tulsa, OK, 74136, United States; Department of Community Medicine, Oxley Health Sciences, The University of Tulsa, 1215 S. Boulder Ave, Tulsa, OK, 74119, United States; Department of Psychiatry, University of California, San Diego, United States. Electronic address:

Background: There is a lack of neuroscience-based biomarkers for the diagnosis, treatment and monitoring of individuals with substance use disorders (SUD). The resource allocation index (RAI), a measure of the interrelationship between salience, executive control and default-mode brain networks (SN, ECN, and DMN), has been proposed as one such biomarker. However, the RAI has yet to be extensively tested in SUD samples.

Methods: The present analysis compared RAI scores between individuals with stimulant and/or opioid use disorders (SUD; n = 139, abstinent 4-365 days) and healthy controls (HC; n = 56) who had completed resting-state functional magnetic resonance imaging (fMRI) scans within the context of the Tulsa 1000 cohort. First, we used independent component analysis (ICA) to identify the SN, ECN, and DMN and extract their time series data. Second, we used multiple permutations of automatically identified networks to compute RAI as reported in the fMRI literature.

Results: First, the RAI as a metric depended substantially on the approach that was used to define the network components. Second, regardless of the selection of networks, after controlling for multiple testing there was no difference in RAI scores between SUD and HC. Third, the RAI was not associated with any substance use-related self-report measures.

Conclusion: Taken together, these findings do not provide evidence that RAI can be used as an fMRI-derived biomarker for the severity or diagnosis of individuals with SUD.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609625PMC
November 2020

Imprecise action selection in substance use disorder: Evidence for active learning impairments when solving the explore-exploit dilemma.

Drug Alcohol Depend 2020 10 6;215:108208. Epub 2020 Aug 6.

Laureate Institute for Brain Research, Tulsa, OK, USA.

Background: Substance use disorders (SUDs) are a major public health risk. However, mechanisms accounting for continued patterns of poor choices in the face of negative life consequences remain poorly understood.

Methods: We use a computational (active inference) modeling approach, combined with multiple regression and hierarchical Bayesian group analyses, to examine how treatment-seeking individuals with one or more SUDs (alcohol, cannabis, sedatives, stimulants, hallucinogens, and/or opioids; N = 147) and healthy controls (HCs; N = 54) make choices to resolve uncertainty within a gambling task. A subset of SUDs (N = 49) and HCs (N = 51) propensity-matched on age, sex, and verbal IQ were also compared to replicate larger group findings.

Results: Results indicate that: (a) SUDs show poorer task performance than HCs (p = 0.03, Cohen's d = 0.33), with model estimates revealing less precise action selection mechanisms (p = 0.004, d = 0.43), a lower learning rate from losses (p = 0.02, d = 0.36), and a greater learning rate from gains (p = 0.04, d = 0.31); and (b) groups do not differ significantly in goal-directed information seeking.

Conclusions: Findings suggest a pattern of inconsistent behavior in response to positive outcomes in SUDs combined with a tendency to attribute negative outcomes to chance. Specifically, individuals with SUDs fail to settle on a behavior strategy despite sufficient evidence of its success. These learning impairments could help account for difficulties in adjusting behavior and maintaining optimal decision-making during and after treatment.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502502PMC
October 2020

Heightened affective response to perturbation of respiratory but not pain signals in eating, mood, and anxiety disorders.

PLoS One 2020 15;15(7):e0235346. Epub 2020 Jul 15.

Laureate Institute for Brain Research, Tulsa, OK, United States of America.

Several studies have recently suggested that an abnormal processing of respiratory interoceptive and nociceptive (painful) stimuli may contribute to eating disorder (ED) pathophysiology. Mood and anxiety disorders (MA) are also characterized by abnormal respiratory symptoms, and show substantial comorbidity with ED. However, no studies have examined both respiratory and pain processing simultaneously within ED and MA. The present study systematically evaluated responses to perturbations of respiratory and nociceptive signals across the levels of physiology, behavior, and symptom report in a transdiagnostic ED sample (n = 51) that was individually matched to MA individuals (n = 51) and healthy comparisons (HC; n = 51). Participants underwent an inspiratory breath-holding challenge as a probe of respiratory interoception and a cold pressor challenge as a probe of pain processing. We expected both clinical groups to report greater stress and fear in response to respiratory and nociceptive perturbation than HCs, in the absence of differential physiological and behavioral responses. During breath-holding, both the ED and MA groups reported significantly more stress, feelings of suffocation, and suffocation fear than HC, with the ED group reporting the most severe symptoms. Moreover, anxiety sensitivity was related to suffocation fear only in the ED group. The heightened affective responses in the current study occurred in the absence of group differences in behavioral (breath hold duration, cold pressor duration) and physiological (end-tidal carbon dioxide, end-tidal oxygen, heart rate, skin conductance) responses. Against our expectations, there were no group differences in the response to cold pain stimulation. A matched-subgroup analysis focusing on individuals with anorexia nervosa (n = 30) produced similar results. These findings underscore the presence of abnormal respiratory interoception in MA and suggest that hyperreactivity to respiratory signals may be a potentially overlooked clinical feature of ED.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235346PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363095PMC
September 2020

Effect of Prior Formal Education on Successful Thoracic Epidural Placement By Anesthesia Residents.

J Cardiothorac Vasc Anesth 2020 Nov 12;34(11):3044-3048. Epub 2020 Jun 12.

Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN.

Objective: Catheter placement for thoracic epidural analgesia (TEA) is technically challenging; however, methods for teaching this technique to anesthesia residents have not been well-studied. The present study aimed to determine optimal teaching methods for proficient TEA catheter placement by comparing video-based formal resident education with traditional bedside training by attending physicians.

Design: Prospective, randomized study.

Setting: Large academic hospital, single institution.

Participants: The study comprised 76 postgraduate year 3 and 4 anesthesiology residents (38 intervention, 38 control).

Interventions: Formal education included an instructional video on proper TEA technique.

Measurements And Main Results: Measures of proficiency in TEA catheter placement included the time needed to complete the procedure successfully and the success of placement as indicated by patient confirmation. Residents who received formal video instruction had similar success in catheter placement and similar procedure times compared with the traditionally trained residents. The overall success rate was 99.2%, with faculty intervention required in only 17% of cases. More experienced residents (ie, having placed more epidural catheters) were faster at TEA catheter placement.

Conclusions: Formal video education for TEA catheter placement provided no additional improvement of resident proficiency compared with traditional training at a high-volume academic center. The success rate was very high in this group of residents; however, experiences at other institutions may vary. Future studies are needed to determine optimum teaching strategies for TEA.
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http://dx.doi.org/10.1053/j.jvca.2020.06.023DOI Listing
November 2020

Attenuated reward activations associated with cannabis use in anxious/depressed individuals.

Transl Psychiatry 2020 06 15;10(1):189. Epub 2020 Jun 15.

Laureate Institute for Brain Research, 6655S. Yale Ave, Tulsa, OK, 74136, USA.

Individuals with mood/anxiety disorders may use cannabis for "self-medication," i.e., to induce positive mood or attenuate aversive mood states. However, little neurobiological evidence supports such use. The goal of this investigation was to test the hypothesis that cannabis use attenuates striatal response to reward in those with mood/anxiety disorders. Reward-related processing was measured using a monetary incentive delay task under functional MRI. Individuals with any lifetime mood/anxiety disorder diagnoses and problematic cannabis use ("Mood/Anxiety+CB"; n = 41) were compared with a propensity score-matched group of similar subjects without cannabis use ("Mood/Anxiety-CB"; n = 41), and a cannabis-naïve healthy control group (n = 35). Activations during win- and loss-anticipations were extracted from bilateral nucleus accumbens, dorsal caudate, and dorsolateral putamen. Mixed models were estimated for each region separately for win- and loss-anticipations, with a test for the main effect of group, condition (e.g., high-win, low-win, neutral), and their interaction. A significant main effect of group for win- and loss-anticipation was observed for each striatal region. Specifically, the Mood/Anxiety+CB group exhibited the lowest striatal activations across condition levels relative to both the Mood/Anxiety-CB and healthy group. A significant group-by-condition interaction was only observed for the dorsolateral putamen and indicated divergent activation modulation as a function of win and loss-magnitude for Mood/Anxiety+CB subjects. Finally, individuals with heavier recent cannabis use showed greater attenuation of gain-related activation in all three striatal regions. There was no such relationship for other illicit drugs. These data support the hypothesis that cannabis use in individuals with mood/anxiety disorders is associated with attenuated brain processing of reward magnitude, which may contribute to persistent affective symptoms.
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http://dx.doi.org/10.1038/s41398-020-0807-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295993PMC
June 2020

Mapping common grey matter volume deviation across child and adolescent psychiatric disorders.

Neurosci Biobehav Rev 2020 08 30;115:273-284. Epub 2020 May 30.

School of Psychology, Institute of Brain Research and Rehabilitation (IBRR), Center for the Study of Applied Psychology and MRI Center, Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, South China Normal University, Guangzhou, China; Key Laboratory of Brain, Cognition and Education Sciences (South China Normal University), Ministry of Education. Electronic address:

Childhood and adolescence represent a time notable for the emergence of many psychiatric disorders, where comorbidity and co-occurrence of symptoms are well-documented. However, it remains unclear whether there exists common brain structural disturbance across psychiatric disorders in youth. Here, we conduct a transdiagnostic meta-analysis of 132 structural neuroimaging experiments in youth consisting of multiple psychiatric diagnoses. Compared to healthy peers, youth psychiatric disorders are characterized by reduced grey matter volume (GMV) of amygdala and lateral orbitofrontal cortex and enhanced GMV of ventromedial prefrontal cortex and precuneus. These four regions were then subjected to functional connectivity and decoding analyses based on healthy participant datasets, allowing for a data-driven quantitative inference on psychophysiological functions. These regions and their networks mapped onto systems implicated in negative valence, positive valence, as well as social and cognitive functioning. Together, our findings are consistent with transdiagnostic models of psychopathology, uncovering common structural disturbance across youth psychiatric disorders, potentially reflecting an intermediate transdiagnostic phenotype in association with broad dimensions of youth psychopathology.
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http://dx.doi.org/10.1016/j.neubiorev.2020.05.015DOI Listing
August 2020

Women with Major Depressive Disorder, Irrespective of Comorbid Anxiety Disorders, Show Blunted Bilateral Frontal Responses during Win and Loss Anticipation.

J Affect Disord 2020 08 11;273:157-166. Epub 2020 May 11.

Laureate Institute for Brain Research, 6655 South Yale Avenue, Tulsa, OK, 74136, USA; Department of Community Medicine, Oxley Health Sciences, University of Tulsa, 800 South Tucker Drive, Tulsa, OK, 74104, USA.

Background: Electroencephalography (EEG) studies suggest that major depressive disorder (MDD) is associated with lower left than right frontal brain activity (asymmetry), a pattern appearing stronger in women than men, and when elicited during emotionally-relevant paradigms versus an uncontrolled resting state. However, it is unclear whether this asymmetry pattern generalizes to the common presentation of MDD with co-occurring anxiety. Moreover, asymmetry may differ for anxiety subtypes, wherein anxious apprehension (AnxApp: worry characteristic of generalized anxiety disorder) appears left-lateralized, but anxious arousal (AnxAro: panic characteristic of social anxiety, posttraumatic stress, and panic disorders) may be right-lateralized.

Methods: This analysis attempted to replicate frontal EEG asymmetry patterns using functional magnetic resonance imaging (fMRI). Participants completed clinical interviews and a monetary incentive delay (MID) task during fMRI recording. We compared five groups of right-handed women from the Tulsa 1000 study, MDD (n=40), MDD-AnxApp (n=26), MDD-AnxAro (n=34), MDD-Both (with AnxApp and AnxAro; n=26), and healthy controls (CTL; n=24), as a function of MID anticipation condition (no win/loss, win, loss) and hemisphere on frontal blood oxygen-level-dependent (BOLD) signal.

Results: CTL exhibited higher bilateral superior, middle, and inferior middle frontal gyrus BOLD signal than the four MDD groups for high arousal (win and loss) conditions. However, frontal attenuations were unrelated to current depression/anxiety symptoms, suggestive of a trait as opposed to a state marker.

Limitations: This was a cross-sectional analysis restricted to women.

Conclusions: Reduced prefrontal cortex recruitment during processing of both positively and negatively valenced stimuli is consistent with the emotion context insensitivity theory of MDD.
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http://dx.doi.org/10.1016/j.jad.2020.04.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306441PMC
August 2020

The role of negative urgency in risky alcohol drinking and binge-eating in United Kingdom male and female students.

Addict Behav Rep 2020 Jun 8;11:100274. Epub 2020 Apr 8.

Division of Psychiatry and Applied Psychology, Institute of Mental Health, University of Nottingham, Innovation Park, United Kingdom.

Identifying students at risk of developing binge-eating and alcohol use disorders is a priority in the United Kingdom (UK). Although relationships between negative urgency (impulsive behavior during times of negative emotion), risky drinking, and binge-eating have been established in students from other countries, these links have yet to be replicated in male and female UK students. UK students aged 18-30 ( = 155) completed the: (1) the Urgency, Pre-meditation, Perseverance, Sensation Seeking (UPPS-P) negative urgency subscale; (2) Alcohol Use Disorders Identification Test (AUDIT); and (3) Binge-Eating Scale (BES). For categorical analysis, participants were assigned to one of four groups as a function of AUDIT and BES clinical cut-off scores: (1) no risk (28%); (2) risky drinkers (47%); (3) binge-eaters (6%); and (4) risky drinkers + binge-eaters (19%). For dimensional analysis, across students with non-zero AUDIT and BES scores ( = 141), BES, AUDIT, gender, and their interactions were entered as predictors in the same block of a regression. UPPS-P negative urgency was the dependent variable. Categorical results indicated that binge-eaters with and without risky drinking endorsed significantly higher negative urgency than students with no risk. Dimensional results showed that although higher BES and AUDIT scores were positively linked to higher negative urgency, but only the BES was significantly associated. Furthermore, BES shared substantially more variance with negative urgency than the AUDIT, and the BES-negative urgency relationship was stronger in male students than female students. High risk students may benefit the most from interventions that help regulate negative emotion.
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http://dx.doi.org/10.1016/j.abrep.2020.100274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171258PMC
June 2020

Neurobiology, Clinical Presentation, and Treatment of Methamphetamine Use Disorder: A Review.

JAMA Psychiatry 2020 09;77(9):959-966

Laureate Institute for Brain Research, Tulsa, Oklahoma.

Importance: The prevalence of and mortality associated with methamphetamine use has doubled during the past 10 years. There is evidence suggesting that methamphetamine use disorder could be the next substance use crisis in the United States and possibly worldwide.

Observation: The neurobiology of methamphetamine use disorder extends beyond the acute effect of the drug as a monoaminergic modulator and includes intracellular pathways focused on oxidative stress, neurotoxic and excitotoxic effects, and neuroinflammation. Similarly, the clinical picture extends beyond the acute psychostimulatory symptoms to include complex cardiovascular and cerebrovascular signs and symptoms that need to be identified by the clinician. Although there are no pharmacologic treatments for methamphetamine use disorder, cognitive behavioral therapy, behavioral activation, and contingency management show modest effectiveness.

Conclusions And Relevance: There is a need to better understand the complex neurobiology of methamphetamine use disorder and to develop interventions aimed at novel biological targets. Parsing the disorder into different processes (eg, craving or mood-associated alterations) and targeting the neural systems and biological pathways underlying these processes may lead to greater success in identifying disease-modifying interventions. Finally, mental health professionals need to be trained in recognizing early cardiovascular and cerebrovascular warning signs to mitigate the mortality associated with methamphetamine use disorder.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.0246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098650PMC
September 2020
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