Mental and Social Health Commons^™

Childhood Trauma And Inflammatory Biomarker Effects On Cortical Thinning In Schizophrenia Spectrum Disorders, Samantha Narvaez, Yizhou Ma, Joshua Chiappelli, Hemalatha Sampath, Alia Warner, Peter Kochunov, Giselli Scaini, Anilkumar Pillai, L Elliot Hong

Faculty, Staff and Student Publications

Patients with schizophrenia spectrum disorders (SSD) have higher risks for early and adult life traumatic events and suffer from a heightened body response to stress and increased inflammatory activities. We hypothesize that in SSD, the effect of stress is associated with prolonged activation of the inflammatory system and causes elevation in immune markers. We examined the effects of childhood trauma and adult stressful life events on a C-reactive protein (CRP) and their combined contribution to cortical thickness thinning in 49 SSD patients and 26 healthy controls. Participants with SSD reported higher levels of childhood trauma (p = 0.015) and lifetime …

Whole-Genome Sequence-Based Association Analysis Of African American Individuals With Bipolar Disorder And Schizophrenia, Runjia Li, Sarah A Gagliano Taliun, Kevin Liao, Matthew Flickinger, Janet L Sobell, Giulio Genovese, Adam E Locke, Rebeca Rothwell Chiu, Jonathon Lefaive, Jiongming Wang, Taylor Martins, Sinéad Chapman, Anna Neumann, Robert E Handsaker, Donna K Arnett, Kathleen C Barnes, Eric Boerwinkle, David Braff, Brian E Cade, Myriam Fornage, Richard A Gibbs, Karin F Hoth, Lifang Hou, Charles Kooperberg, Ruth J F Loos, Ginger A Metcalf, Courtney G Montgomery, Alanna C Morrison, Zhaohui S Qin, Susan Redline, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Kent D Taylor, Karine A Viaud-Martinez, Tim B Bigdeli, Stacey Gabriel, Sebastian Zollner, Albert V Smith, Goncalo Abecasis, Steve A Mccarroll, Michele T Pato, Carlos N Pato, Michael Boehnke, James Knowles, Hyun Min Kang, Roel A Ophoff, Jason Ernst, Laura J Scott

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In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole-genome sequencing (∼27X) of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of …

Lipidomic And Proteomic Insights From Extracellular Vesicles In The Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes, Chioma M Okeoma, Wasifa Naushad, Bryson C Okeoma, Carlos Gartner, Yulica Santos-Ortega, Calvin Vary, Savio Lima-Bastos, Victor Corasolla Carregari, Martin R Larsen, Alessio Noghero, Consuelo Walss-Bass, Rodrigo Grassi-Oliveira

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Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to reactive astrogliosis and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD. In particular, our study investigated neuroinflammatory signatures in SUD patients by isolating EVs from the dorsolateral prefrontal cortex (dlPFC) Brodmann's area 9 (BA9) from postmortem subjects. We isolated BA9-derived …

Defining Treatment-Resistant Bipolar Depression: Recommendations From The Isbd Task Force, Eduard Vieta, Roger S Mcintyre, Trisha Suppes, Tamsyn E Van Rheenen, Balwinder Singh, Kamilla Woznica Miskowiak, Allan H Young, Lakshmi N Yatham, Kyooseob Ha, Michael Berk, Holly A Swartz, Chantal Henry, Maja Pantovic Stefanovic, Gerard Anmella Diaz, Aysegul Ozerdem, Wiesław J Cubała, Diego Hidalgo-Mazzei, Mauricio Tohen, Isabella Pacchiarotti, Paula Villela Nunes, Carlos Lopez-Jaramillo, Ana Gonzalez-Pinto, Paolo Brambilla, Robert Post, Jair C Soares, Michael Bauer, Ana C Andreazza, Xavier Justes Fradera, Montserrat Cosials-Lopez, Giovanna Fico

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Objective: Despite the availability of approved treatments, a substantial proportion of patients with bipolar disorder experience treatment-resistant bipolar depression (TRBD), characterized by persistent depressive symptoms unresponsive to standard therapies. However, a universally accepted definition of TRBD is lacking. This consensus document, developed by the International Society for Bipolar Disorders (ISBD) Task Force on TRBD, aims to provide a standardized definition of TRBD to facilitate clinical trials, research, and treatment strategies.

Methods: The Task Force employed a literature review, clinical trials analysis, and expert consensus meetings to define TRBD.

Results: TRBD was defined as the failure to achieve a significant and …

Defining Treatment-Resistant Bipolar Depression: Recommendations From The Isbd Task Force, Eduard Vieta, Roger S Mcintyre, Trisha Suppes, Tamsyn E Van Rheenen, Balwinder Singh, Kamilla Woznica Miskowiak, Allan H Young, Lakshmi N Yatham, Kyooseob Ha, Michael Berk, Holly A Swartz, Chantal Henry, Maja Pantovic Stefanovic, Gerard Anmella Diaz, Aysegul Ozerdem, Wiesław J Cubała, Diego Hidalgo-Mazzei, Mauricio Tohen, Isabella Pacchiarotti, Paula Villela Nunes, Carlos Lopez-Jaramillo, Ana Gonzalez-Pinto, Paolo Brambilla, Robert Post, Jair C Soares, Michael Bauer, Ana C Andreazza, Xavier Justes Fradera, Montserrat Cosials-Lopez, Giovanna Fico

Faculty, Staff and Student Publications

Objective: Despite the availability of approved treatments, a substantial proportion of patients with bipolar disorder experience treatment-resistant bipolar depression (TRBD), characterized by persistent depressive symptoms unresponsive to standard therapies. However, a universally accepted definition of TRBD is lacking. This consensus document, developed by the International Society for Bipolar Disorders (ISBD) Task Force on TRBD, aims to provide a standardized definition of TRBD to facilitate clinical trials, research, and treatment strategies.

Methods: The Task Force employed a literature review, clinical trials analysis, and expert consensus meetings to define TRBD.

Results: TRBD was defined as the failure to achieve a significant and …

The Impact Of Household Dysfunction On Dating Violence Perpetration Among Adolescents In The United States: A Scoping Review, Sumaita Choudhury, Melissa F Peskin, Timothy J Walker, Emily T Hébert, Nivedhitha Parthasarathy, Kaitlyn L Zajack-Garcia, Lea Sacca, Christine M Markham

Faculty, Staff and Student Publications

Adverse childhood experiences, such as household dysfunction (HD), play a central role in how adolescents establish, experience, and navigate the challenges of relationship formation, maintenance, and dissolution. HD exposures have been independently associated with dating violence (DV) perpetration in both adolescents and adults. However, research examining the association between the concurrent effect of HD on DV perpetration, especially among adolescents remains scarce. Thus, we conducted a scoping review to accumulate and summarize existing research regarding the impact of HD on DV perpetration among adolescents aged 10 to 17 years in the United States. We used three electronic databases, Medline (Ovid), …

Βiv Spectrin Abundancy, Cellular Distribution And Sensitivity To Akt/Gsk3 Regulation In Schizophrenia, Jessica Di Re, Michela Marini, Syed Ibrar Hussain, Aditya K Singh, Akshaya Venkatesh, Musaad A Alshammari, Tahani K Alshammari, Abdul-Rizaq Ali Hamoud, Ali Sajid Imami, Zahra Haghighijoo, Nickolas Fularcyzk, Laura Stertz, Derek Hawes, Angela Mosebarger, Jordan Jernigan, Claire Chaljub, Ralda Nehme, Consuelo Walss-Bass, Anton Schulmann, Marquis P Vawter, Robert Mccullumsmith, Robert D Damoiseaux, Agenor Limon, Demetrio Labate, Michael F Wells, Fernanda Laezza

Faculty, Staff and Student Publications

Schizophrenia (SCZ) is a complex psychiatric disorder with unclear biological mechanisms. Spectrins, cytoskeletal proteins linked to neurodevelopmental disorders, are regulated by the AKT/GSK3 pathway, which is implicated in SCZ. However, the impact of SCZ-related dysregulation of this pathway on spectrin expression and distribution remains unexplored. Here, we show that βIV spectrin protein levels were reduced in neurons of the dorsolateral prefrontal cortex in SCZ postmortem samples compared to healthy control (HC) from the Human Brain Collection Core (HBCC). To investigate potential links between βIV spectrin and the AKT/GSK3 pathway, we analyzed the PsychEncode dataset, revealing elevated SPTBN4 and AKT2 mRNA …

Exploring Predictors Of Treatment Response To Glp-1 Receptor Agonists For Smoking Cessation, Luba Yammine, Constanza De Dios, Robert Suchting, Charles E Green, David A Nielsen, Consuelo Walss-Bass, Joy M Schmitz

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Introduction: Understanding predictors of smoking cessation medication efficacy facilitates the ability to enhance treatment effectiveness. In our pilot trial, exenatide, a glucagon-like peptide-1 receptor agonist, adjunct to nicotine patch improved smoking abstinence compared to nicotine patch alone. This secondary analysis explores potential baseline characteristics associated with differential treatment response to exenatide.

Aims and methods: The parent trial randomized (1:1) 84 smokers with prediabetes and/or overweight to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received nicotine patch (21 mg) and brief smoking cessation counseling, with biologically confirmed 7-day point prevalence abstinence at week 6 (end-of-treatment) deemed the primary outcome. …

Multi-Ancestry Genome-Wide Association Analyses Incorporating Snp-By-Psychosocial Interactions Identify Novel Loci For Serum Lipids, Amy R Bentley, Michael R Brown, Solomon K Musani, Karen L Schwander, Thomas W Winkler, Mario Sims, Tuomas O Kilpeläinen, Hugues Aschard, Traci M Bartz, Lawrence F Bielak, Jin-Fang Chai, Kumaraswamy Naidu Chitrala, Nora Franceschini, Mariaelisa Graff, Xiuqing Guo, Fernando P Hartwig, Andrea R V R Horimoto, Elise Lim, Yongmei Liu, Alisa K Manning, Ilja M Nolte, Raymond Noordam, Melissa A Richard, Albert V Smith, Yun Ju Sung, Dina Vojinovic, Rujia Wang, Yujie Wang, Mary F Feitosa, Sarah E Harris, Leo-Pekka Lyytikäinen, Giorgio Pistis, Rainer Rauramaa, Peter J Van Der Most, Erin Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Dan E Arking, Donna K Arnett, Christie Ballantyne, Eric Boerwinkle, Yii-Der Ida Chen, Martha L Daviglus, Lisa De Las Fuentes, Paul S De Vries, Joseph A C Delaney, Amanda M Fretts, Lynette Ekunwe, Jessica D Faul, Linda C Gallo, Sami Heikkinen, Georg Homuth, M Arfan Ikram, Carmen R Isasi, Jost Bruno Jonas, Liisa Keltikangas-Järvinen, Pirjo Komulainen, Aldi T Kraja, Jose E Krieger, Lenore Launer, Lifelines Cohort Study, Jianjun Liu, Kurt Lohman, Annemarie I Luik, Ani W Manichaikul, Pedro Marques-Vidal, Yuri Milaneschi, Stanford E Mwasongwe, Jeffrey R O'Connell, Kenneth Rice, Stephen S Rich, Pamela J Schreiner, Lars Schwettmann, James M Shikany, Xiao-Ou Shu, Jennifer A Smith, Harold Snieder, Nona Sotoodehnia, E Shyong Tai, Kent D Taylor, Lesley Tinker, Michael Y Tsai, André G Uitterlinden, Cornelia M Van Duijn, Diana Van Heemst, Melanie Waldenberger, Robert B Wallace, Hwee-Lin Wee, David R Weir, Wen-Bin Wei, Ko Willems Van Dijk, Gregory Wilson, Jie Yao, Kristin L Young, Xiaoyu Zhang, Wei Zhao, Xiaofeng Zhu, Alan B Zonderman, Ian J Deary, Christian Gieger, Hans Jörgen Grabe, Timo A Lakka, Terho Lehtimäki, Albertine J Oldehinkel, Martin Preisig, Ya-Xing Wang, Wei Zheng, Michele K Evans, Michael Province, James Gauderman, Vilmundur Gudnason, Catharina A Hartman, Bernardo L Horta, Sharon L R Kardia, Charles Kooperberg, Ching-Ti Liu, Dennis O Mook-Kanamori, Brenda Wjh Penninx, Alexandre C Pereira, Patricia A Peyser, Bruce M Psaty, Jerome I Rotter, Xueling Sim, Kari E North, Dabeeru C Rao, Laura Bierut, Clint L Miller, Alanna C Morrison, Charles N Rotimi, Myriam Fornage, Ervin R Fox

Faculty, Staff and Student Publications

Serum lipid levels, which are influenced by both genetic and environmental factors, are key determinants of cardiometabolic health and are influenced by both genetic and environmental factors. Improving our understanding of their underlying biological mechanisms can have important public health and therapeutic implications. Although psychosocial factors, including depression, anxiety, and perceived social support, are associated with serum lipid levels, it is unknown if they modify the effect of genetic loci that influence lipids. We conducted a genome-wide gene-by-psychosocial factor interaction (G×Psy) study in up to 133,157 individuals to evaluate if G×Psy influences serum lipid levels. We conducted a two-stage meta-analysis …

Perceived Neighborhood Crime And Gun Carrying Behavior: Examining The Role Of A History Of Traumatic Brain Injury, Eric J Connolly, Anne C Wingert, Dennis E Reidy, Jarrad D Hodge, Jeff R Temple

Faculty, Staff and Student Publications

Background: Individuals living in high crime neighborhoods are more likely to carry a firearm. Members of these communities are also more likely to experience a traumatic brain injury (TBI) in their lifetime, which is a common correlate of hypervigilance and aggression. The current study evaluates the independent and interactive effects of TBI on perceived levels of neighborhood crime and gun carrying.

Methods: Data from 2015 to 2017 from a longitudinal ethnically diverse sample of adolescents and young adults are analyzed (Ns = 600-734). Multivariate logistic regression models are estimated to evaluate associations between perceived levels of neighborhood crime, TBI, gun …

Assessment Of Contextualized Reinforcement Pathology In A Community Sample Of Young Adult Substance Users, Ángel García-Pérez, Alba González-Roz, Roberto Secades-Villa, Gema Aonso-Diego, Sara Weidberg, Jin H Yoon

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Background: Alcohol, tobacco, and cannabis are the most commonly used substances among young populations, often leading to polysubstance use, which correlates with problematic consumption and adverse health outcomes. The contextualized reinforcer pathology (CRP) model explains addictive behaviors through several constructs, including the following: drug demand, delay discounting (DD), and substance-free and substance-related reinforcement. Most previous studies have focused on a single CRP construct and the couse of only two substances. This study aimed to characterize three subgroups of young adults reporting past month use of alcohol only, alcohol + tobacco or cannabis, and alcohol + tobacco + cannabis, in terms …

Home-Based Transcranial Direct Current Stimulation For Major Depressive Disorder: 6-Month Follow-Up From Randomised Sham-Controlled Trial And Open-Label Treatment Phases, Rachel D Woodham, Sudhakar Selvaraj, Nahed Lajmi, Harriet Hobday, Gabrielle Sheehan, Ali-Reza Ghazi-Noori, Peter J Lagerberg, Rodrigo Machado-Vieira, Jair C Soares, Allan H Young, Cynthia H Y Fu

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Transcranial direct current stimulation (tDCS) is a potential home-based treatment for major depressive disorder (MDD). In our double-blind randomised controlled trial (RCT) (n = 174; UK and USA), a 10-week course of home-based tDCS demonstrated clinical efficacy (clinical response: 58.3 % active treatment arm and 37.8 % sham (p = 0.017). tDCS was delivered in a bifrontal montage, with anode over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC. Each session was 30 min, with active stimulation at 2 mA and sham at 0 mA, incorporating brief ramp-up and ramp-down phased. Following the 10-week RCT, all participants were …

Development Of An Age-Appropriate Household Dysfunction Measure And Its Concurrent Validity With Multiple Outcomes Among Middle School Adolescents In Southeast Texas, Sumaita Choudhury, Timothy J Walker, Emily T Hébert, Christine M Markham, Ross Shegog, Robert C Addy, Melissa F Peskin

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Existing adverse childhood experience (ACE) measures include a limited number of household dysfunction (HD) items and the use of adult-oriented language that is not always appropriate for middle schoolers. We developed an age-appropriate 10-item HD measure informed by previously validated ACE measures and tested its concurrent validity with dating violence (DV) perpetration, lifetime substance use, and mental health outcomes among middle schoolers in Southeast Texas. This cross-sectional study used the baseline data from a DV prevention intervention program for sixth graders (N = 126), Me & You Tech. Baseline data were collected from March 2023 to April 2023. To …

Development And Pilot Testing Of An Addiction Clinic-Based Pre-Exposure Prophylaxis Uptake And Adherence Intervention For Women With Substance Use Disorders: Protocol For A Pilot Randomized Trial, Angela M Heads, Diane Santa Maria, Mandy J Hill, Robert Suchting, Kimberly N Evans, Zaneta Gaul, Luba Yammine, Constanza De Dios, Joy M Schmitz

Faculty, Staff and Student Publications

Background: Black and Hispanic women in the United States continue to bear disproportionate incidence of HIV related to sexual transmission and injection drug use. Specifically, women with substance use disorders (SUDs) are more likely to engage in vaginal or anal condomless sex associated with HIV transmission. Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention tool but is not widely used by racial or ethnic minority women. Effective interventions for engaging women with SUDs in HIV prevention interventions that are culturally appropriate and, therefore, more appealing to racial or ethnic minority women with SUDs are critically needed.

Objective: This 3-phased …

Social Determinants Of Health Extraction From Clinical Notes Across Institutions Using Large Language Models, Vipina K Keloth, Salih Selek, Qingyu Chen, Christopher Gilman, Sunyang Fu, Yifang Dang, Xinghan Chen, Xinyue Hu, Yujia Zhou, Huan He, Jungwei W Fan, Karen Wang, Cynthia Brandt, Cui Tao, Hongfang Liu, Hua Xu

Faculty, Staff and Student Publications

Detailed social determinants of health (SDoH) is often buried within clinical text in EHRs. Most current NLP efforts for SDoH have limitations, investigating limited factors, deriving data from a single institution, using specific patient cohorts/note types, with reduced focus on generalizability. We aim to address these issues by creating cross-institutional corpora and developing and evaluating the generalizability of classification models, including large language models (LLMs), for detecting SDoH factors using data from four institutions. Clinical notes were annotated with 21 SDoH factors at two levels: level 1 (SDoH factors only) and level 2 (SDoH factors and associated values). Compared to …

Genetic, Transcriptomic, And Epigenomic Insights Into Sjögren's Disease: An Integrative Network Investigation And Immune Diseases Comparison, Nitesh Enduru, Astrid M Manuel, Zhongming Zhao

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Sjögren's disease (SjD) is a systemic autoimmune disorder primarily causing dry eyes and mouth. It frequently overlaps with other autoimmune diseases (AIDs), including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic basis of SjD remains underexplored, limiting our understanding of its connections to other immune-mediated conditions. In this study, we aimed to identify gene networks associated with SjD through the integration of genetic, transcriptomic, and epigenomic data. We further compared the genetic factors of SjD with other immune-mediated diseases. We analyzed genome-wide association studies (GWAS) summary statistics, DNA methylation, and transcriptomic data using our in-house network-based methods, …

Lifespan Reference Curves For Harmonizing Multi-Site Regional Brain White Matter Metrics From Diffusion Mri, Alyssa H Zhu, Talia M Nir, Shayan Javid, Julio E Villalón-Reina, Amanda L Rodrigue, Lachlan T Strike, Greig I De Zubicaray, Katie L Mcmahon, Margaret J Wright, Sarah E Medland, John Blangero, David C Glahn, Peter Kochunov, Douglas E Williamson, Asta K Håberg, Paul M Thompson, Neda Jahanshad

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Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3-95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data …

Neuroimaging-Based Variability In Subtyping Biomarkers For Psychiatric Heterogeneity, Zhenfu Wen, Mira Z Hammoud, Carole E Siegel, Eugene M Laska, Duna Abu-Amara, Amit Etkin, Mohammed R Milad, Charles R Marmar

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Neuroimaging-based subtyping is increasingly used to explain heterogeneity in psychiatric disorders. However, the clinical utility of these subtyping efforts remains unclear, and replication has been challenging. Here we examined how the choice of neuroimaging measures influences the derivation of neuro-subtypes and the consequences for clinical delineation. On a clinically heterogeneous dataset (total n = 566) that included controls (n = 268) and cases (n = 298) of psychiatric conditions, including individuals diagnosed with post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and comorbidity of both (PTSD&TBI), we identified neuro-subtypes among the cases using either structural, resting-state, or task-based measures. The …

Maternal Dysbiosis Produces Long-Lasting Behavioral Changes In Offspring, Jacob Hudobenko, Claudia M Di Gesù, Patrick R Mooz, Joseph Petrosino, Nagireddy Putluri, Bhanu P Ganesh, Kristen Rebeles, Frank W Blixt, Venugopal R Venna, Louise D Mccullough

Faculty, Staff and Student Publications

Advanced maternal age (AMA) is defined as a pregnancy in a woman older than 35 years of age. AMA increases the risk for both maternal and neonatal complications, including miscarriage and stillbirth. AMA has also been linked to neurodevelopmental and neuropsychiatric disorders in the offspring. Recent studies have found that age-associated compositional shifts in the gut microbiota contribute to altered microbial metabolism and enhanced inflammation in the host. We investigated the specific contribution of the maternal microbiome on pregnancy outcomes and offspring behavior by recolonizing young female mice with aged female microbiome prior to pregnancy. We discovered that pre-pregnancy colonization …

Cell Type-Specific Multi-Omics Analysis Of Cocaine Use Disorder In The Human Caudate Nucleus, Lea Zillich, Annasara Artioli, Veronika Pohořalá, Eric Zillich, Laura Stertz, Hanna Belschner, Ammar Jabali, Josef Frank, Fabian Streit, Diana Avetyan, Maja P Völker, Svenja Müller, Anita C Hansson, Thomas D Meyer, Marcella Rietschel, Julia Ladewig, Rainer Spanagel, Ana M M Oliveira, Consuelo Walss-Bass, Rick E Bernardi, Philipp Koch, Stephanie H Witt

Faculty, Staff and Student Publications

Structural and functional alterations in the brain's reward circuitry are present in cocaine use disorder (CocUD), but their molecular underpinnings remain unclear. To investigate these mechanisms, we performed single-nuclei multiome profiling on postmortem caudate nucleus tissue from six individuals with CocUD and eight controls. We profiled 30,030 nuclei, identifying 13 cell types including D1- and D2-medium spiny neurons (MSNs) and glial cells. We observed 1485 differentially regulated genes and 10,342 differentially accessible peaks, with alterations in MSNs and astrocytes related to neurotransmitter activity and synapse organization. Gene regulatory network analysis identified transcription factors including ZEB1 as exhibiting distinct CocUD-specific subclusters, …

Selected Social And Lifestyle Correlates Of Brain Health Markers: The Cross-Cohort Collaboration Consortium, Leslie Grasset, Joshua C Bis, Stefan Frenzel, Daniel Kojis, Jeannette Simino, Amber Yaqub, Alexa Beiser, Claudine Berr, Jan Bressler, Robin Bülow, Charles S Decarli, Alison E Fohner, Laura B Harrington, Catherine Helmer, M Arfan Ikram, Rozenn N Lemaitre, Oscar L Lopez, W T Longstreth, Julia Neitzel, Michelle C Odden, Priya Palta, Carsten O Schmidt, Rajesh Talluri, Meike W Vernooij, Henry Völzke, Trudy Voortman, Quest Whalen, Katharina Wittfeld, Hans J Grabe, Thomas H Mosley, Bruce M Psaty, Frank J Wolters, Sudha Seshadri, Carole Dufouil

Faculty, Staff and Student Publications

Introduction: To investigate the associations of education level, marital status, and physical activity with dementia risk and brain MRI markers.

Methods: Data from six community-based samples from the Cross-Cohort Collaboration Consortium were analyzed. Self-reported education level, marital status, and physical activity at age 60 to 75 years were harmonized. Subsamples of participants with brain MRI markers at time of exposure were selected. Associations with dementia risk and cross-sectional MRI markers were meta-analyzed.

Results: Higher education level was associated with lower dementia risk (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.59; 0.72 vs low level) but not significantly …

Evaluating The Meditation Practices And Barriers To Adopting Mindful Medicine Among Physicians, Tiffany Champagne-Langabeer, Chelsea G Ratcliff, Christine Bakos-Block, Francine Vega, Marylou Cardenas-Turanzas, Aila Malik, Radha Korupolu

Faculty, Staff and Student Publications

Background: Chronic pain affects over 25% of U.S. adults and is a leading cause of disability. Mindfulness meditation (MM) is a nonpharmacologic approach to manage pain and improve well-being. Despite mounting evidence supporting its efficacy, MM remains underutilized in medical practice. Understanding physicians' engagement with MM and the barriers they face can inform strategies for integration into clinical care. This study assessed physicians' attitudes toward MM, including barriers to practice and their likelihood of recommending it to patients.

Methods: A cross-sectional survey of U.S. physicians was conducted from April to July 2024. Participants provided information on demographics, health struggles, and …

An Adaptive Antiretroviral Therapy Adherence Intervention For Youth With Hiv Through Text Message And Cell Phone Support With And Without Incentives: A Sequential Multiple Assignment Randomized Trial (Smart), Marvin E Belzer, Karen Macdonell, Demetria Cain, Samiran Ghosh, Richard Zhao, Julie Mcavoy-Banerjea, Sitaji Gurung, Sylvie Naar

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Youth living with HIV have low rates of medication adherence. Youth ages 15-24 years with adherence ≤ 80% or with HIV RNA PCRs (VL) ≥ 200 recruited through social media and clinical sites were randomized to brief weekday cell phone support (CPS) calls or daily, two-way, personalized text message (SMS) reminders for 3 months. Those with VL ≥ 200 or adherence ≤ 80% were rerandomized to receive SMS or CPS with monthly incentives for those utilizing the intervention at least 75% of days for 3 months. Those with VL < 200 or adherence > 80% after the initial 3 months were rerandomized to usual care …

Intersect Between Brain Mechanisms Of Conditioned Threat, Active Avoidance, And Reward, Muhammad Badarnee, Zhenfu Wen, Mira Z Hammoud, Paul Glimcher, Christopher K Cain, Mohammed R Milad

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Active avoidance is a core behavior for human coping, and its excess is common across psychiatric diseases. The decision to actively avoid a threat is influenced by cost and reward. Yet, threat, avoidance, and reward have been studied in silos. We discuss behavioral and brain circuits of active avoidance and the interactions with fear and threat. In addition, we present a neural toggle switch model enabling fear-to-anxiety transition and approaching reward vs. avoiding harm decision. To fully comprehend how threat, active avoidance, and reward intersect, it is paramount to develop one shared experimental approach across phenomena and behaviors, which will …

Benefits Of Equilibrium Between Microbiota- And Host-Derived Ligands Of The Aryl Hydrocarbon Receptor After Stroke In Aged Male Mice, Pedram Peesh, Maria P Blasco-Conesa, Ahmad El Hamamy, Romeesa Khan, Gary U Guzman, Parisa Honarpisheh, Eric C Mohan, Grant W Goodman, Justin N Nguyen, Anik Banerjee, Bryce E West, Kyung Ae Ko, Janelle M Korf, Chunfeng Tan, Huihui Fan, Gabriela D Colpo, Hilda Ahnstedt, Lucy Couture, Solji Roh, Julia K Kofler, Jose F Moruno-Manchon, Michael E Maniskas, Jaroslaw Aronowski, Rodney M Ritzel, Juneyoung Lee, Jun Li, Robert M Bryan, Anjali Chauhan, Venugopal Reddy Venna, Louise D Mccullough, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Recent studies have highlighted the crucial role of microglia (MG) and their interactions with the gut microbiome in post-stroke neuroinflammation. The activation of immunoregulatory pathways, including the aryl hydrocarbon receptor (AHR) pathway, is influenced by a dynamic balance of ligands derived from both the host and microbiota. This study aimed to investigate the association between stroke-induced dysbiosis and the resultant imbalance in AHR ligand sources (loss of microbiota-derived [indole-based] and increase of host-derived [kynurenine-based]) after stroke. Microbiota-derived AHR ligands decreased in human plasma and remained low for days following an ischemic stroke highlighting the translational significance. Transient-middle-cerebral-artery-occlusion was performed in …

Classification Of Schizophrenia, Bipolar Disorder And Major Depressive Disorder With Comorbid Traits And Deep Learning Algorithms, Xiangning Chen, Yimei Lu, Joan Manuel Cue, Mira V Han, Vishwajit L Nimgaonkar, Daniel R Weinberger, Shizhong Han, Zhongming Zhao, Jingchun Chen

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Many psychiatric disorders share genetic liabilities, but whether these shared liabilities can be utilized to classify and differentiate psychiatric disorders remains unclear. In this study, we use polygenic risk scores (PRSs) of 42 traits comorbid with schizophrenia (SCZ), bipolar disorder (BIP), and major depressive disorder (MDD) to evaluate their utilities. We found that combining target specific PRS with PRSs of comorbid traits can improve the classification of the target disorders. Importantly, without inclusion of PRSs from targeted disorders, we can still classify SCZ (accuracy 0.710 ± 0.008, AUC 0.789 ± 0.011), BIP (accuracy 0.782 ± 0.006, AUC 0.852 ± 0.004), …

A Qualitative Assessment Of Changes In Occupational Exposures Among Healthcare Facility Workers, David Gimeno Ruiz De Porras, Jenil Patel, Sadie Conway, Lisa Pompeii, Laura E Mitchell, Arch Carson, Lawrence W Whitehead, Inkyu Han, Jan-Paul Zock, Paul K Henneberger, Riddhi Patel, Joy De Los Reyes, George L Delclos

Faculty, Staff and Student Publications

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. …

Suicide Phenotyping From Clinical Notes In Safety-Net Psychiatric Hospital Using Multi-Label Classification With Pre-Trained Language Models, Zehan Li, Yan Hu, Scott Lane, Salih Selek, Lokesh Shahani, Rodrigo Machado-Vieira, Jair Soares, Hua Xu, Hongfang Liu, Ming Huang

Faculty, Staff and Student Publications

Accurate identification and categorization of suicidal events can yield better suicide precautions, reducing operational burden, and improving care quality in high-acuity psychiatric settings. Pre-trained language models offer promise for identifying suicidality from unstructured clinical narratives. We evaluated the performance of four BERT-based models using two fine-tuning strategies (multiple single-label and single multi-label) for detecting coexisting suicidal events from 500 annotated psychiatric evaluation notes. The notes were labeled for suicidal ideation (SI), suicide attempts (SA), exposure to suicide (ES), and non-suicidal self-injury (NSSI). RoBERTa outperformed other models using binary relevance (acc=0.86, F1=0.78). MentalBERT (F1=0.74) also exceeded BioClinicalBERT (F1=0.72). RoBERTa fine-tuned with …

Evaluating The Emotional Accuracy Of Ai-Generated Facial Expressions In Neurotypical Individuals, Antonio Pagán, Katherine A Loveland, Ronald Acierno

Faculty, Staff and Student Publications

This study examines the ability of generative artificial intelligence to produce facial expressions representing basic emotions in a neutral context using black-and-white cartoon imagery. Mentalization, the capacity to recognize and interpret one’s own and others’ mental states, is critical for social interaction and emotional regulation. We explored the emotional validation of artificial intelligence (AI)-generated images by assessing the agreement between human interpretations of emotions and those generated by an AI model. Thirty-four participants evaluated images depicting six basic emotions: sadness, anger, happiness, surprise, fear, and disgust. Our findings revealed significant variability in human agreement, with higher concordance for sadness, anger, …

Home-Based Transcranial Direct Current Stimulation Treatment For Major Depressive Disorder: A Fully Remote Phase 2 Randomized Sham-Controlled Trial, Rachel D Woodham, Sudhakar Selvaraj, Nahed Lajmi, Harriet Hobday, Gabrielle Sheehan, Ali-Reza Ghazi-Noori, Peter J Lagerberg, Maheen Rizvi, Sarah S Kwon, Paulette Orhii, David Maislin, Lucia Hernandez, Rodrigo Machado-Vieira, Jair C Soares, Allan H Young, Cynthia H Y Fu

Faculty, Staff and Student Publications

Transcranial direct current stimulation (tDCS) has been proposed as a new treatment in major depressive disorder (MDD). This is a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of 10-week home-based tDCS in MDD. Participants were 18 years or older, with MDD in current depressive episode of at least moderate severity as measured using the Hamilton Depression Rating Scale (mean = 19.07 ± 2.73). A total of 174 participants (120 women, 54 men) were randomized to active (n = 87, mean age = 37.09 ± 11.14 years) or sham (n = 87, mean age = 38.32 ± 10.92 …