Mental and Social Health Commons^™

Functional Brain Connectivity Of The Salience Network In Alcohol Use And Anxiety Disorders, Dhruv M Patel, Guillermo F Poblete, Alexandra Castellanos, Ramiro Salas

Staff and Researcher Publications

The interplay between alcohol use disorder (AUD) and anxiety disorders (ANX) is well-documented, yet the underlying neurobiological mechanisms remain elusive. This study aims to elucidate these mechanisms by examining the resting-state functional connectivity (RSFC) within the salience network and to the amygdala, both implicated in alcohol and anxiety disorders. We analyzed data from 264 inpatient participants culled from a wider group of 518 inpatients at The Menninger Clinic in Houston, TX, categorized into four groups (n = 66 each) based on DSM-IV diagnoses: AUD without ANX (AUD), ANX without AUD (ANX), concurrent AUD and ANX (BOTH), and neither (NEITHER). Our …

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

Faculty, Staff and Student Publications

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

Faculty, Staff and Student Publications

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 …

Misconceptions Among Mental Health Treatment Providers About Ocd And Ptsd, Caitlin M Pinciotti, Gabriella T Ponzini, Gianna M Colombo, Carmen P Mclean, Terri L Fletcher, Natalie E Hundt, Lauren P Wadsworth, Nathaniel Van Kirk, Stephanie Y Wells, Jonathan S Abramowitz, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) share overlapping features for which similar cognitive behavioral treatment (CBT) strategies can be employed. However, the comorbid presence of these conditions poses unique clinical considerations, and a nuanced approach to assessment, conceptualization, and treatment is needed when working with individuals with co-occurring OCD and PTSD. Treatment providers may not be aware of these nuances and may hold misconceptions about co-occurring OCD and PTSD, impacting their approach to assessment, conceptualization, and treatment. The current study sought to examine possible misconceptions among mental health treatment providers of differing specializations. Among 146 primarily CBT-oriented treatment …

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …

Azetukalner, A Novel Kv7 Potassium Channel Opener, In Adults With Major Depressive Disorder: A Randomized Clinical Trial, Noam N Butterfield, Constanza Luzon Rosenblut, Maurizio Fava, Christoph U Correll, Anthony J Rothschild, James W Murrough, Sanjay J Mathew, Gregory N Beatch, Celene Grayson, Cynthia Harden, Jenny Qian, Joe Mcintosh, Rostam Namdari, Christopher Kenney

Staff and Researcher Publications

Importance: Available antidepressants provide inadequate therapeutic responses in many patients with major depressive disorder (MDD), highlighting a substantial unmet need.

Objective: To evaluate the efficacy and safety of azetukalner, a novel, potent KV7 potassium channel opener, in participants with MDD.

Design, setting, and participants: X-NOVA was a multicenter, proof-of-concept, phase 2, randomized, double-blind, parallel-group, placebo-controlled clinical trial that evaluated azetukalner in participants (adults aged ≥18 to ≤65 years) with moderate to severe MDD in a current depressive episode. Participants were enrolled between April 2022 and October 2023, and data analysis occurred from January 2023 to January 2024.

Intervention: Participants were …

Navacaprant, A Novel And Highly Selective Kappa Opioid Receptor Antagonist, In Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial, Sanjay J Mathew, Andrew J Cutler, Nicole C Visitacion, Michael Gold, Jason Yuan, Bill Aurora

Staff and Researcher Publications

PURPOSE/BACKGROUND: This phase 2a randomized, double-blind, placebo-controlled, 8-week trial assessed the efficacy and safety of navacaprant, a highly selective kappa opioid receptor antagonist, in adults with major depressive disorder (MDD).

METHODS/PROCEDURES: Participants with 17-Item Hamilton Depression Rating Scale (HAMD-17) scores of 14 to 30 were randomized 1:1 to once-daily navacaprant 80 mg or placebo (n = 102 each). The primary endpoint was HAMD-17 change from baseline (CFB) to week 8. Secondary endpoints included CFB in Snaith-Hamilton Pleasure Scale (SHAPS). No adjustment for multiple comparisons was made.

FINDINGS/RESULTS: At week 8, HAMD-17 CFB was not statistically significantly improved with navacaprant vs …

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, …

Personality Factors Associated With Manner Of Death: A Psychological Autopsy Study, Christopher I Gurguis, Scott D Lane, Edison Leung, Joy M Schmitz, Consuelo Walss-Bass, Thomas D Meyer

Staff and Researcher Publications

Psychological autopsies are a well-established tool for understanding contributing factors in suicide completion. These tools have been used less often to understand personality characteristics of people with other manners of death (e.g. overdose). This study examined personality characteristics related to the manner of death in 83 autopsy cases using the UTHealth Psychological Autopsy Interview Schedule (UTH-PAIS), a psychological autopsy which assesses the presence of mental illness or substance use disorder but also includes items to capture transdiagnostic personality factors. Exploratory factor analysis of the items assessing personality factors was used to examine patterns in personality, and these factors were confirmed …

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 …

Mind Matters: How Anxiety And Depression Shape Low-Risk Prostate Cancer Active Surveillance Adherence In A Real-World Population, Zachariah Taylor, Kayla Meyer, Danielle Terrenzio, Ryan Wong, Sharon L. Larson, Stephanie Kjelstrom, Natalina Contoreggi, Laurence Belkoff, Ilia Zeltser

Jefferson Hospital Staff Papers and Presentations

PURPOSE: While the mental health impact of a prostate cancer diagnosis, including low-risk prostate cancer, is well-documented, the effect of pre-existing anxiety and/or depression on adherence to active surveillance protocols in low-risk prostate cancer patients remains unclear. This study assessed the association between prior anxiety and/or depression and active surveillance adherence in men with low-risk prostate cancer.

METHODS: We conducted a retrospective, multicenter study involving 426 men diagnosed with low-risk prostate cancer who were recommended active surveillance as the primary management strategy. Active surveillance adherence was defined by completion of both a prostate-specific antigen test and a prostate biopsy within …

Preoperative Brain Volume Loss Is Associated With Postoperative Delirium In Advanced Heart Failure Patients Supported By Left Ventricular Assist Device, Iván Murrieta-Álvarez, Jacob P Scioscia, José M Benítez-Salazar, Jason Uwaeze, Zicheng Xu, Guangyao Zheng, Shiyi Li, Vladimir Braverman, Carl P Walther, Alexis E Shafii, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Delirium is a common neurological complication in patients with advanced heart failure (ADHF) following left ventricular assist device (LVAD) implantation, significantly impacting recovery. This study aimed to analyze non-contrast computed tomography (CT) scans of the brain in ADHF patients undergoing LVAD implantation to determine the association between pre-existing brain atrophy and postoperative delirium. A study involving 166 ADHF patients was conducted from March 2020 to July 2023. Non-contrast CT scans were analyzed using advanced quantitative neuroimaging techniques before implantation. The primary marker assessed was the lateral ventricle fraction (LVF), with secondary markers including cortical gray matter fraction (cGMF), white matter …

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. …

Acceptance And Commitment Therapy With Huntington's Disease: A Narrative Review And Case Report Of A Caregiver-Assisted Intervention, Simone H. Schriger, Chelsi N. Nurse, C. Virginia O'Hayer

Department of Psychiatry and Human Behavior Faculty Papers

Acceptance and commitment therapy (ACT) is an experiential, action-oriented talk therapy that emphasizes acceptance of painful inner experience through increased psychological flexibility. In this narrative review and case report, we first review the extant literature on applications of ACT to patients with a variety of mental and physical health challenges, including neurodegenerative disorders, and their caregivers. We then discuss applications of ACT to Huntington's disease (HD). We provide a case report of a 52-year-old man living with HD who, accompanied by his caregiver, received a virtually-delivered 6-session ACT intervention. We measured the patient's self-reported symptoms of depression (PHQ-9) and anxiety …

Discontiguous Recurrences Of Idh-Wildtype Glioblastoma Share A Common Origin With The Initial Tumor And Are Frequently Hypermutated, Malcolm F Mcdonald, Sricharan Gopakumar, Tareq A Juratli, Ilker Y Eyüpoglu, Ganesh Rao, Jacob J Mandel, Ali Jalali

Faculty, Staff and Students Publications

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences …

Associations Between Deficit Accumulation Frailty And Baseline Markers Of Lifestyle In The Us Pointer Trial, Mark A Espeland, Yitbarek N Demesie, Kayloni Olson, Samuel N Lockhart, Sarah E Tomaszewski Farias, Maryjo L Cleveland, Christy C Tangney, Lucia Crivelli, Heather M Snyder, Michele K York, Laura D Baker, Rachel A Whitmer, Rena R Wing, Katelyn R Garcia, Kathryn E Callahan

Faculty, Staff and Students Publications

BACKGROUND: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions.

METHODS: We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores …

Us Military Veterans’ Perceived Concordance With Their Providers Regarding Persistent Physical Symptoms Prospectively Predicts Satisfaction With Care And Adherence To Care Plans, L Alison Phillips, Laura M Lesnewich, Katharine Bloeser, Yong Lin, Rachel L Boska, Justeen K Hyde, Peter J Bayley, Helena K Chandler, Matthew J Reinhard, Susan L Santos, Rachel Stewart, Drew A Helmer, Lisa M Mcandrew

Center for Medical Ethics and Health Policy Staff Publications

Background: Medically unexplained, persistent physical symptoms and syndromes are commonly seen in primary care. These are debilitating for patients and difficult to treat, causing frustration for patients and providers.

Purpose: This study investigates how well US military veterans with multiple persistent physical symptoms (PPS), called Gulf War illness (GWI), agree with their healthcare providers about their illness. This agreement, called perceived concordance, is hypothesized to influence veterans' satisfaction with care, adherence to care plans, and disability levels.

Methods: Participants were 230 veterans with GWI deployed to the 1990-1991 Gulf War who were recruited from Veteran Affairs primary care and War …

The Pointer Imaging Baseline Cohort: Associations Between Multimodal Neuroimaging Biomarkers, Cardiovascular Health, And Cognition, Theresa M Harrison, Tyler Ward, Jacinda Taggett, Pauline Maillard, Samuel N Lockhart, Youngkyoo Jung, Laura C Lovato, Robert Koeppe, William J Jagust, Danielle Harvey, Joseph C Masdeu, Hwamee Oh, Darren R Gitelman, Neelum T Aggarwal, Mark A Espeland, Maryjo L Cleveland, Rachel Whitmer, Sarah Tomaszewski Farias, Stephen Salloway, Valory Pavlik, Melissa Yu, Christine Tangney, Heather Snyder, Maria Carrillo, Laura D Baker, Prashanthi Vemuri, Charles Decarli, Susan M Landau

Staff and Researcher Publications

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of the POINTER Imaging ancillary study.

Methods: Participants underwent health and cognitive assessments and neuroimaging with multimodal positron emission tomography (PET) (beta-amyloid [Aβ] and tau) and magnetic resonance imaging (MRI). Framingham risk score (FRS) was used to quantify cardiovascular disease (CVD) risk.

Results: A total of 1052 participants (31% from underrepresented ethnoracial groups) were enrolled. Compared to Aβ-, Aβ+ (29%) participants were older, …

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 …

Association Between Trust In The Incumbent President And Covid-19 Preventive Behaviors During The Pandemic In Four Latin American Countries, Juliana Mejía-Grueso, Gloria Isabel Niño-Cruz, Javiera Alarcón-Aguilar, Pablo Roa-Urrutia, Sergio Mauricio Moreno-López, Adriano Akira Ferreira Hino, Alexandre Augusto De Paula Da Silva, Fernando López, Deborah Salvo, Rodrigo Siqueira Reis, Guillermo Rosas, Andrea Ramírez-Varela

Faculty, Staff and Student Publications

The COVID-19 pandemic revealed disparities in policy responses in Latin America. We examined the association between trust in the president and COVID-19 preventive behaviors in Brazil, Chile, Colombia, and Mexico. We used data from the Collaborative COVID-19 Response Survey by the McDonnell Academy at Washington University in St. Louis (United States), from September 2020 to March 2021. Nonprobabilistic sampling included adult citizens from the four countries. Multivariate negative binomial regression models were applied. The study included 8,125 participants, with Brazil showing the lowest adherence to preventive behaviors (65.5%). Increased adoption of preventive behaviors was linked with ages 18-26 (aIRR = …

Aperiodic Spectral Slope Tracks The Effects Of Brain State On Saliency Responses In The Human Auditory Cortex, Madaline Mocchi, Eleonora Bartoli, John Magnotti, Jan Willem De Gee, Brian Metzger, Bailey Pascuzzi, Raissa Mathura, Suhruthaa Pulapaka, Wayne Goodman, Sameer Sheth, Matthew J Mcginley, Kelly Bijanki

Faculty, Staff and Students Publications

Alteration of responses to salient stimuli occurs in a wide range of brain disorders and may be rooted in pathophysiological brain state dynamics. Specifically, tonic and phasic modes of activity in the reticular activating system (RAS) influence, and are influenced by, salient stimuli, respectively. The RAS influences the spectral characteristics of activity in the neocortex, shifting the balance between low- and high-frequency fluctuations. Aperiodic '1/f slope' has emerged as a promising composite measure of these brain state dynamics. However, the relationship of 1/f slope to state-dependent processes, such as saliency, is less explored, particularly intracranially in humans. Here, we record …

Centering Autonomy And Choice To Support Oral Prep Utilization Among People Who Inject Drugs: Qualitative Lessons From Hptn 094 Integra, Amaya Perez-Brumer, Rose Schmidt, Rebecca Kennedy, Jordan E Lake, Yolanda R Villarreal, Sydney Bornstein, Irene Kuo, Omar Nieto, Julie Franks, Cecile Denis, Nabila El-Bassel, Steve Shoptaw, Peter Davidson, Laramie R Smith

Faculty, Staff and Student Publications

Background: Oral Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission. However, despite high rates of HIV risk behaviors among people who inject drugs (PWID), this population remains underserved by current HIV prevention efforts in the United States. To address this challenge, we conducted an in-depth exploration of perspectives on using oral PrEP among PWID engaged in the HIV Prevention Trials Network (HPTN) 094 INTEGRA Study.

Methods: Guided by the Practical, Robust, Implementation, and Sustainability Model (PRISM), our qualitative study drew on semi-structured interviews conducted as part of the embedded implementation science evaluation of HPTN 094 INTEGRA. Seventy-seven PWID participants …

Global Impact Of Aging On The Hemodynamic Response Function In The Gray Matter Of Human Cerebral Cortex, Nooshin J Fesharaki, Amanda Taylor, Keisjon Mosby, Ruosha Li, Jung Hwan Kim, David Ress

Faculty, Staff and Students Publications

In functional magnetic resonance imaging, the hemodynamic response function (HRF) is a stereotypical response to local changes in cerebral hemodynamics and oxygen metabolism due to briefly (< 4 s) evoked neural activity. Accordingly, the HRF is often used as an impulse response with the assumption of linearity in data analysis. In cognitive aging studies, it has been very common to interpret differences in brain activation as age-related changes in neural activity. Contrary to this assumption, however, evidence has accrued that normal aging may also significantly affect the vasculature, thereby affecting cerebral hemodynamics and metabolism, confounding interpretation of fMRI cognitive aging studies. In this study, use was made of a multisensory task to evoke the HRF in ~87% of cerebral cortex in cognitively intact adults with ages ranging from 22 to 75 years. This widespread activation enabled us to investigate age trends in the spatial distributions of HRF characteristics within the majority of cortical gray matter, which we termed as global age trends. The task evoked both positive and negative HRFs, which were characterized using model-free parameters in native-space coordinates. We found significant global age trends in the distributions of HRF parameters in terms of both amplitudes (e.g., peak amplitude and contrast-to-noise ratio) and temporal dynamics (e.g., full-width-at-half-maximum). Our findings offer insight into how age-dependent changes affect neurovascular coupling and show promise for use of HRF parameters as non-invasive indicators for age-related pathology.

The Use Of Cloud Based Machine Learning To Predict Outcome In Intracerebral Haemorrhage Without Explicit Programming Expertise, Ajay Hegde, Deepu Vijaysenan, Pitchaiah Mandava, Girish Menon

Faculty, Staff and Students Publications

Machine Learning (ML) techniques require novel computer programming skills along with clinical domain knowledge to produce a useful model. We demonstrate the use of a cloud-based ML tool that does not require any programming expertise to develop, validate and deploy a prognostic model for Intracerebral Haemorrhage (ICH). The data of patients admitted with Spontaneous Intracerebral haemorrhage from January 2015 to December 2019 was accessed from our prospectively maintained hospital stroke registry. 80% of the dataset was used for training, 10% for validation, and 10% for testing. Seventeen input variables were used to predict the dichotomized outcomes (Good outcome mRS 0-3/ …

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Alison M Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H Kramer, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …

Global And Risk-Group Stratified Well-Being And Mental Health During The Covid-19 Pandemic In Adults: Results From The International Coh-Fit Study, Marco Solmi, Trevor Thompson, Andrés Estradé, Agorastos Agorastos, Joaquim Radua, Samuele Cortese, Elena Dragioti, Davy Vancampfort, Lau Caspar Thygesen, Harald Aschauer, Monika Schlögelhofer, Elena Aschauer, Andres Schneeberger, Christian G Huber, Gregor Hasler, Philippe Conus, Kim Q Do Cuénod, Roland Von Känel, Gonzalo Arrondo, Paolo Fusar-Poli, Philip Gorwood, Pierre-Michel Llorca, Marie-Odile Krebs, Elisabetta Scanferla, Taishiro Kishimoto, Golam Rabbani, Karolina Skonieczna-Żydecka, Paolo Brambilla, Angela Favaro, Akihiro Takamiya, Leonardo Zoccante, Marco Colizzi, Julie Bourgin, Karol Kamiński, Maryam Moghadasin, Soraya Seedat, Evan Matthews, John Wells, Emilia Vassilopoulou, Ary Gadelha, Kuan-Pin Su, Jun Soo Kwon, Minah Kim, Tae Young Lee, Oleg Papsuev, Denisa Manková, Andrea Boscutti, Cristiano Gerunda, Diego Saccon, Elena Righi, Francesco Monaco, Giovanni Croatto, Guido Cereda, Jacopo Demurtas, Natascia Brondino, Nicola Veronese, Paolo Enrico, Pierluigi Politi, Valentina Ciappolino, Andrea Pfennig, Andreas Bechdolf, Andreas Meyer-Lindenberg, Kai G Kahl, Katharina Domschke, Michael Bauer, Nikolaos Koutsouleris, Sibylle Winter, Stefan Borgwardt, Istvan Bitter, Judit Balazs, Pál Czobor, Zsolt Unoka, Dimitris Mavridis, Konstantinos Tsamakis, Vasilios P Bozikas, Chavit Tunvirachaisakul, Michael Maes, Teerayuth Rungnirundorn, Thitiporn Supasitthumrong, Ariful Haque, Andre R Brunoni, Carlos Gustavo Costardi, Felipe Barreto Schuch, Guilherme Polanczyk, Jhoanne Merlyn Luiz, Lais Fonseca, Luana V Aparicio, Samira S Valvassori, Merete Nordentoft, Per Vendsborg, Sofie Have Hoffmann, Jihed Sehli, Norman Sartorius, Sabina Heuss, Daniel Guinart, Jane Hamilton, John Kane, Jose Rubio, Michael Sand, Ai Koyanagi, Aleix Solanes, Alvaro Andreu-Bernabeu, Antonia San José Cáceres, Celso Arango, Covadonga M Díaz-Caneja, Diego Hidalgo-Mazzei, Eduard Vieta, Javier Gonzalez-Peñas, Lydia Fortea, Mara Parellada, Miquel A Fullana, Norma Verdolini, Eva Andrlíková, Karolina Janků, Mark J Millan, Mihaela Honciuc, Anna Moniuszko-Malinowska, Igor Łoniewski, Jerzy Samochowiec, Łukasz Kiszkiel, Maria Marlicz, Paweł Sowa, Wojciech Marlicz, Georgina Spies, Brendon Stubbs, Joseph Firth, Sarah Sullivan, Asli Enez Darcin, Hatice Aksu, Nesrin Dilbaz, Onur Noyan, Momoko Kitazawa, Shunya Kurokawa, Yuki Tazawa, Alejandro Anselmi, Cecilia Cracco, Ana Inés Machado, Natalia Estrade, Diego De Leo, Jackie Curtis, Michael Berk, Andre F Carvalho, Philip Ward, Scott Teasdale, Simon Rosenbaum, Wolfgang Marx, Adrian Vasile Horodnic, Liviu Oprea, Ovidiu Alexinschi, Petru Ifteni, Serban Turliuc, Tudor Ciuhodaru, Alexandra Bolos, Valentin Matei, Dorien H Nieman, Iris Sommer, Jim Van Os, Therese Van Amelsvoort, Ching-Fang Sun, Ta-Wei Guu, Can Jiao, Jieting Zhang, Jialin Fan, Liye Zou, Xin Yu, Xinli Chi, Philippe De Timary, Ruud Van Winkel, Bernardo Ng, Edilberto Peña De León, Ramon Arellano, Raquel Roman, Thelma Sanchez, Larisa Movina, Pedro Morgado, Sofia Brissos, Oleg Aizberg, Anna Mosina, Damir Krinitski, James Mugisha, Dena Sadeghi-Bahmani, Farshad Sheybani, Masoud Sadeghi, Samira Hadi, Serge Brand, Antonia Errazuriz, Nicolas Crossley, Dragana Ignjatovic Ristic, Carlos López-Jaramillo, Dimitris Efthymiou, Praveenlal Kuttichira, Roy Abraham Kallivayalil, Afzal Javed, Muhammad Iqbal Afridi, Bawo James, Omonefe Joy Seb-Akahomen, Jess Fiedorowicz, Jeff Daskalakis, Lakshmi N Yatham, Lin Yang, Tarek Okasha, Aïcha Dahdouh, Jari Tiihonen, Jae Il Shin, Jinhee Lee, Ahmed Mhalla, Lotfi Gaha, Takoua Brahim, Kuanysh Altynbekov, Nikolay Negay, Saltanat Nurmagambetova, Yasser Abu Jamei, Mark Weiser, Christoph U Correll

Faculty, Staff and Students Publications

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score, and their associations with COVID-19 deaths/restrictions, 12 a-priori defined risk individual/cumulative factors, and coping strategies during COVID-19 pandemic (26/04/2020-26/06/2022) in 30 languages (representative, weighted non-representative, adults). T-test, χ2, penalized cubic splines, linear regression, correlation analyses were conducted. Analyzing 121,066/142,364 initiated surveys, WHO-5/P-score worsened intra-pandemic by 11.1±21.1/13.2±17.9 points (effect size d=0.50/0.60) (comparable results in representative/weighted non-probability samples). Persons with …

Genome-Derived Ampullary Adenocarcinoma Classifier And Postresection Prognostication, Brett L Ecker, Kenneth Seier, Austin M Eckhoff, Gabriella N Tortorello, Peter J Allen, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Danielle Fortuna, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Kevin C Soares, Charles M Vollmer, Alice C Wei, Sabino Zani, Robert E Roses, Mithat Gonen, William R Jarnagin

Faculty, Staff and Students Publications

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use.

Objective: To test external validity of the prognostic value of the hidden genome classifier of AA.

Design, setting, and participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020.

Exposures: The multilevel meta-feature regression model previously trained on …

Mortality Risks Associated With Depression In Men With Prostate Cancer, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Men diagnosed with prostate cancer (PC) have an increased risk of depression; however, it is unclear to what extent depression affects long-term survival. A better understanding of such effects is needed to improve long-term care and outcomes for men with PC.

Objective: To determine the associations between major depression and mortality in a national cohort of men with PC.

Design, setting, and participants: A national cohort study was conducted of all 180 189 men diagnosed with PC in Sweden during 1998-2017. Subsequent diagnoses of major depression were ascertained from nationwide outpatient and inpatient records through 2018.

Outcome measurements and …

Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation For Depression: A Randomized Clinical Trial, Dongsheng Zhou, Xingxing Li, Shuochi Wei, Chang Yu, Dongmei Wang, Yuchen Li, Jiaxin Li, Junyao Liu, Shen Li, Wenhao Zhuang, Yanli Li, Ruichenxi Luo, Zhiwang Liu, Jimeng Liu, Yongming Xu, Jialin Fan, Guidong Zhu, Weiqian Xu, Yiping Tang, Raymond Y Cho, Thomas R Kosten, Xiang-Yang Zhang

Staff and Researcher Publications

IMPORTANCE: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are both recognized as effective treatments for depression when applied individually. However, it is unknown whether rTMS combined with tDCS has better efficacy in the treatment of major depressive disorder (MDD).

OBJECTIVE: To investigate the clinical effectiveness and safety of rTMS, tDCS, tDCS + rTMS, and sham tDCS + sham rTMS after 2 weeks of treatment in patients with MDD.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, sham-controlled randomized clinical trial was conducted from November 2021 to April 2023 at 3 hospitals in China (Kangning Hospital affiliated with Ningbo …

Age-Related Decline In Blood-Brain Barrier Function Is More Pronounced In Males Than Females In Parietal And Temporal Regions, Xingfeng Shao, Qinyang Shou, Kimberly Felix, Brandon Ojogho, Xuejuan Jiang, Brian T Gold, Megan M Herting, Eric L Goldwaser, Peter Kochunov, Elliot Hong, Ioannis Pappas, Meredith Braskie, Hosung Kim, Steven Cen, Kay Jann, Danny J J Wang

Faculty, Staff and Student Publications

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial …