We’ve all been wrong about provisional tic disorder
(2024) Comprehensive Psychiatry, 134, art. no. 152510, .
Grossen, S.C.a , Arbuckle, A.L.b , Bihun, E.C.b , Koller, J.M.b , Song, D.Y.a , Reiersen, A.M.b , Schlaggar, B.L.c , Greene, D.J.d , Black, K.J.e
a Departments of Psychiatry and Neurology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychiatry, Washington University in St. Louis, St. LouisMO, United States
c Kennedy Krieger Institute, Baltimore, MD, Departments of Neurology and Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
d Department of Cognitive Science, University of California San Diego, La Jolla, CA, United States
e Departments of Psychiatry, Neurology, Radiology, Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Background: Provisional Tic Disorder (PTD) is common in childhood. The received wisdom among clinicians is that PTD is short-lived and mild, with at most a few tics, and rarely includes complex tics, premonitory phenomena or comorbid illnesses. However, such conclusions come from clinical experience, with biased ascertainment and limited follow-up. Methods: Prospective study of 89 children with tics starting 0–9 months ago (median 4 months), fewer than half from clinical sources. Follow-up at 12 (± 24, 36, 48) months after the first tic. Results: At study entry, many children had ADHD (39), an anxiety disorder (27), OCD (9) or enuresis (17). All had at least two current tics, with a mean total since onset of 6.9 motor and 2.0 phonic tics. Forty-one had experienced a complex tic, and 69 could suppress some tics. Tics were clinically meaningful: 64 had tics severe enough for a clinical trial, and 76 families sought medical attention for the tics. At 12 months, 79 returned, and 78 still had tics. Of these, 29 manifested no tics during history and extended examination, but only via audio-visual monitoring when the child was seated alone. Only 12/70 now had plans to see a doctor for tics. Most who returned at 2–4 years still had tics known to the child and family, but medical impact was low. Conclusions: Our results do not contradict previous data, but overturn clinical lore. The data strongly argue against the longstanding but arbitrary tradition of separating tic disorders into recent-onset versus chronic. © 2024 The Authors
Author Keywords
Provisional Tic Disorder; Tic disorders/classification (MeSH); Tic disorders/psychology (MeSH); Tourette syndrome (MeSH)
Funding details
Alvin J. Siteman Cancer CenterSCC
National Institutes of HealthNIHR01MH104030, K24MH087913, K01MH104592, R21NS091635
National Institutes of HealthNIH
P30CA091842
Institute of Clinical and Translational SciencesICTSUL1TR000448, UL1RR024992
Institute of Clinical and Translational SciencesICTS
K23DC006638, U54HD087011
Document Type: Article
Publication Stage: Final
Source: Scopus
Co-occurring psychiatric disorders in young people with eating disorders: An multi-state and real-time analysis of real-world administrative data
(2024) General Hospital Psychiatry, 90, pp. 30-34.
Lin, B.Y.a b , Liu, A.c , Xie, H.d , Eddington, S.e , Moog, D.f , Xu, K.Y.g h
a Department of Psychosomatic Medicine, Shanghai East Hospital, School of Medicine, Tongji University, 145 Rushan Rd, Shanghai, 200120, China
b Department of Psychiatry and Behavioral Medicine, Carilion Clinic- Virginia Tech Carilion School of Medicine, 2017 S Jefferson St 2nd Floor, Roanoke, VA 24014, United States
c Northwell Health at Zucker Hillside Hospital, 75-59 263rd St, Glen Oaks, NY 11004, United States
d Zilber School of Public Health, University of Wisconsin-Milwaukee, 1240 N. 10th St., Milwaukee, WI 53205, United States
e Department of Psychiatry, Washington University School of Medicine, 4940 Children’s Place, Saint Louis, MO 63110, United States
f Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
g Health & Behavior Research Center, Division of Addiction Science, Prevention & Treatment, Department of Psychiatry, Washington University School of Medicine, 4940 Children’s Place, Saint Louis, MO 63110, United States
h Center for the Study of Race, Ethnicity & Equity and Institute for Public Health, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
Abstract
Objective: We aimed to use real-world data to characterize the burden of psychiatric comorbidities in young people with eating disorders (EDs) relative to peers without EDs. Method: This retrospective cohort study used a large federated multi-national network of real-time electronic health records. Our cohort consisted of 124,575 people (14,524 people receiving their index, first-ever, ED diagnosis, compared to 110,051 peers without EDs initiating antidepressants). After 1:1 propensity score matching of the two cohorts by pre-existing demographic and clinical characteristics, we used multivariable logistic regression to compute the adjusted odds ratio (aOR) of psychiatric diagnoses arising in the year following the index event (either first ED diagnosis or first antidepressant script). Results: Over 50% of people with EDs had prior psychiatric diagnoses in the year preceding the index EDs diagnosis, with mood disorders, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), specific phobia (SP), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) being the most common. Adjusted analyses showed higher odds for mood disorders (aOR = 1.20 [95% CI = 1.14–1.26]), GAD (aOR = 1.28 [1.21–1.35]), PTSD (aOR = 1.29 [1.18–1.40]), and SP (aOR = 1.45 [1.31–1.60]) in the EDs cohort compared to antidepressant-initiating peers without EDs, although rates of ADHD and ASD were similar in both cohorts. Conclusion: This large-scale real-time analysis of administrative data illustrates a high burden of co-occurring psychiatric disorders in people with EDs. © 2024 Elsevier Inc.
Author Keywords
Big data; Co-occurring disorders; Eating disorders; Real world data
Funding details
American Psychiatric AssociationAPA
National Institutes of HealthNIHK12 DA041449
National Institutes of HealthNIH
Document Type: Article
Publication Stage: Final
Source: Scopus
Transparency and reproducibility in the Adolescent Brain Cognitive Development (ABCD) study
(2024) Developmental Cognitive Neuroscience, 68, art. no. 101408, .
Lopez, D.A.a s , Cardenas-Iniguez, C.b , Subramaniam, P.c , Adise, S.d , Bottenhorn, K.L.b , Badilla, P.e , Mukwekwerere, E.f , Tally, L.g , Ahanmisi, O.h , Bedichek, I.L.i , Matera, S.D.j , Perez-Tamayo, G.M.c , Sissons, N.k , Winters, O.l , Harkness, A.m , Nakiyingi, E.f , Encizo, J.f , Xiang, Z.n , Wilson, I.G.o , Smith, A.N.p , Hill, A.R.a , Adames, A.K.q , Robertson, E.l , Boughter, J.R.f , Lopez-Flores, A.a , Skoler, E.R.e , Dorholt, L.r , Nagel, B.J.a s , Huber, R.S.a c s
a Department of Psychiatry, Oregon Health & Science University, Portland, OR, United States
b Department of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States
c Department of Psychiatry, University of Utah, Salt Lake City, UT, United States
d Division of Endocrinology, Diabetes and Metabolism, Children’s Hospital of Los Angeles, Los Angeles, CA, United States
e Institute for Behavioral Genetics, University of Colorado, Boulder, CO, United States
f Department of Psychology, Psychiatry, and Radiology, Washington University in St. Louis, St. Louis, MO, United States
g Center for Children and Families and Department of Psychology, Florida International University, Miami, FL, United States
h Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland, Baltimore, MD, United States
i Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, United States
j The Frederick J. and Marion A. Schindler Cognitive Neurophysiology Laboratory Department of Neuroscience and The Ernest J. Del Monte Institute for Neuroscience University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
k Departments of Psychiatry and Radiology, University of Vermont, Burlington, VT, United States
l Department of Psychiatry, Medical University of South Carolina, Charleston, SC, United States
m Center for Health Sciences, SRI International, Menlo Park, CS, United States
n Department of Psychology, Yale University, New Haven, CT, United States
o Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, WI, United States
p Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States
q Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
r Department of Psychology, University of Minnesota, Minneapolis, MN, United States
s Center for Mental Health Innovation, Oregon Health & Science University, Portland, OR, United States
Abstract
Background: Transparency can build trust in the scientific process, but scientific findings can be undermined by poor and obscure data use and reporting practices. The purpose of this work is to report how data from the Adolescent Brain Cognitive Development (ABCD) Study has been used to date, and to provide practical recommendations on how to improve the transparency and reproducibility of findings. Methods: Articles published from 2017 to 2023 that used ABCD Study data were reviewed using more than 30 data extraction items to gather information on data use practices. Total frequencies were reported for each extraction item, along with computation of a Level of Completeness (LOC) score that represented overall endorsement of extraction items. Univariate linear regression models were used to examine the correlation between LOC scores and individual extraction items. Post hoc analysis included examination of whether LOC scores were correlated with the logged 2-year journal impact factor. Results: There were 549 full-length articles included in the main analysis. Analytic scripts were shared in 30 % of full-length articles. The number of participants excluded due to missing data was reported in 60 % of articles, and information on missing data for individual variables (e.g., household income) was provided in 38 % of articles. A table describing the analytic sample was included in 83 % of articles. A race and/or ethnicity variable was included in 78 % of reviewed articles, while its inclusion was justified in only 41 % of these articles. LOC scores were highly correlated with extraction items related to examination of missing data. A bottom 10 % of LOC score was significantly correlated with a lower logged journal impact factor when compared to the top 10 % of LOC scores (β=-0.77, 95 % −1.02, −0.51; p-value < 0.0001). Conclusion: These findings highlight opportunities for improvement in future papers using ABCD Study data to readily adapt analytic practices for better transparency and reproducibility efforts. A list of recommendations is provided to facilitate adherence in future research. © 2024 The Authors
Author Keywords
Adolescent; Best practices; Cognitive; Neuroimaging; Reproducibility; Transparency
Funding details
T32ES013678
National Institute on Minority Health and Health DisparitiesNIMHDP50MD017344
National Institute on Minority Health and Health DisparitiesNIMHD
National Institutes of HealthNIHU24DA041123, U01DA041025, U01DA051039, U01DA051016, U01DA041028, U01DA041022, U01DA051018, U01DA041174, U01DA041120, U01DA041093, U01DA041048, U01DA051038, U24DA041147, U01DA041134, U01DA041148, U01DA041117, U01DA050988, U01DA051037, U01DA041106, U01DA041089, U01DA050987, U01DA050989, U01DA041156
National Institutes of HealthNIH
R01-ES032295, R01-ES031074, K99-MH135075
K01 DK135847
Document Type: Article
Publication Stage: Final
Source: Scopus
Airy-beam holographic sonogenetics for advancing neuromodulation precision and flexibility
(2024) Proceedings of the National Academy of Sciences of the United States of America, 121 (26), pp. e2402200121.
Hu, Z.a , Yang, Y.a , Yang, L.a , Gong, Y.a , Chukwu, C.a , Ye, D.a , Yue, Y.a , Yuan, J.a , Kravitz, A.V.b , Chen, H.a c d
a Department of Biomedical Engineering, Washington University in St. LouisSaint Louis MO 63130, Seychelles
b Department of Psychiatry, Washington University School of MedicineSaint Louis MO 63110, Seychelles
c Department of Neurosurgery, Washington University School of MedicineSaint Louis MO 63110, Seychelles
d Mallinckrodt Institute of Radiology, Washington University School of MedicineSaint Louis MO 63110, Seychelles
Abstract
Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain areas without invasive techniques. Here, we introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type-specific, spatially precise, and flexible neuromodulation approach in freely moving mice. AhSonogenetics utilizes wearable ultrasound devices manufactured using 3D-printed Airy-beam holographic metasurfaces. These devices are designed to manipulate neurons genetically engineered to express ultrasound-sensitive ion channels, enabling precise modulation of specific neuronal populations. By dynamically steering the focus of Airy beams through ultrasound frequency tuning, AhSonogenetics is capable of modulating neuronal populations within specific subregions of the striatum. One notable feature of AhSonogenetics is its ability to flexibly stimulate either the left or right striatum in a single mouse. This flexibility is achieved by simply switching the acoustic metasurface in the wearable ultrasound device, eliminating the need for multiple implants or interventions. AhSonogentocs also integrates seamlessly with in vivo calcium recording via fiber photometry, showcasing its compatibility with optical modalities without cross talk. Moreover, AhSonogenetics can generate double foci for bilateral stimulation and alleviate motor deficits in Parkinson’s disease mice. This advancement is significant since many neurological disorders, including Parkinson’s disease, involve dysfunction in multiple brain regions. By enabling precise and flexible cell type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders.
Author Keywords
Airy beam; focused ultrasound; hologram; neuromodulation; sonogenetics
Document Type: Article
Publication Stage: Final
Source: Scopus
Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia
(2024) Science Advances, 10 (25), p. eadj9173.
Bhuiyan, S.A.a , Xu, M.a b , Yang, L.a c , Semizoglou, E.a , Bhatia, P.a , Pantaleo, K.I.a , Tochitsky, I.d , Jain, A.d , Erdogan, B.e , Blair, S.e , Cat, V.e , Mwirigi, J.M.f , Sankaranarayanan, I.f , Tavares-Ferreira, D.f , Green, U.g , McIlvried, L.A.c , Copits, B.A.c , Bertels, Z.c , Del Rosario, J.S.c , Widman, A.J.c , Slivicki, R.A.c , Yi, J.c , Sharif-Naeini, R.b , Woolf, C.J.d , Lennerz, J.K.g , Whited, J.L.e , Price, T.J.f , Robert W Gereau Ivc , Renthal, W.a
a Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, United States
b Alan Edwards Center for Research on Pain and Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada
c Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, United States
d F.M. Kirby Neurobiology Center and Department of Neurobiology, Boston Children’s Hospital and Harvard Medical School, 3 Blackfan Cir., Boston, MA 02115, United States
e Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, United States
f Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, 800 W Campbell Rd, Richardson, TX 75080, United States
g Department of Pathology, Center for Integrated Diagnostics, Massachussetts General Hospital and Havard Medical School, Boston, MA 02114, United States
Abstract
Sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli to the central nervous system. Single-cell RNA sequencing has provided insights into the diversity of sensory ganglia cell types in rodents, nonhuman primates, and humans, but it remains difficult to compare cell types across studies and species. We thus constructed harmonized atlases of the DRG and TG that describe and facilitate comparison of 18 neuronal and 11 non-neuronal cell types across six species and 31 datasets. We then performed single-cell/nucleus RNA sequencing of DRG from both human and the highly regenerative axolotl and found that the harmonized atlas also improves cell type annotation, particularly of sparse neuronal subtypes. We observed that the transcriptomes of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The resources presented here can guide future studies in comparative transcriptomics, simplify cell-type nomenclature differences across studies, and help prioritize targets for future analgesic development.
Document Type: Article
Publication Stage: Final
Source: Scopus
Crizanlizumab for retinal vasculopathy with cerebral leukoencephalopathy in a phase II clinical study
(2024) Journal of Clinical Investigation, 134 (12), art. no. e180916, .
Wang, W.X.a , Spiegelman, D.a , Rao, P.K.a , Ford, A.L.b , Apte, R.S.a c
a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Medicine, Washington University, St. Louis, MO, United States
Abstract
BACKGROUND. Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, autosomal dominant, universally fatal disease without effective treatment options. This study explores the safety and preliminary efficacy of crizanlizumab, a humanized monoclonal antibody against P-selectin approved for the prevention of sickle cell crises, in slowing retinal nonperfusion and preserving vision in patients with RVCL-S. METHODS. Eleven patients with RVCL-S with confirmed exonuclease 3 prime repair exonuclease 1 (TREX1) mutations received monthly crizanlizumab infusions over 2 years. The study measured the nonperfusion index within 3 retinal zones and the total retina with fluorescein angiography, visual acuity, intraocular pressure (IOP), and optical coherence tomography central subfield thickness (CST) at baseline, 1 year, and 2 years. A mixed repeated-measures analysis was performed to assess the progression rates and changes from baseline. RESULTS. Eleven participants received crizanlizumab infusions. All of the participants tolerated crizanlizumab well, with 8 of 11 (72.7%) reporting mild adverse effects such as nausea, fatigue, and gastrointestinal symptoms. The change in total retinal nonperfusion was 7.22% [4.47, 9.97] in year 1 and –0.69% [–4.06, 2.68] in year 2 (P < 0.001). In the mid periphery, the change in nonperfusion was 10.6% [5.1, 16.1] in year 1 and –0.68% [–3.98, 5.35] in year 2 (P < 0.01), demonstrating a reduction in progression of nonperfusion in the second year of treatment. Visual acuity, IOP, and CST remained stable. CONCLUSION. Crizanlizumab has an acceptable safety profile. These results show promising potential for examining crizanlizumab in larger studies of RVCL-S and similar small-vessel diseases and for using the retina as a biomarker for systemic disease. © 2024, Wang et al.
Funding details
Research to Prevent BlindnessRPB
National Institute of Neurological Disorders and StrokeNINDS
Novartis
National Heart, Lung, and Blood InstituteNHLBI
Denardo Education and Research Foundation
Perelman School of Medicine, University of Pennsylvania
R01HL129241
RF1NS116565
Document Type: Article
Publication Stage: Final
Source: Scopus
Cannabis, Tobacco Use, and COVID-19 Outcomes
(2024) JAMA Network Open, 7 (6), p. e2417977.
Griffith, N.B.a , Baker, T.B.b , Heiden, B.T.c d , Smock, N.e , Pham, G.e , Chen, J.e , Yu, J.a , Reddy, J.e , Lai, A.M.a , Hogue, E.a , Bierut, L.J.e , Chen, L.-S.e f
a Washington University School of Medicine, St Louis, MO, United States
b Center for Tobacco Research and Intervention, School of Medicine and Public Health, University of Wisconsin, Madison, United States
c Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO, United States
d Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, United States
e Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
f Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital, Washington University School of Medicine, St Louis, MO, United States
Abstract
Importance: It is unclear whether cannabis use is associated with adverse health outcomes in patients with COVID-19 when accounting for known risk factors, including tobacco use. Objective: To examine whether cannabis and tobacco use are associated with adverse health outcomes from COVID-19 in the context of other known risk factors. Design, Setting, and Participants: This retrospective cohort study used electronic health record data from February 1, 2020, to January 31, 2022. This study included patients who were identified as having COVID-19 during at least 1 medical visit at a large academic medical center in the Midwest US. Exposures: Current cannabis use and tobacco smoking, as documented in the medical encounter. Main Outcomes and Measures: Health outcomes of hospitalization, intensive care unit (ICU) admission, and all-cause mortality following COVID-19 infection. The association between substance use (cannabis and tobacco) and these COVID-19 outcomes was assessed using multivariable modeling. Results: A total of 72 501 patients with COVID-19 were included (mean [SD] age, 48.9 [19.3] years; 43 315 [59.7%] female; 9710 [13.4%] had current smoking; 17 654 [24.4%] had former smoking; and 7060 [9.7%] had current use of cannabis). Current tobacco smoking was significantly associated with increased risk of hospitalization (odds ratio [OR], 1.72; 95% CI, 1.62-1.82; P < .001), ICU admission (OR, 1.22; 95% CI, 1.10-1.34; P < .001), and all-cause mortality (OR, 1.37, 95% CI, 1.20-1.57; P < .001) after adjusting for other factors. Cannabis use was significantly associated with increased risk of hospitalization (OR, 1.80; 95% CI, 1.68-1.93; P < .001) and ICU admission (OR, 1.27; 95% CI, 1.14-1.41; P < .001) but not with all-cause mortality (OR, 0.97; 95% CI, 0.82-1.14, P = .69) after adjusting for tobacco smoking, vaccination, comorbidity, diagnosis date, and demographic factors. Conclusions and Relevance: The findings of this cohort study suggest that cannabis use may be an independent risk factor for COVID-19-related complications, even after considering cigarette smoking, vaccination status, comorbidities, and other risk factors.
Document Type: Article
Publication Stage: Final
Source: Scopus
An interpretable machine learning-based cerebrospinal fluid proteomics clock for predicting age reveals novel insights into brain aging
(2024) Aging Cell, .
Melendez, J.a b , Sung, Y.J.c d , Orr, M.e , Yoo, A.f , Schindler, S.b , Cruchaga, C.b c , Bateman, R.a b
a Tracy Family SILQ Center, Washington University in St. Louis, St. Louis, MO, United States
b Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
d Department of Biostatistics, Washington University in St. Louis, St. Louis, MO, United States
e Department of Internal Medicine, Wake Forest School of Medicine Section of Gerontology and Geriatric Medicine Medical Center Boulevard, Winston-Salem, NC, United States
f Department of Developmental Biology, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Machine learning can be used to create “biologic clocks” that predict age. However, organs, tissues, and biofluids may age at different rates from the organism as a whole. We sought to understand how cerebrospinal fluid (CSF) changes with age to inform the development of brain aging-related disease mechanisms and identify potential anti-aging therapeutic targets. Several epigenetic clocks exist based on plasma and neuronal tissues; however, plasma may not reflect brain aging specifically and tissue-based clocks require samples that are difficult to obtain from living participants. To address these problems, we developed a machine learning clock that uses CSF proteomics to predict the chronological age of individuals with a 0.79 Pearson correlation and mean estimated error (MAE) of 4.30 years in our validation cohort. Additionally, we analyzed proteins highly weighted by the algorithm to gain insights into changes in CSF and uncover novel insights into brain aging. We also demonstrate a novel method to create a minimal protein clock that uses just 109 protein features from the original clock to achieve a similar accuracy (0.75 correlation, MAE 5.41). Finally, we demonstrate that our clock identifies novel proteins that are highly predictive of age in interactions with other proteins, but do not directly correlate with chronological age themselves. In conclusion, we propose that our CSF protein aging clock can identify novel proteins that influence the rate of aging of the central nervous system (CNS), in a manner that would not be identifiable by examining their individual relationships with age. © 2024 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Author Keywords
aging; brain aging; cerebrospinal fluid; neurodegeneration; neurodegenerative diseases; proteomics
Funding details
Hope Center for Neurological Disorders, Washington University in St. Louis
Chan Zuckerberg InitiativeCZI
Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. LouisKGAD
University of WashingtonUW
Michael J. Fox Foundation for Parkinson’s ResearchMJFF
National Institutes of HealthNIHR01AG044546, RF1AG058501, RF1AG074007, U01AG058922, RF1AG053303, P30AG066444, P01AG026276, P01AG003991
National Institutes of HealthNIH
Alzheimer’s Disease Neuroimaging InitiativeADNIU19 AG024904
Alzheimer’s Disease Neuroimaging InitiativeADNI
U.S. Department of DefenseDODW81XWH‐12‐2‐0012
U.S. Department of DefenseDOD
Alzheimer’s AssociationAAZEN‐22‐848604
Alzheimer’s AssociationAA
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Differential network knockoff filter with application to brain connectivity analysis
(2024) Statistics in Medicine, .
Ji, J.a , Hou, Z.a , He, Y.a , Liu, L.b , Xue, F.c , Chen, H.c , Yuan, Z.c
a Institute for Financial Studies, Shandong University, Shandong, Jinan, China
b Division of Biostatistics, Washington University in St. Louis, St. Louis, MO, United States
c Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Shandong, Jinan, China
Abstract
The brain functional connectivity can typically be represented as a brain functional network, where nodes represent regions of interest (ROIs) and edges symbolize their connections. Studying group differences in brain functional connectivity can help identify brain regions and recover the brain functional network linked to neurodegenerative diseases. This process, known as differential network analysis focuses on the differences between estimated precision matrices for two groups. Current methods struggle with individual heterogeneity in measuring the brain connectivity, false discovery rate (FDR) control, and accounting for confounding factors, resulting in biased estimates and diminished power. To address these issues, we present a two-stage FDR-controlled feature selection method for differential network analysis using functional magnetic resonance imaging (fMRI) data. First, we create individual brain connectivity measures using a high-dimensional precision matrix estimation technique. Next, we devise a penalized logistic regression model that employs individual brain connectivity data and integrates a new knockoff filter for FDR control when detecting significant differential edges. Through extensive simulations, we showcase the superiority of our approach compared to other methods. Additionally, we apply our technique to fMRI data to identify differential edges between Alzheimer’s disease and control groups. Our results are consistent with prior experimental studies, emphasizing the practical applicability of our method. © 2024 John Wiley & Sons Ltd.
Author Keywords
brain functional connectivity; differential network analysis; FDR control; knockoff filter; matrix-variate data; neurodegenerative disease
Funding details
Shandong UniversitySDU
National Natural Science Foundation of ChinaNSFC82373686, 82173625, T2341018, 82173624
National Natural Science Foundation of ChinaNSFC
Taishan Scholar Project of Shandong Provincetsqn202211025
Taishan Scholar Project of Shandong Province
Natural Science Foundation of Shandong Province2022LY031, ZR2019ZD02
Natural Science Foundation of Shandong Province
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Vaccination reduces central nervous system IL-1β and memory deficits after COVID-19 in mice
(2024) Nature Immunology, .
Vanderheiden, A.a b , Hill, J.D.a b , Jiang, X.a b , Deppen, B.a b , Bamunuarachchi, G.b , Soudani, N.b , Joshi, A.b , Cain, M.D.b , Boon, A.C.M.b c , Klein, R.S.d e
a Center for Neuroimmunology and Neuroinfectious Diseases, Washington University School of Medicine, St. Louis, MO, United States
b Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
c Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United States
d Schulich School of Medicine and Dentistry, Department of Microbiology and Immunology, Western University, London, ON, Canada
e Schulich School of Medicine and Dentistry, Western Institute of Neuroscience, Western University, London, ON, Canada
Abstract
Up to 25% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit postacute cognitive sequelae. Although millions of cases of coronavirus disease 2019 (COVID-19)-mediated memory dysfunction are accumulating worldwide, the underlying mechanisms and how vaccination lowers risk are unknown. Interleukin-1 (IL-1), a key component of innate immune defense against SARS-CoV-2 infection, is elevated in the hippocampi of individuals with COVID-19. Here we show that intranasal infection of C57BL/6J mice with SARS-CoV-2 Beta variant leads to central nervous system infiltration of Ly6Chi monocytes and microglial activation. Accordingly, SARS-CoV-2, but not H1N1 influenza virus, increases levels of brain IL-1β and induces persistent IL-1R1-mediated loss of hippocampal neurogenesis, which promotes postacute cognitive deficits. Vaccination with a low dose of adenoviral-vectored spike protein prevents hippocampal production of IL-1β during breakthrough SARS-CoV-2 infection, loss of neurogenesis and subsequent memory deficits. Our study identifies IL-1β as one potential mechanism driving SARS-CoV-2-induced cognitive impairment in a new mouse model that is prevented by vaccination. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
Funding details
St. Louis Children’s HospitalSLCHCDI-CORE-2019-813, CDI-CORE-2015-505
St. Louis Children’s HospitalSLCH
Foundation for Barnes-Jewish HospitalFBJHR01NS104471, F32NS128065, R01 AI160188, R35 NS122310, 4642, 3770, R01-AI139251
Foundation for Barnes-Jewish HospitalFBJH
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
The Causes and Consequences of Drifting Expectations
(2024) Psychological Science, .
Villano, W.J.a , Kraus, N.I.a , Reneau, T.R.b , Jaso, B.A.c , Otto, A.R.d , Heller, A.S.a
a Department of Psychology, University of Miami, United States
b Department of Psychiatry, Washington University in St. Louis, United States
c Reliant Medical Group, OptumCare, Worcester, MA, United States
d Department of Psychology, McGill University, Canada
Abstract
Awaiting news of uncertain outcomes is distressing because the news might be disappointing. To prevent such disappointments, people often “brace for the worst,” pessimistically lowering expectations before news arrives to decrease the possibility of surprising disappointment (a negative prediction error, or PE). Computational decision-making research commonly assumes that expectations do not drift within trials, yet it is unclear whether expectations pessimistically drift in real-world, high-stakes settings, what factors influence expectation drift, and whether it effectively buffers emotional responses to goal-relevant outcomes. Moreover, individuals learn from PEs to accurately anticipate future outcomes, but it is unknown whether expectation drift also impedes PE-based learning. In a sample of students awaiting exam grades (N = 625), we found that expectations often drift and tend to drift pessimistically. We demonstrate that bracing is preferentially modulated by uncertainty; it transiently buffers the initial emotional impact of negative PEs but impairs PE-based learning, counterintuitively sustaining uncertainty into the future. © The Author(s) 2024.
Author Keywords
bracing; ecological momentary assessment; emotion; expectation; expectation drift; learning; naturalistic methods; prediction error
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Migraine headache in patients with spontaneous coronary artery dissection: A report of the iSCAD Registry
(2024) Vascular Medicine (United Kingdom), .
Wells, B.J.a , Wood, M.J.b c , O’Duffy, A.E.d , Sumner, J.A.e , Chi, G.f , Grodzinsky, A.g , Gornik, H.L.h , Kadian-Dodov, D.i , Taylor, A.j , Hess, C.N.k , Sanghavi, M.l , Henkin, S.m n , Wells, G.o p , Tam, L.q , Orford, J.r , Lindley, K.s t , Kumbhani, D.J.u , Vitarello, C.f , Alkhalfan, F.f , Gibson, C.M.f , Leon, K.K.v , Naderi, S.w , Kim, E.S.H.t x
a Division of Cardiology, Emory University School of Medicine, Atlanta, GA, United States
b Division of Cardiology, Massachusetts General Hospital, Boston, MA, United States
c Lee Health Heart Institute, Fort Myers, FL, United States
d Division of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States
e Department of Psychology, University of California, Los Angeles, Los Angeles, CA, United States
f Department of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
g Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas CityMO, United States
h Harrington Heart & Vascular Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, United States
i Zena and Michael A Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
j Division of Cardiology, University of Virginia Health System, Charlottesville, VA, United States
k University of Colorado School of Medicine, Aurora, CO, United States
l Department of Medicine, Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
m Heart and Vascular Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
n Current: Gonda Vascular Center, Mayo Clinic, Rochester, MN, United States
o University of Kentucky College of Medicine, Lexington, KY, United States
p University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, United States
q Providence Heart Institute, Portland, OR, United States
r Intermountain Heart Institute, Intermountain Medical Center, Murray, UT, United States
s Division of Cardiovascular Medicine, Washington University, St Louis, MO, United States
t Current: Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
u Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, United States
v SCAD Alliance, Alexandria, VA, United States
w Kaiser Permanente Northern California, San Francisco, CA, United States
x Atrium Health, Sanger Heart and Vascular Institute, Charlotte, NC, United States
Abstract
Introduction: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified. Methods: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine. Results: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were more likely to be women (96.9% vs 90.3%, p = 0.0003). The presence of underlying carotid fibromuscular dysplasia was associated with migraine (35% vs 27%, p = 0.0175). There was not a significant association with carotid artery dissection and migraine. Current migraine frequency was less than monthly (58%), monthly (24%), weekly (16%), and daily (3%). Triptan use was reported in 32.5% of patients, and 17.5% used daily migraine prophylactic medications. Using the MIDAS to quantify disability related to migraine, 60.2% reported little or no disability, 14.4% mild, 12.7% moderate, and 12.7% severe. The mean MIDAS score was 9.9 (mild to moderate disability). Patients with SCAD had higher rates of depression and anxiety (28.2% vs 17.7% [p = 0.0004] and 35.3% vs 26.7% [p = 0.0099], respectively). Conclusions: Migraines are common, frequent, and a source of disability in patients with SCAD. The association between female sex, anxiety, and depression may provide some insight for potential treatment modalities. © The Author(s) 2024.
Author Keywords
fibromuscular dysplasia (FMD); migraine headache; myocardial infarction; spontaneous coronary artery dissection (SCAD)
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Statistical considerations when estimating time-saving treatment effects in Alzheimer’s disease clinical trials
(2024) Alzheimer’s and Dementia, .
Wang, G.a b , Cutter, G.c , Oxtoby, N.P.d , Shan, G.e , Wang, W.f , Mangal, B.g , Liao, Y.h , Llibre-Guerra, J.J.a , Li, Y.a , Xiong, C.b , McDade, E.a , Delmar, P.i , Bateman, R.J.a , Schneider, L.j
a Department of Neurology, Division of Biostatistics, School of Medicine, Washington University, St. Louis, MO, United States
b Division of Biostatistics, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United States
d Department of Computer Science, University College London, London, United Kingdom
e Department of Biostatistics, University of Florida, Gainesville, FL, United States
f Tenaya Therapeutics, South San Francisco, CA, United States
g Solara Consulting Corp., North Vancouver, BC, Canada
h Neogene Therapeutics, Inc., Santa Monica, CA, United States
i F. Hoffmann-La Roche Ltd., Basel, Switzerland
j Department of Psychiatry and The Behavioral Sciences, Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
Abstract
INTRODUCTION: Estimating treatment effects as time savings in disease progression may be more easily interpretable than assessing the absolute difference or a percentage reduction. In this study, we investigate the statistical considerations of the existing method for estimating time savings and propose alternative complementary methods. METHODS: We propose five alternative methods to estimate the time savings from different perspectives. These methods are applied to simulated clinical trial data that mimic or modify the Clinical Dementia Rating Sum of Boxes progression trajectories observed in the Clarity AD lecanemab trial. RESULTS: Our study demonstrates that the proposed methods can generate more precise estimates by considering two crucial factors: (1) the absolute difference between treatment arms, and (2) the observed progression rate in the treatment arm. DISCUSSION: Quantifying treatment effects as time savings in disease progression offers distinct advantages. To provide comprehensive estimations, it is important to use various methods. Highlights: We explore the statistical considerations of the current method for estimating time savings. We proposed alternative methods that provide time savings estimations based on the observed absolute differences. By using various methods, a more comprehensive estimation of time savings can be achieved. © 2024 The Author(s). Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.
Author Keywords
Alzheimer’s disease; proportional mixed models for repeated measures; semi-real trial data; time savings
Funding details
Alzheimer’s AssociationAA
Avid Radiopharmaceuticals
Biogen
GHR FoundationGHR
Roche Canada
National Institute on AgingNIA
UK Research and InnovationUKRIK01AG073526, AG067505, AARFD‐21‐851415, SG‐20‐690363
UK Research and InnovationUKRI
Foundation for the National Institutes of HealthFNIHR01AG046179, R01AG053267‐S1
Foundation for the National Institutes of HealthFNIH
National Institutes of HealthNIHU01AG042791
National Institutes of HealthNIH
Document Type: Article
Publication Stage: Article in Press
Source: Scopus