Protocol to study inter-tissue communication between the hypothalamus and white adipose tissue and lifespan using a chemogenetic approach in aged mice
(2025) STAR Protocols, 6 (1), art. no. 103551, .
Tokizane, K.a , Imai, S.-I.a b
a Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Here, we present a protocol for assessing the impact of a chemogenetic manipulation in a subpopulation of the hypothalamic neurons on aging and lifespan control using a mouse model developed specifically for this purpose. We describe steps for stereotaxic viral injection and assess inter-tissue communication between protein phosphatase 1 regulatory subunit 17 (Ppp1r17)-expressing neurons in the dorsomedial hypothalamus and white adipose tissue. We then detail procedures for lifespan measurements following chemogenetic manipulation in aged mice. For complete details on the use and execution of this protocol, please refer to Tokizane et al.1 © 2024 The Author(s)
Author Keywords
Metabolism; Model Organisms; Neuroscience
Document Type: Article
Publication Stage: Final
Source: Scopus
Active learning of enhancers and silencers in the developing neural retina
(2025) Cell Systems, 16 (1), art. no. 101163, .
Friedman, R.Z.a b , Ramu, A.a b , Lichtarge, S.a b , Wu, Y.a b , Tripp, L.a b , Lyon, D.a b , Myers, C.A.c , Granas, D.M.a b , Gause, M.c , Corbo, J.C.c , Cohen, B.A.a b , White, M.A.a b
a The Edison Family Center for Genome Sciences & Systems Biology, Saint Louis, MO 63110, United States
b Department of Genetics, Saint Louis, MO 63110, United States
c Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, United States
Abstract
Deep learning is a promising strategy for modeling cis-regulatory elements. However, models trained on genomic sequences often fail to explain why the same transcription factor can activate or repress transcription in different contexts. To address this limitation, we developed an active learning approach to train models that distinguish between enhancers and silencers composed of binding sites for the photoreceptor transcription factor cone-rod homeobox (CRX). After training the model on nearly all bound CRX sites from the genome, we coupled synthetic biology with uncertainty sampling to generate additional rounds of informative training data. This allowed us to iteratively train models on data from multiple rounds of massively parallel reporter assays. The ability of the resulting models to discriminate between CRX sites with identical sequence but opposite functions establishes active learning as an effective strategy to train models of regulatory DNA. A record of this paper’s transparent peer review process is included in the supplemental information. © 2024 The Author(s)
Author Keywords
active learning; cis-regulatory elements; enhancers; gene regulation; machine learning; retina; silencers; transcription factors
Document Type: Article
Publication Stage: Final
Source: Scopus
A propofol binding site in the voltage sensor domain mediates inhibition of HCN1 channel activity
(2025) Science Advances, 11 (1), p. eadr7427.
Burtscher, V.a b , Wang, L.a c d , Cowgill, J.e , Chen, Z.-W.a , Edge, C.f , Smith, E.g , Chang, Y.a b , Delemotte, L.h , Evers, A.S.a i , Chanda, B.a b j k
a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Center for Membrane Excitability Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
d Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, 430022, China
e Department of Biochemistry and Biophysics, SciLifeLab, Stockholm University, Solna, 17121, Sweden
f Department of Life Sciences, Imperial College, London, SW7 2AZ, United Kingdom
g Department of Biophysics, Imperial College of Science, Medicine and Technology, London, SW7 2AZ, United Kingdom
h Department of Applied Physics, SciLifeLab, KTH Royal Institute of Technology, Solna, 17121, Sweden
i Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States
j Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
k Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) ion channels are members of the cyclic nucleotide-binding family and are crucial for regulating cellular automaticity in many excitable cells. HCN channel activation contributes to pain perception, and propofol, a widely used anesthetic, acts as an analgesic by inhibiting the voltage-dependent activity of HCN channels. However, the molecular determinants of propofol action on HCN channels remain unknown. Here, we use a propofol-analog photoaffinity labeling reagent to identify propofol binding sites in the human HCN1 isoform. Mass spectrometry analyses combined with molecular dynamics simulations show that a binding pocket is formed by extracellularly facing residues in the S3 and S4 transmembrane segments in the resting voltage-sensor conformation. Mutations of residues within the putative binding pocket mitigate or eliminate voltage-dependent modulation of HCN1 currents by propofol. Together, these findings reveal a conformation-specific propofol binding site that underlies voltage-dependent inhibition of HCN currents and provides a framework for identifying highly specific modulators of HCN channel gating.
Document Type: Article
Publication Stage: Final
Source: Scopus
A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations
(2025) Journal of Clinical Investigation, 135 (1), art. no. e177793, .
Cantoni, C.a , Smirnov, R.A.b , Firulyova, M.b , Andhey, P.S.b , Bradstreet, T.R.b , Esaulova, E.b , Terekhova, M.b , Schwarzkopf, E.A.b , Abdalla, N.M.b , Kleverov, M.b , Sabatino, J.J., Jr.c , Liu, K.d , Schwab, N.e , Meyer Zu Hörste, G.e , Cross, A.H.f , Artyomov, M.N.b , Edelson, B.T.b , Wu, G.F.b f g
a Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
c Weill Institute for Neurosciences, UCSF, San Francisco, CA, United States
d Regeneron Pharmaceuticals, Tarrytown, NY, United States
e Department of Neurology, Institute of Translational Neurology, University Hospital Münster, Münster, Germany
f Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
g Neurology Service, Veterans Affairs St. Louis Health Care System, St. Louis, MO, United States
Abstract
Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG+ dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases. Copyright: © 2025, Cantoni et al.
Document Type: Article
Publication Stage: Final
Source: Scopus
Tofersen treatment leads to sustained stabilization of disease in SOD1 ALS in a “real-world” setting
(2025) Annals of Clinical and Translational Neurology, .
Smith, S.E., McCoy-Gross, K., Malcolm, A., Oranski, J., Markway, J.W., Miller, T.M., Bucelli, R.C.
Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Objective: Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and disease stabilization with recovery of function in some patients. We report our clinical experience with treating patients with SOD1 ALS and the effects of tofersen on outcome measures. Methods: This was a single-center observational study of patients with SOD1 ALS receiving treatment with tofersen. The effects of tofersen treatment on neurofilament levels, muscle strength, and clinical outcome measures were assessed. Several patients had outpatient neuromuscular rehabilitation in addition to tofersen treatment and we report changes in functional outcomes. Results: Seven SOD1 ALS patients received treatment at our institution. All patients showed robust and sustained declines in serum NfL and CSF pNFH (mean change serum NfL: −57.9%; mean change CSF pNFH: −67.6%). There was apparent disease stabilization as assessed by the ALSFRS-R total score, mean change 1.1 (SD = 0.7). There was notable improvement in functional independence measured by the FIM motor score, mean change 5.13 points (SD = 3.85). Interpretation: This study provides evidence that tofersen treatment in SOD1 ALS can lead to meaningful preservation of function and suggestions of sustained improvement in neurologic function in some patients, and strongly supports the role of neurofilaments as therapeutic biomarkers. © 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Patient stratification by genetic risk in Alzheimer’s disease is only effective in the presence of phenotypic heterogeneity
(2025) PLoS ONE, 20 (1 January), art. no. e0310977, .
Euesden, J.a , Ali, M.b , Robins, C.c , Surendran, P.d , Gormley, P.e , Pulford, D.d , Cruchaga, C.b , Alzheimer’s Disease Neuroimaging Initiative (ADNI)f
a GSK Pharma R&D, Stevenage, Hertfordshire, United Kingdom
b Washington University School of Medicine, NeuroGenomics and Informatics Center, St. Louis, MO, United States
c GSK Pharma R&D, Collegeville, PA, United States
d GSK Pharma R&D, Stevenage, Hertfordshire, United Kingdom
e GSK Pharma R&D, Cambridge, MA, United States
Abstract
Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer’s disease (AD), where longitudinal cohorts measure disease “progression,” defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving polygenic risk scores (PRS) for AD risk and severity and tested the value of these scores in predicting progression. Genome-wide association studies identified no loci associated with progression at genome-wide significance (α = 5×10−8); MR analyses provided no significant evidence of an association between cognitive decline in AD patients and protein levels in brain, cerebrospinal fluid (CSF), and plasma. Polygenic risk scores for AD risk did not reliably stratify fast from slow progressors; however, a deeper investigation found that APOE ε4 status predicts amyloid-β and tau positive versus negative patients (odds ratio for an additional APOE ε4 allele = 5.78 [95% confidence interval: 3.76–8.89], P<0.001) when restricting to a subset of patients with available CSF biomarker data. These results provided no evidence for large-effect, common-variant loci involved in the rate of memory decline, suggesting that patient stratification based on common genetic risk factors for progression may have limited utility. Where clinically relevant biomarkers suggest diagnostic heterogeneity, there is evidence that a priori identified genetic risk factors may have value in patient stratification. Mendelian randomization was less tractable due to the lack of large-effect loci, and future analyses with increased samples sizes are needed to replicate and validate our results. Copyright: © 2025 Euesden et al.
Document Type: Article
Publication Stage: Final
Source: Scopus
Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort
(2025) International Journal of Molecular Sciences, 26 (1), art. no. 286, .
Puerta, R.a b , Cano, A.a c , García-González, P.a c , García-Gutiérrez, F.a , Capdevila, M.a d , de Rojas, I.a c , Olivé, C.a , Blázquez-Folch, J.a , Sotolongo-Grau, O.a , Miguel, A.a , Montrreal, L.a , Martino-Adami, P.e , Khan, A.f , Orellana, A.a c , Sung, Y.J.g h , Frikke-Schmidt, R.i j , Marchant, N.k , Lambert, J.C.l m , Rosende-Roca, M.a , Alegret, M.a c , Fernández, M.V.a c , Marquié, M.a c , Valero, S.a c , Tárraga, L.a c , Cruchaga, C.g h , Ramírez, A.e n o p q , Boada, M.a c , Smets, B.f , Cabrera-Socorro, A.f , Ruiz, A.a c r
a Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, 08029, Spain
b PhD Program in Biotecnology, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, 08028, Spain
c Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), National Institute of Health Carlos III, Madrid, 28029, Spain
d Departament de Farmacologia, Toxicologia i Química Terapèutica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, 08007, Spain
e Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, 50937, Germany
f Janssen Pharmaceutica NV, a Johnson & Johnson Company, Beerse, 2340, Belgium
g NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63108, United States
h Hope Center for Neurological Disorders, Washington University, St. Louis, MO 63110, United States
i Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2100, Denmark
j Department of Clinical Medicine, University of Copenhagen, Copenhagen, 2200, Denmark
k Division of Psychiatry, University College London, London, W1T 7NK, United Kingdom
l Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, Université de Lille, Lille, F-59000, France
m Institut Pasteur de Lille, Inserm U1167, CHU de Lille, LabEx DISTALZ, Université de Lille, Lille, F-59000, France
n Department of Neurodegenerative Diseases and Geriatric Psychiatry, Medical Faculty, University Hospital Bonn, Bonn, 53127, Germany
o German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Germany
p Department of Psychiatry and Glenn, Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, San Antonio, TX 78229, United States
q Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, 50931, Germany
r Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, TX 77204, United States
Abstract
High-throughput proteomic platforms are crucial to identify novel Alzheimer’s disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan® 7k) and antibody-based (Olink® Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan® assays analyzing the same samples, and between SomaScan® and Olink® results. Association analyses were performed between proteomic measures, CSF biological traits, sample demographics, and AD endophenotypes. Our 12-category metric of reproducibility combining correlation analyses identified 2428 highly reproducible SomaScan CSF measures, with over 600 proteins well reproduced on another proteomic platform. The association analyses among AD clinical phenotypes revealed that the significant associations mainly involved reproducible proteins. The validation of reproducibility in these novel proteomics platforms, measured using this scarce biomaterial, is essential for accurate analysis and proper interpretation of innovative results. This classification metric could enhance confidence in multiplexed proteomic platforms and improve the design of future panels. © 2024 by the authors.
Author Keywords
Alzheimer’s disease; biomarkers; cerebrospinal fluid; mild cognitive impairment; Olink; proteomics; SomaScan
Document Type: Article
Publication Stage: Final
Source: Scopus
Neuroanatomical Variability and Substance Use Initiation in Late Childhood and Early Adolescence
(2024) JAMA Network Open, 7 (12), p. e2452027. Cited 1 time.
Miller, A.P.a , Baranger, D.A.A.b , Paul, S.E.b , Garavan, H.c , MacKey, S.c , Tapert, S.F.d , Leblanc, K.H.e , Agrawal, A.f , Bogdan, R.b
a Department of Psychiatry, Indiana University, School of Medicine, Indianapolis, United States
b Department of Psychological and Brain Sciences, Washington University, St Louis, MO, United States
c Department of Psychiatry, University of Vermont, Larner College of Medicine, Burlington, United States
d Department of Psychiatry, University of California, San Diego, United States
e Division of Extramural Research, National Institute on Drug Abuse, Bethesda, MD, United States
f Department of Psychiatry, Washington University, St Louis School of Medicine, St Louis, MO, United States
Abstract
Importance: The extent to which neuroanatomical variability associated with early substance involvement, which is associated with subsequent risk for substance use disorder development, reflects preexisting risk and/or consequences of substance exposure remains poorly understood. Objective: To examine neuroanatomical features associated with early substance use initiation and to what extent associations may reflect preexisting vulnerability. Design, Setting, and Participants: Cohort study using data from baseline through 3-year follow-up assessments of the ongoing longitudinal Adolescent Brain Cognitive Development Study. Children aged 9 to 11 years at baseline were recruited from 22 sites across the US between June 1, 2016, and October 15, 2018. Data were analyzed from February to September 2024. Exposures: Substance use initiation through 3-year follow-up (ie, age <15 years). Main Outcomes and Measures: Self-reported alcohol, nicotine, cannabis, and other substance use initiation and baseline magnetic resonance imaging (MRI)-derived estimates of brain structure (ie, global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume). Covariates included family (eg, familial relationships), pregnancy (eg, prenatal exposure to substances), child (eg, sex and pubertal status), and MRI (eg, scanner model) variables. Results: Among 9804 children (mean [SD] baseline age, 9.9 [0.6] years; 5160 boys [52.6%]; 213 Asian [2.2%], 1474 Black [15.0%], 514 Hispanic/Latino [5.2%], 29 American Indian [0.3%], 10 Pacific Islander [0.1%], 7463 White [76.1%], and 75 other [0.7%]) with nonmissing baseline neuroimaging and covariate data, 3460 (35.3%) reported substance use initiation before age 15. Initiation of any substance or alcohol use was associated with thinner cortex in prefrontal regions (eg, rostral middle frontal gyrus, β = -0.03; 95% CI, -0.02 to -0.05; P = 6.99 × 10-6) but thicker cortex in all other lobes, larger globus pallidus and hippocampal volumes, as well as greater global indices of brain structure (eg, larger whole brain volume, β = 0.05; 95% CI, 0.03 to 0.06; P = 2.80 × 10-8) following Bonferroni or false discovery rate multiple testing correction. Cannabis use initiation was associated with lower right caudate volume (β = -0.03; 95% CI, -0.01 to -0.05; P =.002). Post hoc examinations restricting to postbaseline initiation suggested that the majority of associations, including thinner prefrontal cortex and greater whole brain volume, preceded initiation. Conclusions and Relevance: In this cohort study of children, preexisting neuroanatomical variability was associated with substance use initiation. In addition to putative neurotoxic effects of substance exposure, brain structure variability may reflect predispositional risk for initiating substance use earlier in life with potential cascading implications for development of later problems. © 2024 American Medical Association. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
Major Depressive Disorder and Driving Behavior among Older Adults
(2024) JAMA Network Open, p. e2452038.
Babulal, G.M.a b c , Chen, L.d , Trani, J.-F.b c e f , Brown, D.C.a , Carr, D.B.g , Ances, B.M.a , Lenze, E.J.h
a Department of Neurology, Washington University in St Louis, St Louis, MO, United States
b Institute of Public Health, Washington University in St Louis, St Louis, MO, United States
c Department of Psychology, Faculty of Humanities, University of Johannesburg, Johannesburg, South Africa
d Division of Biostatistics, Washington University in St Louis, St Louis, MO, United States
e Brown School of Social Work, Washington University in St Louis, St Louis, MO, United States
f National Conservatory of Arts and Crafts, Paris, France
g Department of Medicine, Washington University in St Louis, St Louis, MO, United States
h Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States
Abstract
Importance: Depression and antidepressant use are independently associated with crash risk among older drivers. However, it is unclear what factors impact daily driving that increase safety risk for drivers with depression. Objective: To examine differences in naturalistic driving behavior and safety between older adults with and without major depressive disorder (MDD). Design, Setting, and Participants: A prospective longitudinal cohort study was conducted among older adults (≥65 years) from the Driving Real-World In-Vehicle Evaluation System Project collected from July 1, 2021, to December 30, 2023. The sample included 85 participants with MDD and 310 participants without. Neurological, clinical, mood, and neuropsychological tests were collected annually. Daily driving behavior was recorded using a commercial data logger. Statistical analysis was performed from January 31 to June 24, 2024. Exposure: MDD and antidepressant usage. Main outcomes and measures: Linear mixed models with propensity score weighting compared slopes of driving behaviors over time (trips taken at night, speeding, hard braking, entropy, and radius of gyration) between groups. Results: In a sample of 395 participants, 85 were classified as individuals with MDD (mean [SD] age, 69.6 [6.1] years; 60 [70.6%] female; 8 [9.4%] non-Hispanic Black and 77 [90.6%] non-Hispanic White) and 310 as individuals in the control group without depression (mean [SD] age, 70.1 [5.1] years; 153 [49.4%] female; 40 [12.9%] non-Hispanic Black and 270 [87.1%] non-Hispanic White). Adults with MDD had greater depressive symptoms (mean [SD], 8.35 [5.35] vs 2.33 [2.72]; difference, 6.02; 95% CI for difference, 5.17 to 6.85; P <.001), comorbidities (mean [SD], 4.08 [2.07] vs 2.79 [1.67]; difference, 1.29; 95% CI for difference, 0.87 to 1.70; P <.001), used more antidepressants (mean [SD], 0.94 [0.81] vs 0.27 [0.54]; χ21= 65.8; P <.001), and had a higher number of medications (mean [SD], 3.80 [3.27] vs 1.98 [2.21]; χ21= 21.0; P <.001) compared with controls at baseline. Longitudinal analysis demonstrated an association between adults with MDD and hard braking (mean [SE], 3.17 × 10-4[7.30 × 10-5] vs 6.70 × 10-5[4.00 × 10-5]; difference, 2.50 × 10-4; 95% CI for difference, 1.74 × 10-4to 4.61 × 10-4; P <.001) and hard cornering events per trip (mean [SE], 0.80 [0.64] vs 0.57 [0.25]; difference, 0.23; 95% CI for difference, 0.08 to 1.06; P =.04), greater distances driven from home (mean [SE], 31.19 [7.35] vs 7.76 [3.80] km; difference, 23.43; 95% CI for difference, 0.28 to 15.2; P <.001), more unique destinations visited (mean [SE], 0.34 [0.10] vs -0.27 [0.03]; difference, 0.61; 95% CI for difference, 0.14 to 0.54; P <.001), and higher random entropy (mean [SE], 0.01 [0.01] vs -0.02 [0.00]; difference, 0.03; 95% CI for difference, -0.03 to -0.01; P <.001) over time. Conclusions and relevance: In this longitudinal cohort study of older drivers, adcauults with MDD demonstrated distinct and riskier driving behaviors than those in the control group without depression, with higher rates of hard braking, cornering, and unpredictability in driving patterns over time. Routine depression screening and tailored interventions are essential for enhancing driving safety and maintaining independence among older adults with MDD. Comprehensive care approaches addressing both mental and physical health are crucial for this vulnerable population.. © 2024 American Medical Association. All rights reserved.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus