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Yang YP, Ji MJ, Guo YH, Yao N. Association of heart rate variability index with depressive symptoms and lung function in chronic obstructive pulmonary disease. World J Psychiatry 2025; 15:103269. [DOI: 10.5498/wjp.v15.i5.103269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/05/2025] [Accepted: 04/03/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND Depression is a common comorbidity in patients with chronic obstructive pulmonary disease (COPD). Research indicates that COPD affects cardiac autonomic control, and heart rate variability (HRV) serves as a simple, non-invasive measure of autonomic nerve activity. However, the relationship between HRV and lung function, as well as the impact of depressive symptoms, remains unclear.
AIM To investigate the correlation between HRV indicators and depressive symptoms and lung function in patients with COPD.
METHODS A retrospective cross-sectional study involving 120 COPD patients hospitalized from January 2018 to January 2024 at our institution was conducted. Demographic and clinical characteristics were collected, and depressive symptoms were assessed using the Beck Depression Inventory (BDI). Patients were categorized into a depressed group (BDI ≥ 16) and a non-depressed group (BDI < 16). A control group consisting of 60 healthy volunteers who underwent check-ups at the same institution was also included. Statistical analyses were performed using SPSS 26.0 software. Pearson correlation coefficients were calculated to determine and compare the relationships between HRV parameters, lung function measures, and depressive symptoms across the groups.
RESULTS Of the 120 patients with COPD, 35.8% (43/120) were diagnosed with depression, compared to 5.0% (3/60) in the control group. The HRV index in COPD patients was significantly lower than that in the control group (P < 0.05), and the value in the depressed group was significantly lower than that in the non-depressed group (P < 0.05). Similarly, the COPD group had a significantly lower pulmonary forced vital capacity (FVC), first-second expiratory volume (FEV1) and FEV1/FVC ratios than the control group (P < 0.05), and the depressed group was significantly lower than that in the non-depressed group (P < 0.05). Pearson correlation analysis revealed that the standard deviation of normal R-R intervals, standard deviation of the mean of 5-minute normal R-R intervals, root mean square of successive differences of normal R-R intervals, percentage of normal R-R intervals greater than 50 ms, high-frequency, and low-frequency indices showed positive correlations with lung function parameters (P < 0.05) and negative correlations with BDI scores (P < 0.05).
CONCLUSION Compared to patients without COPD, the incidence of depressive symptoms is higher among patients with COPD and is negatively correlated with the patients’ HRV indices. In contrast, HRV indices are positively correlated with the patients’ pulmonary function parameters. Patients and healthcare professionals should enhance their awareness of depression, actively conduct depression assessment screenings, and incorporate HRV indices into disease management. This approach aims to improve the psychological health of patients and ultimately enhance their prognosis and quality of life.
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Affiliation(s)
- Ya-Ping Yang
- Department of Respiratory and Critical Care Medicine, The First Hospital of Zhangjiakou, Zhangjiakou 075000, Hebei Province, China
| | - Mei-Jia Ji
- Department of Geriatrics One, The First Hospital of Zhangjiakou, Zhangjiakou 075000, Hebei Province, China
| | - Yue-Han Guo
- Department of Psychiatric, Wuhan Mental Health Center, Wuhan 430000, Hubei Province, China
| | - Na Yao
- Department of Respiratory and Critical Care Medicine, The First Hospital of Zhangjiakou, Zhangjiakou 075000, Hebei Province, China
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Kikinis Z, Castañeyra-Perdomo A, González-Mora JL, Rushmore RJ, Toppa PH, Haggerty K, Papadimitriou G, Rathi Y, Kubicki M, Kikinis R, Heller C, Yeterian E, Besteher B, Pallanti S, Makris N. Investigating the structural network underlying brain-immune interactions using combined histopathology and neuroimaging: a critical review for its relevance in acute and long COVID-19. Front Psychiatry 2024; 15:1337888. [PMID: 38590789 PMCID: PMC11000670 DOI: 10.3389/fpsyt.2024.1337888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 02/23/2024] [Indexed: 04/10/2024] Open
Abstract
Current views on immunity support the idea that immunity extends beyond defense functions and is tightly intertwined with several other fields of biology such as virology, microbiology, physiology and ecology. It is also critical for our understanding of autoimmunity and cancer, two topics of great biological relevance and for critical public health considerations such as disease prevention and treatment. Central to this review, the immune system is known to interact intimately with the nervous system and has been recently hypothesized to be involved not only in autonomic and limbic bio-behaviors but also in cognitive function. Herein we review the structural architecture of the brain network involved in immune response. Furthermore, we elaborate upon the implications of inflammatory processes affecting brain-immune interactions as reported recently in pathological conditions due to SARS-Cov-2 virus infection, namely in acute and post-acute COVID-19. Moreover, we discuss how current neuroimaging techniques combined with ad hoc clinical autopsies and histopathological analyses could critically affect the validity of clinical translation in studies of human brain-immune interactions using neuroimaging. Advances in our understanding of brain-immune interactions are expected to translate into novel therapeutic avenues in a vast array of domains including cancer, autoimmune diseases or viral infections such as in acute and post-acute or Long COVID-19.
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Affiliation(s)
- Zora Kikinis
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Agustin Castañeyra-Perdomo
- Universidad de La Laguna, Área de Anatomía y Fisiología. Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud, San Cristobal de la Laguna, Spain
| | - José Luis González-Mora
- Universidad de La Laguna, Área de Anatomía y Fisiología. Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud, San Cristobal de la Laguna, Spain
- Universidad de La Laguna, Instituto Universitario de Neurosciencias, Facultad de Ciencias de la Salud, San Cristobal de la Laguna, Spain
| | - Richard Jarrett Rushmore
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- Department of Anatomy and Neurobiology, Boston University School of Medicine, San Cristobal de la Laguna, Spain
- Departments of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Poliana Hartung Toppa
- Departments of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Kayley Haggerty
- Departments of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - George Papadimitriou
- Departments of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Yogesh Rathi
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- Departments of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Marek Kubicki
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- Departments of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Ron Kikinis
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Carina Heller
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
| | - Edward Yeterian
- Departments of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
- Department of Psychology, Colby College, Waterville, ME, United States
| | - Bianca Besteher
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany
| | - Stefano Pallanti
- Department of Psychiatry and Behavioural Science, Albert Einstein College of Medicine, Bronx, NY, United States
- Istituto di Neuroscienze, Florence, Italy
| | - Nikos Makris
- Department of Psychiatry, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- Universidad de La Laguna, Área de Anatomía y Fisiología. Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud, San Cristobal de la Laguna, Spain
- Universidad de La Laguna, Instituto Universitario de Neurosciencias, Facultad de Ciencias de la Salud, San Cristobal de la Laguna, Spain
- Department of Anatomy and Neurobiology, Boston University School of Medicine, San Cristobal de la Laguna, Spain
- Departments of Psychiatry and Neurology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
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Iosef C, Knauer MJ, Nicholson M, Van Nynatten LR, Cepinskas G, Draghici S, Han VKM, Fraser DD. Plasma proteome of Long-COVID patients indicates HIF-mediated vasculo-proliferative disease with impact on brain and heart function. J Transl Med 2023; 21:377. [PMID: 37301958 PMCID: PMC10257382 DOI: 10.1186/s12967-023-04149-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 04/25/2023] [Indexed: 06/12/2023] Open
Abstract
AIMS Long-COVID occurs after SARS-CoV-2 infection and results in diverse, prolonged symptoms. The present study aimed to unveil potential mechanisms, and to inform prognosis and treatment. METHODS Plasma proteome from Long-COVID outpatients was analyzed in comparison to matched acutely ill COVID-19 (mild and severe) inpatients and healthy control subjects. The expression of 3072 protein biomarkers was determined with proximity extension assays and then deconvoluted with multiple bioinformatics tools into both cell types and signaling mechanisms, as well as organ specificity. RESULTS Compared to age- and sex-matched acutely ill COVID-19 inpatients and healthy control subjects, Long-COVID outpatients showed natural killer cell redistribution with a dominant resting phenotype, as opposed to active, and neutrophils that formed extracellular traps. This potential resetting of cell phenotypes was reflected in prospective vascular events mediated by both angiopoietin-1 (ANGPT1) and vascular-endothelial growth factor-A (VEGFA). Several markers (ANGPT1, VEGFA, CCR7, CD56, citrullinated histone 3, elastase) were validated by serological methods in additional patient cohorts. Signaling of transforming growth factor-β1 with probable connections to elevated EP/p300 suggested vascular inflammation and tumor necrosis factor-α driven pathways. In addition, a vascular proliferative state associated with hypoxia inducible factor 1 pathway suggested progression from acute COVID-19 to Long-COVID. The vasculo-proliferative process predicted in Long-COVID might contribute to changes in the organ-specific proteome reflective of neurologic and cardiometabolic dysfunction. CONCLUSIONS Taken together, our findings point to a vasculo-proliferative process in Long-COVID that is likely initiated either prior hypoxia (localized or systemic) and/or stimulatory factors (i.e., cytokines, chemokines, growth factors, angiotensin, etc). Analyses of the plasma proteome, used as a surrogate for cellular signaling, unveiled potential organ-specific prognostic biomarkers and therapeutic targets.
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Affiliation(s)
- Cristiana Iosef
- Children's Health Research Institute, Victoria Research Laboratories, 800 Commissioners Road East, London, ON, N6C 2V5, Canada.
| | - Michael J Knauer
- Department of Pathology and Laboratory Medicine, London, ON, N6A 5C1, Canada
| | - Michael Nicholson
- Department of Medicine, Western University, London, ON, N6A 5C1, Canada
| | | | - Gediminas Cepinskas
- Lawson Health Research Institute, London, ON, N6C 2R5, Canada
- Department of Medical Biophysics, Western University, London, ON, N6A 5C1, Canada
| | - Sorin Draghici
- Department of Computer Science College of Engineering, Wayne State University, Ann Arbor, MI, 48202, USA
- Advaita Bioinformatics, Ann Arbor, 48105-2552, USA
- National Science Foundation, Alexandria, VA, 22314, USA
| | - Victor K M Han
- Children's Health Research Institute, Victoria Research Laboratories, 800 Commissioners Road East, London, ON, N6C 2V5, Canada
- Department of Pediatrics, Western University, London, ON, N6A 5C1, Canada
| | - Douglas D Fraser
- Children's Health Research Institute, Victoria Research Laboratories, 800 Commissioners Road East, London, ON, N6C 2V5, Canada.
- Lawson Health Research Institute, London, ON, N6C 2R5, Canada.
- Department of Pediatrics, Western University, London, ON, N6A 5C1, Canada.
- Department of Physiology & Pharmacology, Western University, London, ON, N6A 5C1, Canada.
- Department of Clinical Neurological Sciences, Western University, London, ON, N6A 5C1, Canada.
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