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Shen Q, Tan C, Wang M, Cai S, Liu Q, Li X, Tang Y, Liao H. Pattern of cortical thickness in depression among early-stage Parkinson's disease: A potential neuroimaging indicator for early recognition. Behav Brain Res 2025; 490:115622. [PMID: 40319944 DOI: 10.1016/j.bbr.2025.115622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 04/20/2025] [Accepted: 05/02/2025] [Indexed: 05/07/2025]
Abstract
PURPOSE This study aims to investigate the early change in cortical thickness and surface area in early-stage depressed PD (dPD) patients, and its associations with severity of depression. METHODS 59 patients with dPD, 27 patients with non-depressed PD (ndPD), and 43 healthy controls (HC) were recruited. The dPD patients were subclassified into mild-depressed PD (mi-dPD, n = 24), moderate-depressed PD (mo-dPD, n = 21) and severe-depressed PD (se-dPD, n = 14) subgroups. Structural MRI and surface-based morphometry analysis were applied to compare differences in cortical thickness and surface area among groups, and their correlations with Beck Depression Inventory (BDI) scores were analyzed. RESULTS Compared with ndPD, dPD exhibited cortical thinning in the dorsolateral prefrontal cortex (dlPFC, mainly involving the left superior frontal and bilateral middle frontal gyri), the right pars opercularis and bilateral lateral occipital gyri. The mean cortical thickness values within these regions negatively correlated with BDI scores. Subgroup analysis revealed that patients with mi-dPD had cortical thinning only in the right middle frontal gyrus, while se-dPD showed cortical thinning more extensively involving the right fusiform gyrus, posterior cingulate gyrus, and pars opercularis. There was no significant change in cortical surface area in either the dPD or its subgroups. CONCLUSION Our findings indicated that PD-related depression was associated with decrease of cortical thickness, instead of surface area, of which the patterns correlated with the severity of depression. Cortical thinning in dlPFC, mainly involving the left middle frontal gyrus, may serve as a potential neuroimaging indicator for early recognition of depression in PD patients.
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Affiliation(s)
- Qin Shen
- Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Changlian Tan
- Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Min Wang
- Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Sainan Cai
- Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Qinru Liu
- Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Xv Li
- Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Yuqing Tang
- Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Haiyan Liao
- Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, China.
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Lai TT, Xiang W, Stanojlovic M, Käufer C, Feja M, Lau K, Zunke F, Richter F. The basolateral amygdala and striatum propagate alpha-synuclein pathology causing increased fear response in a Parkinson's disease model. Brain Behav Immun 2025; 128:469-486. [PMID: 40274000 DOI: 10.1016/j.bbi.2025.04.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 03/30/2025] [Accepted: 04/21/2025] [Indexed: 04/26/2025] Open
Abstract
Alpha-synuclein (aSyn)-related pathology crucially contributes to the pathogenesis of Parkinson's disease, a frequent and incurable neurodegenerative disease characterized by progressive motor and non-motor symptoms. Anxiety and fear- related neuropsychiatric symptoms develop frequently and early in the disease, but a lack of understanding of pathogenesis hampers rational therapy. This study aimed to decipher whether aSyn pathology in the basolateral amygdala (BLA) is causative of fear and anxiety. Bilateral stereotaxic injections of human aSyn-preformed amyloid fibrils (PFF) in BLA, striatum, or substantia nigra were conducted in female mice overexpressing human aSyn (Thy1-aSyn) and in wildtype littermates (WT). We characterized the propagation of aSyn pathology and related neuropathological changes across brain regions and examined the behavioral and fear responses in mice up to 2 months post-injection of PFF. While PFF injections induced local aSyn fibril pathology close to all respective injection sites in transgenic mice, we observed differences in propagation, downstream pathology and behavioral alterations. The BLA and the striatum, but not the substantia nigra, effectively propagated aSyn pathology to connected brain regions at 2.5 months post injection. This involved enhanced microgliosis and astrogliosis in the nigrostriatal system and loss of GABAergic parvalbuminergic interneurons in the striatum and corticolimbic brain regions. Intra-BLA PFF injections resulted in increased cued fear response in both transgenic mice and WT mice at 1 month post injection. The effect was more pronounced in the transgenic mice. Conversely, intra-striatal PFF injections enhanced contextual fear in WT at 2 months post injection. These findings imply that increased fear is inducible by aSyn pathology, especially if originating in the BLA or striatum. Furthermore, both regions are hub regions of aSyn pathology propagation, thereby contributing to disease progression. These insights provide mechanisms that can guide rational therapeutic development.
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Affiliation(s)
- Thuy Thi Lai
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience Hannover, Germany
| | - Wei Xiang
- Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Germany
| | - Milos Stanojlovic
- Department of Neurobiology, Institute for Biological Research Siniša Stanković - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Christopher Käufer
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience Hannover, Germany
| | - Malte Feja
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience Hannover, Germany
| | - Kristina Lau
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience Hannover, Germany
| | - Friederike Zunke
- Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Germany
| | - Franziska Richter
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience Hannover, Germany.
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She Z, Qi X, Shi X, Peng H, Zheng J, Ma J, Sun Y, Zhang M, Wang Y, Xu Q, Gu Q, Chen S, Li X. Serum sirtuin 3 levels and multimodal abnormalities in brain structure and function in parkinson's disease patients with depression. Neurol Sci 2025:10.1007/s10072-025-08170-2. [PMID: 40259181 DOI: 10.1007/s10072-025-08170-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 04/04/2025] [Indexed: 04/23/2025]
Abstract
BACKGROUND Depression is a common nonmotor symptom in patients with Parkinson's disease (PD). Currently, few studies have investigated the relationships between serum markers and neuroimaging changes associated with depression in PD patients. OBJECTIVE To explore the correlations among depression, serum SIRT3 levels, and brain structural and functional alterations in PD patients. METHODS The Hamilton Depression Scale-17 (HAMD-17) was used to assess depression. Serum SIRT3 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Voxel-based morphometry (VBM) and resting-state functional magnetic resonance imaging (rs-fMRI) were used to examine structural and functional alterations. RESULTS Compared to healthy individuals, serum SIRT3 levels were lower in PD patients, especially in those with depression. PD patients with depression had lower total gray matter volume/total intracranial volume (GMV/TIV) ratio, and GMVs of the right amygdala, lower fractional amplitude of low-frequency fluctuations (fALFF) values of the left middle frontal gyrus (MidFG.L) and left superior parietal lobule (SPL.L), and altered functional connectivity(FC) primarily involving the Salience Network (SN) and the default Mode Network (DMN) compared to those without depression. Serum SIRT3 levels, total GMV/TIV ratios, and fALFF values of the MidFG.L and SPL.L have diagnostic value for PD patients with depression, and their combination can improve predictive accuracy. CONCLUSIONS Depression in PD patients is associated with lower serum SIRT3 levels, right amygdala atrophy, decreased spontaneous activity in MidFG.L and SPL.L, and altered FC in the DMN and SN.
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Affiliation(s)
- Zonghan She
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Xuelin Qi
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Xiaoxue Shi
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
- Department of Neurology, Henan University People's Hospital, Zhengzhou, China
| | - Haoran Peng
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
- Department of Neurology, Henan University People's Hospital, Zhengzhou, China
| | - Jinhua Zheng
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China.
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.
- Department of Neurology, Henan University People's Hospital, Zhengzhou, China.
| | - Jianjun Ma
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China.
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.
- Department of Neurology, Henan University People's Hospital, Zhengzhou, China.
| | - Yunfei Sun
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Mengyan Zhang
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Yingyun Wang
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Qing Xu
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
- Department of Neurology, Henan University People's Hospital, Zhengzhou, China
| | - Qi Gu
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
- Department of Neurology, Henan University People's Hospital, Zhengzhou, China
| | - Siyuan Chen
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
- Department of Neurology, Henan University People's Hospital, Zhengzhou, China
| | - Xue Li
- Department of Neurology, Zhengzhou University People's Hospital, Zhengzhou, China
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
- Department of Neurology, Henan University People's Hospital, Zhengzhou, China
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Wang L, Xiong X, Liu J, Liu R, Liao J, Li F, Lu S, Wang W, Zhuo L, Li H. Gray matter structural and functional brain abnormalities in Parkinson's disease: a meta-analysis of VBM and ALFF data. J Neurol 2025; 272:276. [PMID: 40106017 DOI: 10.1007/s00415-025-12934-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/21/2025] [Accepted: 01/22/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND Previous studies based on resting-state functional imaging and voxel-based morphometry (VBM) have revealed structural and functional alterations in several brain regions in patients with Parkinson's disease (PD), but their results have been inconsistent. Furthermore, no studies have investigated specific and common functional and structural alterations in PD. METHODS The whole-brain voxel-wise meta-analyses on the VBM and amplitude of low-frequency fluctuation (ALFF) studies were conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software, respectively, with multimodal overlapping to comprehensively identify the gray matter volume (GMV) and spontaneous functional activity changes in patients with PD. RESULTS A total of 30 independent studies for ALFF (1413 PD and 1424 HCs) and 27 independent studies for VBM (1236 PD and 1185 HCs) were included. Compared with HCs, patients with PD displayed significantly decreased spontaneous functional activity in the left striatum. For the VBM meta-analysis, patients with PD showed significantly decreased GMV in the right temporal pole: superior temporal gyrus (extending to the right hippocampus, parahippocampal gyrus, and amygdala), the left superior temporal gyrus (extending to the left insula, and temporal pole: superior temporal gyrus), and the left striatum. Furthermore, after overlapping functional and structural differences, patients with PD displayed a conjoint decrease of spontaneous functional activity and GMV in the left striatum. CONCLUSION The multimodal meta-analysis revealed that PD showed similar pattern of aberrant brain functional activity and structure in the striatum. In addition, some brain regions within the within the temporal lobe and limbic system displayed only structural deficits. These findings provide useful insights for understanding the underlying pathophysiology of PD.
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Affiliation(s)
- Lu Wang
- Department of Radiology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China
- Medical Imaging College, North Sichuan Medical College, Nanchong, 637000, China
| | - Xin Xiong
- Department of Radiology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China
| | - Junqi Liu
- Department of Radiology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China
| | - Ruishan Liu
- Department of Radiology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China
| | - Juan Liao
- Department of Radiology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China
- Medical Imaging College, North Sichuan Medical College, Nanchong, 637000, China
| | - Fan Li
- Department of Radiology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China
| | - Shangxiong Lu
- Department of Radiology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China
| | - Weiwei Wang
- Department of Psychiatry, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China
| | - Lihua Zhuo
- Department of Radiology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China.
| | - Hongwei Li
- Department of Radiology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, 621000, China.
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Kim JH, Yoon HJ, Choi Y, Kim JS, Ju IG, Eo H, Lee S, Cho JY, Park BY, Hong SP, Park HJ, Oh MS. 6-Shogaol, a neuro-nutraceutical derived from ginger, alleviates motor symptoms and depression-like behaviors and modulates the release of monoamine neurotransmitters in Parkinson's disease mice. Eur J Nutr 2025; 64:116. [PMID: 40063144 DOI: 10.1007/s00394-025-03639-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 01/22/2025] [Indexed: 04/17/2025]
Abstract
PURPOSE Parkinson's disease (PD) disrupts the regulation of neurotransmitters in the brain, causing patients to experience not only motor symptoms but also non-motor symptoms such as depression. 6-shogaol (6S) is a potential neuro-nutraceutical derived from ginger, and is known to ameliorate motor symptoms by suppressing inflammation in PD mice. In this study, we investigated whether 6S can attenuate motor symptoms and depression-like behaviors through neurotransmitter regulation and to elucidate which neurotransmitters are intimately correlated with these effects. METHODS C57BL/6 J mice were injected with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 5 d to induce PD. 6S was administered via oral gavage for 11 d, including the MPTP injection period. RESULTS 6S alleviated MPTP-induced motor symptoms and depression-like behaviors. MPTP injection decreased the levels of seven neurotransmitters in the striatum and four neurotransmitters in the hippocampus. Administration of 6S increased striatal dopamine, serotonin, and norepinephrine levels and hippocampal dopamine, norepinephrine, serotonin, and γ-aminobutyric acid levels. Moreover, correlation analysis shown that the motor symptom improvement effect of 6S was associated with striatal dopamine, norepinephrine, serotonin, and 5-hydroxyindoleacetic acid levels. The effect of 6S on depressive-like behavior was significantly correlated with striatal dopamine metabolites and serotonin and hippocampal dopamine, norepinephrine, and serotonin. Immunohistochemistry showed that 6S upregulated the expression of the vesicular monoamine transporter 2, which was reduced by MPTP in the striatum and hippocampus. CONCLUSION This study demonstrated that 6S improved motor symptoms and depression-like behaviors by regulating the release of monoamine neurotransmitters.
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Affiliation(s)
- Jin Hee Kim
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Hae-Jee Yoon
- Department of Integrated Drug Development and Natural Products, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Yujin Choi
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Jin Se Kim
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - In Gyoung Ju
- Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Hyeyoon Eo
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Food and Nutrition, College of Biotechnology and Natural Resources, Chung-Ang University, Anseong, 17546, Republic of Korea
| | - Seungmin Lee
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Jun-Young Cho
- Department of Fundamental Pharmaceutical Science, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Boyoung Y Park
- Department of Fundamental Pharmaceutical Science, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Seon-Pyo Hong
- Department of Integrated Drug Development and Natural Products, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Hi-Joon Park
- Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Myung Sook Oh
- Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
- Department of Integrated Drug Development and Natural Products, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
- Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.
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Ramos-Molina AR, Tejeda-Martínez AR, Viveros-Paredes JM, Chaparro-Huerta V, Urmeneta-Ortíz MF, Ramírez-Jirano LJ, Flores-Soto ME. Beta-caryophyllene inhibits the permeability of the blood-brain barrier in MPTP-induced parkinsonism. Neurologia 2025; 40:191-203. [PMID: 40054982 DOI: 10.1016/j.nrleng.2025.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 11/29/2022] [Indexed: 05/13/2025] Open
Abstract
INTRODUCTION Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Although the precise pathogenesis of PD remains unclear, several studies demonstrate that oxidative stress, inflammation, low levels of antioxidants, and the presence of biomolecules that generate reactive oxygen species can disrupt the blood-brain barrier (BBB) as an essential feature of the disease. AIMS This study aimed to test whether agonism to cannabinoid receptor type 2 (CB2) through the administration of β-caryophyllene (BCP) could correct BBB permeability in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonism induction model. METHODS We conducted a molecular assessment of proteins (immunochemistry and western blot), BBB permeability, and related biomarkers of PD (lipid peroxidation) in the MPTP mouse model of the disease. RESULTS Expression of zonula occludens (ZO-1) and occludin tight junction (TJ) proteins was dampened in the striatum and substantia nigra pars compacta of mice, while lipid peroxidation and BBB permeability increased in the striatum in the MPTP-treated group, and these effects were reversed under BCP administration. This phytocannabinoid was able to restore protein expression and immunoreactivity of tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP), as well as nuclear factor-erythroid 2-related factor (NRF2) translocation to the nucleus, and NADPH quinone oxidase 1 (NQO1) expression in mice treated with MPTP. CONCLUSION These results highlight the role of CB2 as a therapeutic target for PD, suggesting that its activation may ameliorate PD-related BBB disruption and oxidative stress, reducing the selective death of dopaminergic neurons.
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Affiliation(s)
- A R Ramos-Molina
- Centro Universitario de los Lagos, Universidad de Guadalajara, Lagos de Moreno, Jalisco, Mexico; Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
| | - A R Tejeda-Martínez
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
| | - J M Viveros-Paredes
- Laboratorio de Investigación y Desarrollo Farmacéutico, Departamento de Farmacología, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico
| | - V Chaparro-Huerta
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico
| | - M F Urmeneta-Ortíz
- Centro Universitario de los Lagos, Universidad de Guadalajara, Lagos de Moreno, Jalisco, Mexico
| | - L J Ramírez-Jirano
- División de Neurociencias, Centro de Investigación Biomédica Occidente (IMSS), Guadalajara, Mexico
| | - M E Flores-Soto
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico.
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Hosseini E, Sepehrinezhad A, Momeni J, Ascenzi BM, Gorji A, Sahab-Negah S. The Telencephalon. FROM ANATOMY TO FUNCTION OF THE CENTRAL NERVOUS SYSTEM 2025:401-427. [DOI: 10.1016/b978-0-12-822404-5.00014-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Chudzik A. Machine Learning Recognizes Stages of Parkinson's Disease Using Magnetic Resonance Imaging. SENSORS (BASEL, SWITZERLAND) 2024; 24:8152. [PMID: 39771887 PMCID: PMC11679256 DOI: 10.3390/s24248152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 12/01/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025]
Abstract
Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD) and Parkinson's disease (PD), are debilitating conditions that affect millions worldwide, and the number of cases is expected to rise significantly in the coming years. Because early detection is crucial for effective intervention strategies, this study investigates whether the structural analysis of selected brain regions, including volumes and their spatial relationships obtained from regular T1-weighted MRI scans (N = 168, PPMI database), can model stages of PD using standard machine learning (ML) techniques. Thus, diverse ML models, including Logistic Regression, Random Forest, Support Vector Classifier, and Rough Sets, were trained and evaluated. Models used volumes, Euclidean, and Cosine distances of subcortical brain structures relative to the thalamus to differentiate among control (HC), prodromal (PR), and PD groups. Based on three separate experiments, the Logistic Regression approach was optimal, providing low feature complexity and strong predictive performance (accuracy: 85%, precision: 88%, recall: 85%) in PD-stage recognition. Using interpretable metrics, such as the volume- and centroid-based spatial distances, models achieved high diagnostic accuracy, presenting a promising framework for early-stage PD identification based on MRI scans.
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Affiliation(s)
- Artur Chudzik
- Faculty of Computer Science, Polish-Japanese Academy of Information Technology, 86 Koszykowa Street, 02-008 Warsaw, Poland
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Kouba BR, Rodrigues ALS. Neuroplasticity-related effects of vitamin D relevant to its neuroprotective effects: A narrative review. Pharmacol Biochem Behav 2024; 245:173899. [PMID: 39447683 DOI: 10.1016/j.pbb.2024.173899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 10/12/2024] [Accepted: 10/15/2024] [Indexed: 10/26/2024]
Abstract
The pathophysiology of a wide range of central nervous system (CNS) disorders, such as neurodegenerative and psychiatric diseases, has been associated with impairment of neurogenic and synaptogenic processes. Therefore, pharmacological and/or nutritional strategies based on the stimulation and/or restoration of these processes may have beneficial effects against diseases in which these processes are impaired. In this context, vitamin D has emerged as a promising neuroprotective compound. Due to its pleiotropic properties, it can interact with multiple molecular targets and thereby affect different cell types, including neurons and glial cells. This neurosteroid contributes to CNS homeostasis by non-genomic and genomic mechanisms through its interaction with vitamin D receptors (VDRs). Among several properties of this vitamin, its role in neuronal proliferation and differentiation as well as in synaptic plasticity has received attention. Considering this background, this narrative review aims to highlight the neuroplasticity-related mechanisms of vitamin D that may be associated with its neuroprotective effects.
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Affiliation(s)
- Bruna R Kouba
- Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil
| | - Ana Lúcia S Rodrigues
- Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
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Song Q, E S, Zhang Z, Liang Y. Neuroplasticity in the transition from acute to chronic pain. Neurotherapeutics 2024; 21:e00464. [PMID: 39438166 PMCID: PMC11585895 DOI: 10.1016/j.neurot.2024.e00464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 09/10/2024] [Accepted: 09/27/2024] [Indexed: 10/25/2024] Open
Abstract
Acute pain is a transient sensation that typically serves as part of the body's defense mechanism. However, in certain patients, acute pain can evolve into chronic pain, which persists for months or even longer. Neuroplasticity refers to the capacity for variation and adaptive alterations in the morphology and functionality of neurons and synapses, and it plays a significant role in the transmission and modulation of pain. In this paper, we explore the molecular mechanisms and signaling pathways underlying neuroplasticity during the transition of pain. We also examine the effects of neurotransmitters, inflammatory mediators, and central sensitization on neuroplasticity, as well as the potential of neuroplasticity as a therapeutic strategy for preventing chronic pain. The aims of this article is to clarify the role of neuroplasticity in the transformation from acute pain to chronic pain, with the hope of providing a novel theoretical basis for unraveling the pathogenesis of chronic pain and offering more effective strategies and approaches for its diagnosis and treatment.
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Affiliation(s)
- Qingbiao Song
- School of Anesthesiology, Shandong Second Medical University, Weifang 261053, China
| | - Sihan E
- School of Anesthesiology, Shandong Second Medical University, Weifang 261053, China
| | - Zhiyu Zhang
- Department of Orthopedics, Affiliated Hospital of Shandong Second Medical University, Weifang 261035, China
| | - Yingxia Liang
- School of Anesthesiology, Shandong Second Medical University, Weifang 261053, China.
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11
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He G, Huang X, Sun H, Xing Y, Gu S, Ren J, Liu W, Lu M. Gray matter volume alterations in de novo Parkinson's disease: A mediational role in the interplay between sleep quality and anxiety. CNS Neurosci Ther 2024; 30:e14867. [PMID: 39031989 PMCID: PMC11259571 DOI: 10.1111/cns.14867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 06/24/2024] [Accepted: 07/07/2024] [Indexed: 07/22/2024] Open
Abstract
OBJECTIVE Parkinson's disease (PD) is increasingly recognized for its non-motor symptoms, among which emotional disturbances and sleep disorders frequently co-occur. The commonality of neuroanatomical underpinnings for these symptoms is not fully understood. This study is intended to investigate the differences in gray matter volume (GMV) between PD patients with anxiety (A-PD) and those without anxiety (NA-PD). Additionally, it seeks to uncover the interplay between GMV variations and the manifestations of anxiety and sleep quality. METHODS A total of 37 A-PD patients, 43 NA-PD patients, and 36 healthy controls (HCs) were recruited, all of whom underwent voxel-based morphometry (VBM) analysis. Group differences in GMV were assessed using analysis of covariance (ANCOVA). Partial correlation between GMV, anxiety symptom, and sleep quality were analyzed. Mediation analysis explored the mediating role of the volume of GMV-distinct brain regions on the relationship between sleep quality and anxiety within the PD patient cohort. RESULTS A-PD patients showed significantly lower GMV in the fusiform gyrus (FG) and right inferior temporal gyrus (ITG) compared to HCs and NA-PD patients. GMV in these regions correlated negatively with Hamilton Anxiety Rating Scale (HAMA) scores (right ITG: r = -0.690, p < 0.001; left FG: r = -0.509, p < 0.001; right FG: r = -0.576, p < 0.001) and positively with sleep quality in PD patients (right ITG: r = 0.592, p < 0.001; left FG: r = 0.356, p = 0.001; right FG: r = 0.470, p < 0.001). Mediation analysis revealed that GMV in the FG and right ITG mediated the relationship between sleep quality and anxiety symptoms, with substantial effect sizes accounted for by the right ITG (25.74%) and FG (left: 11.90%, right: 15.59%). CONCLUSION This study has shed further light on the relationship between sleep disturbances and anxiety symptoms in PD patients. Given the pivotal roles of the FG and the ITG in facial recognition and the recognition of emotion-related facial expressions, our findings indicate that compromised sleep quality, under the pathological conditions of PD, may exacerbate the reduction in GMV within these regions, impairing the recognition of emotional facial expressions and thereby intensifying anxiety symptoms.
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Affiliation(s)
- Guixiang He
- Department of NeurologyAffiliated Nanjing Brain Hospital, Nanjing Medical UniversityNanjingChina
- The Yancheng School of Clinical Medicine of Nanjing Medical UniversityYancheng Third People's HospitalYanchengChina
- Jiangsu Key Laboratory of Neurodegeneration, Department of PharmacologyNanjing Medical UniversityNanjingChina
| | - Xiaofang Huang
- Department of NeurologyAffiliated Nanjing Brain Hospital, Nanjing Medical UniversityNanjingChina
| | - Haihua Sun
- The Yancheng School of Clinical Medicine of Nanjing Medical UniversityYancheng Third People's HospitalYanchengChina
| | - Yi Xing
- Department of NeurologyAffiliated Nanjing Brain Hospital, Nanjing Medical UniversityNanjingChina
| | - Siyu Gu
- The Yancheng School of Clinical Medicine of Nanjing Medical UniversityYancheng Third People's HospitalYanchengChina
| | - Jingru Ren
- Department of NeurologyAffiliated Nanjing Brain Hospital, Nanjing Medical UniversityNanjingChina
| | - Weiguo Liu
- Department of NeurologyAffiliated Nanjing Brain Hospital, Nanjing Medical UniversityNanjingChina
| | - Ming Lu
- Jiangsu Key Laboratory of Neurodegeneration, Department of PharmacologyNanjing Medical UniversityNanjingChina
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12
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Nakos Bimpos M, Karali K, Antoniou C, Palermos D, Fouka M, Delis A, Tzieras I, Chrousos GP, Koutmani Y, Stefanis L, Polissidis A. Alpha-synuclein-induced stress sensitivity renders the Parkinson's disease brain susceptible to neurodegeneration. Acta Neuropathol Commun 2024; 12:100. [PMID: 38886854 PMCID: PMC11181569 DOI: 10.1186/s40478-024-01797-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 05/12/2024] [Indexed: 06/20/2024] Open
Abstract
A link between chronic stress and Parkinson's disease (PD) pathogenesis is emerging. Ample evidence demonstrates that the presynaptic neuronal protein alpha-synuclein (asyn) is closely tied to PD pathogenesis. However, it is not known whether stress system dysfunction is present in PD, if asyn is involved, and if, together, they contribute to neurodegeneration. To address these questions, we assess stress axis function in transgenic rats overexpressing full-length wildtype human asyn (asyn BAC rats) and perform multi-level stress and PD phenotyping following chronic corticosterone administration. Stress signaling, namely corticotropin-releasing factor, glucocorticoid and mineralocorticoid receptor gene expression, is also examined in post-mortem PD patient brains. Overexpression of human wildtype asyn leads to HPA axis dysregulation in rats, while chronic corticosterone administration significantly aggravates nigrostriatal degeneration, serine129 phosphorylated asyn (pS129) expression and neuroinflammation, leading to phenoconversion from a prodromal to an overt motor PD phenotype. Interestingly, chronic corticosterone in asyn BAC rats induces a robust, twofold increase in pS129 expression in the hypothalamus, the master regulator of the stress response, while the hippocampus, both a regulator and a target of the stress response, also demonstrates elevated pS129 asyn levels and altered markers of stress signalling. Finally, defective hippocampal stress signalling is mirrored in human PD brains and correlates with asyn expression levels. Taken together, our results link brain stress system dysregulation with asyn and provide evidence that elevated circulating glucocorticoids can contribute to asyn-induced neurodegeneration, ultimately triggering phenoconversion from prodromal to overt PD.
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Affiliation(s)
- Modestos Nakos Bimpos
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
| | - Katerina Karali
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
- German Center for Neurodegenerative Diseases, Feodor-Lynen-Straße 17, 81377, Munich, Germany
- Athens International Master's Programme in Neurosciences, Department of Biology, National and Kapodistrian University of Athens, 15784, Illisia, Athens, Greece
| | - Christine Antoniou
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
- Athens International Master's Programme in Neurosciences, Department of Biology, National and Kapodistrian University of Athens, 15784, Illisia, Athens, Greece
| | - Dionysios Palermos
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
| | - Maria Fouka
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
| | - Anastasios Delis
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
| | - Iason Tzieras
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
| | - George Panagiotis Chrousos
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
- University Research Institute on Maternal and Child Health and Precision Medicine, and UNESCO Chair on Adolescent Health Care, Aghia Sophia Children's Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece
| | - Yassemi Koutmani
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
| | - Leonidas Stefanis
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece
- 1St Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece
| | - Alexia Polissidis
- Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens - BRFAA, 11527, Athens, Greece.
- Department of Science and Mathematics, ACG-Research Center, Deree - American College of Greece, 15342, Athens, Greece.
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13
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Qu M, Gao B, Jiang Y, Li Y, Pei C, Xie L, Zhang Y, Song Q, Miao Y. Atrophy patterns in hippocampus and amygdala subregions of depressed patients with Parkinson's disease. Brain Imaging Behav 2024; 18:475-484. [PMID: 38170304 PMCID: PMC11222218 DOI: 10.1007/s11682-023-00844-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2023] [Indexed: 01/05/2024]
Abstract
We aimed to explore the subregional atrophy patterns of the amygdala and hippocampus in Parkinson's disease (PD) with depression and their correlation with the severity of the depressive symptom. MRI scans were obtained for 34 depressed PD patients (DPD), 22 nondepressed PD patients (NDPD), and 28 healthy controls (HC). Amygdala and hippocampal subregions were automatically segmented, and the intergroup volume difference was compared. The relationships between the volumes of the subregions and depression severity were investigated. Logistic analysis and Receiver operator characteristic curve were used to find independent predictors of DPD. Compared with the HC group, atrophy of the bilateral lateral nucleus, left accessory basal nucleus, right cortical nucleus, right central nucleus, and right medial nucleus subregions of the amygdala were visible in the DPD group, while the right lateral nucleus subregion of the amygdala was smaller in the DPD group than in the NDPD group. The DPD group showed significant atrophy in the left molecular layer, left GC-DG, left CA3, and left CA4 subregions compared with the HC group for hippocampal subregion volumes. Also, the right lateral nuclei volume and disease duration were independent predictors of DPD. To sum up, DPD patients showed atrophy in multiple amygdala subregions and left asymmetric hippocampal subregions. The decreased amygdala and hippocampal subregion volumes were correlated with the severity of depressive symptoms. The volume of right lateral nuclei and disease duration could be used as a biomarker to detect DPD.
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Affiliation(s)
- Mingrui Qu
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Xigang District, Dalian, 116011, China
| | - Bingbing Gao
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Xigang District, Dalian, 116011, China
| | - Yuhan Jiang
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Xigang District, Dalian, 116011, China
| | - Yuan Li
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Xigang District, Dalian, 116011, China
| | - Chenhui Pei
- Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | | | - Yukun Zhang
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Xigang District, Dalian, 116011, China
| | - Qingwei Song
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Xigang District, Dalian, 116011, China
| | - Yanwei Miao
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Xigang District, Dalian, 116011, China.
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14
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Samanci B, Tan S, Michielse S, Kuijf ML, Temel Y. The habenula in Parkinson's disease: Anatomy, function, and implications for mood disorders - A narrative review. J Chem Neuroanat 2024; 136:102392. [PMID: 38237746 DOI: 10.1016/j.jchemneu.2024.102392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 01/07/2024] [Accepted: 01/12/2024] [Indexed: 01/31/2024]
Abstract
Parkinson's disease (PD), a widespread neurodegenerative disorder, often coexists with mood disorders. Degeneration of serotonergic neurons in brainstem raphe nuclei have been linked to depression and anxiety. Additionally, the locus coeruleus and its noradrenergic neurons are among the first areas to degenerate in PD and contribute to stress, emotional memory, motor, sensory, and autonomic symptoms. Another brain region of interest is habenula, which is especially related to anti-reward processing, and its function has recently been linked to PD and to mood-related symptoms. There are several neuroimaging studies that investigated role of the habenula in mood disorders. Differences in habenular size and hemispheric symmetry were found in healthy controls compared to individuals with mood disorders. The lateral habenula, as a link between the dopaminergic and serotonergic systems, is thought to contribute to depressive symptoms in PD. However, there is only one imaging study about role of habenula in mood disorders in PD, although the relationship between PD and mood disorders is known. There is little known about habenula pathology in PD but given these observations, the question arises whether habenular dysfunction could play a role in PD and the development of PD-related mood disorders. In this review, we evaluate neuroimaging techniques and studies that investigated the habenula in the context of PD and mood disorders. Future studies are important to understand habenula's role in PD patients with mood disorders. Thus, new potential diagnostic and treatment opportunities would be found for mood disorders in PD.
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Affiliation(s)
- Bedia Samanci
- School for Mental Health and Neurosciences, Maastricht University, Maastricht, the Netherlands; Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
| | - Sonny Tan
- School for Mental Health and Neurosciences, Maastricht University, Maastricht, the Netherlands; Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium
| | - Stijn Michielse
- School for Mental Health and Neurosciences, Maastricht University, Maastricht, the Netherlands
| | - Mark L Kuijf
- School for Mental Health and Neurosciences, Maastricht University, Maastricht, the Netherlands; Department of Neurology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Yasin Temel
- School for Mental Health and Neurosciences, Maastricht University, Maastricht, the Netherlands; Department of Neurosurgery, Maastricht University Medical Centre, Maastricht, the Netherlands
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15
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Camacho M, Wilms M, Almgren H, Amador K, Camicioli R, Ismail Z, Monchi O, Forkert ND. Exploiting macro- and micro-structural brain changes for improved Parkinson's disease classification from MRI data. NPJ Parkinsons Dis 2024; 10:43. [PMID: 38409244 PMCID: PMC10897162 DOI: 10.1038/s41531-024-00647-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 01/22/2024] [Indexed: 02/28/2024] Open
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disease. Accurate PD diagnosis is crucial for effective treatment and prognosis but can be challenging, especially at early disease stages. This study aimed to develop and evaluate an explainable deep learning model for PD classification from multimodal neuroimaging data. The model was trained using one of the largest collections of T1-weighted and diffusion-tensor magnetic resonance imaging (MRI) datasets. A total of 1264 datasets from eight different studies were collected, including 611 PD patients and 653 healthy controls (HC). These datasets were pre-processed and non-linearly registered to the MNI PD25 atlas. Six imaging maps describing the macro- and micro-structural integrity of brain tissues complemented with age and sex parameters were used to train a convolutional neural network (CNN) to classify PD/HC subjects. Explainability of the model's decision-making was achieved using SmoothGrad saliency maps, highlighting important brain regions. The CNN was trained using a 75%/10%/15% train/validation/test split stratified by diagnosis, sex, age, and study, achieving a ROC-AUC of 0.89, accuracy of 80.8%, specificity of 82.4%, and sensitivity of 79.1% on the test set. Saliency maps revealed that diffusion tensor imaging data, especially fractional anisotropy, was more important for the classification than T1-weighted data, highlighting subcortical regions such as the brainstem, thalamus, amygdala, hippocampus, and cortical areas. The proposed model, trained on a large multimodal MRI database, can classify PD patients and HC subjects with high accuracy and clinically reasonable explanations, suggesting that micro-structural brain changes play an essential role in the disease course.
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Affiliation(s)
- Milton Camacho
- Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB, Canada.
- Department of Radiology, University of Calgary, Calgary, AB, Canada.
| | - Matthias Wilms
- Department of Radiology, University of Calgary, Calgary, AB, Canada
- Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada
- Department of Pediatrics and Community Health Sciences, University of Calgary, Calgary, AB, Canada
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
| | - Hannes Almgren
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
| | - Kimberly Amador
- Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB, Canada
- Department of Radiology, University of Calgary, Calgary, AB, Canada
| | - Richard Camicioli
- Neuroscience and Mental Health Institute and Department of Medicine (Neurology), University of Alberta, Edmonton, AB, Canada
| | - Zahinoor Ismail
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
- Department of Psychiatry, University of Calgary, Calgary, AB, Canada
- College of Medicine and Health, University of Exeter, Exeter, UK
| | - Oury Monchi
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
- Department of Radiology, Radio-oncology and Nuclear Medicine, Université de Montréal, Montréal, QC, Canada
- Centre de Recherche, Institut Universitaire de Gériatrie de Montréal, Montréal, QC, Canada
| | - Nils D Forkert
- Department of Radiology, University of Calgary, Calgary, AB, Canada
- Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada
- Department of Pediatrics and Community Health Sciences, University of Calgary, Calgary, AB, Canada
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
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16
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Yuan J, Liu Y, Liao H, Tan C, Cai S, Shen Q, Liu Q, Wang M, Tang Y, Li X, Liu J, Zi Y. Alterations in cortical volume and complexity in Parkinson's disease with depression. CNS Neurosci Ther 2024; 30:e14582. [PMID: 38421103 PMCID: PMC10851315 DOI: 10.1111/cns.14582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 11/09/2023] [Accepted: 12/17/2023] [Indexed: 03/02/2024] Open
Abstract
AIMS The aim of this study is to investigate differences in gray matter volume and cortical complexity between Parkinson's disease with depression (PDD) patients and Parkinson's disease without depression (PDND) patients. METHODS A total of 41 PDND patients, 36 PDD patients, and 38 healthy controls (HC) were recruited and analyzed by Voxel-based morphometry (VBM) and surface-based morphometry (SBM). Differences in gray matter volume and cortical complexity were compared using the one-way analysis of variance (ANOVA) and correlated with the Hamilton Depression Scale-17 (HAMD-17) scores. RESULTS PDD patients exhibited significant cortical atrophy in various regions, including bilateral medial parietal-occipital-temporal lobes, right dorsolateral temporal lobes, bilateral parahippocampal gyrus, and bilateral hippocampus, compared to HC and PDND groups. A negative correlation between the GMV of left precuneus and HAMD-17 scores in the PDD group tended to be significant (r = -0.318, p = 0.059). Decreased gyrification index was observed in the bilateral insular and dorsolateral temporal cortex. However, there were no significant differences found in fractal dimension and sulcal depth. CONCLUSION Our research shows extensive cortical structural changes in the insular cortex, parietal-occipital-temporal lobes, and hippocampal regions in PDD. This provides a morphological perspective for understanding the pathophysiological mechanism underlying depression in Parkinson's disease.
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Affiliation(s)
- Jiaying Yuan
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
| | - Yujing Liu
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
| | - Haiyan Liao
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
- Clinical Research Center For Medical Imaging in Hunan ProvinceChangshaChina
| | - Changlian Tan
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
| | - Sainan Cai
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
| | - Qin Shen
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
| | - Qinru Liu
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
| | - Min Wang
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
| | - Yuqing Tang
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
| | - Xu Li
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
| | - Jun Liu
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
- Clinical Research Center For Medical Imaging in Hunan ProvinceChangshaChina
| | - Yuheng Zi
- Department of Radiology, The Second Xiangya HospitalCentral South UniversityChangshaChina
- Department of Radiology, The First Affiliated Hospital, Hengyang Medical SchoolUniversity of South ChinaHengyangChina
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Stark AJ, Song AK, Petersen KJ, Hay KR, Lin YC, Trujillo P, Kang H, Collazzo JM, Donahue MJ, Zald DH, Claassen DO. Accentuated Paralimbic and Reduced Mesolimbic D 2/3-Impulsivity Associations in Parkinson's Disease. J Neurosci 2023; 43:8733-8743. [PMID: 37852792 PMCID: PMC10727183 DOI: 10.1523/jneurosci.1037-23.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/31/2023] [Accepted: 10/10/2023] [Indexed: 10/20/2023] Open
Abstract
Impulsivity is a behavioral trait that is elevated in many neuropsychiatric disorders. Parkinson's disease (PD) patients can exhibit a specific pattern of reward-seeking impulsive-compulsive behaviors (ICBs), as well as more subtle changes to generalized trait impulsivity. Prior studies in healthy controls (HCs) suggest that trait impulsivity is regulated by D2/3 autoreceptors in mesocorticolimbic circuits. While altered D2/3 binding is noted in ICB+ PD patients, there is limited prior assessment of the trait impulsivity-D2/3 relationship in PD, and no prior direct comparison with patterns in HCs. We examined 54 PD (36 M; 18 F) and 31 sex- and age-matched HC (21 M; 10 F) subjects using [18F]fallypride, a high-affinity D2/3 receptor ligand, to measure striatal and extrastriatal D2/3 nondisplaceable binding potential (BPND). Subcortical and cortical assessment exclusively used ROI or exploratory-voxelwise methods, respectively. All completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. Subcortical ROI analyses indicated a negative relationship between trait impulsivity and D2/3 BPND in the ventral striatum and amygdala of HCs but not in PD. By contrast, voxelwise methods demonstrated a positive trait impulsivity-D2/3 BPND correlation in ventral frontal olfactocentric-paralimbic cortex of subjects with PD but not HCs. Subscale analysis also highlighted different aspects of impulsivity, with significant interactions between group and motor impulsivity in the ventral striatum, and attentional impulsivity in the amygdala and frontal paralimbic cortex. These results suggest that dopamine functioning in distinct regions of the mesocorticolimbic circuit influence aspects of impulsivity, with the relative importance of regional dopamine functions shifting in the neuropharmacological context of PD.SIGNIFICANCE STATEMENT The biological determinants of impulsivity have broad clinical relevance, from addiction to neurodegenerative disorders. Here, we address biomolecular distinctions in Parkinson's disease. This is the first study to evaluate a large cohort of Parkinson's disease patients and age-matched healthy controls with a measure of trait impulsivity and concurrent [18F]fallypride PET, a method that allows quantification of D2/3 receptors throughout the mesocorticolimbic network. We demonstrate widespread differences in the trait impulsivity-dopamine relationship, including (1) loss of subcortical relationships present in the healthy brain and (2) emergence of a new relationship in a limbic cortical area. This illustrates the loss of mechanisms of behavioral regulation present in the healthy brain while suggesting a potential compensatory response and target for future investigation.
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Affiliation(s)
- Adam J Stark
- School of Medicine, Vanderbilt University, Nashville, Tennessee 37232
| | - Alexander K Song
- Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37232
| | - Kalen J Petersen
- Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63310
| | - Kaitlyn R Hay
- Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37232
| | - Ya-Chen Lin
- Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee 37232
- Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232
| | - Paula Trujillo
- Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37232
| | - Hakmook Kang
- Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee 37232
- Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232
| | - Jenna M Collazzo
- School of Medicine, Temple University, Philadelphia, Pennsylvania 19140
| | - Manus J Donahue
- Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37232
| | - David H Zald
- Department of Psychiatry, Rutgers University, Piscataway, New Jersey 08901
| | - Daniel O Claassen
- Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37232
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18
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Shen Q, Liao H, Cai S, Liu Q, Wang M, Song C, Zhou F, Liu Y, Yuan J, Tang Y, Li X, Liu J, Tan C. Cortical gyrification pattern of depression in Parkinson's disease: a neuroimaging marker for disease severity? Front Aging Neurosci 2023; 15:1241516. [PMID: 38035271 PMCID: PMC10682087 DOI: 10.3389/fnagi.2023.1241516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 10/30/2023] [Indexed: 12/02/2023] Open
Abstract
Background Although the study of the neuroanatomical correlates of depression in Parkinson's Disease (PD) is gaining increasing interest, up to now the cortical gyrification pattern of PD-related depression has not been reported. This study was conducted to investigate the local gyrification index (LGI) in PD patients with depression, and its associations with the severity of depression. Methods LGI values, as measured using FreeSurfer software, were compared between 59 depressed PD (dPD), 27 non-depressed PD (ndPD) patients and 43 healthy controls. The values were also compared between ndPD and mild-depressed PD (mi-dPD), moderate-depressed PD (mo-dPD) and severe-depressed PD (se-dPD) patients as sub-group analyses. Furthermore, we evaluated the correlation between LGI values and depressive symptom scores within dPD group. Results Compared to ndPD, the dPD patients exhibited decreased LGI in the left parietal, the right superior-frontal, posterior cingulate and paracentral regions, and the LGI values within these areas negatively correlated with the severity of depression. Specially, reduced gyrification was observed in mo-dPD and involving a larger region in se-dPD, but not in mi-dPD group. Conclusion The present study demonstrated that cortical gyrification is decreased within specific brain regions among PD patients with versus without depression, and those changes were associated with the severity of depression. Our findings suggested that cortical gyrification might be a potential neuroimaging marker for the severity of depression in patients with PD.
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Nápoles-Medina AY, Aguilar-Uscanga BR, Solís-Pacheco JR, Tejeda-Martínez AR, Ramírez-Jirano LJ, Urmeneta-Ortiz MF, Chaparro-Huerta V, Flores-Soto ME. Oral Administration of Lactobacillus Inhibits the Permeability of Blood-Brain and Gut Barriers in a Parkinsonism Model. Behav Neurol 2023; 2023:6686037. [PMID: 38025189 PMCID: PMC10653970 DOI: 10.1155/2023/6686037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 09/26/2023] [Accepted: 10/16/2023] [Indexed: 12/01/2023] Open
Abstract
It has recently been shown that the administration of probiotics can modulate the microbiota-gut-brain axis and may have favorable effects in models of Parkinson's disease. In this study, we used a hemiparkinsonism model induced by the neurotoxin 6-OHDA to evaluate the efficacy of the administration of a four-week administration of a mixture containing the microorganisms Lactobacillus fermentum LH01, Lactobacillus reuteri LH03, and Lactobacillus plantarum LH05. The hemiparkinsonism model induced an increase in rotations in the apomorphine test, along with a decrease in the latency time to fall in the rotarod test on days 14 and 21 after surgery, respectively. The administration of probiotics was sufficient to improve this condition. The model also showed a decrease in tyrosine hydroxylase immunoreactivity in the striatum and the number of labeled cells in the substantia nigra, both of which were counteracted by the administration of probiotics. The permeability of the blood-brain barrier was increased in the model, but this effect was reversed by the probiotics for both brain regions. The gut barrier was permeated with the model, and this effect was reversed and dropped to lower levels than the control group after the administration of probiotics. Finally, lipid peroxidation showed a pattern of differences similar to that of permeabilities. The inhibition of the permeability of the blood-brain and gut barriers mediated by the administration of probiotics will likely provide protection by downregulating oxidative stress, thus affecting the rotarod test performance.
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Affiliation(s)
- Angélica Y. Nápoles-Medina
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Sierra Mojada #800, Independencia Oriente, C.P. 44340 Guadalajara, Jalisco, Mexico
- Departamento de Farmacobiología, Laboratorio de Microbiología Industrial, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García Barragán # 1421, Olímpica, C.P. 44430 Guadalajara, Jalisco, Mexico
| | - Blanca R. Aguilar-Uscanga
- Departamento de Farmacobiología, Laboratorio de Microbiología Industrial, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García Barragán # 1421, Olímpica, C.P. 44430 Guadalajara, Jalisco, Mexico
| | - Josué R. Solís-Pacheco
- Departamento de Farmacobiología, Laboratorio de Microbiología Industrial, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García Barragán # 1421, Olímpica, C.P. 44430 Guadalajara, Jalisco, Mexico
| | - Aldo R. Tejeda-Martínez
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Sierra Mojada #800, Independencia Oriente, C.P. 44340 Guadalajara, Jalisco, Mexico
| | - Luis J. Ramírez-Jirano
- División de Neurociencias, Centro de Investigación Biomédica Occidente (IMSS), Guadalajara, Mexico
| | - María F. Urmeneta-Ortiz
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Sierra Mojada #800, Independencia Oriente, C.P. 44340 Guadalajara, Jalisco, Mexico
| | - Veronica Chaparro-Huerta
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Sierra Mojada #800, Independencia Oriente, C.P. 44340 Guadalajara, Jalisco, Mexico
| | - Mario E. Flores-Soto
- Laboratorio de Neurobiología Celular y Molecular, División de Neurociencias, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social, Sierra Mojada #800, Independencia Oriente, C.P. 44340 Guadalajara, Jalisco, Mexico
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20
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An JH, Han KD, Jung JH, Jeon HJ. Association of physical activity with the risk of Parkinson's disease in depressive disorder: A nationwide longitudinal cohort study. J Psychiatr Res 2023; 167:93-99. [PMID: 37862909 DOI: 10.1016/j.jpsychires.2023.10.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 09/14/2023] [Accepted: 10/14/2023] [Indexed: 10/22/2023]
Abstract
Regular physical activity (PA) has been suggested as effective disease preventable strategies for Parkinson's disease (PD). Depression often precedes PD but whether PA also would reduce the risk of PD in patients with depression has not been known. The aim of study is to examine the association of regular PA with risk of PD among patients with depressive disorder. A total of 1,342,282 patients with depressive disorder were identified from a nationwide health screening cohort from 2010 to 2016. The exposure was changes in pattern of regular PA between pre-and post-diagnosis of depressive disorder, categorized as four groups; 1) no PA, 2) increased PA, 3) decreased PA, and 4) maintaining PA. The outcome was risk of incident PD, calculated using multivariate adjusted Cox proportional hazards regressions according to the PA categorization. Total of 8901 PD cases (0.66%) were developed during 5.3 years of follow-up period. Maintaining PA group was associated with the lowest risk of PD (adjusted hazard ratio [aHR] 0.89, 95% CI 0.83-0.97) among all other PA groups with depressive disorder (with no PA group as reference). Otherwise, decreased PA group significantly increased the risk of PD (aHR 1.10, 95% CI 1.03-1.16). Those who maintained PA before and after diagnosis of depressive disorder were associated with lower risk of incident PD.
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Affiliation(s)
- Ji Hyun An
- Department of Psychiatry, Depression Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kyung-do Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea
| | - Jin-Hyung Jung
- Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, South Korea
| | - Hong Jin Jeon
- Department of Psychiatry, Depression Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Health Sciences & Technology, Department of Medical Device Management& Research, and Department of Clinical Research Design & Evaluation, Samsung Advanced, Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea.
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21
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Ay U, Yıldırım Z, Erdogdu E, Kiçik A, Ozturk-Isik E, Demiralp T, Gurvit H. Shrinkage of olfactory amygdala connotes cognitive impairment in patients with Parkinson's disease. Cogn Neurodyn 2023; 17:1309-1320. [PMID: 37786655 PMCID: PMC10542039 DOI: 10.1007/s11571-022-09887-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 09/04/2022] [Accepted: 09/14/2022] [Indexed: 11/03/2022] Open
Abstract
During the caudo-rostral progression of Lewy pathology, the amygdala is involved relatively early in Parkinson's disease (PD). However, lesser is known about the volumetric differences at the amygdala subdivisions, although the evidence mainly implicates the olfactory amygdala. We aimed to investigate the volumetric differences between the amygdala's nuclear and sectoral subdivisions in the PD cognitive impairment continuum compared to healthy controls (HC). The volumes of nine nuclei of the amygdala were estimated with FreeSurfer (nuclear parcellation-NP) from T1-weighted images of PD patients with normal cognition (PD-CN), PD with mild cognitive impairment (PD-MCI), PD with dementia (PD-D), and HC. The appropriate nuclei were then merged to obtain three sectors of the amygdala (sectoral parcellation-SP). The nuclear and sectoral volumes were compared among the four groups and between the hyposmic and normosmic PD patients. There was a significant difference in the total amygdala volume among the four groups. In terms of nuclei, the bilateral cortico-amygdaloid transition area (CAT) and sectors superficial cortex-like region (sCLR) volumes of PD-MCI and PD-D were less than those of the PD-CN and HC. A linear discriminant analysis revealed that left CAT and left sCLR volumes classified the PD-CN and cognitively impaired PD (PD-CI: PD-MCI plus PD-D) with 90.7% accuracy according to NP and 85.2% accuracy to SP. Similarly, left CAT and sCLR volumes correctly identified the hyposmic and normosmic PD with 64.8% and 61.1% accuracies. Notably, the left olfactory amygdala volume successfully discriminated cognitive impairment in PD and could be used as neuroimaging-based support for PD-CI diagnosis. Supplementary Information The online version contains supplementary material available at 10.1007/s11571-022-09887-y.
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Affiliation(s)
- Ulaş Ay
- Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093 Istanbul, Turkey
- Neuroimaging Unit, Hulusi Behcet Life Sciences Research Laboratory, Istanbul University, 34093 Istanbul, Turkey
- Graduate School of Health Sciences, Istanbul University, 34126 Istanbul, Turkey
| | - Zerrin Yıldırım
- Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093 Istanbul, Turkey
- Neuroimaging Unit, Hulusi Behcet Life Sciences Research Laboratory, Istanbul University, 34093 Istanbul, Turkey
- Department of Neurology, Bagcilar Education and Research Hospital, 34200 Istanbul, Turkey
| | - Emel Erdogdu
- Neuroimaging Unit, Hulusi Behcet Life Sciences Research Laboratory, Istanbul University, 34093 Istanbul, Turkey
- Department of Psychology, Faculty of Arts and Sciences, Isik University, 34980 Istanbul, Turkey
| | - Ani Kiçik
- Neuroimaging Unit, Hulusi Behcet Life Sciences Research Laboratory, Istanbul University, 34093 Istanbul, Turkey
- Department of Physiology, Faculty of Medicine, Demiroglu Bilim University, 34394 Istanbul, Turkey
| | - Esin Ozturk-Isik
- Institute of Biomedical Engineering, Bogazici University, 34684 Istanbul, Turkey
| | - Tamer Demiralp
- Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, 34093 Istanbul, Turkey
| | - Hakan Gurvit
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, 34093 Istanbul, Turkey
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22
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Lai TT, Gericke B, Feja M, Conoscenti M, Zelikowsky M, Richter F. Anxiety in synucleinopathies: neuronal circuitry, underlying pathomechanisms and current therapeutic strategies. NPJ Parkinsons Dis 2023; 9:97. [PMID: 37349373 DOI: 10.1038/s41531-023-00547-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 06/09/2023] [Indexed: 06/24/2023] Open
Abstract
Synucleinopathies are neurodegenerative disorders characterized by alpha-synuclein (αSyn) accumulation in neurons or glial cells, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). αSyn-related pathology plays a critical role in the pathogenesis of synucleinopathies leading to the progressive loss of neuronal populations in specific brain regions and the development of motor and non-motor symptoms. Anxiety is among the most frequent non-motor symptoms in patients with PD, but it remains underrecognized and undertreated, which significantly reduces the quality of life for patients. Anxiety is defined as a neuropsychiatric complication with characteristics such as nervousness, loss of concentration, and sweating due to the anticipation of impending danger. In patients with PD, neuropathology in the amygdala, a central region in the anxiety and fear circuitry, may contribute to the high prevalence of anxiety. Studies in animal models reported αSyn pathology in the amygdala together with alteration of anxiety or fear learning response. Therefore, understanding the progression, extent, and specifics of pathology in the anxiety and fear circuitry in synucleinopathies will suggest novel approaches to the diagnosis and treatment of neuropsychiatric symptoms. Here, we provide an overview of studies that address neuropsychiatric symptoms in synucleinopathies. We offer insights into anxiety and fear circuitry in animal models and the current implications for therapeutic intervention. In summary, it is apparent that anxiety is not a bystander symptom in these disorders but reflects early pathogenic mechanisms in the cortico-limbic system which may even contribute as a driver to disease progression.
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Affiliation(s)
- Thuy Thi Lai
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
- Center for Systems Neuroscience, Hannover, Germany
| | - Birthe Gericke
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
- Center for Systems Neuroscience, Hannover, Germany
| | - Malte Feja
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany
- Center for Systems Neuroscience, Hannover, Germany
| | | | | | - Franziska Richter
- Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
- Center for Systems Neuroscience, Hannover, Germany.
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23
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Jiang X, Zhang L, Liu H, Su H, Jiang J, Qiang C, Wang Q, Qu X, Sun W, Bi H. Efficacy of non-pharmacological interventions on depressive symptoms in patients with Parkinson's disease: a study protocol for a systematic review and network meta-analysis. BMJ Open 2023; 13:e068019. [PMID: 37130665 PMCID: PMC10163538 DOI: 10.1136/bmjopen-2022-068019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/04/2023] Open
Abstract
INTRODUCTION Depression is the most dominant non-motor symptom of Parkinson's disease (PD), with a prevalence of up to 50%, and can lead to a range of psychiatric and psychological problems that can affect quality of life and overall functioning. While several randomised controlled trials (RCTs) have tested the effect of certain non-pharmacological interventions on the outcome of PD depression symptoms, the comparative benefits and harms of these remain unclear. We will conduct a systematic review and network meta-analysis to compare the efficacy and safety of different non-pharmacological interventions for patients with PD depression. METHODS AND ANALYSIS We will search PubMed, Web of Science, Cochrane, Embase, Google Scholar, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database, WanFang Data and the Chongqing VIP Database from their inception date to June 2022. The studies will be limited to results published in English or Chinese. The primary outcomes will be the changes in the depressive symptoms, while secondary outcomes will include adverse effects and the quality of life. Two researchers will screen those documents that meet the inclusion criteria, extracting data according to the preset table and evaluating the methodological quality of the included studies using the Cochrane Risk of Bias 2.0 Tool. The STATA and ADDIS statistical software will be used to conduct a systematic review and network meta-analysis. A traditional pairwise meta-analysis and a network meta-analysis will be performed to compare the efficacy and safety of different non-pharmacological interventions, ensuring the robustness of the findings. The Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the overall quality of the body of evidence associated with the main results. The publication bias assessment will be conducted using comparison-adjusted funnel plots. ETHICS AND DISSEMINATION All the data for this study will be extracted from published RCTs. As a literature-based systematic review, this study does not require ethical approval. The results will be disseminated through peer-reviewed journals and national/international conference presentations. PROSPERO REGISTRATION NUMBER CRD42022347772.
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Affiliation(s)
- Xiaoyu Jiang
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Linlin Zhang
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Huifen Liu
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Hang Su
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Jiahui Jiang
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Chen Qiang
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Qing Wang
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Xinjie Qu
- College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Wenyu Sun
- Department of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, Shandong, China
| | - Hongyan Bi
- Department of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, Shandong, China
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24
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Ahmad MH, Rizvi MA, Ali M, Mondal AC. Neurobiology of depression in Parkinson's disease: Insights into epidemiology, molecular mechanisms and treatment strategies. Ageing Res Rev 2023; 85:101840. [PMID: 36603690 DOI: 10.1016/j.arr.2022.101840] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 12/25/2022] [Accepted: 12/31/2022] [Indexed: 01/03/2023]
Abstract
Parkinson's disease (PD) is characterized mainly by motor dysfunctions due to the progressive loss of dopaminergic neurons. However, PD patients experience a multitude of debilitating non-motor symptoms, including depression, which may have deleteriously detrimental effects on life. Depression is multifactorial and exhibits a bimodal progression in PD, but its underlying molecular mechanisms are poorly understood. Studies demonstrating the pathophysiology of depression in PD and the specific treatment strategies for depression-like symptoms in PD patients are largely lacking, often underrated, under-recognized and, consequently, inadequately/under-treated. Nevertheless, reports suggest that the incidence of depression is approximately 20-30% of PD patients and may precede the onset of motor symptoms. Diagnosing depression in PD becomes difficult due to the clinical overlap in symptomatology between the two diseases, and the nigrostriatal dysfunction alone is insufficient to explain depressive symptoms in PD. Therefore, the current study provides an overview of the molecular mechanisms underlying the development of depression in PD and new insights into developing current antidepressant strategies to treat depression in PD. This review will identify and understand the molecular pathological mechanisms of depression in PD that will fundamentally help tailoring therapeutic interventions for depressive symptoms in PD.
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Affiliation(s)
- Mir Hilal Ahmad
- Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India; Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India
| | - Moshahid Alam Rizvi
- Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India
| | - Mansoor Ali
- Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
| | - Amal Chandra Mondal
- Laboratory of Cellular and Molecular Neurobiology, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
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25
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Wang J, Sun L, Chen L, Sun J, Xie Y, Tian D, Gao L, Zhang D, Xia M, Wu T. Common and distinct roles of amygdala subregional functional connectivity in non-motor symptoms of Parkinson's disease. NPJ Parkinsons Dis 2023; 9:28. [PMID: 36806219 PMCID: PMC9938150 DOI: 10.1038/s41531-023-00469-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 02/02/2023] [Indexed: 02/19/2023] Open
Abstract
Neuroimaging studies suggest a pivotal role of amygdala dysfunction in non-motor symptoms (NMS) of Parkinson's disease (PD). However, the relationship between amygdala subregions (the centromedial (CMA), basolateral (BLA) and superficial amygdala (SFA)) and NMS has not been delineated. We used resting-state functional MRI to examine the PD-related alterations in functional connectivity for amygdala subregions. The left three subregions and right BLA exhibited between-group differences, and were commonly hypo-connected with the frontal, temporal, insular cortex, and putamen in PD. Each subregion displayed distinct hypoconnectivity with the limbic systems. Partial least-squares analysis revealed distinct amygdala subregional involvement in diverse NMS. Hypo-connectivity of all four subregions was associated with emotion, pain, olfaction, and cognition. Hypo-connectivity of the left SFA was associated with sleepiness. Our findings highlight the hypofunction of the amygdala subregions in PD and their preliminary associations with NMS, providing new insights into the pathogenesis of NMS.
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Affiliation(s)
- Junling Wang
- grid.24696.3f0000 0004 0369 153XCenter for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070 China
| | - Lianglong Sun
- grid.20513.350000 0004 1789 9964State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100091 China ,grid.20513.350000 0004 1789 9964Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing, 100091 China ,grid.20513.350000 0004 1789 9964IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100091 China
| | - Lili Chen
- grid.24696.3f0000 0004 0369 153XCenter for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070 China
| | - Junyan Sun
- grid.24696.3f0000 0004 0369 153XCenter for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070 China
| | - Yapei Xie
- grid.20513.350000 0004 1789 9964State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100091 China ,grid.20513.350000 0004 1789 9964Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing, 100091 China ,grid.20513.350000 0004 1789 9964IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100091 China
| | - Dezheng Tian
- grid.20513.350000 0004 1789 9964State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100091 China ,grid.20513.350000 0004 1789 9964Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing, 100091 China ,grid.20513.350000 0004 1789 9964IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100091 China
| | - Linlin Gao
- grid.417031.00000 0004 1799 2675Department of General Medicine, Tianjin Union Medical Center, Tianjin, 300122 China
| | - Dongling Zhang
- grid.24696.3f0000 0004 0369 153XCenter for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070 China
| | - Mingrui Xia
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100091, China. .,Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing, 100091, China. .,IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100091, China.
| | - Tao Wu
- Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
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26
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Bai W, Zhang J, Smith RD, Cheung T, Su Z, Ng CH, Zhang Q, Xiang YT. Inter-relationship between cognitive performance and depressive symptoms and their association with quality of life in older adults: A network analysis based on the 2017-2018 wave of Chinese Longitudinal Healthy Longevity Survey (CLHLS). J Affect Disord 2023; 320:621-627. [PMID: 36206885 DOI: 10.1016/j.jad.2022.09.159] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/25/2022] [Accepted: 09/30/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Depressive symptoms and cognitive impairment are common psychiatric conditions and often co-occur in older adults. Network analysis has been widely used in exploring the inter-connections between psychiatric symptoms. The aim of this study was to explore the network model of depressive symptoms and cognitive performance, and their association with quality of life in people aged 65 years or above based on the 2017-2018 wave of Chinese Longitudinal Healthy Longevity Survey (CLHLS). METHOD Global cognitive performance, depressive symptoms, and global quality of life (QoL) were measured using the validated Chinese version of the Mini Mental State Examination (MMSE), the 10-item Center for Epidemiologic Studies Short Depression Scale (CES-D), and the World Health Organization Quality of Life-brief version (WHOQOL-BREF), respectively. Central symptoms and bridge symptoms were identified via strength and bridge strength, respectively. The flow network was used to identify symptoms directly related to QoL. Network stability was examined using the case dropping bootstrap method. RESULTS A total of 9023 participants were included in the network analysis. CESD3 "Feeling blue/depressed", CESD4 "Everything was an effort", and At_C "Attention and Calculation" were the central (influential) symptoms that had the highest strength value. Three bridge symptoms (i.e., Nam "Naming", CESD2 "Difficulty with concentrating", and Lan "Language") were also identified. CESD10 "Sleep disturbances" had the strongest direct connection to QoL. CONCLUSIONS This exploratory study highlights the inter-relationships between cognitive performance and depressive symptoms in older adults in the general population. Interventions targeting bridge symptoms have the potential to alleviate depressive and cognitive symptoms in this population. Furthermore, improving sleep quality in older adults may reduce the negative impact of depression and cognition decline on QoL.
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Affiliation(s)
- Wei Bai
- Unit of Psychiatry, Department of Public Health and Medicinal Administration, & Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China; Centre for Cognitive and Brain Sciences, University of Macau, Macao SAR, China
| | - Juan Zhang
- Faculty of Education, University of Macau, Macao SAR, China
| | - Robert D Smith
- Unit of Psychiatry, Department of Public Health and Medicinal Administration, & Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China
| | - Teris Cheung
- School of Nursing, Hong Kong Polytechnic University, Hong Kong, SAR, China
| | - Zhaohui Su
- Center on Smart and Connected Health Technologies, Mays Cancer Center, School of Nursing, UT Health San Antonio, San Antonio, TX, USA
| | - Chee H Ng
- Department of Psychiatry, The Melbourne Clinic and St Vincent's Hospital, University of Melbourne, Richmond, Victoria, Australia.
| | - Qinge Zhang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
| | - Yu-Tao Xiang
- Unit of Psychiatry, Department of Public Health and Medicinal Administration, & Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China; Centre for Cognitive and Brain Sciences, University of Macau, Macao SAR, China.
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Wang H, Xu J, Yu M, Zhou G, Ren J, Wang Y, Zheng H, Sun Y, Wu J, Liu W. Functional and structural alterations as diagnostic imaging markers for depression in de novo Parkinson's disease. Front Neurosci 2023; 17:1101623. [PMID: 36908791 PMCID: PMC9992430 DOI: 10.3389/fnins.2023.1101623] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 02/08/2023] [Indexed: 02/24/2023] Open
Abstract
Background Depression in Parkinson's disease (PD) is identified and diagnosed with behavioral observations and neuropsychological measurements. Due to the large overlaps of depression and PD symptoms in clinical manifestations, it is challenging for neurologists to distinguish and diagnose depression in PD (DPD) in the early clinical stage of PD. The advancement in magnetic resonance imaging (MRI) technology provides potential clinical utility in the diagnosis of DPD. This study aimed to explore the alterations of functional and structural MRI in DPD to produce neuroimaging markers in discriminating DPD from non-depressed PD (NDPD) and healthy controls (HC). Methods We recruited 20 DPD, 37 NDPD, and 41 HC matched in age, gender, and education years. The patients' diagnosis with PD was de novo. The differences in regional homogeneity (ReHo), voxel-wise degree centrality (DC), cortical thickness, cortical gray matter (GM) volumes, and subcortical GM volumes among these groups were detected, and the relationship between altered indicators and depression was analyzed. Moreover, the receiver operating characteristic (ROC) analysis was performed to assess the diagnostic efficacy of altered indicators for DPD. Results Compared to NDPD and HC, DPD showed significantly increased ReHo in left dorsolateral superior frontal gyrus (DSFG) and DC in left inferior temporal gyrus (ITG), and decreased GM volumes in left temporal lobe and right Amygdala. Among these altered indicators, ReHo value in left DSFG and DC values in left ITG and left DSFG were significantly correlated with the severity of depression in PD patients. Comparing DPD and NDPD, the ROC analysis revealed a better area under the curve value for the combination of ReHo value in left DSFG and DC value in left ITG, followed by each independent indicator. However, the difference is not statistically significant. Conclusion This study demonstrates that both functional and structural impairments are present in DPD. Among them, ReHo value of left DSFG and DC value of left ITG are equally well suited for the diagnosis and differential diagnosis of DPD, with a combination of them being slightly preferable. The multimodal MRI technique represents a promising approach for the classification of subjects with PD.
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Affiliation(s)
- Hui Wang
- Department of Neurology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang Affiliated Hospital of Nanjing University of Chinese Medicine, Lianyungang, China
| | - Jianxia Xu
- Department of Neurology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
| | - Miao Yu
- Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Gaiyan Zhou
- Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Jingru Ren
- Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Yajie Wang
- Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Huifen Zheng
- Department of Neurology, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Yu Sun
- International Laboratory of Children Medical Imaging Research, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
| | - Jun Wu
- Department of Clinical Laboratory, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Weiguo Liu
- Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
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Deng JH, Zhang HW, Liu XL, Deng HZ, Lin F. Morphological changes in Parkinson's disease based on magnetic resonance imaging: A mini-review of subcortical structures segmentation and shape analysis. World J Psychiatry 2022; 12:1356-1366. [PMID: 36579355 PMCID: PMC9791612 DOI: 10.5498/wjp.v12.i12.1356] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 11/02/2022] [Accepted: 11/22/2022] [Indexed: 12/16/2022] Open
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra, resulting in clinical symptoms, including bradykinesia, resting tremor, rigidity, and postural instability. The pathophysiological changes in PD are inextricably linked to the subcortical structures. Shape analysis is a method for quantifying the volume or surface morphology of structures using magnetic resonance imaging. In this review, we discuss the recent advances in morphological analysis techniques for studying the subcortical structures in PD in vivo. This approach includes available pipelines for volume and shape analysis, focusing on the morphological features of volume and surface area.
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Affiliation(s)
- Jin-Huan Deng
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
| | - Han-Wen Zhang
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
| | - Xiao-Lei Liu
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
| | - Hua-Zhen Deng
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
| | - Fan Lin
- Department of Radiology, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen 518035, Guangdong Province, China
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Li DN, Lian TH, Zhang WJ, Zhang YN, Guo P, Guan HY, Li JH, He MY, Zhang WJ, Zhang WJ, Luo DM, Wang XM, Zhang W. Potential roles of oxidative distress on neurodegeneration in Parkinson's disease with neuropsychiatric symptoms. Front Aging Neurosci 2022; 14:875059. [PMID: 36589540 PMCID: PMC9797725 DOI: 10.3389/fnagi.2022.875059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 11/07/2022] [Indexed: 12/23/2022] Open
Abstract
Background Neuropsychiatric symptoms (NPSs) belong to a category of non-motor symptoms of Parkinson's disease (PD), which seriously compromise the quality of life and prognosis of PD. This study focused on the correlations between NPSs, free radicals, neuroinflammatory factors, and neuropathological proteins in cerebrospinal fluid (CSF) in patients with PD, aiming to provide insights into the potential mechanisms and therapeutic target for PD with NPSs (PD-NPSs). Methods In total, 129 patients with PD were enrolled and assessed by the Neuropsychiatric Symptoms Inventory (NPI); they were divided into the PD-NPSs group (75 patients) and PD with no NPSs (PD-nNPSs) group (54 patients). The levels of hydrogen peroxide (H2O2) and nitric oxide (NO), and hydroxyl radical (·OH), anti-oxidative enzyme, neuroinflammatory factors, and neuropathological proteins in CSF from patients with PD were measured. The levels of the above variables were compared between PD-NPSs and PD-nNPSs groups, and correlation analyses among the above variables were conducted. Results (1) The levels of H2O2 and NO in CSF from the PD-NPSs group were significantly elevated compared with the PD-nNPSs group (p = 0.001), and NPI score positively correlated with the levels of H2O2 and NO (r = 0.283, P = 0.001; r = 0.231, P = 0.008). Reversely, total superoxide dismutase (tSOD) activity in CSF from the PD-NPSs group was significantly reduced compared with the PD-nNPSs group (p = 0.011), and negatively correlated with NPI score (r = -0.185, p = 0.036). (2) The tumor necrosis factor (TNF)-α level in CSF from the PD-NPSs group was significantly decreased compared with the PD-nNPSs group (p = 0.002) and negatively correlated with NPI score (r = -0.211, p = 0.016). (3) The total tau (T-tau) level in CSF from the PD-NPSs group was significantly higher than in the PD-nNPSs group (p = 0.014) and positively correlated with the NPI score (r = 0.167, p = 0.060). (4) The levels of H2O2 and NO positively correlated with the T-tau level in CSF from the PD-NPSs group (r = 0.183, p = 0.039; r = 0.251, P = 0.004), and the levels of TNF-α and T-tau showed a negative correlation (r = -0.163, p = 0.067). Conclusion Oxidative distress characterized by the elevations of H2O2 and NO levels may closely correlate with the neurodegeneration in brain regions related to PD-NPSs. Thus, therapeutic antioxidants may become an important target for PD-NPSs therapy.
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Affiliation(s)
- Dan-ning Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Teng-hong Lian
- Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wei-Jiao Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Ya-nan Zhang
- Department of Blood Transfusion, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Peng Guo
- Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Hui-ying Guan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jing-hui Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Ming-yue He
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wen-jing Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wei-jia Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Dong-mei Luo
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xiao-min Wang
- Department of Physiology, Capital Medical University, Beijing, China
| | - Wei Zhang
- Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China,Beijing Key Laboratory on Parkinson's Disease, Beijing, China,*Correspondence: Wei Zhang
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Salehi MA, Mohammadi S, Gouravani M, Javidi A, Dager SR. Brain microstructural alterations of depression in Parkinson's disease: A systematic review of diffusion tensor imaging studies. Hum Brain Mapp 2022; 43:5658-5680. [PMID: 35855597 PMCID: PMC9704780 DOI: 10.1002/hbm.26015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/11/2022] [Accepted: 06/22/2022] [Indexed: 01/15/2023] Open
Abstract
Depression, a leading cause of disability worldwide, is also the most prevalent psychiatric problem among Parkinson disease patients. Both depression and Parkinson disease are associated with microstructural anomalies in the brain. Diffusion tensor imaging techniques have been developed to characterize the abnormalities in cerebral tissue. We included 11 studies investigating brain microstructural abnormalities in depressed Parkinson's disease patients. The included studies found alterations to essential brain structural networks, including impaired network integrity for specific cortical regions, such as the temporal and frontal cortices. Additionally, findings indicate that microstructural changes in specific limbic structures, such as the prefronto-temporal regions and connecting white matter pathways, are altered in depressed Parkinson's disease compared to non-depressed Parkinson's disease and healthy controls. There remain inconsistencies between studies reporting DTI measures and depression severity in Parkinson disease participants. Additional research evaluating underlying neurobiological relationships between major depression, depressed Parkinson's disease, and non-depressed Parkinson's disease is required to disentangle further mechanisms that underlie depression and related somatic symptoms, in Parkinson disease.
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Affiliation(s)
| | - Soheil Mohammadi
- School of MedicineTehran University of Medical SciencesTehranIran
| | - Mahdi Gouravani
- School of MedicineTehran University of Medical SciencesTehranIran
| | - Arian Javidi
- School of MedicineTehran University of Medical SciencesTehranIran
| | - Stephen R. Dager
- Department of RadiologyUniversity of WashingtonSeattleWashingtonUSA
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Yan W, Zhu H, Zhang P, Sun T, Gong S, Sun G, Ren Z. Heterotopic 4T1 breast cancer transplantation induces hippocampal inflammation and depressive-like behaviors in mice. Metab Brain Dis 2022; 37:2955-2963. [PMID: 35947291 DOI: 10.1007/s11011-022-01058-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 07/29/2022] [Indexed: 10/15/2022]
Abstract
Cancer and its accompanying treatments can lead to numerous physical and emotional concerns, including subclinical or clinical depression and anxiety, which could significantly impact one's well-being, quality of life, and survival. A large number of studies have elucidated that neuroinflammation is associated with depression. Here, we report the hippocampal pathological changes and depressive behaviors of a heterotopic breast cancer transplantation mouse model; hence, a heterotopic 4T1 breast cancer transplantation mouse model was established. Assessment of cognitive and locomotive functions of the experimental animals was conducted using open- and closed-field tests, including a tail suspension test. Expression levels of monoaminergic system markers, brain-derived neurotrophic factor (BDNF), pro-inflammatory cytokines, and nuclear factor-kappa B (NFκB) in the hippocampus and serum were detected using immunochemistry and western and enzyme-linked immunosorbent assay analysis. A comparison of the differences between model and control animals was performed. As per our findings, 4T1 tumor-bearing mice displayed cancer-related anorexia/cachexia with significant reductions in the travel distance and the total number of squares crossed in the open- and closed-field tests. Additionally, the 4T1 tumor-bearing mice withstood a more extended period of immobility during the tail suspension test. Immunohistochemistry studies revealed reduced levels of serotonin, norepinephrine, and BDNF in the hippocampus and serum. Elevated levels of NFκB and pro-inflammatory cytokines in the hippocampus were also observed. These findings suggest that hippocampal inflammation may have played an important role in the neurological function and depressive behavior in heterotopic 4T1 breast cancer transplantation mice.
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Affiliation(s)
- Wenjing Yan
- School of Nursing, Xuzhou Medical University, Xuzhou, China
| | - Hulin Zhu
- Department of Stomatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Pengbo Zhang
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, 221004, People's Republic of China
| | - Ting Sun
- Department of Administration, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Shuai Gong
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, 221004, People's Republic of China
| | - Guoxiu Sun
- School of Nursing, Xuzhou Medical University, Xuzhou, China
| | - Zeqiang Ren
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, 221004, People's Republic of China.
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Zhang J, Zhang N, Lei J, Jing B, Li M, Tian H, Xue B, Li X. Fluoxetine shows neuroprotective effects against LPS-induced neuroinflammation via the Notch signaling pathway. Int Immunopharmacol 2022; 113:109417. [DOI: 10.1016/j.intimp.2022.109417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 10/24/2022] [Accepted: 10/31/2022] [Indexed: 11/11/2022]
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Jellinger KA. The pathobiological basis of depression in Parkinson disease: challenges and outlooks. J Neural Transm (Vienna) 2022; 129:1397-1418. [PMID: 36322206 PMCID: PMC9628588 DOI: 10.1007/s00702-022-02559-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022]
Abstract
Depression, with an estimated prevalence of about 40% is a most common neuropsychiatric disorder in Parkinson disease (PD), with a negative impact on quality of life, cognitive impairment and functional disability, yet the underlying neurobiology is poorly understood. Depression in PD (DPD), one of its most common non-motor symptoms, can precede the onset of motor symptoms but can occur at any stage of the disease. Although its diagnosis is based on standard criteria, due to overlap with other symptoms related to PD or to side effects of treatment, depression is frequently underdiagnosed and undertreated. DPD has been related to a variety of pathogenic mechanisms associated with the underlying neurodegenerative process, in particular dysfunction of neurotransmitter systems (dopaminergic, serotonergic and noradrenergic), as well as to disturbances of cortico-limbic, striato-thalamic-prefrontal, mediotemporal-limbic networks, with disruption in the topological organization of functional mood-related, motor and other essential brain network connections due to alterations in the blood-oxygen-level-dependent (BOLD) fluctuations in multiple brain areas. Other hypothetic mechanisms involve neuroinflammation, neuroimmune dysregulation, stress hormones, neurotrophic, toxic or metabolic factors. The pathophysiology and pathogenesis of DPD are multifactorial and complex, and its interactions with genetic factors, age-related changes, cognitive disposition and other co-morbidities awaits further elucidation.
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Affiliation(s)
- Kurt A Jellinger
- Institute of Clinical Neurobiology, Alberichgasse 5/13, 1150, Vienna, Austria.
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Should patients with Parkinson’s disease only visit a neurologist’s office? - a narrative review of neuropsychiatric disorders among people with Parkinson’s disease. CURRENT PROBLEMS OF PSYCHIATRY 2022. [DOI: 10.2478/cpp-2022-0021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Abstract
Introduction: Parkinson’s disease is a neurodegenerative disease that is often accompanied by disorders such as depression, psychotic disorders, cognitive disorders, anxiety disorders, sleep disorders, impulse control disorders. The aim of the study was to review the literature and present the characteristics of neuropsychiatric disorders occurring in people suffering from Parkinson’s disease, with the specification of the above-mentioned disorders.
Material and method: The literature available on the PubMed platform from 1986 to 2022 was reviewed using the following keywords: Parkinson’s disease, depression, anxiety disorders, psychotic disorders, sleep disorders, cognitive disorders, impulse control disorders. Original studies, reviews, meta-analyzes and internet sources were analyzed.
Results: The above-mentioned neuropsychiatric disorders appear with different frequency among people suffering from Parkinson’s disease and occur at different times of its duration or even precede its onset for many years. The non-motor symptoms in the form of depressed mood, energy loss or changes in the rhythm of the day may result in a delay of appropriate therapy and thus in complications. Neuropathological changes in the course of Parkinson’s disease as well as dopaminergic drugs used in its therapy influence the development of neuropsychiatric disorders.
Conclusions: In order to avoid misdiagnosis, practitioners should use, e.g. scales intended for patients with Parkinson’s disease. To prevent the consequences of the aforementioned disease entities, methods of early diagnosis, determination of risk factors and standardization of the treatment process must be determined. Consistent care for patients with Parkinson’s disease is significant, not only in the neurological field, but also in the psychiatric one.
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Ratajska AM, Scott BM, Lopez FV, Kenney LE, Foote KD, Okun MS, Price C, Bowers D. Differential contributions of depression, apathy, and anxiety to neuropsychological performance in Parkinson's disease versus essential tremor. J Clin Exp Neuropsychol 2022; 44:651-664. [PMID: 36600515 PMCID: PMC10013508 DOI: 10.1080/13803395.2022.2157796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 12/07/2022] [Indexed: 01/06/2023]
Abstract
INTRODUCTION Mood symptoms are common features of Parkinson's disease (PD) and essential tremor (ET) and have been linked to worse cognition. The goals of the present study were to compare the severity of anxiety, apathy, and depressive symptoms in PD, ET, and healthy controls (HC) and to examine differential relationships between mood and cognition. METHOD Older adults with idiopathic PD (N = 448), ET (N = 128), or HC (N = 136) completed a multi-domain neuropsychological assessment consisting of memory, executive function, and attention/working memory domains. Participants also completed self-reported mood measures. Between-group differences in mood and cognition were assessed, and hierarchical regression models were conducted to examine relationships between mood and cognition in each group. RESULTS Relative to the HC group, the PD and ET groups reported more mood symptoms and scored lower across all cognitive measures. There were no differences between the two movement disorder groups. Mood variables explained 3.9-13.7% of the total variance in cognitive domains, varying by disease group. For PD, apathy was the only unique predictor of executive function (β = -.114, p = .05), and trait anxiety was the only unique predictor of attention/working memory (β = -.188, p < .05). For ET, there were no unique predictors, though the overall models significantly predicted performance in the executive function and attention/working memory domains. CONCLUSIONS In a large cohort of ET and PD, we observed that the two groups had similar self-reported mood symptoms. Mood symptoms were differentially associated with cognition in PD versus ET. In PD, increased apathy was associated with worse executive function and higher trait anxiety predicted worse attention/working memory. For ET, there were no unique predictors, though the overall mood symptom severity was related to cognition. Our study highlights the importance of considering the relationship between mood and neuropsychological performance in individuals with movement disorders.
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Affiliation(s)
- Adrianna M. Ratajska
- Department of Clinical and Health Psychology, University of Florida, Gainesville, FL
| | - Bonnie M. Scott
- Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX
| | - Francesca V. Lopez
- Department of Clinical and Health Psychology, University of Florida, Gainesville, FL
| | - Lauren E. Kenney
- Department of Clinical and Health Psychology, University of Florida, Gainesville, FL
| | - Kelly D. Foote
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL
| | - Michael S. Okun
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL
| | - Catherine Price
- Department of Clinical and Health Psychology, University of Florida, Gainesville, FL
| | - Dawn Bowers
- Department of Clinical and Health Psychology, University of Florida, Gainesville, FL
- Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL
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Zhang J, Xue B, Jing B, Tian H, Zhang N, Li M, Lu L, Chen L, Diao H, Chen Y, Wang M, Li X. LPS activates neuroinflammatory pathways to induce depression in Parkinson’s disease-like condition. Front Pharmacol 2022; 13:961817. [PMID: 36278237 PMCID: PMC9582846 DOI: 10.3389/fphar.2022.961817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 09/22/2022] [Indexed: 11/13/2022] Open
Abstract
Aim: This study aimed to observe the effects of lipopolysaccharide (LPS) intraperitoneal (i.p.) injection on rats and investigate how neuroinflammation contributes to the pathogenesis of depression in Parkinson’s disease (dPD). Methods: Rats were administered LPS (0.5 mg/kg, i.p.) for either 1, 2, or 4 consecutive days to establish a rat model of dPD. The sucrose preference test (SPT), the open field test (OFT), and the rotarod test evaluated depression-like and motor behaviors. Magnetic resonance imaging was used to detect alterations in the intrinsic activity and the integrity of white matter fibers in the brain. The expression of c-Fos, ionized calcium-binding adapter molecule (Iba-1), and tyrosine hydroxylase (TH) was evaluated using immunohistochemistry. The concentration of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and interleukin-10 (IL-10) was measured using Luminex technology. Results: LPS i.p. injections decreased sucrose preference in the SPT, horizontal and center distance in the OFT, and standing time in the rotarod test. The intrinsic activities in the hippocampus (HIP) were significantly reduced in the LPS-4 d group. The integrity of white matter fibers was greatly destroyed within 4 days of LPS treatment. The expression of c-Fos and Iba-1 in the prefrontal cortex, HIP, and substantia nigra increased dramatically, and the number of TH+ neurons in the substantia nigra decreased considerably after LPS injection. The levels of IL-6, TNF-α, and IL-10 were higher in the LPS-4 d group than those in the control group. Conclusion: Injection of LPS (0.5 mg/kg, i.p.) for 4 consecutive days can activate microglia, cause the release of inflammatory cytokines, reduce intrinsic activities in the HIP, destroy the integrity of white matter fibers, induce anhedonia and behavioral despair, and finally lead to dPD. This study proved that LPS injection (0.5 mg/kg, i.p.) for 4 consecutive days could be used to successfully create a rat model of dPD.
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Affiliation(s)
- Jing Zhang
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Bing Xue
- Core Facility Center, Capital Medical University, Beijing, China
| | - Bin Jing
- School of Biomedical Engineering, Capital Medical University, Beijing, China
| | - Huiling Tian
- School of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Naiwen Zhang
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Mengyuan Li
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Lihua Lu
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Lin Chen
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Huaqiong Diao
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yufei Chen
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Min Wang
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaoli Li
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Xiaoli Li,
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Liu Y, Ding L, Xianyu Y, Nie S, Yang J. Research on depression in Parkinson disease: A bibliometric and visual analysis of studies published during 2012-2021. Medicine (Baltimore) 2022; 101:e29931. [PMID: 35945720 PMCID: PMC9351875 DOI: 10.1097/md.0000000000029931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND The diagnosis and treatment rate of Parkinson disease (PD) with depression has a low diagnostic rate, and there is no consensus on the choice of treatment mode. This study evaluates the global research trends of scientific outputs related to depression in PD from multiple perspectives, using a bibliometric analysis and visualization tool to scientifically analyze the knowledge from the literature. METHODS Literature related to depression in PD published from 2012 to 2021 was included and selected from the Web of Science Core Collection database in October 2021. CiteSpace software was used to visualize and analyze co-occurrence analyses for countries, institutions, authors, and keywords. RESULTS A total of 4533 articles from the Web of Science database were included. The United States made the largest contribution with the majority of publications (1215; 29.40%). Toronto University was the most productive institution. PD, depression, quality of life, dementia, nonmotor symptom, prevalence, anxiety, Alzheimer disease, symptom, and disorder would be significantly correlated with depression in PD. The current hot spots in this field focus on the following: risk factors for depression in PD, assessment scale of depression in PD, and rehabilitation of depression in PD. CONCLUSIONS This analysis not only reveals the current research trends and hotspots but also provides some instructive suggestions on the development of depression in PD.
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Affiliation(s)
- Yan Liu
- Department of Nursing, Renmin Hospital of Wuhan University, Wuhan, China
- *Correspondence: Yan Liu, Department of Nursing, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan 430060, China (e-mail: )
| | - Linlin Ding
- School of Nursing, Hubei University of Chinese Medicine, Wuhan, China
| | - Yunyan Xianyu
- Department of Nursing, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shuke Nie
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jiying Yang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
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Association between Baseline Cognitive Score and Postoperative Delirium in Parkinson’s Disease Patients following Deep Brain Stimulation Surgery. PARKINSON'S DISEASE 2022; 2022:9755129. [PMID: 36338872 PMCID: PMC9635975 DOI: 10.1155/2022/9755129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 04/24/2022] [Accepted: 06/13/2022] [Indexed: 11/20/2022]
Abstract
Background Deep brain stimulation of the subthalamic nuclei (STN-DBS) is a standard treatment option for advanced Parkinson's disease (PD) patients. Delirium following DBS electrode implantation is common, by several studies, and cognitive impairment is a risk factor for developing postoperative delirium (POD). This prospective observational study was conducted to identify whether preoperative baseline cognitive status has an association with POD in PD patients undergoing DBS surgery. Methods Preoperatively, neuropsychiatric and neuropsychological assessments of the patients were performed including clinical dementia rating (CDR) score, instrumental activities of daily living (IADL) score, mini-mental state exam (MMSE) score, Montreal cognitive assessment (MoCA) score, Hamilton anxiety (HAMA) and Hamilton depression (HAMD) scores, and numerical cancellation test. POD was identified by the confusion assessment method (CAM) twice per day on postoperative day 1 until discharge. Results Twenty-seven (21.6%) of 125 patients developed POD. Among the variables screened, age, CDR score, MMSE score, and HAMA score were indicated to be independent influence factors of POD. The cutoff score, AUC, sensitivity, and specificity of age, CDR score, MMSE score, and HAMA score associated with POD was 58.5, 0.751, 92.6%, 52.0%; 0.5, 0.848, 77.8%, 91.8%; 27.5, 0.827, 88.9%, 62.2%; and 12.5, 0.706, 85.2%, 54.1%, respectively. Conclusions We observed age, CDR score, MMSE score, and HAMA score were independent influence factors of POD in PD patients who received DBS. It is necessary to assess the cognitive status of PD patients before surgery to identify high-risk patients.
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Yang Y, Yang Y, Pan A, Xu Z, Wang L, Zhang Y, Nie K, Huang B. Identifying Depression in Parkinson's Disease by Using Combined Diffusion Tensor Imaging and Support Vector Machine. Front Neurol 2022; 13:878691. [PMID: 35795798 PMCID: PMC9251067 DOI: 10.3389/fneur.2022.878691] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 05/20/2022] [Indexed: 12/02/2022] Open
Abstract
Objective To investigate white matter microstructural alterations in Parkinson's disease (PD) patients with depression using the whole-brain diffusion tensor imaging (DTI) method and to explore the DTI–based machine learning model in identifying depressed PD (dPD). Methods The DTI data were collected from 37 patients with dPD and 35 patients with non-depressed PD (ndPD), and 25 healthy control (HC) subjects were collected as the reference. An atlas-based analysis method was used to compare fractional anisotropy (FA) and mean diffusivity (MD) among the three groups. A support vector machine (SVM) was trained to examine the probability of discriminating between dPD and ndPD. Results As compared with ndPD, dPD group exhibited significantly decreased FA in the bilateral corticospinal tract, right cingulum (cingulate gyrus), left cingulum hippocampus, bilateral inferior longitudinal fasciculus, and bilateral superior longitudinal fasciculus, and increased MD in the right cingulum (cingulate gyrus) and left superior longitudinal fasciculus-temporal part. For discriminating between dPD and ndPD, the SVM model with DTI features exhibited an accuracy of 0.70 in the training set [area under the receiver operating characteristic curve (ROC) was 0.78] and an accuracy of 0.73 in the test set (area under the ROC was 0.71). Conclusion Depression in PD is associated with white matter microstructural alterations. The SVM machine learning model based on DTI parameters could be valuable for the individualized diagnosis of dPD.
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Affiliation(s)
- Yunjun Yang
- Department of Radiology, The First People's Hospital of Foshan, Foshan, China
| | - Yuelong Yang
- Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Aizhen Pan
- Department of Radiology, The First People's Hospital of Foshan, Foshan, China
| | - Zhifeng Xu
- Department of Radiology, The First People's Hospital of Foshan, Foshan, China
| | - Lijuan Wang
- Department of Neurology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yuhu Zhang
- Department of Neurology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Kun Nie
- Department of Neurology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Biao Huang
- Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- *Correspondence: Biao Huang
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40
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Laansma MA, Bright JK, Jahanshad N, Thompson PM, van der Werf YD. Reply to: "Parkinson's Disease, Premature Mortality, and Amygdala". Mov Disord 2022; 37:1111-1112. [PMID: 35587628 DOI: 10.1002/mds.29004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 03/15/2022] [Indexed: 11/08/2022] Open
Affiliation(s)
- Max A Laansma
- Amsterdam UMC location Vrije Universiteit Amsterdam, Anatomy & Neurosciences, De Boelelaan 1117, Amsterdam, The Netherlands.,Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
| | - Joanna K Bright
- Social Genetic Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom
| | - Neda Jahanshad
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA
| | - Paul M Thompson
- Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA
| | - Ysbrand D van der Werf
- Amsterdam UMC location Vrije Universiteit Amsterdam, Anatomy & Neurosciences, De Boelelaan 1117, Amsterdam, The Netherlands.,Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands
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41
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Holmberg M, Malmgren H, Heckemann RA, Johansson B, Klasson N, Olsson E, Skau S, Starck G, Filipsson Nyström H. A Longitudinal Study of Medial Temporal Lobe Volumes in Graves Disease. J Clin Endocrinol Metab 2022; 107:1040-1052. [PMID: 34752624 PMCID: PMC8947220 DOI: 10.1210/clinem/dgab808] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Indexed: 11/23/2022]
Abstract
CONTEXT Neuropsychiatric symptoms are common features of Graves disease (GD) in hyperthyroidism and after treatment. The mechanism behind these symptoms is unknown, but reduced hippocampal volumes have been observed in association with increased thyroid hormone levels. OBJECTIVE This work aimed at investigating GD influence on regional medial temporal lobe (MTL) volumes. METHODS Sixty-two women with newly diagnosed GD underwent assessment including magnetic resonance (MR) imaging in hyperthyroidism and 48 of them were followed up after a mean of 16.4 ± 4.2 SD months of treatment. Matched thyroid-healthy controls were also assessed twice at a 15-month interval. MR images were automatically segmented using multiatlas propagation with enhanced registration. Regional medial temporal lobe (MTL) volumes for amygdalae and hippocampi were compared with clinical data and data from symptom questionnaires and neuropsychological tests. RESULTS Patients had smaller MTL regions than controls at inclusion. At follow-up, all 4 MTL regions had increased volumes and only the volume of the left amygdala remained reduced compared to controls. There were significant correlations between the level of thyrotropin receptor antibodies (TRAb) and MTL volumes at inclusion and also between the longitudinal difference in the levels of free 3,5,3'-triiodothyronine and TRAb and the difference in MTL volumes. There were no significant correlations between symptoms or test scores and any of the 4 MTL volumes. CONCLUSION Dynamic alterations in the amygdalae and hippocampi in GD reflect a previously unknown level of brain involvement both in the hyperthyroid state of the condition and after treatment. The clinical significance, as well as the mechanisms behind these novel findings, warrant further study of the neurological consequences of GD.
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Affiliation(s)
- Mats Holmberg
- ANOVA, Karolinska University Hospital, Stockholm, Sweden
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Correspondence: Mats Holmberg, PhD, ANOVA, Karolinska University Hospital, Norra Stationsgatan 69, SE-17176 Stockholm, Sweden.
| | - Helge Malmgren
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- MedTech West at University of Gothenburg and Sahlgrenska University Hospital, Göteborg, Sweden
| | - Rolf A Heckemann
- MedTech West at University of Gothenburg and Sahlgrenska University Hospital, Göteborg, Sweden
- Institute of Clinical Sciences, Department of Medical Radiation Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Birgitta Johansson
- Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Niklas Klasson
- MedTech West at University of Gothenburg and Sahlgrenska University Hospital, Göteborg, Sweden
- Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Erik Olsson
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Simon Skau
- MedTech West at University of Gothenburg and Sahlgrenska University Hospital, Göteborg, Sweden
- Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Göran Starck
- Institute of Clinical Sciences, Department of Medical Radiation Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Göteborg, Sweden
| | - Helena Filipsson Nyström
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden
- Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Göteborg, Sweden
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Li XN, Hao DP, Qu MJ, Zhang M, Ma AB, Pan XD, Ma AJ. Development and Validation of a Plasma FAM19A5 and MRI-Based Radiomics Model for Prediction of Parkinson's Disease and Parkinson's Disease With Depression. Front Neurosci 2022; 15:795539. [PMID: 34975391 PMCID: PMC8718551 DOI: 10.3389/fnins.2021.795539] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 11/26/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Prediction and early diagnosis of Parkinson’s disease (PD) and Parkinson’s disease with depression (PDD) are essential for the clinical management of PD. Objectives: The present study aimed to develop a plasma Family with sequence similarity 19, member A5 (FAM19A5) and MRI-based radiomics nomogram to predict PD and PDD. Methods: The study involved 176 PD patients and 181 healthy controls (HC). Sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure FAM19A5 concentration in the plasma samples collected from all participants. For enrolled subjects, MRI data were collected from 164 individuals (82 in the PD group and 82 in the HC group). The bilateral amygdala, head of the caudate nucleus, putamen, and substantia nigra, and red nucleus were manually labeled on the MR images. Radiomics features of the labeled regions were extracted. Further, machine learning methods were applied to shrink the feature size and build a predictive radiomics signature. The resulting radiomics signature was combined with plasma FAM19A5 concentration and other risk factors to establish logistic regression models for the prediction of PD and PDD. Results: The plasma FAM19A5 levels (2.456 ± 0.517) were recorded to be significantly higher in the PD group as compared to the HC group (2.23 ± 0.457) (P < 0.001). Importantly, the plasma FAM19A5 levels were also significantly higher in the PDD subgroup (2.577 ± 0.408) as compared to the non-depressive subgroup (2.406 ± 0.549) (P = 0.045 < 0.05). The model based on the combination of plasma FAM19A5 and radiomics signature showed excellent predictive validity for PD and PDD, with AUCs of 0.913 (95% CI: 0.861–0.955) and 0.937 (95% CI: 0.845–0.970), respectively. Conclusion: Altogether, the present study reported the development of nomograms incorporating radiomics signature, plasma FAM19A5, and clinical risk factors, which might serve as potential tools for early prediction of PD and PDD in clinical settings.
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Affiliation(s)
- Xue-Ning Li
- Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Da-Peng Hao
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Mei-Jie Qu
- Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Meng Zhang
- Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - An-Bang Ma
- Shanghai Xunshi Technology Co., Ltd., Shanghai, China
| | - Xu-Dong Pan
- Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Institute of Cerebrovascular, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ai-Jun Ma
- Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Institute of Cerebrovascular, The Affiliated Hospital of Qingdao University, Qingdao, China
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Siddique Y. Neurodegenerative Disorders and the Current State, Pathophysiology, and Management of Parkinson's Disease. CNS & NEUROLOGICAL DISORDERS DRUG TARGETS 2022; 21:574-595. [PMID: 34477534 DOI: 10.2174/1871527320666210903101841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/14/2020] [Accepted: 02/13/2021] [Indexed: 06/13/2023]
Abstract
In the last few decades, major knowledge has been gained about pathophysiological aspects and molecular pathways behind Parkinson's Disease (PD). Based on neurotoxicological studies and postmortem investigations, there is a general concept of how environmental toxicants (neurotoxins, pesticides, insecticides) and genetic factors (genetic mutations in PD-associated proteins) cause depletion of dopamine from substantia nigra pars compacta region of the midbrain and modulate cellular processes leading to the pathogenesis of PD. α-Synuclein, a neuronal protein accumulation in oligomeric form, called protofibrils, is associated with cellular dysfunction and neuronal death, thus possibly contributing to PD propagation. With advances made in identifying loci that contribute to PD, molecular pathways involved in disease pathogenesis are now clear, and introducing therapeutic strategy at the right time may delay the progression. Biomarkers for PD have helped monitor PD progression; therefore, personalized therapeutic strategies can be facilitated. In order to further improve PD diagnostic and prognostic accuracy, independent validation of biomarkers is required.
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Affiliation(s)
- Yasir Siddique
- Drosophila Transgenic Laboratory, Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202002, Uttar Pradesh, India
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Liu X, Chen W, Wang C, Liu W, Hayashi T, Mizuno K, Hattori S, Fujisaki H, Ikejima T. Silibinin ameliorates depression/anxiety-like behaviors of Parkinson's disease mouse model and is associated with attenuated STING-IRF3-IFN-β pathway activation and neuroinflammation. Physiol Behav 2021; 241:113593. [PMID: 34536434 DOI: 10.1016/j.physbeh.2021.113593] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 09/10/2021] [Accepted: 09/13/2021] [Indexed: 11/16/2022]
Abstract
Depression and anxiety are common neuropsychiatric symptom of Parkinson's disease (PD), reflecting reduced quality of life in patients with PD. Silibinin (silybin), a flavonoid extracted and isolated from the fruit of Silybum marianum (L.) Gaertn, is widely used for the treatment of hepatic diseases. We report here that silibinin shows anti-depressant and anti-anxiety effects on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model mice with PD. All the results of open field test, elevated plus maze test, tail suspension test and forced swimming test demonstrated that silibinin administration significantly attenuated MPTP-induced depression/anxiety. Hematoxylin-eosin (HE) staining and Nissl staining results showed that MPTP injection caused the damage of hippocampal neurons, but this was ameliorated by oral administration of silibinin. Silibinin significantly restored hippocampal levels of 5-hydroxyptramine (5-HT) and noradrenaline (NA), two important neurotransmitters for regulating mood, which decreased in MPTP-injected mice. Neuroinflammation, as reflected by the increased expressions of IL-1β, TNFα and IFN-β, was marked in the hippocampus of MPTP-treated mice, accompanying increased stimulator of interferon genes (STING) and interferon regulatory factor-3 (IRF3). Silibinin administration, however, down-regulated the levels of IL-1β, TNFα and IFN-β, as well as STING and IRF3, protecting MPTP-induced PD model mice. These findings indicate that silibinin has a potential of being further developed as a therapeutic for depression and anxiety in PD.
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Affiliation(s)
- Xiumin Liu
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
| | - Wenhui Chen
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
| | - Chenkang Wang
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
| | - Weiwei Liu
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
| | - Toshihiko Hayashi
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China; Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, 2665-1, Nakanomachi, Hachioji, Tokyo, 192-0015, Japan; Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017, Japan
| | - Kazunori Mizuno
- Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017, Japan
| | - Shunji Hattori
- Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017, Japan
| | - Hitomi Fujisaki
- Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017, Japan
| | - Takashi Ikejima
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning, China.
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Shen Q, Liu Y, Guo J, Zhang H, Xiang Y, Liao H, Cai S, Zhou B, Wang M, Liu S, Yi J, Zhang Z, Tan C. Impaired white matter microstructure associated with severe depressive symptoms in patients with PD. Brain Imaging Behav 2021; 16:169-175. [PMID: 34410611 DOI: 10.1007/s11682-021-00488-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/27/2021] [Indexed: 11/29/2022]
Abstract
Depression is a common occurrence in patients with Parkinson's disease (PD); however, its pathophysiology is still unclear. This study assessed the association between the integrity of white matter and depressive symptoms in patients with PD. 67 patients with PD were divided into a non-depressed PD group (ndPD, n = 30) and a depressed PD group (dPD, n = 37). The dPD group was further subdivided into a mild-moderately depressed PD (mdPD, n = 22) and a severely depressed PD group (sdPD, n = 15). Tract-Based Spatial Statistics was used to compare fractional anisotropy (FA) between groups. Region-of-interest analysis was used to explore changes in diffusivity indices in the regions showing FA abnormalities. The sdPD patients exhibited significantly reduced FA in the left superior longitudinal fasciculus, uncinate fasciculus, anterior corona radiata, corticospinal tract, and bilateral inferior fronto-occipital fasciculus when compared with the ndPD patients, but the decreased FA was within a smaller area when compared with the mdPD patients. No significant difference in FA was found between the mdPD and ndPD groups. Among the dPD patients, FA values in the left superior longitudinal fasciculus negatively correlated with BDI scores. Impaired white matter integrity in the prefronto-limbic/temporal circuitry, mainly in the left hemisphere, is associated with severe, but not mild-moderate depressive symptoms in patients with PD.
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Affiliation(s)
- Qin Shen
- Department of Radiology, the Second Xiangya Hospital, Central South University, 139 Renmin Zhong Road, Changsha, 410011, Hunan, China
| | - Yawu Liu
- Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.,Department of Radiology, Kuopio University Hospital, Kuopio, Finland
| | - Jie Guo
- National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, China
| | - Hongchun Zhang
- Department of Radiology, the First Affiliated Hospital, University of Science and Technology of China, Hefei, China
| | - Yijuan Xiang
- Department of Radiology, the Second Xiangya Hospital, Central South University, 139 Renmin Zhong Road, Changsha, 410011, Hunan, China
| | - Haiyan Liao
- Department of Radiology, the Second Xiangya Hospital, Central South University, 139 Renmin Zhong Road, Changsha, 410011, Hunan, China
| | - Sainan Cai
- Department of Radiology, the Second Xiangya Hospital, Central South University, 139 Renmin Zhong Road, Changsha, 410011, Hunan, China
| | - Bing Zhou
- Department of Radiology, the Second Xiangya Hospital, Central South University, 139 Renmin Zhong Road, Changsha, 410011, Hunan, China
| | - Min Wang
- Department of Radiology, the Second Xiangya Hospital, Central South University, 139 Renmin Zhong Road, Changsha, 410011, Hunan, China
| | - Siyu Liu
- Department of Radiology, the Second Xiangya Hospital, Central South University, 139 Renmin Zhong Road, Changsha, 410011, Hunan, China
| | - Jinyao Yi
- Medical Psychological Center, the Second Xiangya Hospital, Central South University, Changsha, China
| | - Zishu Zhang
- Department of Radiology, the Second Xiangya Hospital, Central South University, 139 Renmin Zhong Road, Changsha, 410011, Hunan, China
| | - Changlian Tan
- Department of Radiology, the Second Xiangya Hospital, Central South University, 139 Renmin Zhong Road, Changsha, 410011, Hunan, China.
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Sakurai M, Iwasa R, Sakai Y, Morimoto M. Minocycline prevents depression-like behavior in streptozotocin-induced diabetic mice. Neuropathology 2021; 41:109-117. [PMID: 33230848 DOI: 10.1111/neup.12706] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 08/09/2020] [Accepted: 08/23/2020] [Indexed: 12/20/2022]
Abstract
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia. Diabetic patients are known to have a higher prevalence and a higher risk of depression compared with the general population. The pathogenesis of diabetes-related depression is unclear, and the treatment is not well-established. Therefore, the prevention of diabetes-related depression is important for improving the quality of life of diabetic patients. Minocycline, a second-generation tetracycline antibiotic, has recently gained attention as a new agent for depression. In this study, we investigated the effect of minocycline on diabetes-related depression in a streptozotocin-induced mouse model of diabetes. Eight-week-old male C57BL/6 mice were injected with streptozotocin (200 mg/kg, i.p.). Seven days after injection, the mice received minocycline treatment through drinking water. We compared these mice with vehicle-treated control mice and diabetic mice not receiving minocycline treatment. On day 34, depression-like behavior was investigated using the forced swim test. On the following day, brain samples were collected, and formalin-fixed, paraffin-embedded specimens were prepared for immunohistochemistry. Compared with the control group, the diabetic mice not receiving minocycline treatment showed a prolonged duration of immobility in the forced swim test, the observation being interpreted as a depression-like behavior. Immunohistochemistry revealed an increase in microglia with an activated morphology in the diabetic mice without minocycline treatment. The expression of tumor necrosis factor alpha in microglia was increased. In addition, a decrease in the number of doublecortin-positive immature neurons was found in the hippocampus of diabetic mice. Minocycline treatment of diabetic animals prevented the depression-like behavior and microglial activation; however, minocycline did not reverse impaired hippocampal neurogenesis. These results indicate that minocycline has a preventive effect on diabetes-related depression. Inhibition of microglial activation would be a critical target for the antidepressant mechanism of minocycline. Impaired hippocampal neurogenesis was observed in diabetic mice; however, this may not be involved in the pathogenesis of depression.
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Affiliation(s)
- Masashi Sakurai
- Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yoshida, Japan
| | - Ryoi Iwasa
- Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yoshida, Japan
| | - Yusuke Sakai
- Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yoshida, Japan
| | - Masahiro Morimoto
- Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yoshida, Japan
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Impaired neurogenesis in the hippocampus of an adult VPS35 mutant mouse model of Parkinson's disease through interaction with APP. Neurobiol Dis 2021; 153:105313. [PMID: 33636388 DOI: 10.1016/j.nbd.2021.105313] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 02/22/2021] [Indexed: 12/27/2022] Open
Abstract
Vacuolar protein sorting protein 35 (VPS35) is a core component of the retromer complex involved in regulating protein trafficking and retrieval. Recently, a missense mutation, Asp620Asn (D620N), in VPS35 (PARK17) has been identified as a pathogenic mutation for late-onset autosomal dominant Parkinson's disease (PD). Although PD is characterized by a range of motor symptoms associated with loss of dopaminergic neurons in the substantial nigra, non-motor symptoms such as impaired hippocampal neurogenesis were observed in both PD patients and animal models of PD caused by multiple PD-linked pathogenic genes such as alpha-synuclein and leucine-rich repeat kinase 2 (LRRK2). However, the role of the VPS35 D620N mutation in adult hippocampal neurogenesis remains unknown. Here, we showed that the VPS35 D620N mutation impaired hippocampal neurogenesis in adult transgenic mice expressing the VPS35 D620N gene. Specifically, we showed a reduction in the neural stem cell pool and neural proliferation and differentiation, retarded migration, and impaired neurite outgrowth in 3-month-old VPS35 D620N mutant mice. Moreover, we found that the VPS35 D620N mutant hyperphosphorylates amyloid precursor protein (APP) at Thr668and interacts with APP. Notably, by crossing the VPS35 D620N mutant mice with APP knockout (KO) mice, we showed that loss of APP function rescues VPS35 D620N-inhibited neurogenesis, neural migration, and maturation. Our study provides important evidence that APP is involved in the VPS35 D620N mutation in regulating adult neurogenesis, which sheds light on the pathogenic mechanisms in PD.
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48
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Tinaz S, Kamel S, Aravala SS, Sezgin M, Elfil M, Sinha R. Distinct neural circuits are associated with subclinical neuropsychiatric symptoms in Parkinson's disease. J Neurol Sci 2021; 423:117365. [PMID: 33636663 DOI: 10.1016/j.jns.2021.117365] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 01/24/2021] [Accepted: 02/18/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND Parkinson's disease (PD) can present with neuropsychiatric symptoms (here, anxiety, depression, and apathy) at any stage of the disease. We investigated the neural correlates of subclinical neuropsychiatric symptoms in relation to motor and cognitive symptoms in a high-functioning PD cohort. METHODS Brain morphometry of the cognitively intact, early-stage (Hoehn & Yahr 2) PD group (n = 48) was compared to matched controls (n = 37). Whole-brain, pairwise, resting-state functional connectivity measures were correlated with neuropsychiatric symptom, motor exam, and global cognitive scores of the PD group. RESULTS Factor analysis of highly collinear anxiety, depression, and apathy scores revealed a single principal component (i.e., composite neuropsychiatric symptom score) explaining 71.6% of variance. There was no collinearity between the neuropsychiatric, motor, and cognitive scores. Compared to controls, PD group showed only subcortical changes including amygdala and nucleus accumbens atrophy, and greater pallidal volume. Reduced functional connectivity in the limbic cortical-striatal circuits and increased functional connectivity between the cerebellum and occipito-temporal regions were associated with a more impaired neuropsychiatric profile. This functional connectivity pattern was distinct from those associated with motor deficits and global cognitive functioning. The individual components of the neuropsychiatric symptoms also exhibited unique connectivity patterns. LIMITATIONS Patients were scanned in "on-medication" state only and a control group with similar neuropsychiatric symptoms was not included. CONCLUSION Abnormal functional connectivity of distinct neural circuits is present even at the subclinical stage of neuropsychiatric symptoms in PD. Neuropsychiatric phenotyping is important and may facilitate early interventions to "reorganize" these circuits and delay/prevent clinical symptom onset.
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Affiliation(s)
- Sule Tinaz
- Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA; Yale University School of Medicine, Clinical Neurosciences Imaging Center, 789 Howard Ave, New Haven, CT 06519, USA.
| | - Serageldin Kamel
- Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA
| | - Sai S Aravala
- Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA
| | - Mine Sezgin
- Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA; Istanbul University Faculty of Medicine, Department of Neurology, Millet Street, Fatih, Istanbul 34093, Turkey
| | - Mohamed Elfil
- Yale University School of Medicine, Department of Neurology, Division of Movement Disorders, 15 York St, LCI 710, New Haven, CT 06510, USA
| | - Rajita Sinha
- Yale School of Medicine, Yale Stress Center, 2 Church St South, Suite 209, New Haven, CT 06519, USA; Yale School of Medicine, Department of Psychiatry, 300 George St, New Haven, CT 06511, USA; Yale School of Medicine, Department of Neuroscience, 333 Cedar St, SHM-L-200, New Haven, CT 06510, USA
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Sun W, Zheng J, Ma J, Wang Z, Shi X, Li M, Huang S, Hu S, Zhao Z, Li D. Increased Plasma Heme Oxygenase-1 Levels in Patients With Early-Stage Parkinson's Disease. Front Aging Neurosci 2021; 13:621508. [PMID: 33643023 PMCID: PMC7906968 DOI: 10.3389/fnagi.2021.621508] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 01/22/2021] [Indexed: 12/19/2022] Open
Abstract
Introduction: Heme oxygenase-1 (HO-1) is a 32 kDa stress-response protein implicated in the pathogenesis of Parkinson’s disease (PD). Biliverdin is derived from heme through a reaction mediated by HO-1 and protects cells from oxidative stress. However, iron and carbon monoxide produced by the catabolism of HO-1 exert detrimental effects on patients with PD. The purpose of this study was to determine whether plasma HO-1 levels represent a biomarker of PD and to further explore the underlying mechanism of increased HO-1 levels by applying voxel-based morphometry (VBM).Methods: We measured plasma HO-1 levels using an enzyme-linked immunosorbent assay (ELISA) in 156 subjects, including 81 patients with early- and advanced-stage PD and 75 subjects without PD. The analyses were adjusted to control for confounders such as age, sex, and medication. We analyzed T1-weighted magnetic resonance imaging (MRI) data from 74 patients with PD using VBM to elucidate the association between altered brain volumes and HO-1 levels. Then, we compared performance on MMSE sub-items between PD patients with low and high levels of HO-1 using Mann-Whitney U tests.Results: Plasma HO-1 levels were significantly elevated in PD patients, predominantly those with early-stage PD, compared with controls (p < 0.05). The optimal cutoff value for patients with early PD was 2.245 ng/ml HO-1 [area under the curve (AUC) = 0.654]. Plasma HO-1 levels were unaffected by sex, age, and medications (p > 0.05). The right hippocampal volume was decreased in the subset of PD patients with high HO-1 levels (p < 0.05). A weak correlation was observed between right hippocampal volume and plasma HO-1 levels (r = −0.273, p = 0.018). There was no difference in total MMSE scores between the low- and high-HO-1 groups (p > 0.05), but the high-HO-1 group had higher language scores than the low-HO-1 group (p < 0.05).Conclusions: Plasma HO-1 levels may be a promising biomarker of early PD. Moreover, a high plasma concentration of the HO-1 protein is associated with a reduction in right hippocampal volume.
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Affiliation(s)
- Wenhua Sun
- Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China.,Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Jinhua Zheng
- Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China.,Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.,Department of Neurology, People's Hospital of Henan University, Zhengzhou, China
| | - Jianjun Ma
- Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China.,Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.,Department of Neurology, People's Hospital of Henan University, Zhengzhou, China
| | - Zhidong Wang
- Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China.,Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Xiaoxue Shi
- Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China.,Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Mingjian Li
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.,Department of Neurology, People's Hospital of Henan University, Zhengzhou, China
| | - Shen Huang
- Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China.,Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Shiyu Hu
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.,Department of Neurology, People's Hospital of Henan University, Zhengzhou, China
| | - Zhenxiang Zhao
- Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China.,Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.,Department of Neurology, People's Hospital of Henan University, Zhengzhou, China
| | - Dongsheng Li
- Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China.,Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China.,Department of Neurology, People's Hospital of Henan University, Zhengzhou, China
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Liao H, Cai S, Shen Q, Fan J, Wang T, Zi Y, Mao Z, Situ W, Liu J, Zou T, Yi J, Zhu X, Tan C. Networks Are Associated With Depression in Patients With Parkinson's Disease: A Resting-State Imaging Study. Front Neurosci 2021; 14:573538. [PMID: 33633526 PMCID: PMC7901489 DOI: 10.3389/fnins.2020.573538] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 12/22/2020] [Indexed: 11/13/2022] Open
Abstract
Background Disturbance of networks was recently proposed to be associated with the occurrence of depression in Parkinson's disease (PD). However, the neurobiological mechanism of depression underlying PD remains unclear. Objective This study was conducted to investigate whether intra-network and inter-network brain connectivity is differently changed in PD patients with and without depression (PDD and PDND patients, respectively). Methods Forty-one PDD patients, 64 PDND patients, and 55 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI). The default mode network (DMN), executive control network (ECN), salience network (SN), precuneus network (PCUN), and sensorimotor network (SMN) were extracted using independent component analysis (ICA), and then the functional connectivity (FC) values within and between these networks were measured. Results PDD patients exhibited abnormal FC values within the DMN, ECN, SN, PCUN, and SMN. In addition, PDD patients demonstrated decreased connectivity between anterior SN (aSN) and bilateral ECN, between posterior SN (pSN) and dorsal DMN (dDMN), and between PCUN and dDMN/SMN/bilateral ECN. Connectivity within the left hippocampus of dDMN and the right medial superior frontal gyrus of aSN was a significant predictor of depression level in PD patients. Conclusions Aberrant intra- and inter-network FC is involved in several important hubs in the large-scale networks, which can be a biomarker for distinguishing PDD from PDND.
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Affiliation(s)
- Haiyan Liao
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Sainan Cai
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Qin Shen
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Jie Fan
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Tianyu Wang
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yuheng Zi
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Zhenni Mao
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Weijun Situ
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Jun Liu
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ting Zou
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Jinyao Yi
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiongzhao Zhu
- Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Changlian Tan
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
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