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Ma S, Xiang D, Hu Z, Lv H, Gong Q, Yang J, Liu Z. Developing an individual depression risk score based on traditional risk factors and routine biochemical markers. J Affect Disord 2025; 370:449-459. [PMID: 39537106 DOI: 10.1016/j.jad.2024.11.027] [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: 05/16/2024] [Revised: 11/05/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Early identification of individuals at high risk for depression is essential for effective implementation of interventions. This study utilized the UK Biobank database to construct an individual depression risk score using nomogram and explored the potential of traditional risk factors and routine biochemical markers for the auxiliary diagnosis of individual depression. METHODS A total of 369,407 participants were included in the study and divided into training and testing sets. LASSO regression was employed to select predictive variables for depression from 16 traditional risk factors and 28 routine biochemical markers. Following variable selection, two multivariable logistic regression models were constructed. Nomograms were then generated to visualize the relationships between these variables and depression risk, and to facilitate the calculation of individual depression risk scores. RESULTS Twelve traditional risk factors and nine biochemical markers were selected for model building. Model 1, using only traditional risk factors, achieved the area under the curve (AUC) of 0.913 (95 % CI: 0.910-0.915), while Model 2, incorporating both traditional and routine biochemical markers, yielded an AUC of 0.914 (95 % CI: 0.912-0.917). Based on optimal cut-off values, Model 1 exhibited a sensitivity of 81.99 % and a specificity of 83.76 %, while Model 2 demonstrated a sensitivity of 81.54 % and a specificity of 84.31 %. LIMITATIONS External validation is still needed to confirm the model's generalizability. CONCLUSIONS While the depression risk scoring model built using traditional risk factors effectively identifies high-risk individuals for depression and demonstrates good clinical performance, incorporating routine biochemical markers did not significantly improve the model's performance.
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Affiliation(s)
- Simeng Ma
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China
| | - Dan Xiang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhiyi Hu
- School of Information Engineering, Wuhan University of Technology, Wuhan, China
| | - Honggang Lv
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qian Gong
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jun Yang
- School of Information Engineering, Wuhan University of Technology, Wuhan, China.
| | - Zhongchun Liu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
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Li Y, Ye Z, Ran X, Luo J, Li H, Zhou P, Shen S, Li J. Association between depression and liver function biomarkers among US cancer survivors in NHANES 2005-2020. Sci Rep 2024; 14:27501. [PMID: 39528812 PMCID: PMC11555283 DOI: 10.1038/s41598-024-78890-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024] Open
Abstract
Depression frequently comorbidities with cancer, adversely affecting survivors' quality of life. Liver dysfunction is also prevalent among cancer survivors. However, the association between these two conditions remains unclear. This study aimed to explore the relationship between depression and liver function biomarkers in US cancer survivors. A cross-sectional study was conducted utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2005-2020. Cancer survivors were screened and depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), and 18 liver function biomarkers were included. Survey-weighted generalized linear models with multiple covariables adjusted were employed to examine the associations between depression and liver function biomarkers. A total of 4118 cancer survivors were included, representing a weighted population of 21 501 237. After adjusted with age, gender, race, marital status, education level, family income-to-poverty ratio, and number of cancer types, 8 biomarkers demonstrated positive correlations with depression in cancer survivors, included alanine aminotransferase (ALT, OR = 1.007, 95% CI: 1.000 to 1.013), alkaline phosphatase (ALP, 1.006 [1.002, 1.010]), gamma glutamyl transferase (GGT, 1.004 [1.001, 1.007]), lactate dehydrogenase (LDH, 1.004 [1.000, 1.009]), total protein (TP, 1.040 [1.009, 1.072]), globulin (GLB, 1.060 [1.030, 1.091]), total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) ratio (1.162 [1.050, 1.286]), and low-density lipoprotein cholesterol (LDL-C) to HDL-C ratio (1.243 [1.012, 1.526]); while 4 other biomarkers exhibited negative correlations, included HDL-C (0.988 [0.980, 0.997]), total bilirubin (TBi, 0.501 [0.284, 0.883]), aspartate aminotransferase (AST) to ALT ratio (0.588 [0.351, 0.986]), albumin (ALB) to GLB ratio (0.384 [0.229, 0.642]). Following sensitivity analysis, 5 biomarkers included LDH, HDL-C, TBi, AST/ALT and LDL-C/HDL-C lost their statistical significance for the association. This study identified certain associations between 7 liver function biomarkers and depression in US cancer survivors. Further research, particularly prospective longitudinal studies, is warranted to elucidate the causal relationships and explore the potential of improving liver function for the management of depression in cancer patients.
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Affiliation(s)
- Yanlong Li
- The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Zhikang Ye
- The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China
| | - Xingyu Ran
- The Second Clinical College, Heilongjiang University of Chinese Medicine, Harbin, 150000, China
| | - Jintian Luo
- The Second Clinical College, Heilongjiang University of Chinese Medicine, Harbin, 150000, China
| | - Hui Li
- The Second Clinical College, Heilongjiang University of Chinese Medicine, Harbin, 150000, China
| | - Peng Zhou
- The Second Clinical College, Heilongjiang University of Chinese Medicine, Harbin, 150000, China
| | - Si Shen
- Heilongjiang Academy of Chinese Medical Sciences, Harbin, 150000, China
| | - Jing Li
- Integrative Cancer Centre, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
- Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou, 510000, China.
- Department of Rehabilitation, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 510000, Guangzhou, China.
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Gao Y, Ling Y, Li J, Xu Y, Ge J, Xia Q. Neuropathological implication of high blood bilirubin in patients and model rats with depression. Brain Res Bull 2024; 215:111028. [PMID: 38992775 DOI: 10.1016/j.brainresbull.2024.111028] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 07/02/2024] [Accepted: 07/04/2024] [Indexed: 07/13/2024]
Abstract
PURPOSE Elevated bilirubin levels have been associated with major depressive disorder (MDD); however, the exact impact of bilirubin on MDD and the underlying molecular mechanisms remain unclear. Here, we explored the influence of bilirubin on MDD and sought to identify the mechanisms via which bilirubin induces depressive-like behavior. PATIENTS AND METHODS Forty patients who were diagnosed with MDD and received treatment with selective serotonin reuptake inhibitors (SSRIs) were included, with 43 healthy volunteers serving as controls. Clinical symptoms were evaluated using Hamilton depression rating scale-24 (HAMD-24) and the Hamilton anxiety rating scale. Serum concentrations of total bilirubin (TBIL) and indirect bilirubin (IBIL) were measured at baseline and after treatment using an automated biochemical analyzer. The connection between clinical symptoms and TBIL or IBIL was examined using Pearson correlation. Chronic restraint stress (CRS) was employed to generate a rat model of depression. TBIL, IBIL in rat serum were measured by ELISA. Reactive oxygen species (ROS) contents in rat hippocampal tissues were quantified by flow cytometry. The levels of microglial markers and the extent of neuronal damage in the rat hippocampus were assessed by immunofluorescence and transmission electron microscopy, respectively. RESULTS Serum TBIL and IBIL levels were higher in patients with MDD than in the healthy controls. After treatment with SSRIs, the serum levels of TBIL and IBIL in MDD patients were significantly reduced. The levels of TBIL and IBIL were associated with HAMD-24 in MDD patients. Compared with the controls, the serum levels of TBIL, IBIL and the hippocampal ROS contents were elevated in CRS-exposed rats. Fluoxetine lowered inflammatory factor levels, mitigated oxidative stress. CONCLUSION Our findings indicate a possible correlation between elevated serum bilirubin and depressive symptoms. Increases in ROS levels, along with neuronal damage, may represent pathological mechanisms underlying MDD.
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Affiliation(s)
- Yejun Gao
- School of Pharmacy, Anhui Medical University, Hefei, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Hefei Fourth People's Hospital, Hefei, China; Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China; Anhui Clinical Research Center for Mental Disorders, Hefei, China; Anhui Mental Health Center, Hefei, China.
| | - Yian Ling
- Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Hefei Fourth People's Hospital, Hefei, China; Anhui Mental Health Center, Hefei, China.
| | - Jing Li
- School of Pharmacy, Anhui Medical University, Hefei, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Hefei Fourth People's Hospital, Hefei, China; Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China; Anhui Clinical Research Center for Mental Disorders, Hefei, China; Anhui Mental Health Center, Hefei, China.
| | - Yayun Xu
- School of Pharmacy, Anhui Medical University, Hefei, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
| | - Jinfang Ge
- School of Pharmacy, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Hefei, China; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
| | - Qingrong Xia
- School of Pharmacy, Anhui Medical University, Hefei, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei, China; Hefei Fourth People's Hospital, Hefei, China; Psychopharmacology Research Laboratory, Anhui Mental Health Center, Hefei, China; Anhui Clinical Research Center for Mental Disorders, Hefei, China; Anhui Mental Health Center, Hefei, China.
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Ye ML, Wang JK. Association of total bilirubin with depression risk in adults with diabetes: A cross-sectional study. World J Clin Cases 2024; 12:3428-3437. [PMID: 38983435 PMCID: PMC11229937 DOI: 10.12998/wjcc.v12.i18.3428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/30/2024] [Accepted: 05/17/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Individuals with diabetes mellitus are more likely to experience depression, although most patients remain undiagnosed. The relation between total bilirubin and depression has been increasingly discussed, but limited studies have examined the association of total bilirubin with depression risk in adults with diabetes, which warrants attention. AIM To investigate the association between total bilirubin levels and the risk of depression in adults with diabetes. METHODS The study included adults with diabetes from the National Health and Nutrition Examination Survey 2007-2018. Depression was determined using the Patient Health Questionnaire-9. Multivariable logistic regression, propensity score-matched analysis and restricted cubic spline models were utilized to investigate the association between total bilirubin levels and depression risk in adults with diabetes. RESULTS The study included 4758 adults with diabetes, of whom 602 (12.7%) were diagnosed with depression. After adjusting for covariates, we found that diabetic adults with lower total bilirubin levels had a higher risk of depression (OR = 1.230, 95%CI: 1.006-1.503, P = 0.043). This association was further confirmed after propensity score matching (OR = 1.303, 95%CI: 1.034-1.641, P = 0.025). Subgroup analyses showed no significant dependence of age, body mass index, sex, race or hypertension on this association. Restricted cubic spline models displayed an inverted U-shaped association of total bilirubin levels with depression risk within the lower range of total bilirubin levels. The depression risk heightened with the increasing levels of total bilirubin, reaching the highest risk at 6.81 μmol/L and decreasing thereafter. CONCLUSION In adults with diabetes, those with lower levels of total bilirubin were more likely to have depressive symptoms. Serum total bilirubin levels may be used as an additional indicator to assess depression risk in adults with diabetes.
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Affiliation(s)
- Man-Li Ye
- Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Jie-Ke Wang
- Department of Hand and Plastic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
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Lin C, Yeh FC, Glynn NW, Gmelin T, Wei YC, Chen YL, Huang CM, Shyu YC, Chen CK. Associations of depression and perceived physical fatigability with white matter integrity in older adults. Psychiatry Res Neuroimaging 2024; 340:111793. [PMID: 38373367 PMCID: PMC11842153 DOI: 10.1016/j.pscychresns.2024.111793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 01/31/2024] [Accepted: 02/07/2024] [Indexed: 02/21/2024]
Abstract
BACKGROUNDS Fatigability is prevalent in older adults. However, it is often associated with depressed mood. We aim to investigate these two psychobehavioral constructs by examining their underpinning of white matter structures in the brain and their associations with different medical conditions. METHODS Twenty-seven older adults with late-life depression (LLD) and 34 cognitively normal controls (CN) underwent multi-shell diffusion MRI. Fatigability was measured with the Pittsburgh Fatigability Scale. We examined white matter integrity by measuring the quantitative anisotropy (QA), a fiber tracking parameter with better accuracy than the traditional imaging technique. RESULTS We found those with LLD had lower QA in the 2nd branch of the left superior longitudinal fasciculus (SLF-II), and those with more physical fatigability had lower QA in more widespread brain regions. In tracts associated with more physical fatigability, the lower QA in left acoustic radiation and left superior thalamic radiation correlated with higher blood glucose (r = - 0.46 and - 0.49). In tracts associated with depression, lower QA in left SLF-II correlated with higher bilirubin level (r = - 0.58). DISCUSSION Depression and fatigability were associated with various white matter integrity changes, which correlated with biochemistry biomarkers all related to inflammation.
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Affiliation(s)
- Chemin Lin
- Department of Psychiatry, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan; College of Medicine, Chang Gung University, Taoyuan County, Taiwan; Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Keelung, Taiwan
| | - Fang-Cheng Yeh
- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Nancy W Glynn
- Center for Aging and Population Health, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Theresa Gmelin
- Center for Aging and Population Health, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Yi-Chia Wei
- College of Medicine, Chang Gung University, Taoyuan County, Taiwan; Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Keelung, Taiwan; Department of Neurology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan
| | - Yao-Liang Chen
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Mao Huang
- Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Yu-Chiau Shyu
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Keelung, Taiwan
| | - Chih-Ken Chen
- Department of Psychiatry, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan; College of Medicine, Chang Gung University, Taoyuan County, Taiwan; Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Keelung, Taiwan.
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Liu Y, Wang Z, Li D, Lv B. Bilirubin and postpartum depression: an observational and Mendelian randomization study. Front Psychiatry 2024; 15:1277415. [PMID: 38525255 PMCID: PMC10957769 DOI: 10.3389/fpsyt.2024.1277415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 02/12/2024] [Indexed: 03/26/2024] Open
Abstract
Background Postpartum depression (PPD) is one of the most common complications of delivery and is usually disregarded. Several risk factors of PPD have been identified, but its pathogenesis has not been completely understood. Serum bilirubin has been found to be a predictor of depression, whose relationship with PPD has not been investigated. Methods Observational research was performed followed by a two-sample Mendelian randomization (MR) analysis. From 2017 to 2020, the clinical data of pregnant women were retrospectively extracted. Logistic regression and random forest algorithm were employed to assess the risk factors of PPD, including the serum levels of total bilirubin and direct bilirubin. To further explore their potential causality, univariable and multivariable Mendelian randomization (MVMR) were conducted. Sensitivity analyses for MR were performed to test the robustness of causal inference. Results A total of 1,810 patients were included in the PPD cohort, of which 631 (34.87%) were diagnosed with PPD. Compared with the control group, PPD patients had a significantly lower level of total bilirubin (9.2 μmol/L, IQR 7.7, 11.0 in PPD; 9.7 μmol/L, IQR 8.0, 12.0 in control, P < 0.001) and direct bilirubin (2.0 μmol/L, IQR 1.6, 2.6 in PPD; 2.2 μmol/L, IQR 1.7, 2.9 in control, P < 0.003). The prediction model identified eight independent predictive factors of PPD, in which elevated total bilirubin served as a protective factor (OR = 0.94, 95% CI 0.90-0.99, P = 0.024). In the MR analyses, genetically predicted total bilirubin was associated with decreased risk of PPD (IVW: OR = 0.86, 95% CI 0.76-0.97, P = 0.006), which remained consistent after adjusting educational attainment, income, and gestational diabetes mellitus. Conversely, there is a lack of solid evidence to support the causal relationship between PPD and bilirubin. Conclusion Our results suggested that decreased total bilirubin was associated with the incidence of PPD. Future studies are warranted to investigate its potential mechanisms and illuminate the pathogenesis of PPD.
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Affiliation(s)
- Yi Liu
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
- Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhihao Wang
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China
| | - Duo Li
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Lv
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
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Geng D, Wu B, Lin Y, Chen J, Tang W, Liu Y, He J. High total bilirubin-to-uric acid ratio predicts poor sleep quality after acute ischemic stroke: a prospective nested case-control study. Psychogeriatrics 2023; 23:897-907. [PMID: 37525331 DOI: 10.1111/psyg.12992] [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: 03/14/2023] [Revised: 05/11/2023] [Accepted: 05/29/2023] [Indexed: 08/02/2023]
Abstract
BACKGROUND Sleep disorders are prevalent after stroke, resulting in high recurrence rates and mortality. But the biomarkers of sleep disorders in stroke patients remain to be elucidated. This study aimed to explore the relationship between total bilirubin-to-uric acid ratio (TUR) and sleep quality after acute ischemic stroke (AIS). METHODS Three hundred twenty-six AIS patients were recruited and followed up 1 month after stroke in our study. Serum total bilirubin and uric acid levels were obtained within 24 h after admission. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality 1 month after stroke. We conducted receiver operating characteristic (ROC) curve analysis and screened the optimal biomarker to differentiate sleep disorders after stroke. Then the TUR was stratified according to the best cut-off value (0.036) of the ROC and further analysed by binary logistic regression analysis. Additionally, the interaction was used to explore the difference in its effect on post-stroke sleep quality in different subgroups. RESULTS Three hundred thirty-one patients (40.2%) were considered as having poor sleep quality during the one-month follow-up. Compared to patients with good sleep, patients with poor sleep were more likely to have higher TUR (IQR), 0.05 (0.03-0.06) versus 0.03 (0.02-0.04), P < 0.001. After adjusting for confounding factors, binary regression analysis demonstrated that a high TUR (≥0.036) was independently related to post-stroke poor sleep quality (OR = 3.75, 95% CI = 2.02-6.96, P < 0.001). CONCLUSIONS High TUR is associated with an increased risk of poor sleep quality in AIS patients, especially in females, diabetics, and patients with hyperlipidaemia.
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Affiliation(s)
- Dandan Geng
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Beilan Wu
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yisi Lin
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jiahao Chen
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Wenjie Tang
- The First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, China
| | - Yuntao Liu
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jincai He
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Gong J, Zhang Y, Zhong X, Zhang Y, Chen Y, Wang H. Liver function test indices-based prediction model for post-stroke depression: a multicenter, retrospective study. BMC Med Inform Decis Mak 2023; 23:127. [PMID: 37468891 PMCID: PMC10357817 DOI: 10.1186/s12911-023-02241-0] [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: 12/21/2022] [Accepted: 07/13/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Post-stroke depression (PSD) was one of the most prevalent and serious neuropsychiatric effects after stroke. Nevertheless, the association between liver function test indices and PSD remains elusive, and there is a lack of effective prediction tools. The purpose of this study was to explore the relationship between the liver function test indices and PSD, and construct a prediction model for PSD. METHODS All patients were selected from seven medical institutions of Chongqing Medical University from 2015 to 2021. Variables including demographic characteristics and liver function test indices were collected from the hospital electronic medical record system. Univariate analysis, least absolute shrinkage and selection operator (LASSO) and logistic regression analysis were used to screen the predictors. Subsequently, logistic regression, random forest (RF), extreme gradient boosting (XGBoost), gradient boosting decision tree (GBDT), categorical boosting (CatBoost) and support vector machine (SVM) were adopted to build the prediction model. Furthermore, a series of evaluation indicators such as area under curve (AUC), sensitivity, specificity, F1 were used to assess the performance of the prediction model. RESULTS A total of 464 PSD and 1621 stroke patients met the inclusion criteria. Six liver function test items, namely AST, ALT, TBA, TBil, TP, ALB/GLB, were closely associated with PSD, and included for the construction of the prediction model. In the test set, logistic regression model owns the AUC of 0.697. Compared with the other four machine learning models, the GBDT model has the best predictive performance (F1 = 0.498, AUC = 0.761) and was chosen to establish the prediction tool. CONCLUSIONS The prediction model constructed using these six predictors with GBDT algorithm displayed a promising prediction ability, which could be used for the participating hospital units or individuals by mobile phone or computer.
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Affiliation(s)
- Jun Gong
- Department of Information Center, University-town Hospital of Chongqing Medical University, Chongqing, China
- Medical Data Science Academy, Chongqing Medical University, Chongqing, China
| | - Yalian Zhang
- Department of Rehabilitation, Children's Hospital of Chongqing Medical University, Chongqing, China
- National Clinical Research Center for Child Health and Disorders, Chongqing, China
| | - Xiaogang Zhong
- NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- College of Basic Medicine, Chongqing Medical University, Chongqing, China
| | - Yi Zhang
- Department of Information Center, Rehabilitation Hospital of Chongqing Medical University, Chongqing, China
| | - Yanhua Chen
- Department of Pain and Rehabilitation, The Seventh People's Hospital of Chongqing, Chongqing, China.
| | - Huilai Wang
- Department of Information Center, University-town Hospital of Chongqing Medical University, Chongqing, China.
- Medical Data Science Academy, Chongqing Medical University, Chongqing, China.
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Sun S, Li Z, Xiao Q, Tan S, Hu B, Jin H. An updated review on prediction and preventive treatment of post-stroke depression. Expert Rev Neurother 2023; 23:721-739. [PMID: 37427452 DOI: 10.1080/14737175.2023.2234081] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 07/04/2023] [Indexed: 07/11/2023]
Abstract
INTRODUCTION Post-stroke depression (PSD), one of the most common complications following stroke, affects approximately one-third of stroke patients and is significantly associated with increased disability and mortality as well as decreased quality of life, which makes it an important public health concern. Treatment of PSD significantly ameliorates depressive symptoms and improves the prognosis of stroke. AREAS COVERED The authors discuss the critical aspects of the clinical application of prediction and preventive treatment of PSD. Then, the authors update the biological factors associated with the onset of PSD. Furthermore, they summarize the recent progress in pharmacological preventive treatment in clinical trials and propose potential treatment targets. The authors also discuss the current roadblocks in the preventive treatment of PSD. Finally, the authors put postulate potential directions for future studies so as to discover accurate predictors and provide individualized preventive treatment. EXPERT OPINION Sorting out high-risk PSD patients using reliable predictors will greatly assist PSD management. Indeed, some predictors not only predict the incidence of PSD but also predict prognosis, which indicates that they might also aid the development of an individualized treatment scheme. Preventive application of antidepressants may also be considered.
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Affiliation(s)
- Shuai Sun
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhifang Li
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qinghui Xiao
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Senwei Tan
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Bo Hu
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Huijuan Jin
- Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Wang Y, Sun W, Miao J, Zhu Z, Liang W, Qiu X, Pan C, Li G, Lan Y, Zhao X, Xu Y. Nomogram including indirect bilirubin for the prediction of post-stroke depression at 3 months after mild acute ischemic stroke onset. Front Neurol 2023; 14:1093146. [PMID: 36846136 PMCID: PMC9945073 DOI: 10.3389/fneur.2023.1093146] [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: 11/08/2022] [Accepted: 01/16/2023] [Indexed: 02/11/2023] Open
Abstract
Background Post-stroke depression (PSD) has been proven to be associated with stroke severity. Thus, we hypothesized that the prevalence of PSD would be lower in patients with mild stroke. We aim to explore predictors of depression at 3 months after mild acute ischemic stroke (MAIS) onset and to develop a practical and convenient prediction model for the early identification of patients at high risk. Methods A total of 519 patients with MAIS were consecutively recruited from three hospitals in Wuhan city, Hubei province. MAIS was defined as a National Institute of Health Stroke Scale (NIHSS) score of ≤5 at admission. Meeting the DSM-V diagnostic criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) score of >7 at their 3-month follow-up were considered the primary outcomes. A multivariable logistic regression model was used to determine the factors adjusted for potential confounders, and all independent predictors were brought into the construction of a nomogram to predict PSD. Results The prevalence of PSD is up to 32% at 3 months after MAIS onset. After adjusting for potential confounders, indirect bilirubin (p = 0.029), physical activity (p = 0.001), smoking (p = 0.025), hospitalization days (p = 0.014), neuroticism (p < 0.001), and MMSE (p < 0.001) remained independently and significantly related with PSD. The concordance index (C-index) of the nomogram jointly constructed by the aforementioned six factors was 0.723 (95% CI: 0.678-0.768). Conclusion The prevalence of PSD seems equally high even if the ischemic stroke is mild, which calls for great concern from clinicians. In addition, our study found that a higher level of indirect bilirubin can lower the risk of PSD. This finding may provide a potential new approach to PSD treatment. Furthermore, the nomogram including bilirubin is convenient and practical to predict PSD after MAIS onset.
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Affiliation(s)
- Yanyan Wang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenzhe Sun
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jinfeng Miao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhou Zhu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenwen Liang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiuli Qiu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Chensheng Pan
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Guo Li
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yan Lan
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xin Zhao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yi Xu
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Lan Y, Pan C, Qiu X, Miao J, Sun W, Li G, Zhao X, Zhu Z, Zhu S. Nomogram for Persistent Post-Stroke Depression and Decision Curve Analysis. Clin Interv Aging 2022; 17:393-403. [PMID: 35411138 PMCID: PMC8994611 DOI: 10.2147/cia.s357639] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 03/30/2022] [Indexed: 12/15/2022] Open
Abstract
Purpose Patients and Methods Results Conclusion
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Affiliation(s)
- Yan Lan
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Chensheng Pan
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Xiuli Qiu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Jinfeng Miao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Wenzhe Sun
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Guo Li
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Xin Zhao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Zhou Zhu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
- Correspondence: Zhou Zhu; Suiqiang Zhu, Tel +86-18171081029; +86-13035101141, Email ;
| | - Suiqiang Zhu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
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Qiu X, Wang H, Lan Y, Miao J, Pan C, Sun W, Li G, Wang Y, Zhao X, Zhu Z, Zhu S. Blood biomarkers of post-stroke depression after minor stroke at three months in males and females. BMC Psychiatry 2022; 22:162. [PMID: 35241021 PMCID: PMC8896360 DOI: 10.1186/s12888-022-03805-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 02/22/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. Studies on the underlying mechanisms and biological markers of sex differences in PSD are of great significance, but there are still few such studies. Therefore, the main objective of this study was to investigate the association of biomarkers with PSD at 3 months after minor stroke in men and women. METHODS This was a prospective multicenter cohort study that enrolled 530 patients with minor stroke (males, 415; females, 115). Demographic information and blood samples of patients were collected within 24 h of admission, and followed up at 3 months after stroke onset. PSD was defined as a depressive disorder due to another medical condition with depressive features, major depressive-like episode, or mixed-mood features according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V). Univariate analysis was performed using the chi-square test, Mann-Whitney U test, or t-test. Partial least-squares discriminant analysis (PLS-DA) was used to distinguish between patients with and without PSD. Factors with variable importance for projection (VIP) > 1.0 were classified as the most important factors in the model segregation. RESULTS The PLS-DA model mainly included component 1 and component 2 for males and females. For males, the model could explain 13% and 16.9% of the variables, respectively, and 29.9% of the variables in total; the most meaningful predictors were exercise habit and fibrinogen level. For females, the model could explain 15.7% and 10.5% of the variables, respectively, and 26.2% of the variables in total; the most meaningful predictors in the model were brain-derived neurotrophic factor (BDNF), magnesium and free T3. Fibrinogen was positively correlated with the Hamilton Depression Scale-17 items (HAMD-17) score. BDNF, magnesium, and free T3 levels were negatively correlated with the HAMD-17 score. CONCLUSIONS This was a prospective cohort study. The most important markers found to be affecting PSD at 3 months were fibrinogen in males, and free T3, magnesium, and BDNF in females. TRIAL REGISTRATION ChiCTR-ROC-17013993 .
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Affiliation(s)
- Xiuli Qiu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - He Wang
- Department of Medical Affair, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Yan Lan
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Jinfeng Miao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Chensheng Pan
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Wenzhe Sun
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Guo Li
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Yanyan Wang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Xin Zhao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Zhou Zhu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Suiqiang Zhu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
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Cao J, Qiu W, Yu Y, Li N, Wu H, Chen Z. The association between serum albumin and depression in chronic liver disease may differ by liver histology. BMC Psychiatry 2022; 22:5. [PMID: 34983435 PMCID: PMC8729006 DOI: 10.1186/s12888-021-03647-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 12/06/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND There are conflicting results regarding the association between chronic liver disease (CLD) and depression and the underlying biological mechanisms are lack of investigation. To address the impact of depression and its effects on the management of CLD, its biological marker is critical to be identified. The present study explored the association between serum albumin and depression in CLD patients and whether the association varied in different liver histological stages. METHODS Based on the United States National Health and Nutrition Examination Survey 2017-2018, the data of serum albumin and depressive symptoms from 627 participants with CLD were used. Depression symptoms were assessed with the nine-item Patient Health Questionnaire (PHQ-9). We used multivariate linear regression to evaluate the association between serum albumin and PHQ-9 scores. Stratified analysis was performed according to the liver histology examined by vibration controlled transient elastography. RESULTS Serum albumin level was inversely associated with PHQ-9 scores in the multivariate regression model after adjusting for mainly potential confounders (β = - 1.113, 95% CI: - 2.065 to - 0.162, P = 0.0221). In the subgroup analysis stratified by gender, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), the inverse association remained significant in female (β = - 2.002, 95% CI: - 3.515 to - 0.489, P = 0.0100), patients with CAP < 274 dB/m (β = - 2.215, 95% CI: - 3.621 to - 0.808, P = 0.0023) and patients with LSM ≥8.2 kPa (β = - 4.074, 95% CI: - 6.237 to - 1.911, P = 0.0003). Moreover, the association was much stronger when the serum albumin was higher than 3.4 g/dL among patients with LSM ≥8.2 kPa (β = - 4.835, 95% CI: - 7.137 to - 2.533, P < 0.0001). CONCLUSION Our study revealed an inverse association between serum albumin and depression in CLD patients and this association differed according to liver histological changes. Serum albumin could be a warning marker for depressive symptoms in CLD patients. It is essential for taking corresponding intervention strategies.
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Affiliation(s)
- Junyan Cao
- grid.412558.f0000 0004 1762 1794Department of Medical Ultrasonics, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630 China
| | - Weihong Qiu
- grid.412558.f0000 0004 1762 1794Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630 China
| | - Yong Yu
- grid.412558.f0000 0004 1762 1794Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630 China
| | - Na Li
- grid.412558.f0000 0004 1762 1794Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630 China
| | - Huixiang Wu
- grid.412558.f0000 0004 1762 1794Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630 China
| | - Zhaocong Chen
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China.
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Wang Y, Sun W, Miao J, Qiu X, Lan Y, Pan C, Li G, Zhao X, Zhu Z, Zhu S. Higher fasting C-peptide is associated with post-stroke depression: a multicenter prospective cohort study. BMC Neurol 2021; 21:383. [PMID: 34607565 PMCID: PMC8489065 DOI: 10.1186/s12883-021-02413-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 09/23/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Fasting C-peptide (FCP) has been shown to play an important role in the pathophysiology of mood disorders including depression and schizophrenia, but it is unknown whether it also predicts post-stroke depression (PSD). This study examined the association between FCP and PSD at 6 months after acute ischemic-stroke onset among Chinese subjects. METHODS A total of 656 stroke patients were consecutively recruited from three hospitals of Wuhan city, Hubei province. Clinical and laboratory data were collected on admission. PSD status was evaluated by DSM-V criteria and 17-item Hamilton Rating Scale for Depression (HAMD-17) at 6 months after acute ischemic stroke. The χ2-test, Mann-Whitney U-test, and t-test were used to check for statistical significance. Multivariate logistic regression model was used to explore independent predictor of PSD. RESULTS In the univariate analysis, significant differences were found between the PSD and non-PSD groups in terms of FCP level (p = 0.009). After multivariate adjustments, FCP remained a significant independent predictor of PSD, with an adjusted odds ratio of 1.179 (95%CI: 1.040-1.337, p = 0.010). CONCLUSIONS Higher FCP levels on admission were found to be associated with PSD at 6 months after acute ischemic-stroke onset. For stroke patients, doctors should pay attention to the baseline FCP for screening high-risk PSD in clinical practice.
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Affiliation(s)
- Yanyan Wang
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Wenzhe Sun
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Jinfeng Miao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Xiuli Qiu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Yan Lan
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Chensheng Pan
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Guo Li
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Xin Zhao
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Zhou Zhu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
| | - Suiqiang Zhu
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 Hubei China
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15
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Lin Z, Lawrence WR, Huang Y, Lin Q, Gao Y. Classifying depression using blood biomarkers: A large population study. J Psychiatr Res 2021; 140:364-372. [PMID: 34144440 DOI: 10.1016/j.jpsychires.2021.05.070] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 05/06/2021] [Accepted: 05/29/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Depression is a common mood disorder characterized by persistent low mood or lack of interest in activities. People with other chronic medical conditions such as obesity and diabetes are at greater risk of depression. Diagnosing depression can be a challenge for primary care providers and others who lack specialized training for these disorders and have insufficient time for in-depth clinical evaluation. We aimed to create a more objective low-cost diagnostic tool based on patients' characteristics and blood biomarkers. METHODS Blood biomarker results were obtained from the National Health and Nutrition Examination Survey (NHANES, 2007-2016). A prediction model utilizing random forest (RF) in NHANES (2007-2014) to identify depression was derived and validated internally using out-of-bag technique. Afterwards, the model was validated externally using a validation dataset (NHANES, 2015-2016). We performed four subgroup comparisons (full dataset, overweight and obesity dataset (BMI≥25), diabetes dataset, and metabolic syndrome dataset) then selected features using backward feature selection from RF. RESULTS Family income, Gamma-glutamyl transferase (GGT), glucose, Triglyceride, red cell distribution width (RDW), creatinine, Basophils count or percent, Eosinophils count or percent, and Bilirubin were the most important features from four models. In the training set, AUC from full, overweight and obesity, diabetes, and metabolic syndrome datasets were 0.83, 0.80, 0.82, and 0.82, respectively. In the validation set, AUC were 0.69, 0.63, 0.66, and 0.64, respectively. CONCLUSION Results of routine blood laboratory tests had good predictive value for distinguishing depression cases from control groups not only in the general population, but also individuals with metabolism-related chronic diseases.
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Affiliation(s)
- Ziqiang Lin
- Department of Preventive Medicine, School of Basic Medicine and Public Health, Jinan University, Guangzhou, 510632, China; Department of Psychiatry, New York University School of Medicine, One Park Ave, New York, NY, 10016, USA; Department of Mathematics and Statistics, College of Arts and Sciences, University at Albany, State University of New York, 1400 Washington Ave, Albany, NY, 12222, USA
| | - Wayne R Lawrence
- Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, 1 University Place, Rensselaer, NY, 12144, USA
| | - Yanhong Huang
- Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, China
| | - Qiaoxuan Lin
- Department of Statistics, Guangzhou Health Technology Identification & Human Resources Assessment Center, Guangzhou, Guangdong, 510000, China
| | - Yanhui Gao
- Department of Preventive Medicine, School of Basic Medicine and Public Health, Jinan University, Guangzhou, 510632, China; Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, China.
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Li Y, Dong Y, Meng L, Yu P, Zhao P, Gong M, Gao Q, Shi H, Meng C, Gao Y. Effects of Exogenous Biliverdin Treatment on Neurobehaviors in Mice. Biol Pharm Bull 2021; 44:325-331. [PMID: 33642542 DOI: 10.1248/bpb.b20-00340] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The neuroprotective effects of heme oxygenase (HO) have been well investigated. The potential effects of exogenous supplementation of biliverdin (BVD), one of the main products catalyzed by HO, on neurobehaviors are still largely unknown. The present study aimed to investigate the effects of BVD treatment on depression, anxiety, and memory in adult mice. Mice were injected with BVD through tail vein daily for a total 5 d, and depression- and anxiety-like behaviors were conducted by using open field test (OFT), novelty suppressed feeding (NSF), forced swimming test (FST) and tail suspension test (TST) since the third day of BVD administration. Novel object recognition (NOR) paradigm was used for memory formation test. After the final test, serum and hippocampal levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) of mice were analyzed by enzyme-linked immunosorbent assay (ELISA). The results showed that BVD treatment at low dose (2 mg/kg) induced depression-like behaviors, and high dose (8 mg/kg) BVD injection increased anxiety-like behaviors and impaired memory formation in mice. ELISA data showed that BVD treatment significantly increased hippocampal IL-6 and TNF-α level while only decreasing serum IL-6 level of mice. The present data suggest that exogenous BVD treatment induced depression- and anxiety-like phenotypes, which may be related to inflammatory factors, providing BVD may be a potential target for the prevention of mental disorders.
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Affiliation(s)
- Yueyi Li
- Neuroscience Research Center, Institute of Medical and Health Science of HeBMU, Hebei Medical University
| | - Yan Dong
- Intensive Care Unit of Hebei Hospital of Traditional Chinese Medicine, Hebei University of Chinese Medicine
| | - Li Meng
- Neuroscience Research Center, Institute of Medical and Health Science of HeBMU, Hebei Medical University
| | - Panpan Yu
- Department of State Assets and Laboratory Administrative, Hebei Medical University
| | - Penghui Zhao
- Neuroscience Research Center, Institute of Medical and Health Science of HeBMU, Hebei Medical University
| | - Miao Gong
- Neuroscience Research Center, Institute of Medical and Health Science of HeBMU, Hebei Medical University
| | - Qiang Gao
- Neuroscience Research Center, Institute of Medical and Health Science of HeBMU, Hebei Medical University
| | - Haishui Shi
- Neuroscience Research Center, Institute of Medical and Health Science of HeBMU, Hebei Medical University
- Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medicinal University
- Hebei Key Laboratory of Neurophysiology, Hebei Medicinal University
| | - Cuili Meng
- Department of Biochemistry, School of Basic Medicine, Xingtai Medical College
| | - Yuan Gao
- Neuroscience Research Center, Institute of Medical and Health Science of HeBMU, Hebei Medical University
- Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medicinal University
- Hebei Key Laboratory of Neurophysiology, Hebei Medicinal University
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Sarkar A, Sarmah D, Datta A, Kaur H, Jagtap P, Raut S, Shah B, Singh U, Baidya F, Bohra M, Kalia K, Borah A, Wang X, Dave KR, Yavagal DR, Bhattacharya P. Post-stroke depression: Chaos to exposition. Brain Res Bull 2020; 168:74-88. [PMID: 33359639 DOI: 10.1016/j.brainresbull.2020.12.012] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 12/09/2020] [Accepted: 12/18/2020] [Indexed: 12/12/2022]
Abstract
Cerebral ischemia contributes to significant disabilities worldwide, impairing cognitive function and motor coordination in affected individuals. Stroke has severe neuropsychological outcomes, the major one being a stroke. Stroke survivors begin to show symptoms of depression within a few months of the incidence that overtime progresses to become a long-term ailment. As the pathophysiology for the progression of the disease is multifactorial and complex, it limits the understanding of the disease mechanism completely. Meta-analyses and randomized clinical trials have shown that intervening early with tricyclic antidepressants and selective serotonin receptor inhibitors can be effective. However, these pharmacotherapies possess several limitations that have given rise to newer approaches such as brain stimulation, psychotherapy and rehabilitation therapy, which in today's time are gaining attention for their beneficial results in post-stroke depression (PSD). The present review highlights numerous factors like lesion location, inflammatory mediators and genetic abnormalities that play a crucial role in the development of depression in stroke patients. Further, we have also discussed various mechanisms involved in post-stroke depression (PSD) and strategies for early detection and diagnosis using biomarkers that may revolutionize treatment for the affected population. Towards the end, along with the preclinical scenario, we have also discussed the various treatment approaches like pharmacotherapy, traditional medicines, psychotherapy, electrical stimulation and microRNAs being utilized for effectively managing PSD.
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Affiliation(s)
- Ankan Sarkar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Deepaneeta Sarmah
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Aishika Datta
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Harpreet Kaur
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Priya Jagtap
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Swapnil Raut
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Birva Shah
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Upasna Singh
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Falguni Baidya
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Mariya Bohra
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Kiran Kalia
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India
| | - Anupom Borah
- Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, India
| | - Xin Wang
- Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Kunjan R Dave
- Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Dileep R Yavagal
- Department of Neurology and Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Pallab Bhattacharya
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat, India.
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Hamilton PJ, Chen EY, Tolstikov V, Peña CJ, Picone JA, Shah P, Panagopoulos K, Strat AN, Walker DM, Lorsch ZS, Robinson HL, Mervosh NL, Kiraly DD, Sarangarajan R, Narain NR, Kiebish MA, Nestler EJ. Chronic stress and antidepressant treatment alter purine metabolism and beta oxidation within mouse brain and serum. Sci Rep 2020; 10:18134. [PMID: 33093530 PMCID: PMC7582177 DOI: 10.1038/s41598-020-75114-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 10/09/2020] [Indexed: 12/14/2022] Open
Abstract
Major depressive disorder (MDD) is a complex condition with unclear pathophysiology. Molecular disruptions within limbic brain regions and the periphery contribute to depression symptomatology and a more complete understanding the diversity of molecular changes that occur in these tissues may guide the development of more efficacious antidepressant treatments. Here, we utilized a mouse chronic social stress model for the study of MDD and performed metabolomic, lipidomic, and proteomic profiling on serum plus several brain regions (ventral hippocampus, nucleus accumbens, and medial prefrontal cortex) of susceptible, resilient, and unstressed control mice. To identify how commonly used tricyclic antidepressants impact the molecular composition in these tissues, we treated stress-exposed mice with imipramine and repeated our multi-OMIC analyses. Proteomic analysis identified three serum proteins reduced in susceptible animals; lipidomic analysis detected differences in lipid species between resilient and susceptible animals in serum and brain; and metabolomic analysis revealed dysfunction of purine metabolism, beta oxidation, and antioxidants, which were differentially associated with stress susceptibility vs resilience by brain region. Antidepressant treatment ameliorated stress-induced behavioral abnormalities and affected key metabolites within outlined networks, most dramatically in the ventral hippocampus. This work presents a resource for chronic social stress-induced, tissue-specific changes in proteins, lipids, and metabolites and illuminates how molecular dysfunctions contribute to individual differences in stress sensitivity.
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Affiliation(s)
- Peter J Hamilton
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA. .,Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
| | - Emily Y Chen
- BERG LLC, 500 Old Connecticut Path, Framingham, MA, 01701, USA
| | | | - Catherine J Peña
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA
| | - Joseph A Picone
- Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, 23298, USA
| | - Punit Shah
- BERG LLC, 500 Old Connecticut Path, Framingham, MA, 01701, USA
| | | | - Ana N Strat
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA
| | - Deena M Walker
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA
| | - Zachary S Lorsch
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA
| | - Hannah L Robinson
- Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, 23298, USA
| | - Nicholas L Mervosh
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA
| | - Drew D Kiraly
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA
| | | | - Niven R Narain
- BERG LLC, 500 Old Connecticut Path, Framingham, MA, 01701, USA
| | | | - Eric J Nestler
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA
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Ghojazadeh M, Sagheb Asl E, Vahed N, Hassanpour R, Sanaie S, Mahmoodpoor A, Hosseini MS, Soleimanpour H. Determination of the Predictive Value of Serum Bilirubin in Patients with Ischemic Stroke: A Systematic Review. ARCHIVES OF NEUROSCIENCE 2020; 7. [DOI: 10.5812/ans.99302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
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Lin S, Luan X, He W, Ruan Y, Yuan C, Fan A, Chen X, He J. Post-Stroke Depression and Estimated Glomerular Filtration Rate: A Prospective Stroke Cohort. Neuropsychiatr Dis Treat 2020; 16:201-208. [PMID: 32021214 PMCID: PMC6982452 DOI: 10.2147/ndt.s225905] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Accepted: 11/12/2019] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Post-stroke depression (PSD) is a frequent comorbidity in patients presenting with acute ischemic stroke. Impaired kidney function has been associated with depression in non-stroke subjects. We would like to evaluate whether the estimated glomerular filtration rate (eGFR) on admission is associated with the development of PSD. PATIENTS AND METHODS Total of 268 patients with acute ischemic stroke were recruited and completed 1-month follow-up visit. eGFR was calculated from the serum creatinine value, race, age, and sex by using the chronic kidney disease epidemiology collaboration equation (CKD-EPI creatinine equation). The 17-item Hamilton Depression Scale was used to evaluate depression symptoms. Patients with a depression score of ≥7 were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for diagnosing post-stroke depression at 1 month. Meanwhile, 114 normal control subjects were also recruited. RESULTS Ninety-three (34.7%) patients were diagnosed as having PSD at 1 month. There was a significant intergroup difference in eGFR levels within 24 hrs after admission (F=13.608, p<0.001). The levels of eGFR within 24 hrs after admission were significantly lower in both non-PSD patients and PSD patients than in normal controls. In logistic regression, the level of eGFR (<82mL/min/1.73m2) was independently associated with increased risk of PSD even after adjusting for confounders (OR=2.328, 95% CI:1.092-4.965, p=0.029). CONCLUSION Reduced eGFR was found to be correlated with the development of PSD and it suggests the need for greater attentions and potential interventions for depression in patients with stroke and with reduced eGFR.
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Affiliation(s)
- Shasha Lin
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People's Republic of China
| | - Xiaoqian Luan
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People's Republic of China
| | - Weilei He
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People's Republic of China
| | - Yiting Ruan
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People's Republic of China
| | - Chengxiang Yuan
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People's Republic of China
| | - Aiyue Fan
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People's Republic of China
| | - Xiachan Chen
- Department of Neurology, Wenzhou 325000, Zhejiang Province, People's Republic of China
| | - Jincai He
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People's Republic of China
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Brichacek AL, Brown CM. Alkaline phosphatase: a potential biomarker for stroke and implications for treatment. Metab Brain Dis 2019; 34:3-19. [PMID: 30284677 PMCID: PMC6351214 DOI: 10.1007/s11011-018-0322-3] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 09/24/2018] [Indexed: 12/14/2022]
Abstract
Stroke is the fifth leading cause of death in the U.S., with more than 100,000 deaths annually. There are a multitude of risks associated with stroke, including aging, cardiovascular disease, hypertension, Alzheimer's disease (AD), and immune suppression. One of the many challenges, which has so far proven to be unsuccessful, is the identification of a cost-effective diagnostic or prognostic biomarker for stroke. Alkaline phosphatase (AP), an enzyme first discovered in the 1920s, has been evaluated as a potential biomarker in many disorders, including many of the co-morbidities associated with stroke. This review will examine the basic biology of AP, and its most common isoenzyme, tissue nonspecific alkaline phosphatase (TNAP), with a specific focus on the central nervous system. It examines the preclinical and clinical evidence which supports a potential role for AP in stroke and suggests potential mechanism(s) of action for AP isoenzymes in stroke. Lastly, the review speculates on the clinical utility of AP isoenzymes as potential blood biomarkers for stroke or as AP-targeted treatments for stroke patients.
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Affiliation(s)
- Allison L Brichacek
- Department of Microbiology, Immunology, and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9177, Morgantown, WV, 26506, USA
- Department of Neuroscience, Emergency Medicine, and Microbiology, Immunology and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9303, Morgantown, WV, 26506, USA
| | - Candice M Brown
- Department of Microbiology, Immunology, and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9177, Morgantown, WV, 26506, USA.
- Department of Neuroscience, Emergency Medicine, and Microbiology, Immunology and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9303, Morgantown, WV, 26506, USA.
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Boeck C, Gumpp AM, Koenig AM, Radermacher P, Karabatsiakis A, Kolassa IT. The Association of Childhood Maltreatment With Lipid Peroxidation and DNA Damage in Postpartum Women. Front Psychiatry 2019; 10:23. [PMID: 30833908 PMCID: PMC6387959 DOI: 10.3389/fpsyt.2019.00023] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 01/14/2019] [Indexed: 12/21/2022] Open
Abstract
Childhood maltreatment (CM) is associated with an increased risk for the development of psychiatric and somatic disorders in later life. A potential link could be oxidative stress, which is defined as the imbalance between the amount of reactive oxygen species (ROS) and the neutralizing capacity of anti-oxidative defense systems. However, the findings linking CM with oxidative stress have been inconsistent so far. In this study, we aimed to further explore this association by investigating biological markers of DNA and lipid damage due to oxidation in a comprehensive approach over two study cohorts of postpartum women (study cohort I and study cohort II). The severity of CM experiences (maltreatment load) was assessed in both studies using the Childhood Trauma Questionnaire. In study cohort I (N = 30), we investigated whether CM was associated with higher levels of structural DNA damage in peripheral blood mononuclear cells (PBMC) by two methods that are highly sensitive for detecting nuclear DNA strand breaks (comet assay and γH2AX staining). In study cohort II (N = 117), we then assessed in a larger cohort, that was specifically controlled for potential confounders for oxidative stress measurements, two established serum and plasma biomarkers of oxidative stress, one representing oxidative DNA and RNA damage (8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanosine; 8-OH(d)G) and the other representing lipid peroxidation (8-isoprostane). In study cohort I, the analyses revealed no significant main effects of maltreatment load on cellular measures of nuclear DNA damage. The analyses of peripheral oxidative stress biomarkers in study cohort II revealed a significant main effect of maltreatment load on free 8-isoprostane plasma levels, but not on total 8-isprostane plasma levels and 8-OH(d)G serum levels. Taken together, by combining different methods and two study cohorts, we found no indications for higher oxidative DNA damages with higher maltreatment load in postpartum women. Further research is needed to investigate whether this increase in free 8-isoprostane is a marker for oxidative stress or whether it is instead functionally involved in ROS-related signaling pathways that potentially regulate inflammatory processes following a history of CM.
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Affiliation(s)
- Christina Boeck
- Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany
| | - Anja M Gumpp
- Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany
| | - Alexandra M Koenig
- Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany
| | - Peter Radermacher
- Institute of Anesthesiological Pathophysiology and Process Engineering, University Hospital Ulm, Ulm, Germany
| | - Alexander Karabatsiakis
- Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany
| | - Iris-Tatjana Kolassa
- Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany
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23
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Levada OA, Troyan AS. Poststroke Depression Biomarkers: A Narrative Review. Front Neurol 2018; 9:577. [PMID: 30061860 PMCID: PMC6055004 DOI: 10.3389/fneur.2018.00577] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 06/26/2018] [Indexed: 11/13/2022] Open
Abstract
Poststroke depression (PSD) is the most prevalent psychiatric disorder after stroke, which is independently correlated with negative clinical outcome. The identification of specific biomarkers could help to increase the sensitivity of PSD diagnosis and elucidate its pathophysiological mechanisms. The aim of current study was to review and summarize literature exploring potential biomarkers for PSD diagnosis. The PubMed database was searched for papers published in English from October 1977 to December 2017, 90 of which met inclusion criteria for clinical studies related to PSD biomarkers. PSD biomarkers were subdivided into neuroimaging, molecular, and neurophysiological. Some of them could be recommended to support PSD diagnosing. According to the data, lesions affecting the frontal-subcortical circles of mood regulation (prefrontal cortex, basal nuclei, and thalamus) predominantly in the left hemisphere can be considered as neuroimaging markers and predictors for PSD for at least 1 year after stroke. Additional pontine and lobar cerebral microbleeds in acute stroke patients, as well as severe microvascular lesions of the brain, increase the likelihood of PSD. The following molecular candidates can help to differentiate PSD patients from non-depressed stroke subjects: decreased serum BDNF concentrations; increased early markers of inflammation (high-sensitivity C-reactive protein, ferritin, neopterin, and glutamate), serum pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-18, IFN-γ), as well as pro-inflammatory/anti-inflammatory ratios (TNF-α/IL-10, IL-1β/IL-10, IL-6/IL-10, IL-18/IL-10, IFN-γ/IL-10); lowered complement expression; decreased serum vitamin D levels; hypercortisolemia and blunted cortisol awakening response; S/S 5-HTTLPR, STin2 9/12, and 12/12 genotypes of the serotonin transporter gene SLC6A4, 5-HTR2a 1438 A/A, and BDNF met/met genotypes; higher SLC6A4 promoter and BDNF promoter methylation status. Neurophysiological markers of PSD, that reflect a violation of perception and cognitive processing, are the elongation of the latency of N200, P300, and N400, as well as the decrease in the P300 and N400 amplitude of the event-related potentials. The selected panel of biomarkers may be useful for paraclinical underpinning of PSD diagnosis, clarifying various aspects of its multifactorial pathogenesis, optimizing therapeutic interventions, and assessing treatment effectiveness.
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Affiliation(s)
- Oleg A Levada
- State Institution "Zaporizhzhia Medical Academy of Postgraduate Education Ministry of Health of Ukraine", Zaporizhzhia, Ukraine
| | - Alexandra S Troyan
- State Institution "Zaporizhzhia Medical Academy of Postgraduate Education Ministry of Health of Ukraine", Zaporizhzhia, Ukraine
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24
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Serum profile changes in postpartum women with a history of childhood maltreatment: a combined metabolite and lipid fingerprinting study. Sci Rep 2018; 8:3468. [PMID: 29472571 PMCID: PMC5823924 DOI: 10.1038/s41598-018-21763-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 02/07/2018] [Indexed: 12/19/2022] Open
Abstract
Childhood maltreatment (CM) can increase the risk of adverse health consequences in adulthood. A deeper insight in underlying biological pathways would be of high clinical relevance for early detection and intervention. The untargeted investigation of all detectable metabolites and lipids in biological samples represents a promising new avenue to identify so far unknown biological pathways associated with CM. Using an untargeted approach, liquid chromatography-mass spectrometry (LC-MS) was performed on peripheral blood serum samples collected three months postpartum from 105 women with varying degrees of CM exposure. Comprehensive univariate and multivariate statistical analyses consistently identified eight biomarker candidates putatively belonging to antioxidant-, lipid-, and endocannabinoid-associated pathways, which differentiated between women with and without CM. Classification algorithms allowed for clear prediction of the CM status with high accuracy scores (~80-90%). Similar results were obtained when excluding all women with a lifetime psychiatric diagnosis. In order to confirm the identities of these promising biomarker candidates, LC-MS/MS analysis was applied, confirming one of the metabolites as bilirubin IXa, a potent antioxidant with immunomodulatory properties. In sum, our results suggest novel pathways that could explain long-term effects of CM on health and disease by influencing biological patterns associated with energy metabolism, inflammation, and oxidative stress.
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25
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Liu Z, Zhu Z, Zhao J, Ren W, Cai Y, Wang Q, Luan X, Zhao K, He J. Malondialdehyde: A novel predictive biomarker for post-stroke depression. J Affect Disord 2017; 220:95-101. [PMID: 28600933 DOI: 10.1016/j.jad.2017.05.023] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2016] [Revised: 03/29/2017] [Accepted: 05/06/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND There is evidence that stroke is accompanied by oxidative stress. However, the links between oxidative stress and depression in stroke patients are poorly understood. This study examines whether post-stroke depression (PSD) is associated with oxidative stress. METHODS Overall, 216 acute stroke patients were consecutively recruited and followed up for 1 month. Blood specimens were collected within 24h after admission and measured for the following oxidative stress biomarkers: malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). All enrolled patients were divided into the PSD group or the non-PSD group according to an assessment of clinical depression. One hundred normal control subjects were also recruited. RESULTS There was a positive correlation between serum MDA levels and HAMD scores in stroke patients (r=0.536, p<0.001). Based on the Receiver-operating characteristic (ROC) curve, the optimal cutoff value of serum MDA levels as an indicator for an auxiliary diagnosis of PSD was projected to be 2.898 nmol/ml, which yielded a sensitivity of 77.9% and a specificity of 81.1%, with an area under the curve of 0.883 (95% CI, 0.836-0.929). Elevated MDA (≥2.898 nmol/ml) was an independent predictive marker of PSD (odds ratio OR=24.295; 95% CI, 9.461-62.388; p<0.001, adjusted for relevant confounders). LIMITATIONS We excluded patients with severe aphasia or with serious conditions. In addition, the information for dietary intake was not recorded, which may influence oxidative stress levels. CONCLUSION Our study demonstrated that an elevated serum MDA level at admission was positively associated with an increased risk of developing depression after acute stroke, especially minor stroke.
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Affiliation(s)
- Zhihua Liu
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Zhuoying Zhu
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Jiyun Zhao
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Wenwei Ren
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Yan Cai
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Qiongzhang Wang
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Xiaoqian Luan
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Kai Zhao
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Jincai He
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
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Wang L, Xu H, Ren W, Zhu L, Chang Y, Gu Y, Yan M, He J. Low serum prealbumin levels in post-stroke depression. Psychiatry Res 2016; 246:149-153. [PMID: 27693925 DOI: 10.1016/j.psychres.2016.09.021] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Revised: 07/27/2016] [Accepted: 09/14/2016] [Indexed: 01/05/2023]
Abstract
Previous studies have shown that prealbumin is associated with depression. However, the association between prealbumin and post-stroke depression remains unelucidated. This observational cohort study determined whether low baseline serum prealbumin could predict post-stroke depression at 1 month in patients admitted with acute stroke. The study, conducted from October 2013 to September 2014, included 307 patients with acute stroke who were followed-up for 1 month. Serum prealbumin was measured within 24h after admission using an immunoturbidimetric method. The17-item Hamilton Depression Scale was used to evaluate depression symptoms. Patients with a depression score of ≥7 were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for diagnosing post-stroke depression at 1 month. Binary logistic regression analysis was used to evaluate possible predictors of post-stroke depression. Overall, 93 (30.3%) patients were diagnosed with post-stroke depression. Serum prealbumin was significantly lower in patients with versus those without post-stroke depression, and was a significant predictor of post-stroke depression after adjusting for confounding risk factors. In conclusion, baseline serum prealbumin level was associated with post-stroke depression at 1 month, suggesting that prealbumin might be a useful biomarker for post-stroke depression.
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Affiliation(s)
- Liping Wang
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Huiqin Xu
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Wenwei Ren
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lin Zhu
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yaling Chang
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yingying Gu
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Mengjiao Yan
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jincai He
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
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Abstract
Stroke survivors are often affected by psychological distress and neuropsychiatric disturbances. About one-third of stroke survivors experience depression, anxiety or apathy, which are the most common neuropsychiatric sequelae of stroke. Neuropsychiatric sequelae are disabling, and can have a negative influence on recovery, reduce quality of life and lead to exhaustion of the caregiver. Despite the availability of screening instruments and effective treatments, neuropsychiatric disturbances attributed to stroke are currently underdiagnosed and undertreated. Stroke severity, stroke-related disabilities, cerebral small vessel disease, previous psychiatric disease, poor coping strategies and unfavourable psychosocial environment influence the presence and severity of the psychiatric sequelae of stroke. Although consistent associations between psychiatric disturbances and specific stroke locations have yet to be confirmed, functional MRI studies are beginning to unveil the anatomical networks that are disrupted in stroke-associated psychiatric disorders. Evidence regarding biochemical and genetic biomarkers for stroke-associated psychiatric disorders is still limited, and better understanding of the biological determinants and pathophysiology of these disorders is needed. Investigation into the management of these conditions must be continued, and should include pilot studies to assess the benefits of innovative behavioural interventions and large-scale cooperative randomized controlled pharmacological trials of drugs that are safe to use in patients with stroke.
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Zhu L, Han B, Wang L, Chang Y, Ren W, Gu Y, Yan M, Wu C, Zhang XY, He J. The association between serum ferritin levels and post-stroke depression. J Affect Disord 2016; 190:98-102. [PMID: 26496014 DOI: 10.1016/j.jad.2015.09.074] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 08/27/2015] [Accepted: 09/18/2015] [Indexed: 12/28/2022]
Abstract
BACKGROUND Post-stroke depression (PSD) is a common neuropsychiatric affective disorder occurring after stroke. Elevated serum ferritin levels have been reported to contribute to depression. Our aim was to determine whether there is a relationship between serum ferritin levels and PSD. METHODS 196 ischemic stroke patients were consecutively recruited within the first 24h of stroke onset and were followed up for 2 months. Serum ferritin levels were assayed by electrochemiluminescence immunoassay at hospital admission. Clinical depression was diagnosed according to DSM-IV criteria and a HAMD -17 score of ≥ 7. Meanwhile, 100 normal control subjects were also recruited. RESULTS We found that 56 stroke patients (28.6%) were diagnosed with PSD at two months. There was a significant intergroup difference in serum ferritin levels within 24h after admission (F=25.044, P<0.001). Serum ferritin levels were significantly higher at admission in PSD patients than in non-PSD patients and normal controls. There was a positive correlation between serum ferritin levels and hs-CRP at admission in PSD patients (r=0.129, P=0.042). In multivariate analyses, serum levels of ferritin ≥ 130.15 µg/L were independently associated with PSD at two months [odds ratio OR=5.388, 95%CI:1.725-16.829; P=0.004] after adjusting for all possible variables. LIMITATIONS We excluded patients with severe aphasia and with serious conditions.In addition, the information for dietary intake was not recorded, which may influence body iron stores. CONCLUSION Our findings show that elevated serum ferritin levels at admission are associated with PSD and may predict its development at 2 months post-stroke.
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Affiliation(s)
- Lin Zhu
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Bin Han
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Liping Wang
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Yaling Chang
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Wenwei Ren
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Yingying Gu
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Mengjiao Yan
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Chaowen Wu
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Xiang Yang Zhang
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston,TX, USA
| | - Jincai He
- Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Psychology,Wenzhou Medical University, Wenzhou 325000, China.
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Poststroke depression as a factor adversely affecting the level of oxidative damage to plasma proteins during a brain stroke. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2015:408745. [PMID: 25838867 PMCID: PMC4370103 DOI: 10.1155/2015/408745] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/01/2015] [Accepted: 02/20/2015] [Indexed: 11/24/2022]
Abstract
Poststroke depression, the second most serious psychosomatic complication after brain stroke, leads to delay of the rehabilitation process and is associated with an increased disability and cognitive impairment along with increase in term mortality. Research into the biochemical changes in depression is still insufficiently described. The aim of our study was therefore to evaluate the possible association between plasma protein oxidative/nitrative damages and the development of poststroke depression. We evaluated oxidative/nitrative modifications of specific proteins by measurement of 3-nitrotyrosine and carbonyl groups levels using ELISA test. Additionally, we checked differences in proteins thiol groups by spectrophotometric assay based on reaction between DTNB and thiols. We also evaluated catalase activity in erythrocytes measured as ability to decompose H2O2. Correlation analysis was performed using Spearman's rank. We observed significant (P < 0.001) differences in all oxidative/nitrative stress parameters in brain stroke patients compared to healthy group. Our research shows that oxidative damage of proteins is correlated with the degree of poststroke depression, while nitrative changes do not show any relationship. We demonstrate a positive correlation between the concentration of carbonyl groups and the Geriatric Depression Scale and a negative correlation between the degree of depression and the concentration of -SH groups or catalase activity.
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Cheng SY, Zhao YD, Li J, Chen XY, Wang RD, Zeng JW. Plasma levels of glutamate during stroke is associated with development of post-stroke depression. Psychoneuroendocrinology 2014; 47:126-35. [PMID: 25001962 DOI: 10.1016/j.psyneuen.2014.05.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2014] [Revised: 05/01/2014] [Accepted: 05/09/2014] [Indexed: 12/31/2022]
Abstract
BACKGROUND Depression is a frequent mood disorder that affects around 33% of stroke patient. Our aim was to test the possible association between plasma glutamate and the development of post-stroke depression (PSD) in Chinese patients. METHODS The subjects were first-ever acute ischemic stroke (AIS) patients who were hospitalized during the period from November 2011 to September 2013. Clinical information and stroke severity was collected at admission. Neurological and neuropsychological evaluations were conducted at the 3-month follow-up. Plasma glutamate levels were analyzed at baseline using liquid chromatography followed by tandem mass spectrometry. Glutamate oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and blood markers were also tested. Multivariate analyses were performed using logistic regression models. RESULTS During the study period, 209 patients were included in the analysis. Seventy patients (33.5%) were diagnosed as having major depression at 3 month. Patients with major depression showed higher levels of plasma glutamate [299 (235-353) vs. 157 (108-206) μM, P<0.0001] and lower GOT [14 (11-20) vs. 21 (15-32)U/L, P<0.0001] at admission. In multivariate analyses, plasma glutamate and GOT were independent predictors of PSD at 3 months [odds ratio (OR): 1.03 (1.02-1.04), P<0.0001; 0.84 (0.75-0.97), P=0.003]. Plasma levels of glutamate >205 μM were independently associated with PSD (OR, 21.3; 95% CI, 8.28-67.36, P<0.0001), after adjustment for possible variables. CONCLUSION The present study demonstrates a strong relationship between plasma glutamate and GOT levels at admission and the development of PSD within 3 months. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options.
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Affiliation(s)
- Sai-Yu Cheng
- Department of Neurology, Second Affiliated Hospital and Xin Qiao Hospital, Third Military Medical University, Chongqing 400037, China.
| | - Yan-Dong Zhao
- Department of Neurobiology, College of Basic Medical Sciences, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China
| | - Jie Li
- Department of Neurology, Second Affiliated Hospital and Xin Qiao Hospital, Third Military Medical University, Chongqing 400037, China
| | - Xiao-Yan Chen
- Department of Neurology, Second Affiliated Hospital and Xin Qiao Hospital, Third Military Medical University, Chongqing 400037, China
| | - Ruo-Dan Wang
- Department of Neurology, Second Affiliated Hospital and Xin Qiao Hospital, Third Military Medical University, Chongqing 400037, China
| | - Jun-Wei Zeng
- Department of Physiology, Zunyi Medical College, Zunyi 563000, Guizhou Province, China
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