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Chen Z, Lan R, Ran T, Tao L, Zhu Y, Li Y, Zhang C, Mao M, Gao D, Zuo Z. A multimodality score strategy for assessing the risk of immune checkpoint inhibitors related cardiotoxicity. Sci Rep 2024; 14:24821. [PMID: 39438579 PMCID: PMC11496699 DOI: 10.1038/s41598-024-76829-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 10/16/2024] [Indexed: 10/25/2024] Open
Abstract
This study aimed to find the association between four common clinical biomarkers and subsequent ICICT, developing a risk scoring strategy to assess the ICICT risk. Three terminals for ICICT were : Terminal 1, cancer therapy-related cardiomyopathies; Terminal 2, myocarditis or heart failure; and Terminal 3, myocarditis, heart failure, myocardial infarction, cerebral infarction, atrial fibrillation, or death. The thresholds were : N-terminal-pro-B-type-natriuretic-peptide ≥ 125 pg/mL, cardiac troponin T ≥ 6 ng/L, high-sensitivity C-reactive protein ≥ 3 mg/L, and coronary artery calcium score > 10 U. Each of the four abnormal biomarkers received 1 point. The links between biomarkers, score stage, and ICICT were analyzed. 375 patients with a mean follow-up of 1.91 years were included. All four biomarkers measured before immunotherapy were associated with a higher risk of developing ICICT. These scores were also associated with ICICT risk. The highest risk was the very high stage (score = 4) has 7.29, 8.83, and 7.02 folder higher risk compared to low risk group for Terminal 1-3, respectively. The cumulation of incidences also showed that the higher stages of score had an earlier onset and higher incidence of ICICT. 4 biomarkers and the scoring strategy enables clinicians to assess risk easily.
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Affiliation(s)
- Zhulu Chen
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Street, Yuzhong District, Chongqing, 400016, China
| | - Rui Lan
- Department of Clinical Nutrition, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, China
| | - Tao Ran
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Street, Yuzhong District, Chongqing, 400016, China
| | - Li Tao
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yuxi Zhu
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yanwei Li
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Street, Yuzhong District, Chongqing, 400016, China
| | - Chuan Zhang
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Street, Yuzhong District, Chongqing, 400016, China
| | - Min Mao
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Street, Yuzhong District, Chongqing, 400016, China
| | - Diansa Gao
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Street, Yuzhong District, Chongqing, 400016, China
| | - Zhong Zuo
- Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Street, Yuzhong District, Chongqing, 400016, China.
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Chaves-Filho A, Eyres C, Blöbaum L, Landwehr A, Tremblay MÈ. The emerging neuroimmune hypothesis of bipolar disorder: An updated overview of neuroimmune and microglial findings. J Neurochem 2024; 168:1780-1816. [PMID: 38504593 DOI: 10.1111/jnc.16098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 02/26/2024] [Accepted: 02/28/2024] [Indexed: 03/21/2024]
Abstract
Bipolar disorder (BD) is a severe and multifactorial disease, with onset usually in young adulthood, which follows a progressive course throughout life. Replicated epidemiological studies have suggested inflammatory mechanisms and neuroimmune risk factors as primary contributors to the onset and development of BD. While not all patients display overt markers of inflammation, significant evidence suggests that aberrant immune signaling contributes to all stages of the disease and seems to be mood phase dependent, likely explaining the heterogeneity of findings observed in this population. As the brain's immune cells, microglia orchestrate the brain's immune response and play a critical role in maintaining the brain's health across the lifespan. Microglia are also highly sensitive to environmental changes and respond to physiological and pathological events by adapting their functions, structure, and molecular expression. Recently, it has been highlighted that instead of a single population of cells, microglia comprise a heterogeneous community with specialized states adjusted according to the local molecular cues and intercellular interactions. Early evidence has highlighted the contribution of microglia to BD neuropathology, notably for severe outcomes, such as suicidality. However, the roles and diversity of microglial states in this disease are still largely undermined. This review brings an updated overview of current literature on the contribution of neuroimmune risk factors for the onset and progression of BD, the most prominent neuroimmune abnormalities (including biomarker, neuroimaging, ex vivo studies) and the most recent findings of microglial involvement in BD neuropathology. Combining these different shreds of evidence, we aim to propose a unifying hypothesis for BD pathophysiology centered on neuroimmune abnormalities and microglia. Also, we highlight the urgent need to apply novel multi-system biology approaches to characterize the diversity of microglial states and functions involved in this enigmatic disorder, which can open bright perspectives for novel biomarkers and therapeutic discoveries.
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Affiliation(s)
- Adriano Chaves-Filho
- Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
- Women Health Research Institute, Vancouver, British Columbia, Canada
- Brain Health Cluster at the Institute on Aging & Lifelong Health (IALH), Victoria, British Columbia, Canada
| | - Capri Eyres
- Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
| | - Leonie Blöbaum
- Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
| | - Antonia Landwehr
- Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
| | - Marie-Ève Tremblay
- Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
- Women Health Research Institute, Vancouver, British Columbia, Canada
- Brain Health Cluster at the Institute on Aging & Lifelong Health (IALH), Victoria, British Columbia, Canada
- Centre for Advanced Materials and Related Technology (CAMTEC), University of Victoria, Victoria, British Columbia, Canada
- Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
- Neurology and Neurosurgery Department, McGill University, Montréal, Quebec, Canada
- Department of Molecular Medicine, Université Laval, Québec City, Quebec, Canada
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Wang M, Wang S, Yuan G, Gao M, Zhao X, Chu Z, Gao D. Causal role of immune cells in bipolar disorder: a Mendelian randomization study. Front Psychiatry 2024; 15:1411280. [PMID: 39220183 PMCID: PMC11362081 DOI: 10.3389/fpsyt.2024.1411280] [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: 04/02/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024] Open
Abstract
Background The understanding of the immunological mechanisms underlying bipolar disorder (BD) has enhanced in recent years due to the extensive use of high-density genetic markers for genotyping and advancements in genome-wide association studies (GWAS). However, studies on the relationship between immune cells and the risk of BD remain limited, necessitating further investigation. Methods Bidirectional two-sample Mendelian Randomization (MR) analysis was employed to investigate the causal association between immune cell morphologies and bipolar disorder. Immune cell traits were collected from a research cohort in Sardinia, whereas the GWAS summary statistics for BD were obtained from the Psychiatric Genomics Consortium. Sensitivity analyses were conducted, and the combination of MR-Egger and MR-Presso was used to assess horizontal pleiotropy. Cochran's Q test was employed to evaluate heterogeneity, and the results were adjusted for false discovery rate (FDR). Results The study identified six immune cell phenotypes significantly associated with BD incidence (P< 0.01). These phenotypes include IgD- CD27- %lymphocyte, CD33br HLA DR+ CD14- AC, CD8 on CD28+ CD45RA+ CD8br, CD33br HLA DR+ AC, CD14 on CD14+ CD16+ monocyte, and HVEM on CD45RA- CD4+. After adjusting the FDR to 0.2, two immune cell phenotypes remained statistically significant: IgD-CD27-% lymphocyte (OR=1.099, 95% CI: 1.051-1.149, P = 3.51E-05, FDR=0.026) and CD33br HLA DR+ CD14-AC (OR=0.981, 95% CI: 0.971-0.991, P = 2.17E-04, FDR=0.079). In the reverse MR analysis, BD significantly impacted the phenotypes of four monocytes (P< 0.01), including CD64 on CD14+ CD16+ monocyte, CD64 on monocyte, CX3CR1 on CD14- CD16-, CD64 on CD14+ CD16- monocyte. However, after applying the FDR correction (FDR < 0.2), no statistically significant results were observed. Conclusions This MR investigation reveals associations between immune cell phenotypes, bipolar disorder, and genetics, providing novel perspectives on prospective therapeutic targets for bipolar disorder.
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Affiliation(s)
- Mengxuan Wang
- Department of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shuo Wang
- Department of Intelligent and Information Engineering, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Guoshan Yuan
- Department of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Mingzhou Gao
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiyan Zhao
- Department of Foreign Studies, China University of Petroleum (East China), Qingdao, China
| | - Zhenhan Chu
- Department of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Dongmei Gao
- Department of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
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Ye SY, Zhao Y, Liu ZB, Luo CP, Xiong JW, Zhan JQ, Li YH, Wei B, Chen CN, Yang YJ. Lower serum insulin-like growth factor 2 level in patients with bipolar disorder is associated with the severity of manic symptoms during manic episodes. Front Psychiatry 2024; 15:1354999. [PMID: 38563028 PMCID: PMC10982374 DOI: 10.3389/fpsyt.2024.1354999] [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: 12/13/2023] [Accepted: 03/04/2024] [Indexed: 04/04/2024] Open
Abstract
Objective Accumulating evidence has indicated that neurodevelopmental defects may underlie the pathophysiology of bipolar disorder (BD). Insulin-like growth factors (IGFs) are a family of neurotrophic factors that are essential for the survival and development of neurons. The present study aims to investigate whether IGF-2 signaling is implicated in the pathophysiological processes of BD. Method 50 healthy controls and 78 patients with BD, including 23 patients who diagnosed acute depressive episode and 55 patients who diagnosed acute manic episode, were recruited in this study. The 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) were used to assess the severity of the depressive and manic symptoms, respectively. The serum IGF-2 level was determined by an enzyme-linked immunosorbent assay (ELISA). The Kolmogorov-Smirnov and Mann-Whitney U tests were used for between-group comparisons and spearman analysis was used to analyze correlations. Results Patients with BD had lower serum IGF-2 levels (66.08 ± 21.22 ng/ml) when compared to healthy controls (88.72 ± 31.55 ng/ml). BD patients were divided into manic episode and depressive episode subgroups. We found that serum IGF-2 levels were reduced in both the mania and depression subgroups (mania: 67.19 ± 21.52 ng/ml, depression: 63.43 ± 20.67 ng/ml; P < 0.001), while no significant difference was observed between two groups (P > 0.05). Spearman correlation analyses revealed that the levels of serum IGF-2 were negatively correlated with the YMRS scores in BD patients (r = -0.522, P < 0.001). Furthermore, IGF-2 was found to be an independent contributor to the severity of symptoms in patients with manic episodes (B = -0.610, t = -5.299, P < 0.001). Conclusion Lower serum IGF-2 levels were found in BD patients and correlated with the severity of the manic symptoms in these patients during manic episodes. These results suggest that reduced IGF-2 levels might be involved in the pathophysiology of BD, and serum IGF-2 could be a peripheral biomarker for the evaluation of the severity of manic symptoms in BD patients.
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Affiliation(s)
- Shi-Yi Ye
- Department of Psychiatry and Biological Psychiatry Laboratory, Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- The 3 Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Ying Zhao
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhao-Bo Liu
- Department of Psychiatry, Third People’s Hospital of Ji′an City, Ji′an, China
| | - Cui-Pin Luo
- Department of Psychiatry and Biological Psychiatry Laboratory, Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jian-Wen Xiong
- Department of Psychiatry and Biological Psychiatry Laboratory, Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Nanchang City Key Laboratory of Biological Psychiatry, Jiangxi Provincial Clinical Research Center on Mental Disorders, Jiangxi Mental Hospital, Nanchang, Jiangxi, China
| | - Jin-Qiong Zhan
- Department of Psychiatry and Biological Psychiatry Laboratory, Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Nanchang City Key Laboratory of Biological Psychiatry, Jiangxi Provincial Clinical Research Center on Mental Disorders, Jiangxi Mental Hospital, Nanchang, Jiangxi, China
| | - Yi-Heng Li
- Department of Psychiatry and Biological Psychiatry Laboratory, Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Nanchang City Key Laboratory of Biological Psychiatry, Jiangxi Provincial Clinical Research Center on Mental Disorders, Jiangxi Mental Hospital, Nanchang, Jiangxi, China
| | - Bo Wei
- Department of Psychiatry and Biological Psychiatry Laboratory, Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Nanchang City Key Laboratory of Biological Psychiatry, Jiangxi Provincial Clinical Research Center on Mental Disorders, Jiangxi Mental Hospital, Nanchang, Jiangxi, China
| | - Chun-Nuan Chen
- Department of Neurology, The Second Clinical Medical College, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China
| | - Yuan-Jian Yang
- Department of Psychiatry and Biological Psychiatry Laboratory, Jiangxi Mental Hospital & Affiliated Mental Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
- Nanchang City Key Laboratory of Biological Psychiatry, Jiangxi Provincial Clinical Research Center on Mental Disorders, Jiangxi Mental Hospital, Nanchang, Jiangxi, China
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Morales‐Muñoz I, Upthegrove R, Lawrence K, Thayakaran R, Kooij S, Gregory AM, Marwaha S. The role of inflammation in the prospective associations between early childhood sleep problems and ADHD at 10 years: findings from a UK birth cohort study. J Child Psychol Psychiatry 2023; 64:930-940. [PMID: 36597271 PMCID: PMC10952536 DOI: 10.1111/jcpp.13755] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/28/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Several underlying mechanisms potentially account for the link between sleep and attention deficit and hyperactivity disorder (ADHD), including inflammation. However, studies so far have been cross sectional. We investigate (a) the association between early childhood sleep and probable ADHD diagnosis in childhood and (b) whether childhood circulating inflammatory markers mediate these prospective associations. METHODS Data from the Avon Longitudinal Study of Parents and Children were available for 7,658 10-year-old children. Parent-reported sleep duration, night awakening frequency and regular sleep routines were collected at 3.5 years. The Development and Wellbeing Assessment was administered to capture children with clinically relevant ADHD symptoms, or probable ADHD diagnosis. Blood samples were collected at 9 years, from which two inflammatory markers were obtained [interleukin-6 (IL-6) and C-reactive protein (CRP)]. Logistic regression analyses were applied to investigate the associations between sleep variables at 3.5 years and probable ADHD diagnosis at 10 years. Further, path analysis was applied to examine the potential mediating role of inflammation at 9 years (as measured by CRP and IL-6) in the associations between early sleep and ADHD at 10 years. RESULTS Less regular sleep routines (OR = 0.51, 95% CI = 0.28-0.93, p = .029), shorter nighttime sleep (OR = 0.70, 95% CI = 0.56-0.89, p = .004) and higher night awakening frequency (OR = 1.27, 95% CI = 1.06-1.52, p = .009) at 3.5 years were associated with higher odds of ADHD at 10 years. Further, IL-6 at 9 years, but not CRP, mediated the association between irregular sleep routines and ADHD (bias-corrected estimate, -0.002; p = .005) and between night awakening and ADHD (bias-corrected estimate, 0.002; p = .003). CONCLUSIONS Several sleep problems in early childhood constitute a risk factor for probable ADHD diagnosis at 10 years. Further, these associations are partially mediated by IL-6 at 9 years. These results open a new research vista to the pathophysiology of ADHD and highlight sleep and inflammation as potential preventative targets for ADHD.
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Affiliation(s)
| | - Rachel Upthegrove
- Institute for Mental HealthUniversity of BirminghamBirminghamUK
- Early Intervention Service, Birmingham Women's and Children's NHS TrustBirminghamUK
| | - Kate Lawrence
- Department of PsychologySt Mary's University Twickenham LondonLondonUK
| | - Rasiah Thayakaran
- Institute of Applied Health ResearchUniversity of BirminghamBirminghamUK
| | - Sandra Kooij
- Department of Psychiatry, Amsterdam Public Health Research InstituteVU University Medical CenterAmsterdamThe Netherlands
- PsyQ, Expertise Center Adult ADHDThe HagueThe Netherlands
| | - Alice M Gregory
- Department of Psychology, GoldsmithsUniversity of LondonLondonUK
| | - Steven Marwaha
- Institute for Mental HealthUniversity of BirminghamBirminghamUK
- Specialist Mood Disorders ClinicZinnia CentreBirminghamUK
- The Barberry National Centre for Mental HealthBirminghamUK
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Common infectious morbidity and white blood cell count in middle childhood predict behavior problems in adolescence. Dev Psychopathol 2023; 35:301-313. [PMID: 34420539 DOI: 10.1017/s0954579421000675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
We examined the associations of middle childhood infectious morbidity and inflammatory biomarkers with adolescent internalizing and externalizing behavior problems. We recruited 1018 Colombian schoolchildren aged 5-12 years into a cohort. We quantified white blood cell (WBC) counts and C-reactive protein at enrollment and prospectively recorded incidence of gastrointestinal, respiratory, and fever-associated morbidity during the first follow-up year. After a median 6 years, we assessed adolescent internalizing and externalizing behavior problems using child behavior checklist (CBCL) and youth self-report (YSR) questionnaires. Behavior problem scores were compared over biomarker and morbidity categories using mean differences and 95% confidence intervals (CI) from multivariable linear regression. Compared with children without symptoms, CBCL internalizing problem scores were an adjusted 2.5 (95% CI: 0.1, 4.9; p = .04) and 3.1 (95% CI: 1.1, 5.2; p = .003) units higher among children with moderate diarrhea with vomiting and high cough with fever rates, respectively. High cough with fever and high fever rates were associated with increased CBCL somatic complaints and anxious/depressed scores, respectively. WBC >10,000/mm3 was associated with both internalizing problem and YSR withdrawn/depressed scores. There were no associations with externalizing behavior problems. Whether or not decreasing the burden of common infections results in improved neurobehavioral outcomes warrants further investigation.
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Wang W, Du J, Li S, Xie G, Xu J, Ren Y. Demographic, clinical and biochemical correlates of the length of stay for different polarities in Chinese inpatients with bipolar disorder: A real-world study. Front Hum Neurosci 2023; 17:1135403. [PMID: 36936616 PMCID: PMC10014706 DOI: 10.3389/fnhum.2023.1135403] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 02/06/2023] [Indexed: 03/05/2023] Open
Abstract
Introduction: Many patients with bipolar disorder (BD) need hospitalization, while the number of hospital beds for these patients is limited. Managing the length of stay (LOS) is an effective solution to this issue. Research on LOS and its influencing factors in BD is limited in China. This study aimed to identify the factors relevant to LOS in different polarities in Chinese patients with BD. Method: This was a real-world, cross-sectional study. Data were obtained from the electronic medical record system. Patients admitted to Beijing Anding Hospital between Jan 2014 and Dec 2017 and diagnosed with BD were included. Demographic information, clinical characteristics, and biochemical variables were collected. Patients were classified into short and long LOS groups based on a cutoff value. A univariate study and a multivariate logistic regression analysis were performed to identify variables related to LOS in various BD polarities. The receiver operating characteristic (ROC) analysis was utilized to evaluate the discrimination accuracy of the regression model. Result: Four thousand six hundred and seventy-five visits from 4,451 individuals were included in the analysis. For the whole sample, unmarried status, psychotic features, and family history of mental disorders were positively associated with long LOS (all p < 0.05). There was an additive interaction between a family history of mental disorders and polarities (p < 0.05). For manic episodes, unmarried status, psychotic features, and family history of mental disorders were positively associated with long LOS (all p < 0.05). For depressive episodes, psychotic features and high-density lipoprotein cholesterol (HDLC) levels were positively associated with long LOS (all p < 0.05). For mixed states, unmarried status was positively associated with long LOS, while low-density lipoprotein cholesterol (LDLC) levels were negatively associated with LOS (all p < 0.05). The area under the curve (AUC) values for depressive episodes, manic episodes, and mixed states in the combined model were 0.587, 0.553, and 0.619, respectively (all p < 0.05). Discussion: The findings suggested that LOS correlates differed by polarity, with marital status, psychotic features, a family history of mental disorders, and lipid levels strongly linked with LOS in patients with BD.
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Affiliation(s)
- Wei Wang
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
| | - Jing Du
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Sheng Li
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
| | - Gaoming Xie
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
| | - Jinjie Xu
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- *Correspondence: Jinjie Xu Yanping Ren
| | - Yanping Ren
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
- *Correspondence: Jinjie Xu Yanping Ren
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Correlations between peripheral levels of inflammatory mediators and frontolimbic structures in bipolar disorder: an exploratory analysis. CNS Spectr 2022; 27:639-644. [PMID: 34121653 PMCID: PMC8669052 DOI: 10.1017/s1092852921000596] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND Altered peripheral immune/inflammatory system and brain volumetric changes have been implicated in the pathophysiology of bipolar disorder (BD). This study aimed to evaluate how peripheral levels of cytokines are related to volumetric brain changes in euthymic patients with BD. METHODS Euthymic patients with BD (n = 21) and healthy controls (n = 22) were enrolled in this exploratory study. Blood samples were collected on the same day of clinical assessment and neuroimaging. Cytokines were measured through cytometric bead array method. Neuroimaging data were acquired using a sagittal three-dimensional magnetic resonance imaging T1-weighted fast field echo sequence and was processed using FreeSurfer. RESULTS Compared to controls, BD patients had significantly lower volumes in the cingulate, medial-orbitofrontal (MOF) and parahippocampal regions. We found a negative correlation between right MOF volume and interferon-gamma levels (β = -0.431, P = .049) and a positive correlation between interleukin-10 levels and left posterior cingulate volume (β = 0.457, P = .048). CONCLUSION Our results support the involvement of inflammatory pathways in structural brain changes in BD.
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Soares S, Santos AC, Fraga S. Adverse childhood experiences, bullying, inflammation and BMI in 10-year-old children: The biological embodiment. PLoS One 2022; 17:e0273329. [PMID: 35984781 PMCID: PMC9390893 DOI: 10.1371/journal.pone.0273329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 08/05/2022] [Indexed: 12/04/2022] Open
Abstract
Exposure to adversity during the first years of life might already be biologically embedded well before adult life. Thus, the impact of different stressful experiences needs to be explored. This study aims to examine if the association between being victimized (adverse childhood experiences—ACEs and bullying) and (hs-) C-Reactive Protein (CRP) is explained by the influence of adversity on the body mass index (BMI) of the child. We included children from the Portuguese birth cohort Generation XXI (n = 3712) that at 10 years of age completed a questionnaire on the exposure to ACEs and bullying victimization, assessed by an adaptation from the original ACEs study and an adaptation of The Bully Scale Survey, respectively. Following an overnight fast, a venous blood sample was collected by trained nurses and hs-CRP was assayed in fresh blood samples. Weight and height were measured with the child in underwear and bare feet. Weight was measured to the nearest one-tenth of a kilogram with the use of a digital scale (Tanita), and height was measured to the nearest one-tenth of a centimetre with the use of a wall stadiometer (seca®). BMI was calculated as the value of weight (kg) over squared height (m), and computed as an age- and sex-specific BMI standard deviation (SD) score (z-score), according to the World Health Organization Child Growth Standards (5–19 years). Regression coefficients and respective 95% Confidence Interval [β(95%CI)] were computed using path analysis. We observed that ACEs had a positive total effect on hs-CRP at the age of 10 years (β = 0.06; 95%CI: -0.02; 0.15). A direct effect (β = 0.02; 95%CI: -0.01; 0.06) accounted for 66.1% of the association between ACEs and hs-CRP. A positive total effect of bullying victimization on hs-CRP (β = 0.20; 95%CI: 0.06; 0.34) was observed. A direct effect (β = 0.08; 95%CI: -0.05; 0.21) accounted for 40.0% of the association, while an indirect effect through BMI (β = 0.12; 95%CI: 0.06; 0.18) explained 60.0% of the pathway between bullying victimization and hs-CRP. Results suggest that there might be different mechanisms involved in the biological embedding of childhood experiences. BMI seems to explain a great part of the association between exposure to bullying victimization and hs-CRP at 10 years of age. Further research is still needed to better understand the mechanisms explaining the emergence and persistence of health poorer outcomes later in life for victims of abuse.
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Affiliation(s)
- Sara Soares
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Rua das Taipas, Porto, Portugal
- Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
- * E-mail:
| | - Ana Cristina Santos
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Rua das Taipas, Porto, Portugal
- Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
| | - Sílvia Fraga
- EPIUnit—Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas, Porto, Portugal
- Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Rua das Taipas, Porto, Portugal
- Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
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Magyari A, Ye M, Margolis DJ, McCulloch CE, Cummings SR, Yaffe K, Langan SM, Abuabara K. Adult atopic eczema and the risk of dementia: A population-based cohort study. J Am Acad Dermatol 2022; 87:314-322. [PMID: 35367295 DOI: 10.1016/j.jaad.2022.03.049] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 03/03/2022] [Accepted: 03/09/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Chronic inflammatory conditions have been linked to dementia, but little is known about the role of atopic eczema, an inflammatory condition recently recognized to be common among older adults. OBJECTIVE To determine whether active atopic eczema is associated with incident dementia. METHODS A longitudinal cohort study of 1,767,667 individuals aged 60 to 99 years registered with The Health Improvement Network, a primary care cohort in the United Kingdom. The diagnoses of atopic eczema and dementia were identified using medical record codes. RESULTS The incidence of dementia was 57 per 10,000 person-years among those with atopic eczema during follow-up (12.1% of the population) compared with 44 per 10,000 person-years in the control group. This translated to a 27% increased risk of dementia (hazard ratio, 1.27; 95% CI, 1.23-1.30) in adjusted Cox proportional hazard models. Similar associations were observed in subgroup analyses of vascular dementia and Alzheimer's disease. The association persisted after additionally adjusting for the use of systemic corticosteroids (hazard ratio, 1.29; 95% CI, 1.26-1.33) and potential mediators (hazard ratio, 1.19; 95% CI, 1.16-1.22). More severe eczema was associated with a higher risk of dementia. LIMITATIONS Lack of detailed data on severity. CONCLUSION Atopic eczema was associated with a small but increased risk of incident dementia. The association increased with the severity of atopic eczema.
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Affiliation(s)
- Alexa Magyari
- UC Berkeley School of Public Health, Berkeley, California
| | - Morgan Ye
- Department of Dermatology, University of California, San Francisco School of Medicine (UCSF), San Francisco, California
| | - David J Margolis
- Department of Dermatology and Center for Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Charles E McCulloch
- Division of Biostatistics, University of California, San Francisco School of Medicine (UCSF), San Francisco, California
| | - Steven R Cummings
- San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California
| | - Kristine Yaffe
- Center for Population Brain Health, University of California, San Francisco School of Medicine (UCSF), San Francisco, California
| | - Sinéad M Langan
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, United Kingdom
| | - Katrina Abuabara
- UC Berkeley School of Public Health, Berkeley, California; Department of Dermatology, University of California, San Francisco School of Medicine (UCSF), San Francisco, California.
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11
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Alterations in blood proteins in the prodromal stage of bipolar II disorders. Sci Rep 2022; 12:3174. [PMID: 35210508 PMCID: PMC8873249 DOI: 10.1038/s41598-022-07160-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 02/14/2022] [Indexed: 12/12/2022] Open
Abstract
Although early intervention may help prevent the progression of bipolar disorder, there are some controversies over early pharmacological intervention. In this study, we recruited 40 subjects in the prodromal stage of BD-II (BP), according to bipolar at-risk state criteria. We compared the expression of their plasma proteins with that of 48 BD-II and 75 healthy control (HC) to identify markers that could be detected in a high-risk state. The multiple reaction monitoring method was used to measure target peptide levels with high accuracy. A total of 26 significant peptides were identified through analysis of variance with multiple comparisons, of which 19 were differentially expressed in the BP group when compared to the BD-II and HC groups. Two proteins were overexpressed in the BP group; and were related to pro-inflammation and impaired neurotransmission. The other under-expressed peptides in the BP group were related to blood coagulation, immune reactions, lipid metabolism, and the synaptic plasticity. In this study, significant markers observed in the BP group have been reported in patients with psychiatric disorders. Overall, the results suggest that the pathophysiological changes included in BD-II had already occurred with BP, thus justifying early pharmacological treatment to prevent disease progression.
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12
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Serra M, Presicci A, Quaranta L, Achille M, Caputo E, Medicamento S, Margari F, Croce F, Margari L. Associations of High-Sensitivity C-Reactive Protein and Interleukin-6 with Depression in a Sample of Italian Adolescents During COVID-19 Pandemic. Neuropsychiatr Dis Treat 2022; 18:1287-1297. [PMID: 35795592 PMCID: PMC9250896 DOI: 10.2147/ndt.s362536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 05/12/2022] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Many studies highlighted the role of inflammation in the pathogenesis of depression, although not for every patient nor for every symptom. It is widely shared that stressors can increase inflammation and lead to depressive symptoms. Little is known about the symptom-specificity of the inflammation-depression link in adolescence, which we aimed to explore. The single symptom analysis is a core feature of the recent network approach to depression, supposing that psychiatric disorders consist of co-occurring symptoms and their tendency to cause each other. PATIENTS AND METHODS We recruited 52 adolescents diagnosed with a Depressive Disorder during the COVID-19 stressful period. We used regression analysis to measure associations between high sensitivity C-Reactive Protein (hs-CRP) and Interleukin-6 (IL-6) and depressive symptoms assessed by the Children's Depression Inventory 2 (CDI 2). For the study of symptom specificity, we selected 13 items from the CDI 2 Self Report corresponding with the DSM-5 diagnostic criteria for Major Depressive Disorder and we coded them as dichotomous variables to perform a regression analysis. RESULTS We found that a higher CDI 2-Parent Version total score was significantly predicted by higher hs-CRP (coefficient 3.393; p 0.0128) and IL-6 (coefficient 3.128; p 0.0398). The endorsement of the symptom self-hatred, measuring the DSM-5 symptom "feelings of worthlessness", was significantly predicted by hs-CRP (OR 10.97; 95% CI 1.29-93.08; p 0.0282). CONCLUSION A novel symptom-specificity emerged, with hs-CRP significantly predicting the endorsement of the symptom self-hatred, recognized as a core feature of adolescent depression, following the network theory. We considered it a possible phenotypic expression of one depression endophenotype previously causally linked to inflammation. Due to the limited sample size, these preliminary findings require confirmation with future research focusing on the relationship between inflammation and self-hatred and other central nodes of the depression network, representing an opportunity for targeting interventions on crucial symptoms.
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Affiliation(s)
- Maria Serra
- Department of Pharmacy-Pharmaceutical Sciences, University of Bari "Aldo Moro", Bari, Italy
| | - Anna Presicci
- Department of Neuroscience, Sense Organs and Locomotor System, University Hospital "Policlinico", Bari, Italy
| | - Luigi Quaranta
- Department of Computer Science, University of Bari "Aldo Moro", Bari, Italy
| | - Mariaclara Achille
- Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Elvita Caputo
- Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Silvia Medicamento
- Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Francesco Margari
- Department of Basic Medical Science, Neuroscience and Sensory Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Federica Croce
- Department of Basic Medical Science, Neuroscience and Sensory Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Lucia Margari
- Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
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Abstract
Depression and psychosis have a developmental component to their origin. Epidemiologic evidence, which we synthesize in this nonsystematic review, suggests that early-life infection, inflammation, and metabolic alterations could play a role in the etiology of these psychiatric disorders. The risk of depression and psychosis is associated with prenatal maternal and childhood infections, which could be mediated by impaired neurodevelopment. Evidence suggests linear dose-response associations between elevated concentrations of circulating inflammatory markers in childhood, particularly the inflammatory cytokine interleukin 6, and the risk for depression and psychosis subsequently in early adulthood. Childhood inflammatory markers are also associated with persistence of depressive symptoms subsequently in adolescence and early adulthood. Developmental trajectories reflecting persistently high insulin levels during childhood and adolescence are associated with a higher risk of psychosis in adulthood, whereas increased adiposity during and after puberty is associated with the risk of depression. Together, these findings suggest that higher levels of infection, inflammation, and metabolic alterations commonly seen in people with depression and psychosis could be a cause for, rather than simply a consequence of, these disorders. Therefore, early-life immuno-metabolic alterations, as well as factors influencing these alterations such as adversity or maltreatment, could represent targets for prevention of these psychiatric disorders. Inflammation could also be an important treatment target for depression and psychosis. The field requires further research to examine sensitive periods when exposure to such immuno-metabolic alterations is most harmful. Interventional studies are also needed to test the potential usefulness of targeting early-life immuno-metabolic alterations for preventing adult depression and psychosis.
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14
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Perry BI, Upthegrove R, Kappelmann N, Jones PB, Burgess S, Khandaker GM. Associations of immunological proteins/traits with schizophrenia, major depression and bipolar disorder: A bi-directional two-sample mendelian randomization study. Brain Behav Immun 2021; 97:176-185. [PMID: 34280516 PMCID: PMC7612947 DOI: 10.1016/j.bbi.2021.07.009] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 06/18/2021] [Accepted: 07/12/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Schizophrenia, bipolar disorder and depression are associated with inflammation. However, it is unclear whether associations of immunological proteins/traits with these disorders are likely to be causal, or could be explained by reverse causality/residual confounding. METHODS We used bi-directional two-sample Mendelian randomization (MR) and multi-variable MR (MVMR) analysis to examine evidence of causality, specificity and direction of association of 20 immunological proteins/traits (pro-inflammatory cytokines: interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-12, IL-16, IL-17, IL-18; anti-inflammatory cytokines: IL-1 receptor antagonist (RA), IL-10, IL-13; chemokines: IL-8, monocyte chemo-attractant protein-1 (MCP-1); lymphoid growth-factors: soluble (s) IL-2Rα, IL-4, IL-7, IL-9; myeloid growth-factor: IL-5; acute phase protein: C-Reactive Protein (CRP); immune cells: neutrophils, lymphocytes; neurotrophic factor: brain derived neurotrophic factor (BDNF)) with schizophrenia, major depression and bipolar disorder. RESULTS Genetically-predicted IL-6 was associated with increased risk of schizophrenia in univariable MR (OR = 1.24; 95% C.I., 1.05-1.47) and with major depression in MVMR (OR = 1.08; 95% C.I., 1.03-1.12). These results survived Bonferroni-correction. Genetically-predicted sIL-2Rα (OR = 1.07; 95% C.I., 1.01-1.12) and IL-9 (OR = 1.06; 95% C.I., 1.01-1.11) were associated with increased schizophrenia risk. Genetically-predicted BDNF (OR = 0.97; 95% C.I., 0.94-1.00) and MCP-1 (OR = 0.96; 95% C.I., 0.91-0.99) were associated with reduced schizophrenia risk. However, these findings did not survive correction for multiple testing. The CRP-schizophrenia association attenuated completely after taking into account IL-6 and sIL-2Rα in MVMR (OR = 1.02; 95% C.I., 0.81-1.28). No significant associations were observed for bipolar disorder. Evidence from bidirectional MR did not support reverse causality. CONCLUSIONS We report evidence in support of potential causal associations of several immunological proteins/traits with schizophrenia, and of IL-6 with depression. Some of the findings did not survive correction for multiple testing and so replication in larger samples is required. Experimental studies are also required to further examine causality, mechanisms, and treatment potential for these immunological proteins/pathways for schizophrenia and depression.
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Affiliation(s)
- Benjamin I. Perry
- Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, England,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, England
| | - Rachel Upthegrove
- Institute for Mental Health, University of Birmingham, Birmingham, England
| | - Nils Kappelmann
- Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany,International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany
| | - Peter B. Jones
- Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, England,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, England
| | - Stephen Burgess
- MRC Biostatistics Unit, University of Cambridge, Cambridge, England
| | - Golam M. Khandaker
- Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, England,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, England,MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England,Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England,Avon and Wiltshire Mental Health Partnership NHS Trust, Bristol England
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15
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Lacey RE, Bartley M, Kelly-Irving M, Bevilacqua L, Iob E, Kelly Y, Howe LD. Adverse childhood experiences and early life inflammation in the Avon longitudinal study of parents and children. Psychoneuroendocrinology 2020; 122:104914. [PMID: 33129041 PMCID: PMC8188296 DOI: 10.1016/j.psyneuen.2020.104914] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 09/25/2020] [Accepted: 10/05/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Adverse childhood experiences (ACEs) have been associated with poorer health across the life course. Previous studies have used cumulative risk scores (ACE scores) or individual ACEs but these two approaches have important shortcomings. ACE scores assume that each adversity is equally important for the outcome of interest and the single adversity approach assumes that ACEs do not co-occur. Latent class analysis (LCA) is an alternative approach to operationalising ACEs data, identifying groups of people co-reporting similar ACEs. Here we apply these three approaches for ACEs operationalisation with inflammation in childhood with the aim of identifying particular ACEs or ACE combinations that are particularly associated with higher inflammation in early life. METHODS Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) we compare ACE scores, single adversities and LCA-derived ACE clusters in their relationships with Interleukin-6 at age 9 (n = 4935) and C-Reactive Protein (CRP) at age 9 (n = 4887). ACEs included were parental separation/divorce, parental alcohol problems, parental mental health problems, parental offending, inter-parental violence, parental drug misuse, and physical, emotional and sexual abuse. RESULTS Two thirds of the sample reported at least one ACE. Mother's mental health problems was the most frequently reported ACE (32.3 %). LCA identified four ACE classes - 'Low ACEs' (81.1 %), 'Maternal mental health problems' (10.3 %), 'Maternal mental health problems and physical abuse' (6.3 %) and 'Parental conflict, mental health problems and emotional abuse' (2.4 %). Parental separation/divorce was associated with higher IL-6. Parental alcohol problems, paternal mental health problems, parental convictions and emotional abuse were associated with lower levels of IL-6. Associations for paternal mental health problems and emotional abuse were only observed for boys. ACE score and LCA-derived ACE classes were not associated with differences in IL-6. Girls in the 'Maternal mental health problems' cluster had lower CRP levels. CONCLUSIONS Specific adversities and adversity combinations are important for differences in childhood inflammation. Some associations were only observed for girls or boys.
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Affiliation(s)
- Rebecca E Lacey
- Research Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, United Kingdom.
| | - Mel Bartley
- Research Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, United Kingdom.
| | | | - Leonardo Bevilacqua
- Research Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, United Kingdom.
| | - Eleonora Iob
- Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London WC1E 6BT, United Kingdom.
| | - Yvonne Kelly
- Research Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, United Kingdom.
| | - Laura D Howe
- Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Population Health Sciences, Bristol Medical School, University of Bristol, United Kingdom.
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16
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Depressive and anxiety symptomatology among people with asthma or atopic dermatitis: A population-based investigation using the UK Biobank data. Brain Behav Immun 2020; 90:138-144. [PMID: 32791209 DOI: 10.1016/j.bbi.2020.08.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 07/30/2020] [Accepted: 08/07/2020] [Indexed: 12/25/2022] Open
Abstract
The present study investigated the association of depression and anxiety symptomatology (DAS) with asthma and atopic dermatitis (AD) diagnosis during mid-adult years. The study employed data from 502,641 participants in the UK Biobank. Neutrophils to Lymphocytes Ratios (NLRs) of patients with asthma and AD were calculated and evaluated in relation to DAS, measured via the Patient Health Questionnaire-4 (PHQ-4). Age of asthma or AD onset association with DAS were also estimated. Multivariable regression analyses were implemented among participants with asthma or AD, compared to those without these disorders. Out of 58,833 participants with asthma and 13,462 with AD, the prevalence of DAS was 11.7% and 2.7%, respectively. DAS increased among participants with either asthma or AD, being highest within patients having both (β = 0.41, 95% confidence interval (95%CI), 0.34,0.49). NLR showed a linear increase with PHQ scores in asthma patients, (tertile 1, β = 0.30, 95% CI, 0.27,0.34; tertile 2, β = 0.36, 95%CI, 0.32,0.39, and tertile 3, β = 0.43, 95%CI, 0.39,0.46). An inverted U-shaped association was seen between age of asthma onset and PHQ, with the 40-59 age group (β = 0.54, 95%CI, 0.48,0.59) showing the highest risk followed by the 60+ (β = 0.43, 95%CI, 0.34,0.51 and 20-39 groups (β = 0.32, 95%CI, 0.27,0.38). Similar patterns emerged within AD. Asthma and AD were associated with increased DAS during mid-adult years, being strongest among participants reporting both disorders. A dose-response relationship between NLR and DAS was observed. Asthma or AD onset during mid-adult years (40-59) were associated with the highest increment in DAS.
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17
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Bai YM, Chen MH, Hsu JW, Huang KL, Tu PC, Chang WC, Su TP, Li CT, Lin WC, Tsai SJ. A comparison study of metabolic profiles, immunity, and brain gray matter volumes between patients with bipolar disorder and depressive disorder. J Neuroinflammation 2020; 17:42. [PMID: 32000805 PMCID: PMC6990475 DOI: 10.1186/s12974-020-1724-9] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 01/23/2020] [Indexed: 12/22/2022] Open
Abstract
Background Previous individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD). However, few studies have investigated the association between pro-inflammatory cytokines and differences in brain gray matter volumes between BD and UD. Methods In this study, 72 BD patients and 64 UD patients were enrolled, with comparable gender and age distributions (33.8% males and an average age of 39.3 ± 13.7 years). Each participant underwent metabolic profiling (including body mass index (BMI), glucose, triglyceride, high-density lipoprotein (HDL), leptin, insulin, adiponectin), pro-inflammatory cytokine (including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1) examinations, and structural magnetic resonance imaging exams. Voxel-based morphometry was performed to investigate the gray matter volume differences between BD and UD patients. Correlations between pro-inflammatory cytokines and the gray matter volume difference were analyzed. Results Compared to UD patients, the BD group had significantly higher BMI, and higher levels of sIL-6R and sTNF-R1 than the UD patients. The BMI significantly correlated with the level of pro-inflammatory cytokines. Adjusted for age, sex, BMI, duration of illness and total intracranial volume, the BD individuals had significantly more reduced gray matter volumes over 12 areas: R. cerebellar lobule VIII, R. putamen, L. putamen, R. superior frontal gyrus, L. lingual gyrus, L. precentral gyrus, R. fusiform gyrus, L. calcarine, R. precuneus, L. inferior temporal gyrus, L. hippocampus, and L. superior frontal gyrus. These 12 gray matter volume differences between BP and UD patients negatively correlated with sIL-6R and sTNF-R1 levels. Conclusions Our results suggested that BD patients had higher BMI and pro-inflammatory cytokine levels in comparison to UD patients, especially IL-6 and sTNF-R1, which may contribute to greater gray matter reductions in BD patients in comparison to UD patients. The results support the neuro-inflammation pathophysiology mechanism in mood disorder. It is clinically important to monitor BMI, which, in this investigation, positively correlated with levels of inflammatory cytokines.
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Affiliation(s)
- Ya-Mei Bai
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.,Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
| | - Mu-Hong Chen
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.,Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
| | - Ju-Wei Hsu
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.,Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Kai-Lin Huang
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.,Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Pei-Chi Tu
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.,Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Philosophy of Mind and Cognition, National Yang-Ming University, Taipei, Taiwan
| | - Wan-Chen Chang
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.,Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Tung-Ping Su
- Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Cheng Ta Li
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.,Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
| | - Wei-Chen Lin
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.,Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.,Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
| | - Shih-Jen Tsai
- Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan. .,Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.
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18
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The Relationship Between Neuroimmunity and Bipolar Disorder: Mechanism and Translational Application. Neurosci Bull 2019; 35:595-607. [PMID: 31214924 DOI: 10.1007/s12264-019-00403-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 05/01/2019] [Indexed: 12/15/2022] Open
Abstract
Neuroimmune system may be involved in the pathological process of bipolar disorder (BD), but the essential association is not fully understood. Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system (CNS). Meanwhile, neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized, such as neurotransmitter systems, neuroendocrine systems, neurotrophic factors, and oxidative stress. Simultaneously, related genes and immune changes in peripheral blood vary with it. Overall, neuroimmunity may play an important role in the pathogenesis of BD, and the inflammatory cytokines, especially interleukin-6 and tumor necrosis factor-alpha, have potential value for the clinical diagnosis and prognosis of BD, as well as predicting the therapeutic effects of drugs. Large-scale studies are needed to extend the evidence on neuroimmunity in BD, and to examine its clinical value for applications such as early prediction and treatment.
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19
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Gan Z, Wu X, Liao Y, Wu Y, He Z, Yang Z, Zhang Q. The association between low-grade inflammation and the clinical features of bipolar disorder in Han Chinese population. Psychoneuroendocrinology 2019; 101:286-294. [PMID: 30597323 DOI: 10.1016/j.psyneuen.2018.12.239] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 12/25/2018] [Accepted: 12/27/2018] [Indexed: 12/27/2022]
Abstract
Variety of evidence suggests that low-grade inflammation may be involved in the pathophysiology of bipolar disorder (BD). However, the conclusion regarding the relationship between inflammation and BD has been inconsistent. In this study, we aimed to survey the prevalence of low-grade inflammation in a large Han Chinese population with BD and assess its impact on the clinical features of BD. 430 eligible cases were drawn from patients who were admitted or had ever been admitted for BD to the inpatient service of the psychiatric department of the Third Hospital of Sun Yat-sen University. Subjects with current active physical diseases or white blood count (WBC) >19.0 × 109/L (2 times the upper reference) were excluded. Serum C-reactive protein (CRP) levels and WBC were measured with fast blood sample. Low-grade inflammation was defined as CRP>3 mg/L or WBC > 9.5 × 109/L(the upper reference). Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education. If defined as CRP>3 mg/L, the prevalence of low-grade inflammation among BD was 10.1% (41/404), it was positively associated with BMI (p = 0.012), comorbidity of glycolipid metabolic diseases(p = 0.018). After adjusting for BMI, it was found to be positively related to recent suicide attempt (p = 0.03), initiation with (hypo)manic episode(p = 0.047), leaden paralysis (p = 0.037) and family history of mental disorders(p = 0.012), while the association between comorbidity of glycolipid metabolic diseases and low-grade inflammation disappeared (p = 0.330). If defined as WBC > 9.5 × 109/L, the prevalence of low-grade inflammation was 8.1% (33/409), it was positively associated with psychotic features (p = 0.011) and adverse life events before the onset of illness(p < 0.001), but was not significantly influenced by BMI (p = 0.077). A much lower prevalence of low-grade inflammation in BD is found among Han Chinese population than among western population. Low-grade inflammation of different definition impacts differentially on the clinical features of BD.
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Affiliation(s)
- Zhaoyu Gan
- Department of Psychiatry, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Xiuhua Wu
- Department of Psychiatry, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Yingtao Liao
- Department of Psychiatry, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Yingdong Wu
- Department of Psychiatry, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Zimeng He
- Department of Psychiatry, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Zhihua Yang
- Department of Psychiatry, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Qi Zhang
- Biotherapy center, the Third Affiliated Hospital of Sun Yat-sen University, NO.600, Tianhe Road, Tianhe District, Guangzhou, 510630, China.
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Rowland T, Perry BI, Upthegrove R, Barnes N, Chatterjee J, Gallacher D, Marwaha S. Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses. Br J Psychiatry 2018; 213:514-525. [PMID: 30113291 PMCID: PMC6429261 DOI: 10.1192/bjp.2018.144] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND A reliable biomarker signature for bipolar disorder sensitive to illness phase would be of considerable clinical benefit. Among circulating blood-derived markers there has been a significant amount of research into inflammatory markers, neurotrophins and oxidative stress markers.AimsTo synthesise and interpret existing evidence of inflammatory markers, neurotrophins and oxidative stress markers in bipolar disorder focusing on the mood phase of illness. METHOD Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a systematic review was conducted for studies investigating peripheral biomarkers in bipolar disorder compared with healthy controls. We searched Medline, Embase, PsycINFO, SciELO and Web of Science, and separated studies by bipolar mood phase (mania, depression and euthymia). Extracted data on each biomarker in separate mood phases were synthesised using random-effects model meta-analyses. RESULTS In total, 53 studies were included, comprising 2467 cases and 2360 controls. Fourteen biomarkers were identified from meta-analyses of three or more studies. No biomarker differentiated mood phase in bipolar disorder individually. Biomarker meta-analyses suggest a combination of high-sensitivity C-reactive protein/interleukin-6, brain derived neurotrophic factor/tumour necrosis factor (TNF)-α and soluble TNF-α receptor 1 can differentiate specific mood phase in bipolar disorder. Several other biomarkers of interest were identified. CONCLUSIONS Combining biomarker results could differentiate individuals with bipolar disorder from healthy controls and indicate a specific mood-phase signature. Future research should seek to test these combinations of biomarkers in longitudinal studies.Declaration of interestNone.
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Affiliation(s)
- Tobias Rowland
- IHR Academic Clinical Fellow in Psychiatry, Mental Health and Wellbeing, Warwick Medical School, University of Warwick, UK
| | - Benjamin I. Perry
- NIHR Academic Clinical Fellow in Psychiatry, Mental Health and Wellbeing, Warwick Medical School, University of Warwick, UK
| | - Rachel Upthegrove
- Senior Clinical Lecturer in Psychiatry, Institute of Clinical Sciences, School of Clinical and Experimental Medicine, University of Birmingham, UK
| | - Nicholas Barnes
- Professor of Neuropharmacology, Institute of Clinical Sciences, School of Clinical and Experimental Medicine, University of Birmingham, UK
| | - Jayanta Chatterjee
- Consultant Psychiatrist, Affective Disorders Service, Caludon Centre, Coventry, UK
| | - Daniel Gallacher
- Research Associate in Medical Statistics, WMS Population, Evidence and Technologies, Warwick Medical School, University of Warwick, UK
| | - Steven Marwaha
- Reader in Psychiatry, Mental Health and Wellbeing, Warwick Medical School, University of Warwick,UK,Correspondence: Steven Marwaha, Mental Health and Wellbeing, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
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Khandaker GM, Stochl J, Zammit S, Goodyer I, Lewis G, Jones PB. Childhood inflammatory markers and intelligence as predictors of subsequent persistent depressive symptoms: a longitudinal cohort study. Psychol Med 2018; 48:1514-1522. [PMID: 29140226 PMCID: PMC6088526 DOI: 10.1017/s0033291717003038] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Revised: 07/04/2017] [Accepted: 07/05/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND To identify developmental sub-groups of depressive symptoms during the second decade of life, a critical period of brain development, using data from a prospective birth cohort. To test whether childhood intelligence and inflammatory markers are associated with subsequent persistent depressive symptoms. METHODS IQ, a proxy for neurodevelopment, was measured at age 8 years. Interleukin 6 (IL-6) and C-reactive protein, typical inflammatory markers, were measured at age 9 years. Depressive symptoms were measured six times between 10 and 19 years using the short mood and feelings questionnaire (SMFQ), which were coded as binary variable and then used in latent class analysis to identify developmental sub-groups of depressive symptoms. RESULTS Longitudinal SMFQ data from 9156 participants yielded three distinct population sub-groups of depressive symptoms: no symptoms (81.2%); adolescent-onset symptoms (13.2%); persistent symptoms (5.6%). Lower IQ and higher IL-6 levels in childhood were independently associated with subsequent persistent depressive symptoms in a linear, dose-response fashion, but not with adolescent-onset symptoms. Compared with the group with no symptoms the adjusted odds ratio for persistent depressive symptoms per s.d. increase in IQ was 0.80 (95% CI, 0.68-0.95); that for IL-6 was 1.20 (95% CI, 1.03-1.39). Evidence for an association with IL-6 remained after controlling for initial severity of depressive symptoms at 10 years. There was no evidence that IL-6 moderated or mediated the IQ-persistent depressive symptom relationship. CONCLUSIONS The results indicate potentially important roles for two distinct biological processes, neurodevelopment and inflammation, in the aetiology of persistent depressive symptoms in young people.
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Affiliation(s)
- G. M. Khandaker
- Department of Psychiatry, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - J. Stochl
- Department of Psychiatry, University of Cambridge, Cambridge, UK
- Department of Kinanthropology, Charles University, Prague, Czech Republic
| | - S. Zammit
- Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, Bristol, UK
- Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
| | - I. Goodyer
- Department of Psychiatry, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - G. Lewis
- Division of Psychiatry, University College London, London, UK
| | - P. B. Jones
- Department of Psychiatry, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
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Peng HL, Huang WC, Cheng SC, Liou CJ. Fisetin inhibits the generation of inflammatory mediators in interleukin-1β-induced human lung epithelial cells by suppressing the NF-κB and ERK1/2 pathways. Int Immunopharmacol 2018; 60:202-210. [PMID: 29758489 DOI: 10.1016/j.intimp.2018.05.004] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 05/04/2018] [Accepted: 05/08/2018] [Indexed: 12/28/2022]
Abstract
Fisetin, a flavone that can be isolated from fruits and vegetables, has anti-tumor and anti-oxidative properties and ameliorates airway hyperresponsiveness in asthmatic mice. This study investigated whether fisetin can suppress the expression of inflammatory mediators and intercellular adhesion molecule 1 (ICAM-1) in A549 human lung epithelial cells that were stimulated with interleukin-1β (IL-1β) to induce inflammatory responses. A549 cells were treated with fisetin (3-30 μM) and then with IL-1β. Fisetin significantly inhibited COX-2 expression and reduced prostaglandin E2 production, and it suppressed the levels of IL-8, CCL5, monocyte chemotactic protein 1, tumor necrosis factor α, and IL-6. Fisetin also significantly attenuated the expression of chemokine and inflammatory cytokine genes and decreased the expression of ICAM-1, which mediates THP-1 monocyte adhesion to inflammatory A549 cells. Fisetin decreased the translocation of nuclear transcription factor kappa-B (NF-κB) subunit p65 into the nucleus and inhibited the phosphorylation of proteins in the ERK1/2 pathway. Co-treatment of IL-1β-stimulated A549 cells with ERK1/2 inhibitors plus fisetin reduced ICAM-1 expression. Furthermore, fisetin significantly increased the effects of the protective antioxidant pathway by promoting the expression of nuclear factor erythroid-2-related factor-2 and heme oxygenase 1. Taken together, these data suggest that fisetin has anti-inflammatory effects and that it suppresses the expression of chemokines, inflammatory cytokines, and ICAM-1 by suppressing the NF-κB and ERK1/2 signaling pathways in IL-1β-stimulated human lung epithelial A549 cells.
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Affiliation(s)
- Hui-Ling Peng
- Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan
| | - Wen-Chung Huang
- Graduate Institute of Health Industry Technology, Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan; Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Guishan Dist., Taoyuan City 33303, Taiwan.
| | - Shu-Chen Cheng
- Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chian-Jiun Liou
- Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou, Guishan Dist., Taoyuan City 33303, Taiwan; Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, No.261, Wenhua 1st Rd., Guishan Dist., Taoyuan City 33303, Taiwan.
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Osimo EF, Cardinal RN, Jones PB, Khandaker GM. Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: An electronic health record-based study. Psychoneuroendocrinology 2018; 91:226-234. [PMID: 29544672 PMCID: PMC5910056 DOI: 10.1016/j.psyneuen.2018.02.031] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 02/19/2018] [Accepted: 02/27/2018] [Indexed: 12/16/2022]
Abstract
Low-grade inflammation is a risk factor for depression, psychosis and other major psychiatric disorders. It is associated with poor response to antidepressant and antipsychotics, and could potentially be a treatment target. However, there is limited data on the prevalence of low-grade inflammation in major psychiatric disorders, and on the characteristics of patients who show evidence of inflammation. We examined the prevalence of low-grade inflammation and associated socio-demographic and clinical factors in acute psychiatric inpatients. An anonymised search of the electronic patient records of Cambridgeshire and Peterborough NHS Foundation Trust was used to identify patients aged 18-65 years who were hospitalised between 2013 and 2016 (inclusive). We excluded patients on antibiotics or oral steroids, or with missing data. Inflammation was defined using serum C-reactive protein (>3 mg/L) or total white cell count (>9.4 × 109/L) as measured within 14 days of admission. Out of all 599 admissions, the prevalence of inflammation (serum CRP >3 mg/L) in the ICD-10 diagnostic groups of psychotic disorders (F20-29), mood disorders (F30-39), neurotic disorders (F40-48) and personality disorders (F60-69) was 32%, 21%, 22% and 42%, respectively. In multivariable analyses, low-grade inflammation was associated with older age, black ethnicity, being single, self-harm, diagnoses of schizophrenia, bipolar disorder, current treatments with antidepressants, benzodiazepines, and with current treatment for medical comorbidities. A notable proportion of acutely unwell psychiatric patients from all ICD-10 major diagnostic groups show evidence of low-grade inflammation, suggesting inflammation may be relevant for all psychiatric disorders.
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Affiliation(s)
- Emanuele F. Osimo
- Department of Psychiatry, University of Cambridge, Cambridge, England, UK,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, England, UK,Corresponding author at: Department of Psychiatry, University of Cambridge, Herchel Smith Building Cambridge Biomedical Campus, Cambridge CB2 0SZ, UK.
| | - Rudolf N. Cardinal
- Department of Psychiatry, University of Cambridge, Cambridge, England, UK,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, England, UK
| | - Peter B. Jones
- Department of Psychiatry, University of Cambridge, Cambridge, England, UK,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, England, UK
| | - Golam M. Khandaker
- Department of Psychiatry, University of Cambridge, Cambridge, England, UK,Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, England, UK
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Psychoneuroimmunology of mental disorders. REVISTA DE PSIQUIATRIA Y SALUD MENTAL 2017; 11:115-124. [PMID: 28993125 DOI: 10.1016/j.rpsm.2017.07.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 07/04/2017] [Accepted: 07/31/2017] [Indexed: 12/30/2022]
Abstract
The immune system is a key element in the organism's defence system and participates in the maintenance of homeostasis. There is growing interest in the aetiopathogenic and prognostic implications of the immune system in mental disorders, as previous studies suggest the existence of a dysregulation of the immune response and a pro-inflammatory state in patients with mental disorders, as well as an increased prevalence of neuropsychiatric symptoms in patients suffering from autoimmune diseases or receiving immune treatments. This study aims to conduct a narrative review of the scientific literature on the role of Psychoneuroimmunology in mental disorders, with special focus on diagnostic, prognostic and therapeutic issues. The development of this body of knowledge may bring in the future important advances in the vulnerability, aetiopathogenic mechanisms, diagnosis and treatment of some mental disorders.
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Zadka Ł, Dzięgiel P, Kulus M, Olajossy M. Clinical Phenotype of Depression Affects Interleukin-6 Synthesis. J Interferon Cytokine Res 2017; 37:231-245. [PMID: 28418766 DOI: 10.1089/jir.2016.0074] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Major depressive disorder (MDD) is not a single disease, but a number of various ailments that form one entity. Psychomotor retardation, anhedonia, sleep disorders, an increased suicide risk, and anxiety are the main symptoms that often define the clinical diagnosis of depression. Interleukin-6 (IL-6), as one of the proinflammatory cytokines, seems to be overexpressed during certain mental disorders, including MDD. Overexpression of IL-6 in depression is thought to be a factor associated with bad prognosis and worse disease course. IL-6 may directly affect brain functioning and production of neurotransmitters; moreover, its concentration is correlated with certain clinical symptoms within the wide range of depressive symptomatology. Furthermore, there is a strong correlation between IL-6 synthesis and psychosomatic functioning of the patient. This article discusses potential sources and significance of IL-6 in the pathogenesis of depression.
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Affiliation(s)
- Łukasz Zadka
- 1 Department of Histology and Embryology, Wroclaw Medical University , Wrocław, Poland .,2 II Department of Psychiatry and Psychiatric Rehabilitation, Independent Public Teaching Hospital No 1 in Lublin, Medical University of Lublin , Lublin, Poland
| | - Piotr Dzięgiel
- 1 Department of Histology and Embryology, Wroclaw Medical University , Wrocław, Poland
| | - Michał Kulus
- 1 Department of Histology and Embryology, Wroclaw Medical University , Wrocław, Poland
| | - Marcin Olajossy
- 2 II Department of Psychiatry and Psychiatric Rehabilitation, Independent Public Teaching Hospital No 1 in Lublin, Medical University of Lublin , Lublin, Poland
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Fernandes BS, Steiner J, Molendijk ML, Dodd S, Nardin P, Gonçalves CA, Jacka F, Köhler CA, Karmakar C, Carvalho AF, Berk M. C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry 2016; 3:1147-1156. [PMID: 27838212 DOI: 10.1016/s2215-0366(16)30370-4] [Citation(s) in RCA: 163] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Revised: 10/19/2016] [Accepted: 10/19/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND Inflammatory processes and neural-immune interactions have been implicated in the pathogenesis of psychiatric conditions, but studies in bipolar disorder are inconclusive so far. We aimed to investigate whether peripheral concentrations of C-reactive protein (CRP), an acute-phase response protein of inflammatory activity, are increased in bipolar disorder across the mood spectrum. METHODS In this systematic review and meta-analysis, we searched MEDLINE, the Cochrane Library, Scopus, and Web of Knowledge from database inception to Aug 14, 2016, for studies that measured serum and plasma CRP concentrations in adult patients with bipolar disorder (as defined by DSM-IV-TR) and healthy controls. We extracted data from published reports. We did three between-group meta-analyses comparing CRP concentrations in patients in mania, depression, or euthymia, with those in healthy controls (cross-sectional studies), and two within-group meta-analyses comparing changes in CRP concentrations before and after treatment of an index manic or depressive episode (longitudinal studies). We used Hedges' adjusted g to calculate effect sizes and pooled results using random-effect models. We also did meta-regression analyses by mood state to investigate possible moderators of CRP concentrations. FINDINGS We identified 27 studies representing 2161 patients with bipolar disorder and 81 932 healthy controls. Compared with healthy individuals, CRP concentrations were moderately increased in people with bipolar disorder during depression (g 0·67, 95% CI 0·23 to 1·11; p=0·003) and euthymia (0·65, 0·40 to 0·90; p<0·0001) and more substantially increased during mania (0·87, 0·58 to 1·15; p<0·0001). The extent of the increases in CRP concentrations in mania and depression was not related to symptom severity (p=0·256 for mania and p=0·626 for depression). CRP concentrations were moderately decreased after resolution of an index manic episode (-0·36, -0·66 to -0·05; p=0·022) and slightly decreased after resolution of an index depressive episode (-0·18, -0·30 to -0·07; p=0·002). INTERPRETATION CRP concentrations are increased in bipolar disorder regardless of mood state, but are higher during mania than in depression and euthymia, suggesting an increased inflammatory burden in mania. FUNDING None.
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Affiliation(s)
- Brisa S Fernandes
- IMPACT Strategic Research Centre, Deakin University School of Medicine, and Barwon Health, Geelong, VIC, Australia; Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
| | - Johann Steiner
- Department of Psychiatry, University of Magdeburg, Magdeburg, Germany
| | - Marc L Molendijk
- Institute of Psychology, Department of Clinical Psychology, Leiden University Medical Center, Leiden, Netherlands; Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden, Netherlands
| | - Seetal Dodd
- IMPACT Strategic Research Centre, Deakin University School of Medicine, and Barwon Health, Geelong, VIC, Australia
| | - Patricia Nardin
- Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Carlos-Alberto Gonçalves
- Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Felice Jacka
- IMPACT Strategic Research Centre, Deakin University School of Medicine, and Barwon Health, Geelong, VIC, Australia
| | - Cristiano A Köhler
- Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Chandan Karmakar
- Center for Pattern Recognition and Data Analytics, School of Information Technology, Deakin University, Geelong, VIC, Australia
| | - André F Carvalho
- Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Michael Berk
- IMPACT Strategic Research Centre, Deakin University School of Medicine, and Barwon Health, Geelong, VIC, Australia; Florey Institute for Neuroscience and Mental Health, Department of Psychiatry and Orygen, The National Centre of Excellence in Youth Mental Health, University of Melbourne, Parkville, VIC, Australia
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