|
1
|
Zhao H, Li Y, Yin X, Liu Z, Zhou Z, Sun H, Fan Y, Wang S, Xin T. Neuroticism and cerebral small vessel disease: A genetic correlation and Mendelian randomization analysis. Neuroscience 2025; 566:1-8. [PMID: 39681255 DOI: 10.1016/j.neuroscience.2024.12.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 11/25/2024] [Accepted: 12/14/2024] [Indexed: 12/18/2024]
Abstract
OBJECTIVES The association of neuroticism and cerebral small vessel disease (CSVD) development remains unclear. In this study, we used Mendelian randomization (MR) to explore the potential role of neuroticism in CSVD development. METHODS We collected data on ischemic stroke (IS); small vessel stroke (SVS); three neuroimaging markers altered in CSVD, including white matter hyperintensity (WMH), fractional anisotropy (FA), and mean diffusivity (MD); and three neuroticism clusters, including depressed affect, worry, sensitivity to environmental stress and adversity (SESA), from large-scale genome-wide association studies (GWAS). Bidirectional MR analyses were used to evaluate the association between neuroticism and CSVD, primarily estimated using the inverse variance weighted (IVW) method. The linkage disequilibrium score (LDSC) regression was employed to assess the association between various phenotypes. RESULTS LDSC analysis unveiled a noteworthy genetic correlation between depressed affect and IS (rg = 0.111, p = 0.001) as well as between worry and SVS (rg = -0.111, p = 0.032). Our study revealed a causal correlation between SESA and FA using both forward and reverse MR analyses (SESA on FA, odds ratio (OR) = 0.186 (0.071 to 0.483), p = 5.50 × 10-4; FA on SESA, OR = 0.996 (0.9916 to 0.9997), p = 0.035). Meanwhile, FA also exerted a statistical causal influence on depressed affect cluster (OR = 0.992 (0.987 to 0.997), p = 0.001). INTERPRETATION This research suggests a potential correlation between certain aspects of neuroticism and CSVD, with further studies needed to better understand the causal relationship and its implications for patient intervention.
Collapse
Affiliation(s)
- Hongbo Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China; Shandong Engineering Research Center of Precision Diagnosis and Treatment Technology for Neuro-oncology, Jinan, 250014, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, China
| | - Yuming Li
- Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China; Shandong Engineering Research Center of Precision Diagnosis and Treatment Technology for Neuro-oncology, Jinan, 250014, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, China; First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Xianyong Yin
- Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China; Shandong Engineering Research Center of Precision Diagnosis and Treatment Technology for Neuro-oncology, Jinan, 250014, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, China
| | - Zihao Liu
- Shandong Engineering Research Center of Precision Diagnosis and Treatment Technology for Neuro-oncology, Jinan, 250014, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, China; Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Zijian Zhou
- Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China; Shandong Engineering Research Center of Precision Diagnosis and Treatment Technology for Neuro-oncology, Jinan, 250014, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, China; Laboratory of Basic and Translational Neuromedicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China
| | - Haohan Sun
- Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China; Shandong Engineering Research Center of Precision Diagnosis and Treatment Technology for Neuro-oncology, Jinan, 250014, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, China
| | - Yang Fan
- Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China; Shandong Engineering Research Center of Precision Diagnosis and Treatment Technology for Neuro-oncology, Jinan, 250014, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, China; Laboratory of Basic and Translational Neuromedicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China
| | - Shan Wang
- Shandong Key Laboratory of Reproductive Medicine, Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
| | - Tao Xin
- Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China; Shandong Engineering Research Center of Precision Diagnosis and Treatment Technology for Neuro-oncology, Jinan, 250014, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, China; Laboratory of Basic and Translational Neuromedicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China; Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
| |
Collapse
|
|
2
|
Xie JW, Guo YF, Wang M, Tong ML, Zhu XZ, Lin LR. Syphilis susceptibility factors atlas: A wide-angled Mendelian randomization study. Prev Med 2024; 185:108033. [PMID: 38851401 DOI: 10.1016/j.ypmed.2024.108033] [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: 03/11/2024] [Revised: 06/03/2024] [Accepted: 06/05/2024] [Indexed: 06/10/2024]
Abstract
OBJECTIVE The pathogenic mechanisms of syphilis and the host defense mechanisms against syphilis remain poorly understood. Exploration of the susceptibility factors of syphilis may provide crucial clues for unraveling its underlying mechanisms. METHODS A two-sample Mendelian Randomization framework was utilized, and the inverse-variance weighted method was used as the main analysis. All data was sourced from Genome-wide association studies datasets from 2015 to 2022 in Europe, and all participants were of European descent. Only summary-level statistics were used. Sensitivity analyses were conducted to evaluate the heterogeneity and pleiotropy of the datasets. RESULTS Our study established 18 exposure factors (12 risk factors and 6 protective factors) for syphilis susceptibility. Twelve factors encompassing body mass index, waist circumference, darker natural skin, cooked vegetable intake, processed meat intake, diabetes mellitus, glucose regulation disorders, gout, autoimmune diseases, rheumatoid arthritis, diverticulitis, and longer menstrual cycles were found to increase susceptibility to syphilis. In contrast, 6 factors including easier skin tanning, blonde natural hair color, irritability, higher neuroticism scores, extended sleep duration, and delayed age at first sexual intercourse were connected to a reduced risk of syphilis infection (all P < 0.05). CONCLUSIONS This study identified 18 influencing factors of syphilis susceptibility. These findings offered novel insights for further probing into the underlying pathogenic mechanisms of syphilis and underscored the importance of multifaceted prevention strategies against syphilis.
Collapse
Affiliation(s)
- Jia-Wen Xie
- Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China
| | - Yin-Feng Guo
- Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China
| | - Mao Wang
- Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China
| | - Man-Li Tong
- Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China
| | - Xiao-Zhen Zhu
- Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China
| | - Li-Rong Lin
- Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, China.
| |
Collapse
|
|
3
|
Wrede SJS, Claassen K, Rodil dos Anjos D, Kettschau JP, Broding HC. Impact of digital stress on negative emotions and physical complaints in the home office: a follow up study. Health Psychol Behav Med 2023; 11:2263068. [PMID: 37818414 PMCID: PMC10561583 DOI: 10.1080/21642850.2023.2263068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 09/17/2023] [Indexed: 10/12/2023] Open
Abstract
Background Due to the COVID-19 pandemic many employees perform under increasingly digital conditions. Enabling home office environments became mandatory for companies wherever possible in consideration of the ongoing pandemic. Simultaneously, studies reported on digital stress. The current literature lacks rigorous research into digital stress on psychosomatic outcomes, emotions, and disease. Therefore, we endeavor to understand how digital stress developed over the course of the pandemic and if it predicts differences in negative emotions and physical complaints in the home office setting. Methods To answer the research question, we conducted an online survey among 441 employees in 2020 and 398 employees in 2022 from three municipal administrations in Germany, who were working from home at least occasionally. We used a cluster analysis to detect digitally stressed employees. Regression analyses were performed on digital stress, negative emotions, and physical complaints. Results The analysis revealed an increase from 9 to 20% in digital stress, while negative emotions and physical complaints did not show evident differences. In the multivariate model, we observe a change in the proportion of digitally stressed employees between 4 and 17%, while the control variables explain around 9%. Conclusions Digital stress did not significantly affect either negative emotions or physical complaints. However, digital stress appeared to exert a more substantial predictive influence on negative emotions. The study emphasizes rising digital stress, which contradicts a positive adaption to the digital working conditions within the observed period. The psychosomatic relations are low or lagged. Further research investigating digital stress and countermeasures, especially to understand how to prevent harmful long-term effects such as distress resulting from working from home conditions, is needed.
Collapse
Affiliation(s)
- Sammy J. S. Wrede
- Faculty of Health, Department of Human Medicine, Chair of Occupational Medicine and Corporate Health Management, Witten/Herdecke University, Witten, Germany
| | - Kevin Claassen
- Faculty of Health, Department of Human Medicine, Chair of Occupational Medicine and Corporate Health Management, Witten/Herdecke University, Witten, Germany
| | - Dominique Rodil dos Anjos
- Faculty of Health, Department of Human Medicine, Chair of Occupational Medicine and Corporate Health Management, Witten/Herdecke University, Witten, Germany
| | - Jan P. Kettschau
- Faculty of Health, Department of Human Medicine, Chair of Occupational Medicine and Corporate Health Management, Witten/Herdecke University, Witten, Germany
| | - Horst C. Broding
- Faculty of Health, Department of Human Medicine, Chair of Occupational Medicine and Corporate Health Management, Witten/Herdecke University, Witten, Germany
| |
Collapse
|
|
4
|
Hjell G, Rokicki J, Szabo A, Holst R, Tesli N, Bell C, Fischer-Vieler T, Werner MCF, Lunding SH, Ormerod MBEG, Johansen IT, Djurovic S, Ueland T, Andreassen OA, Melle I, Lagerberg TV, Mørch-Johnsen L, Steen NE, Haukvik UK. Impulsivity across severe mental disorders: a cross-sectional study of immune markers and psychopharmacotherapy. BMC Psychiatry 2023; 23:659. [PMID: 37674162 PMCID: PMC10483855 DOI: 10.1186/s12888-023-05154-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 08/29/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Impulsivity is a transdiagnostic feature linked to severe clinical expression and a potential target for psychopharmacological strategies. Biological underpinnings are largely unknown, but involvement of immune dysregulation has been indicated, and the effects of psychopharmacological agents vary. We investigated if impulsivity was associated with circulating immune marker levels and with a range of psychopharmacological treatment regimens in severe mental disorders. METHODS Impulsivity was assessed in a sample (N = 657) of patients with schizophrenia or schizophreniform disorder (SCZ) (N = 116) or bipolar disorder (BD) (N = 159) and healthy participants (N = 382) using the Barratt Impulsiveness Scale (BIS-11) questionnaire. Plasma levels of systemic immune markers (RANTES, IL-1RA, IL-18, IL-18BP, sTNFR-1) were measured by enzyme immunoassays. Patients underwent thorough clinical assessment, including evaluation of psychotropic medication. Associations were assessed using linear regressions. RESULTS Impulsivity was positively associated with SCZ (p < 0.001) and BD (p < 0.001) diagnosis and negatively associated with age (p < 0.05), but not significantly associated with any of the circulating immune markers independently of diagnostic status. Among patients, impulsivity was negatively associated with lithium treatment (p = 0.003) and positively associated with antidepressant treatment (p = 0.011) after controlling for diagnosis, psychotropic co-medications, manic symptoms, and depressive symptoms. CONCLUSIONS We report elevated impulsivity across SCZ and BD but no associations to systemic immune dysregulation based on the current immune marker selection. The present study reveals associations between impulsivity in severe mental disorders and treatment with lithium and antidepressants, with opposite directions. Future studies are warranted to determine the causal directionality of the observed associations with psychopharmacotherapy.
Collapse
Affiliation(s)
- Gabriela Hjell
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- Department of Psychiatry & Department of Clinical Research, Østfold Hospital, Grålum, Norway.
| | - Jaroslav Rokicki
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Centre of Research and Education in Forensic Psychiatry, Oslo University Hospital, Oslo, Norway
| | - Attila Szabo
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- K.G. Jebsen Center of Neurodevelopmental Disorders, University of Oslo, Oslo, Norway
| | - René Holst
- Department of Psychiatry & Department of Clinical Research, Østfold Hospital, Grålum, Norway
- Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Natalia Tesli
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Christina Bell
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Thomas Fischer-Vieler
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Maren Caroline Frogner Werner
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Synve Hoffart Lunding
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | | | - Ingrid Torp Johansen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Srdjan Djurovic
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
- NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Thor Ueland
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway
| | - Ole Andreas Andreassen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ingrid Melle
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Trine Vik Lagerberg
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Lynn Mørch-Johnsen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Psychiatry & Department of Clinical Research, Østfold Hospital, Grålum, Norway
| | - Nils Eiel Steen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Unn Kristin Haukvik
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Centre of Research and Education in Forensic Psychiatry, Oslo University Hospital, Oslo, Norway
- Department of Adult Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| |
Collapse
|
|
5
|
Jones EJ, Marsland AL, Gianaros PJ. Do trait-level emotion regulation strategies moderate associations between retrospective reports of childhood trauma and prospective changes in systemic inflammation? Stress Health 2023; 39:525-538. [PMID: 36265175 PMCID: PMC10518806 DOI: 10.1002/smi.3205] [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: 04/25/2022] [Revised: 07/19/2022] [Accepted: 09/01/2022] [Indexed: 11/11/2022]
Abstract
Childhood trauma may confer risk for poorer adult health through changes in systemic inflammation. Emotion regulation may plausibly moderate associations between childhood trauma and adult psychological well-being, but it remains unclear whether moderation effects extend to differences in systemic inflammation. To examine whether childhood trauma and emotion regulation separately and interactively predict prospective changes in C-reactive protein (CRP) and interleukin-6 (IL-6) and whether biopsychosocial factors account for observed associations. Healthy midlife adults (N = 331) retrospectively reported on childhood trauma, current trait-level cognitive reappraisal and expressive suppression, and had their blood drawn. At baseline and then a median of 2.85 years later, 279 of the 331 participants had their blood drawn, body mass index calculated, and reported on health behaviours (smoking, sleep), psychological distress (perceived stress, depressive symptoms), and years of education. Childhood trauma predicted prospective increases in CRP (B = 0.004, p = 0.049), which were partially accounted for by differences in adiposity, psychological distress, and health behaviours. In contrast, cognitive reappraisal predicted prospective decreases in IL-6 (B = -0.007, p = 0.006), which were independent of biopsychosocial influences. Cognitive reappraisal further moderated the association between childhood trauma and prospective changes in IL-6 (B = -0.001, p = 0.012) such that childhood trauma predicted greater IL-6 increases but only among adults lower in cognitive reappraisal (B = 0.006, p = 0.007). There were no main or moderation effects of expressive suppression (ps > 0.05). Cognitive reappraisal may attenuate IL-6 changes over time and may moderate the prospective association between childhood trauma and systemic inflammation in midlife.
Collapse
Affiliation(s)
- Emily J. Jones
- Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Anna L. Marsland
- Department of Psychology, Kenneth P. Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Peter J. Gianaros
- Department of Psychology, Kenneth P. Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| |
Collapse
|
|
6
|
Singh AS, Borgohain L, Singh B. Aggression and its correlation with plasma C-reactive protein levels in patients with schizophrenia: A hospital based cross-sectional study. Indian J Psychiatry 2023; 65:667-670. [PMID: 37485401 PMCID: PMC10358810 DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_427_22] [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: 06/29/2022] [Revised: 03/02/2023] [Accepted: 05/06/2023] [Indexed: 07/25/2023] Open
Abstract
Background The correlation between plasma C-reactive protein (CRP) and aggression in schizophrenia has recently become an area of interest. As an acute phase reactant, neuro-immuno-modulatory and neurohumoral functions of CRP might have a role in understanding causation of aggression in disease and this may have implications in therapeutic intervention. Aims To assess aggression and plasma CRP in patients with schizophrenia and to compare aggression in patients with normal and elevated CRP. Methods and Material A hospital-based cross-sectional study was carried out over a period of one year (2019-2020). Patients of schizophrenia as per International Classification of Diseases 10 were selected. Modified Overt Aggression Scale was applied, and plasma CRP levels were estimated in the selected patients. Statistical Analysis Mean aggression scores were compared in patients with normal and elevated CRP. And aggression scores were correlated with plasma CRP levels. Results Mean aggression score (22.93 ± 2.80) was significantly (P < .001) higher in patients with elevated CRP. There is a positive correlation (r = 0.855, P < .001) between aggression and plasma CRP. Conclusion Patients with elevated CRP were more aggressive compared to the patients with normal CRP.
Collapse
Affiliation(s)
- Aru Shikha Singh
- Department of Psychiatry, Autonomous State Medical College, Firozabad, Uttar Pradesh, India
| | - Lakshimi Borgohain
- Department of Psychiatry, Lakhimpur Medical College and Hospital, North Lakhimpur, Assam, India
| | - Bhupindar Singh
- Department of General Medicine, Autonomous State Medical College, Firozabad, Uttar Pradesh, India
| |
Collapse
|
|
7
|
Coccaro EF, Lee R, Breen EC, Irwin MR. Plasma and cerebrospinal fluid inflammatory markers and human aggression. Neuropsychopharmacology 2023; 48:1060-1066. [PMID: 36804488 PMCID: PMC10209212 DOI: 10.1038/s41386-023-01541-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 01/05/2023] [Accepted: 01/24/2023] [Indexed: 02/19/2023]
Abstract
A growing body of work suggests that individuals with aggressive behavior and/or aggressive tendencies have evidence of chronic, low level, inflammation as manifested by elevated circulating levels of acute phase reactant proteins and pro-inflammatory cytokines. While animal studies report that direct application of pro-inflammatory proteins in brain increase aggressive behavior, there is no data on the relationship of central levels of these proteins and aggression in human subjects. We simultaneously measured levels of both plasma and lumbar cerebrospinal fluid (CSF) C-Reactive Protein (CRP) and IL-6, IL-8, and TNF-α in 77 medically healthy, drug-free, individuals with varying degrees of aggression including 22 individuals with DSM-5 Intermittent Explosive Disorder (IED). Aggression was assessed using the Life History of Aggression (LHA) and the Buss-Perry Aggression Questionnaire (BPAQ). Plasma and CSF levels of CRP, IL-8, and TNF-α, but not IL-6, correlated significantly with each other. Aggressive individuals with IED displayed elevated plasma, but not CSF, levels of proinflammatory markers and this relationship was specific to IED. Similarly, composite aggression scores correlated significantly with plasma, but not CSF, pro-inflammatory markers. Aggressive behavior in humans is correlated with Plasma, but not CSF, proinflammatory markers despite the observation that these two sets of markers are significantly correlated. Since the direct application of proinflammatory proteins in brains of animals increase aggressive behavior, proinflammatory proteins likely influence brain-based behavior in a manner not reflected in lumbar CSF.
Collapse
Affiliation(s)
- Emil F Coccaro
- Clinical Neuroscience and Psychotherapeutics Research Unit, Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
| | - Royce Lee
- Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA
| | - Elizabeth C Breen
- Department of Psychiatry & Biobehavioral Sciences and Medicine, Norman Cousins Center, and Semel Institute, UCLA School of Medicine, Los Angeles, CA, USA
| | - Michael R Irwin
- Department of Psychiatry & Biobehavioral Sciences and Medicine, Norman Cousins Center, and Semel Institute, UCLA School of Medicine, Los Angeles, CA, USA
| |
Collapse
|
|
8
|
Meruelo AD, Timmins MA, Irwin MR, Coccaro EF. Salivary cortisol awakening levels are reduced in human subjects with intermittent explosive disorder compared with controls. Psychoneuroendocrinology 2023; 151:106070. [PMID: 36863129 PMCID: PMC10262314 DOI: 10.1016/j.psyneuen.2023.106070] [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: 06/26/2022] [Revised: 02/20/2023] [Accepted: 02/20/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND The role of the hypothalamic-pituitary-adrenal (HPA) axis in human aggressive behavior is poorly characterized, though some studies report that, unlike depression, circulating or salivary levels of cortisol are low compared with controls. METHODS In this study, we collected three salivary cortisol levels (two in the morning and one in the evening) on three separate days in 78 adult study participants with (n = 28) and without (n = 52) prominent histories of impulsive aggressive behavior. Plasma C-Reactive Protein (CRP) and Interleukin-6 (IL-6) were also collected in most study participants. Aggressive study participants meet DSM-5 criteria for Intermittent Explosive Disorder (IED) while non-aggressive participants either had a history of a psychiatric disorder or no such history (Controls). RESULTS Morning, but not evening, salivary cortisol levels were significantly lower in IED (p < 0.05), compared with control, study participants. In addition, salivary cortisol levels correlated with measures of trait anger (partial r = -0.26, p < 0.05) and aggression (partial r = -0.25, p < 0.05) but not with measures of impulsivity, psychopathy, depression, history of childhood maltreatment, or other tested variables that often differ in individuals with IED. Finally, plasma CRP levels correlated inversely with morning salivary cortisol levels (partial r = -0.28, p < 0.05); plasma IL-6 levels showed a similar, though not statistically significant (rp = -0.20, p = 0.12) relationship with morning salivary cortisol levels. CONCLUSION The cortisol awakening response appears to be lower in individuals with IED compared with controls. In all study participants, morning salivary cortisol levels correlated inversely with trait anger, trait aggression, and plasma CRP, a marker of systemic inflammation. This suggests the present of a complex interaction between chronic-low level inflammation, the HPA axis, and IED that warrants further investigation.
Collapse
Affiliation(s)
- Alejandro D Meruelo
- Department of Psychiatry, University of California, San Diego, San Diego, CA, USA
| | - Matthew A Timmins
- Clinical Neuroscience and Psychotherapeutics Research Unit, Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Michael R Irwin
- Department of Psychiatry & Biobehavioral Sciences and Medicine, Norman Cousins Center, and Semel Institute, UCLA School of Medicine, Los Angeles, CA, USA
| | - Emil F Coccaro
- Clinical Neuroscience and Psychotherapeutics Research Unit, Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
| |
Collapse
|
|
9
|
Ringwald WR, Kaurin A, DuPont CM, Gianaros PJ, Marsland AL, Muldoon MF, Wright AG, Manuck SB. The personality meta-trait of stability and carotid artery atherosclerosis. J Pers 2023; 91:271-284. [PMID: 35366346 PMCID: PMC10760807 DOI: 10.1111/jopy.12716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 02/07/2022] [Accepted: 03/27/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Several personality traits increase the risk for atherosclerotic cardiovascular disease. Because many of these traits are correlated, their associations with disease risk could reflect shared variance, rather than unique contributions of each trait. We examined a higher-order personality trait of Stability as related to preclinical atherosclerosis and tested whether any such relationship might be explained by correlated variation in cardiometabolic risk factors. METHOD Among 798 community volunteers, lower-order traits of Neuroticism, Agreeableness, and Conscientiousness were modeled as latent variables (from self- and informant ratings) and used to estimate the second-order factor, Stability. Cardiometabolic risk was similarly modeled from indicators of glycemic control, blood pressure, adiposity, and lipids. Carotid artery atherosclerosis was measured as intima-media thickness (IMT) by duplex ultrasonography. RESULT A structural equation model incorporating direct and indirect effects showed lower Stability associated with greater IMT, and this relationship was accounted for by the indirect pathway via cardiometabolic risk. Secondary analyses showed that: (1) Neuroticism, Agreeableness, and Conscientiousness were unrelated to IMT independent of Stability; and (2) Stability predicted variation in IMT when estimated from informant-, but not self-rated, traits. CONCLUSION Personality traits may associate with atherosclerotic burden through their shared, rather than unique, variance, as reflected in Stability.
Collapse
Affiliation(s)
| | - Aleksandra Kaurin
- Faculty of Health/School of Psychology and Psychiatry, Witten/Herdecke University
| | | | | | | | - Matthew F. Muldoon
- Cardiology Division, Department of Medicine, University of Pittsburgh School of Medicine
| | | | | |
Collapse
|
|
10
|
Hjell G, Szabo A, Mørch-Johnsen L, Holst R, Tesli N, Bell C, Fischer-Vieler T, Werner MCF, Lunding SH, Ormerod MBEG, Johansen IT, Dieset I, Djurovic S, Melle I, Ueland T, Andreassen OA, Steen NE, Haukvik UK. Interleukin-18 signaling system links to agitation in severe mental disorders. Psychoneuroendocrinology 2022; 140:105721. [PMID: 35301151 DOI: 10.1016/j.psyneuen.2022.105721] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 02/05/2022] [Accepted: 03/09/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Agitation is a challenging clinical feature in severe mental disorders, but its biological correlates are largely unknown. Inflammasome-related abnormalities have been linked to severe mental disorders and implicated in animal models of agitation. We investigated if levels of circulating inflammasome-related immune markers were associated with agitation in severe mental disorders. METHODS Individuals with a psychotic or affective disorder (N = 660) underwent blood sampling and clinical characterization. Plasma levels of interleukin (IL)-18, IL-18 binding protein (IL-18BP), IL-18 receptor 1 (IL-18R1), IL-18 receptor accessory protein (IL-18RAP), and IL-1 receptor antagonist (IL-1RA) were measured. Agitation levels were estimated with the Positive and Negative Syndrome Scale Excited Component. Multiple linear- and logistic regression were used to investigate the associations between agitation and the immune markers, while controlling for confounders. The influence of psychotic and affective symptoms was assessed in follow-up analyses. RESULTS Agitation was positively associated with IL-18BP (β = 0.13, t = 3.41, p = 0.0007) after controlling for multiple confounders, including BMI, smoking, medication, and substance use. Adjustment for psychotic, manic, and depressive symptoms did not affect the results. There were no significant associations between agitation and the other investigated immune markers (IL-1RA (β = 0.06, t = 1.27, p = 0.20), IL-18 (β = 0.05, t = 1.25, p = 0.21), IL-18R1 (β = 0.04, t = 1.01, p = 0.31), IL-18RAP (odds ratio = 0.96, p = 0.30)). In a subsample (N = 463), we also adjusted for cortisol levels, which yielded unaltered results. CONCLUSION Our findings add to the accumulating evidence of immune system disturbances in severe mental disorders and suggest the IL-18 system as a part of the biological correlate of agitation independent of affective and psychotic symptoms.
Collapse
Affiliation(s)
- Gabriela Hjell
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry & Department of Clinical Research, Østfold Hospital, Grålum, Norway.
| | - Attila Szabo
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Lynn Mørch-Johnsen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry & Department of Clinical Research, Østfold Hospital, Grålum, Norway
| | - René Holst
- Department of Psychiatry & Department of Clinical Research, Østfold Hospital, Grålum, Norway; Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Natalia Tesli
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Christina Bell
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Thomas Fischer-Vieler
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Maren Caroline Frogner Werner
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Synve Hoffart Lunding
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | | | - Ingrid Torp Johansen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ingrid Dieset
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Acute Psychiatric Department, Oslo University Hospital, Oslo, Norway
| | - Srdjan Djurovic
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Ingrid Melle
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Thor Ueland
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway
| | - Ole Andreas Andreassen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Nils Eiel Steen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Unn Kristin Haukvik
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Adult Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| |
Collapse
|
|
11
|
The Neutrophil-Lymphocyte Ratio Is Positively Correlated with Aggression in Schizophrenia. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4040974. [PMID: 35502339 PMCID: PMC9056227 DOI: 10.1155/2022/4040974] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 12/20/2022]
Abstract
To find biomarkers to assess the risk of aggression, we looked at the association between aggression and levels of body inflammation in patients with schizophrenia. The Modified Overt Aggression Scale (MOAS) score was used to divide the aggressive (n = 72) and nonaggressive (n = 141) groups. The Brief Psychiatric Rating Scale (BPRS) is a tool for determining the severity of a patient's condition. After measuring the number of inflammatory cells in the peripheral blood, the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and monocyte-lymphocyte ratio (MLR) were estimated. We investigated the relationship between aggressive behavior, bodily inflammation, and BPRS. Before therapy, the aggressive group's BPRS score, white blood cell (WBC) count, neutrophil count, monocyte count, NLR, and MLR were considerably more significant than the nonaggressive group's. After therapy, statistically significant variations in total BPRS score and neutrophil count between the two groups. According to correlation analysis before and after treatment, aggressive behavior was positively connected with neutrophil count, NLR, and BPRS score. The presence of aggressive behavior in schizophrenic patients indicates the severity of the disorder to some degree. NLR can be used as an objective biomarker to quickly assess the risk of aggression in schizophrenic patients.
Collapse
|
|
12
|
Topal Z, Tufan AE, Karadag M, Gokcen C, Akkaya C, Sarp AS, Bahsi I, Kilinc M. Evaluation of peripheral inflammatory markers, serum B12, folate, ferritin levels and clinical correlations in children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Nord J Psychiatry 2022; 76:150-157. [PMID: 34232109 DOI: 10.1080/08039488.2021.1946712] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
AIM The aim of the current study is to compare serum B12, folate, and ferritin levels and peripheral inflammatory indicators between children with Autism Spectrum Disorders (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and healthy controls (HC) and to evaluate the correlation of those with symptoms. MATERIALS AND METHODS A total of 203 children were evaluated (ASD = 72; ADHD = 61; HC = 70). Diagnoses of ASD and ADHD were ascertained according to Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL). Control group was chosen among the healthy children who applied to general pediatrics outpatient clinic. Gilliam Autism Rating Scale-2 is used to assess autistic symptoms and Atilla Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale is used for ADHD symptoms. RESULTS Neutrophil levels (p = 0.014) and neutrophil/lymphocyte ratio (NLR) (p = 0.016) were higher in the ADHD and ASD groups compared to HC. Neutrophil values explained 70.1% of the variance across groups while NLR explained a further 29.9% of the variance. NLR significantly correlated with social interaction problems in ASD (r = 0.26, p = 0.04). There were no significant differences between groups in terms of vitamin B12, folate and ferritin levels. CONCLUSION Our results may support involvement of inflammation in the underlying pathophysiology of neurodevelopmental disorders. However, these parameters should be analyzed in a wider population to clarify the effect on the etiology and symptomatology of neurodevelopmental disorders.
Collapse
Affiliation(s)
- Zehra Topal
- Department of Child and Adolescent Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Ali Evren Tufan
- Department of Child and Adolescent Psychiatry, Faculty of Medicine, Abant Izzet Baysal University, Bolu, Turkey
| | - Mehmet Karadag
- Department of Child and Adolescent Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Cem Gokcen
- Department of Child and Adolescent Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Canan Akkaya
- Department of Child and Adolescent Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Ayse Sevde Sarp
- Department of Child and Adolescent Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Ilhan Bahsi
- Department of Anatomy, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Metin Kilinc
- Department of Pediatrics, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| |
Collapse
|
|
13
|
Coccaro EF, Irwin M, Arevalo JMG, Dizon T, Cole S. Gene expression in peripheral blood mononuclear cells in impulsive aggression: Intermittent explosive disorder compared with non-aggressive healthy and psychiatric controls. Psychoneuroendocrinology 2022; 136:105453. [PMID: 34864503 DOI: 10.1016/j.psyneuen.2021.105453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 09/07/2021] [Accepted: 10/15/2021] [Indexed: 11/25/2022]
Abstract
Evidence of chronic, systemic, low levels of inflammation is present in several stress-related psychiatric conditions including schizophrenia, depression, and intermittent explosive disorder (IED). We analyzed leukocyte gene expression (mRNA) to quantify the activity of pro and anti-inflammatory signaling pathways. Work performed in non-aggressive populations has uncovered a Conserved Transcriptional Response to Adversity (CTRA) characterized by an upregulation of pro-inflammatory gene transcription in chronically stressed individuals. We used pathway-based bioinformatic analyses of genome-wide transcriptional profiles of peripheral blood leukocyte samples from IED study participants (N = 45) and controls [healthy (n = 45) and psychiatric (n = 34)], with analyses focusing on the pro-inflammatory transcription control pathway mediated by the NF-kB family of transcription factors (typically upregulated in CTRA) and the antiviral transcription control pathway mediated by anti-viral response (IRF) family transcription factors (typically downregulated in CTRA). Compared with both healthy and psychiatric controls, individuals with IED had upregulated transcriptional activity of the antiviral response (IRF), but no evidence of pro-inflammatory NF-kB activation. Analyses implicated CD4 + T cells, CD8 + T cells, and B lymphocytes in IED-related transcriptional alterations, but showed no significant indication of monocyte involvement. This suggests that the inflammatory profile of IED differs substantially from that observed previously in other stress-related disorders, and may involve a pathogen-driven adaptive immune etiology.
Collapse
Affiliation(s)
- Emil F Coccaro
- Clinical Neuroscience & Psychotherapeutics Research Unit, Department of Psychiatry and Behavioral Healthy, Wexner College of Medicine, The Ohio State University, Columbus, OH, United States.
| | - Michael Irwin
- Departments of Psychiatry & Biobehavioral Sciences and Medicine, Norman Cousins Center, and Semel Institute, UCLA School of Medicine, Los Angeles, CA, United States
| | - Jesusa M G Arevalo
- Departments of Psychiatry & Biobehavioral Sciences and Medicine, Norman Cousins Center, and Semel Institute, UCLA School of Medicine, Los Angeles, CA, United States
| | - Thomas Dizon
- Departments of Psychiatry & Biobehavioral Sciences and Medicine, Norman Cousins Center, and Semel Institute, UCLA School of Medicine, Los Angeles, CA, United States
| | - Steven Cole
- Departments of Psychiatry & Biobehavioral Sciences and Medicine, Norman Cousins Center, and Semel Institute, UCLA School of Medicine, Los Angeles, CA, United States
| |
Collapse
|
|
14
|
Castle R, Bushell WC, Mills PJ, Williams MA, Chopra D, Rindfleisch JA. Global Correlations Between Chronic Inflammation and Violent Incidents: Potential Behavioral Consequences of Inflammatory Illnesses Across Socio-Demographic Levels. Int J Gen Med 2021; 14:6677-6691. [PMID: 34675629 PMCID: PMC8520436 DOI: 10.2147/ijgm.s324367] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Accepted: 09/01/2021] [Indexed: 01/05/2023] Open
Abstract
Introduction This review explores the potential correlation between conditions associated with chronic inflammation and measures of violence across five socioeconomic subgroups. The hypothesis being that since chronic inflammation is associated with increased aggression, an extreme version of which is violence, there should be a correlation between incidents of violence and diseases with one or more inflammatory factors, without an equivalent correlation with the contrast group. An extension of this reasoning would predict a higher correlation among lower socio-demographic index (SDI) populations as a result of fewer resources to prevent either inflammatory disease or violent crime. Methods In order to examine this potential correlation, an analysis was made comparing rates of change in incidence between violence, inflammatory conditions, and a contrast group disease of noninflammatory nature, as determined by Pearson's correlation coefficient. Results In the low socio-demographic index, inflammatory conditions demonstrated 80% correlation with interpersonal violence, middle-low socio-demographic index inflammatory conditions demonstrated 60% correlation with interpersonal violence, middle socio-demographic index inflammatory conditions demonstrated 0% correlation with interpersonal violence, middle-high socio-demographic index inflammatory conditions demonstrated 60% correlation with interpersonal violence, and high socio-demographic index inflammatory conditions demonstrated 40% correlation with interpersonal violence. Discussion The majority of socio-demographic groups showed a significant correlation between rates of change in incidence of violence and inflammatory conditions. This correlation was not found with a similar frequency or strength in diseases not causally linked to inflammation. As predicted in the hypothesis, the highest correlations of inflammatory diseases with violence existed in the lower socio-demographic populations, supporting a link between inflammatory levels and incidences of violence.
Collapse
Affiliation(s)
- Ryan Castle
- Science Division, Whole Health Institute, Bentonville, AR, USA
| | | | - Paul J Mills
- Herbert Wertheim School of Public Health and Human Longevity Science, Center of Excellence for Research and Training in Integrative Health, University of California San Diego, La Jolla, CA, USA
| | - Michelle A Williams
- Harvard T.H. Chan School of Public Health, Department of Global Health and Population, Harvard University, Boston, MA, USA
| | | | - James A Rindfleisch
- Education Department, Whole Health School of Medicine and Health Sciences, Bentonville, AR, USA
| |
Collapse
|
|
15
|
Krueger RF, Hobbs KA, Conway CC, Dick DM, Dretsch MN, Eaton NR, Forbes MK, Forbush KT, Keyes KM, Latzman RD, Michelini G, Patrick CJ, Sellbom M, Slade T, South S, Sunderland M, Tackett J, Waldman I, Waszczuk MA, Wright AG, Zald DH, Watson D, Kotov R, HiTOP Utility Workgroup. Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): II. Externalizing superspectrum. World Psychiatry 2021; 20:171-193. [PMID: 34002506 PMCID: PMC8129870 DOI: 10.1002/wps.20844] [Citation(s) in RCA: 129] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical effort to address limitations of traditional mental disorder diagnoses. These include arbitrary boundaries between disorder and normality, disorder co-occurrence in the modal case, heterogeneity of presentation within dis-orders, and instability of diagnosis within patients. This paper reviews the evidence on the validity and utility of the disinhibited externalizing and antagonistic externalizing spectra of HiTOP, which together constitute a broad externalizing superspectrum. These spectra are composed of elements subsumed within a variety of mental disorders described in recent DSM nosologies, including most notably substance use disorders and "Cluster B" personality disorders. The externalizing superspectrum ranges from normative levels of impulse control and self-assertion, to maladaptive disinhibition and antagonism, to extensive polysubstance involvement and personality psychopathology. A rich literature supports the validity of the externalizing superspectrum, and the disinhibited and antagonistic spectra. This evidence encompasses common genetic influences, environmental risk factors, childhood antecedents, cognitive abnormalities, neural alterations, and treatment response. The structure of these validators mirrors the structure of the phenotypic externalizing superspectrum, with some correlates more specific to disinhibited or antagonistic spectra, and others relevant to the entire externalizing superspectrum, underlining the hierarchical structure of the domain. Compared with traditional diagnostic categories, the externalizing superspectrum conceptualization shows improved utility, reliability, explanatory capacity, and clinical applicability. The externalizing superspectrum is one aspect of the general approach to psychopathology offered by HiTOP and can make diagnostic classification more useful in both research and the clinic.
Collapse
Affiliation(s)
| | - Kelsey A. Hobbs
- Department of PsychologyUniversity of MinnesotaMinneapolisMNUSA
| | | | - Danielle M. Dick
- Department of PsychologyVirginia Commonwealth UniversityRichmondVAUSA
| | - Michael N. Dretsch
- US Army Medical Research Directorate ‐ WestWalter Reed Army Institute of Research, Joint Base Lewis‐McChordWAUSA
| | | | - Miriam K. Forbes
- Centre for Emotional Health, Department of PsychologyMacquarie UniversitySydneyNSWAustralia
| | | | | | | | - Giorgia Michelini
- Semel Institute for Neuroscience and Human BehaviorUniversity of California Los AngelesLos AngelesCAUSA
| | | | - Martin Sellbom
- Department of PsychologyUniversity of OtagoDunedinNew Zealand
| | - Tim Slade
- Matilda Centre for Research in Mental Health and Substance UseUniversity of SydneySydneyNSWAustralia
| | - Susan C. South
- Department of Psychological SciencesPurdue UniversityWest LafayetteINUSA
| | - Matthew Sunderland
- Matilda Centre for Research in Mental Health and Substance UseUniversity of SydneySydneyNSWAustralia
| | | | - Irwin Waldman
- Department of PsychologyEmory UniversityAtlantaGAUSA
| | | | | | - David H. Zald
- Department of PsychologyVanderbilt UniversityNashvilleTNUSA
| | - David Watson
- Department of PsychologyUniversity of Notre DameNotre DameINUSA
| | - Roman Kotov
- Department of PsychiatryStony Brook UniversityStony BrookNYUSA
| | | |
Collapse
|
|
16
|
Tripathy S, Marsland AL, Kinnee EJ, Tunno BJ, Manuck SB, Gianaros PJ, Clougherty JE. Long-Term Ambient Air Pollution Exposures and Circulating and Stimulated Inflammatory Mediators in a Cohort of Midlife Adults. ENVIRONMENTAL HEALTH PERSPECTIVES 2021; 129:57007. [PMID: 34014775 PMCID: PMC8136520 DOI: 10.1289/ehp7089] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
Abstract
BACKGROUND Chronic exposure to air pollution may prime the immune system to be reactive, increasing inflammatory responses to immune stimulation and providing a pathway to increased risk for inflammatory diseases, including asthma and cardiovascular disease. Although long-term exposure to ambient air pollution has been associated with increased circulating markers of inflammation, it is unknown whether it also relates to the magnitude of inflammatory response. OBJECTIVES The aim of this study was to examine associations between chronic ambient pollution exposures and circulating and stimulated levels of inflammatory mediators in a cohort of healthy adults. METHODS Circulating interleukin (IL)-6, C-reactive protein (CRP) (n=392), and lipopolysaccharide stimulated production of IL-1β, IL-6, and tumor necrosis factor (TNF)-α (n=379) were measured in the Adult Health and Behavior II cohort. Fine particulate matter [particulate matter with aerodynamic diameter less than or equal to 2.5 μm (PM2.5)] and constituents [black carbon (BC), and lead (Pb), manganese (Mn), zinc (Zn), and iron (Fe)] were estimated for each residential address using hybrid dispersion land use regression models. Associations between pollutant exposures and inflammatory measures were examined using linear regression; models were adjusted for age, sex, race, education, smoking, body mass index, and month of blood draw. RESULTS There were no significant correlations between circulating and stimulated measures of inflammation. Significant positive associations were found between exposure to PM2.5 and BC with stimulated production of IL-6, IL-1β, and TNF-α. Pb, Mn, Fe, and Zn exposures were positively associated with stimulated production of IL-1β and TNF-α. No pollutants were associated with circulating IL-6 or CRP levels. DISCUSSION Exposure to PM2.5, BC, Pb, Mn, Fe, and Zn was associated with increased production of inflammatory mediators by stimulated immune cells. In contrast, pollutant exposure was not related to circulating markers of inflammation. These results suggest that chronic exposure to some pollutants may prime immune cells to mount larger inflammatory responses, possibly contributing to increased risk for inflammatory disease. https://doi.org/10.1289/EHP7089.
Collapse
Affiliation(s)
- Sheila Tripathy
- Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
- Department of Environmental and Occupational Health, Drexel University Dornsife School of Public Health, Philadelphia, Pennsylvania, USA
| | - Anna L. Marsland
- Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Ellen J. Kinnee
- University Center for Social and Urban Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Brett J. Tunno
- Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
| | - Stephen B. Manuck
- Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Peter J. Gianaros
- Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Jane E. Clougherty
- Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
- Department of Environmental and Occupational Health, Drexel University Dornsife School of Public Health, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
17
|
Infection threat shapes our social instincts. Behav Ecol Sociobiol 2021; 75:47. [PMID: 33583997 PMCID: PMC7873116 DOI: 10.1007/s00265-021-02975-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 01/05/2021] [Accepted: 01/11/2021] [Indexed: 02/07/2023]
Abstract
We social animals must balance the need to avoid infections with the need to interact with conspecifics. To that end we have evolved, alongside our physiological immune system, a suite of behaviors devised to deal with potentially contagious individuals. Focusing mostly on humans, the current review describes the design and biological innards of this behavioral immune system, laying out how infection threat shapes sociality and sociality shapes infection threat. The paper shows how the danger of contagion is detected and posted to the brain; how it affects individuals’ mate choice and sex life; why it strengthens ties within groups but severs those between them, leading to hostility toward anyone who looks, smells, or behaves unusually; and how it permeates the foundation of our moral and political views. This system was already in place when agriculture and animal domestication set off a massive increase in our population density, personal connections, and interaction with other species, amplifying enormously the spread of disease. Alas, pandemics such as COVID-19 not only are a disaster for public health, but, by rousing millions of behavioral immune systems, could prove a threat to harmonious cohabitation too.
Collapse
|
|
18
|
Li C, Shi Z, Ji J, Niu G, Liu Z. Associations of C-Reactive Protein, Free Triiodothyronine, Thyroid Stimulating Hormone and Creatinine Levels with Agitation in Patients with Schizophrenia: A Comparative Cross-Sectional Study. Neuropsychiatr Dis Treat 2021; 17:2575-2585. [PMID: 34408419 PMCID: PMC8364367 DOI: 10.2147/ndt.s322005] [Citation(s) in RCA: 7] [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: 05/28/2021] [Accepted: 08/01/2021] [Indexed: 01/11/2023] Open
Abstract
PURPOSE Agitation is prevalent among inpatients with schizophrenia. The aim of this study was to investigate whether biochemical parameters are associated with agitation in schizophrenia. PATIENTS AND METHODS Agitation was evaluated by the Positive and Negative Syndrome Scale-Excited Component questionnaire (PANSS-EC). Fasting serum levels of C-reactive protein (CRP), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), uric acid (UA), creatinine, glucose and lipids were measured. RESULTS The analysis included 154 inpatients with schizophrenia (71 with agitation, 83 without agitation) and 75 healthy control subjects. Patients with schizophrenia and agitation had higher serum levels of CRP, FT3, FT4 and UA as well as lower levels of serum TSH and creatinine than patients without agitation (all P < 0.05). Multivariate logistic regression analysis indicated that serum CRP (odds ratio [OR] = 1.470, P = 0.001), FT3 (OR = 13.026, P < 0.001), TSH (OR = 0.758, P = 0.033) and creatinine (OR = 0.965, P = 0.004) were significantly associated with agitation in schizophrenia. CRP, FT3, TSH and creatinine achieved an area under the ROC curve of 0.626, 0.728, 0.620 and 0.663 respectively in discriminating schizophrenia with or without agitation. CONCLUSION Increased serum CRP and FT3 levels and decreased serum TSH and creatinine levels are independent risk factors for agitation in hospitalized patients with schizophrenia. Inflammation, thyroid hormones and renal function may be involved in the pathogenesis of agitation in schizophrenia.
Collapse
Affiliation(s)
- Chao Li
- Department of Psychiatry, Jining Medical University, Jining, 272067, People's Republic of China
| | - Zhenchun Shi
- Department of Psychiatry, Shandong Mental Health Center, Jinan, 250014, People's Republic of China
| | - Jiacui Ji
- Department of Psychiatry, Shandong Mental Health Center, Jinan, 250014, People's Republic of China
| | - Gengyun Niu
- Department of Psychiatry, Jining Medical University, Jining, 272067, People's Republic of China
| | - Zengxun Liu
- Department of Psychiatry, Shandong Mental Health Center, Jinan, 250014, People's Republic of China
| |
Collapse
|
|
19
|
DuPont CM, Wright AGC, Manuck SB, Muldoon MF, Jennings JR, Gianaros PJ. Is stressor-evoked cardiovascular reactivity a pathway linking positive and negative emotionality to preclinical cardiovascular disease risk? Psychophysiology 2020; 58:e13741. [PMID: 33278305 DOI: 10.1111/psyp.13741] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 11/06/2020] [Accepted: 11/10/2020] [Indexed: 11/28/2022]
Abstract
Stressor-evoked cardiovascular reactivity, trait positive emotionality, and negative emotionality are all associated with cardiovascular disease. It is unknown, however, whether cardiovascular reactivity may constitute a pathway by which trait positive or negative emotionality relates to disease risk. Accordingly, this study modeled the cross-sectional relationships between trait positive and negative emotionality, stressor-evoked cardiovascular reactivity, and severity of a subclinical vascular marker of cardiovascular risk, carotid artery intima-media thickness (CA-IMT). The sample consisted of healthy, midlife adults free from clinical cardiovascular disease (N = 286; ages 30-54; 50% female). Trait positive and negative emotionality were measured by three questionnaires. Heart rate and blood pressure reactivity were assessed across three stressor tasks. CA-IMT was assessed by ultrasonography. Latent factors of positive and negative emotionality, blood pressure reactivity, heart rate reactivity, and CA-IMT were created using structural equation modeling. Greater negative emotionality was marginally associated with more CA-IMT (β = .21; p = .049), but lower blood pressure reactivity (β = -.19; p = .03). However, heightened blood pressure (β = .21; p = .03), but not heart rate reactivity (β = -.05; p = .75), associated with greater CA-IMT. Positive emotionality was uncorrelated with cardiovascular reactivity (blood pressure: β = -.04; p = .61; heart rate: β = .16; p = .11) and CA-IMT (β = .16; p = .07). Although trait negative emotionality associates with a known marker of cardiovascular disease risk, independent of positive emotionality, it is unlikely to occur via a stressor-evoked cardiovascular reactivity pathway.
Collapse
Affiliation(s)
- Caitlin M DuPont
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Aidan G C Wright
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Stephen B Manuck
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Matthew F Muldoon
- Heart and Vascular Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - J Richard Jennings
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.,Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Peter J Gianaros
- Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| |
Collapse
|
|
20
|
Somma A, Krueger RF, Markon KE, Alajmo VBM, Arlotta E, Beretta S, Boni F, Busso SL, Manini R, Nazzaro G, Maffei C, Fossati A. DSM-5 Alternative Model of Personality Disorder Dysfunctional Personality Traits as Predictors of Self-Reported Aggression in an Italian Sample of Consecutively Admitted, Personality-Disordered Psychotherapy Patients. J Pers Disord 2020; 34:5-24. [PMID: 31206343 DOI: 10.1521/pedi_2019_33_430] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
In order to assess the relationships between DSM-5 Alternative Model of Personality Disorder (AMPD) maladaptive personality traits and self-reports of aggression, 508 Italian adult participants who met at least one DSM-IV Axis II/DSM-5 Section II personality disorder (PD) diagnosis were administered the Personality Inventory for DSM-5 (PID-5) and the Aggression Questionnaire (AQ). Analysis results showed that multiple regression results, PID-5 Hostility, Callousness, and Risk Taking trait scale scores explained a large amount of variance in AQ Physical Aggression (PA) scores. Moreover, PID-5 Hostility, Callousness, and Risk Taking explained more than 20% of the variance in the AQ Physical Aggression scale scores that was left unexplained by selected continuously scored DSM-IV Axis II/DSM-5 Section II PDs, whereas SCID-II Paranoid, Narcissistic, Borderline, and Antisocial PDs added only 4% of variance to the amount of variance in AQ Physical Aggression scores that was already explained by the PID-5 trait scale scores.
Collapse
Affiliation(s)
- Antonella Somma
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| | | | | | - Valentina B M Alajmo
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| | - Emanuela Arlotta
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| | - Stefano Beretta
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| | - Francesca Boni
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| | - Stefano L Busso
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| | - Riccardo Manini
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| | - Giovanni Nazzaro
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| | - Cesare Maffei
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| | - Andrea Fossati
- Vita-Salute San Raffaele University, Milan, Italy, and IRCCS San Raffaele Turro Hospital, Milan, Italy
| |
Collapse
|
|
21
|
Nordgreen J, Edwards SA, Boyle LA, Bolhuis JE, Veit C, Sayyari A, Marin DE, Dimitrov I, Janczak AM, Valros A. A Proposed Role for Pro-Inflammatory Cytokines in Damaging Behavior in Pigs. Front Vet Sci 2020; 7:646. [PMID: 33134341 PMCID: PMC7562715 DOI: 10.3389/fvets.2020.00646] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 08/10/2020] [Indexed: 12/28/2022] Open
Abstract
Sickness can change our mood for the worse, leaving us sad, lethargic, grumpy and less socially inclined. This mood change is part of a set of behavioral symptoms called sickness behavior and has features in common with core symptoms of depression. Therefore, the physiological changes induced by immune activation, for example following infection, are in the spotlight for explaining mechanisms behind mental health challenges such as depression. While humans may take a day off and isolate themselves until they feel better, farm animals housed in groups have only limited possibilities for social withdrawal. We suggest that immune activation could be a major factor influencing social interactions in pigs, with outbreaks of damaging behavior such as tail biting as a possible result. The hypothesis presented here is that the effects of several known risk factors for tail biting are mediated by pro-inflammatory cytokines, proteins produced by the immune system, and their effect on neurotransmitter systems. We describe the background for and implications of this hypothesis.
Collapse
Affiliation(s)
- Janicke Nordgreen
- Department of Paraclinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway
| | - Sandra A. Edwards
- School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Laura Ann Boyle
- Teagasc Animal and Grassland Research and Innovation Centre, Fermoy, Ireland
| | - J. Elizabeth Bolhuis
- Adaptation Physiology Group, Wageningen University & Research, Wageningen, Netherlands
| | - Christina Veit
- Department of Paraclinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway
| | - Amin Sayyari
- Department of Production Animal Clinical Science, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway
| | - Daniela E. Marin
- National Institute for Research and Development for Biology and Animal Nutrition, Balotesti, Romania
| | | | - Andrew M. Janczak
- Department of Production Animal Clinical Science, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway
| | - Anna Valros
- Department of Production Animal Medicine, Research Centre for Animal Welfare, University of Helsinki, Helsinki, Finland
| |
Collapse
|
|
22
|
Onaciu A, Munteanu R, Munteanu VC, Gulei D, Raduly L, Feder RI, Pirlog R, Atanasov AG, Korban SS, Irimie A, Berindan-Neagoe I. Spontaneous and Induced Animal Models for Cancer Research. Diagnostics (Basel) 2020; 10:E660. [PMID: 32878340 PMCID: PMC7555044 DOI: 10.3390/diagnostics10090660] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 08/24/2020] [Accepted: 08/24/2020] [Indexed: 12/14/2022] Open
Abstract
Considering the complexity of the current framework in oncology, the relevance of animal models in biomedical research is critical in light of the capacity to produce valuable data with clinical translation. The laboratory mouse is the most common animal model used in cancer research due to its high adaptation to different environments, genetic variability, and physiological similarities with humans. Beginning with spontaneous mutations arising in mice colonies that allow for pursuing studies of specific pathological conditions, this area of in vivo research has significantly evolved, now capable of generating humanized mice models encompassing the human immune system in biological correlation with human tumor xenografts. Moreover, the era of genetic engineering, especially of the hijacking CRISPR/Cas9 technique, offers powerful tools in designing and developing various mouse strains. Within this article, we will cover the principal mouse models used in oncology research, beginning with behavioral science of animals vs. humans, and continuing on with genetically engineered mice, microsurgical-induced cancer models, and avatar mouse models for personalized cancer therapy. Moreover, the area of spontaneous large animal models for cancer research will be briefly presented.
Collapse
Affiliation(s)
- Anca Onaciu
- Research Center for Advanced Medicine - Medfuture, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania; (A.O.); (R.M.); (R.-I.F.)
| | - Raluca Munteanu
- Research Center for Advanced Medicine - Medfuture, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania; (A.O.); (R.M.); (R.-I.F.)
| | - Vlad Cristian Munteanu
- Department of Urology, The Oncology Institute “Prof Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania;
- Department of Anatomy and Embryology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Diana Gulei
- Research Center for Advanced Medicine - Medfuture, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania; (A.O.); (R.M.); (R.-I.F.)
| | - Lajos Raduly
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania; (L.R.); (R.P.)
| | - Richard-Ionut Feder
- Research Center for Advanced Medicine - Medfuture, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania; (A.O.); (R.M.); (R.-I.F.)
| | - Radu Pirlog
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania; (L.R.); (R.P.)
- Department of Morphological Sciences, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Atanas G. Atanasov
- Ludwig Boltzmann Institute for Digital Health and Patient Safety, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria;
- Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, 05-552 Magdalenka, Poland
- Institute of Neurobiology, Bulgarian Academy of Sciences, 23 Acad. G. Bonchev str., 1113 Sofia, Bulgaria
- Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria
| | - Schuyler S. Korban
- Department of Natural Resources and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;
| | - Alexandru Irimie
- 11th Department of Surgical Oncology and Gynaecological Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania;
- Department of Surgery, The Oncology Institute Prof. Dr. Ion Chiricuta, 34–36 Republicii Street, 400015 Cluj-Napoca, Romania
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania; (L.R.); (R.P.)
- Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania
| |
Collapse
|
|
23
|
Weiss A, Costa PT, Deary IJ, Garside DB, Stamler J. The MMPI factor scales and risk of death in men during 45 years of follow-up: The Western Electric study. Psychol Aging 2019; 35:97-111. [PMID: 31714099 DOI: 10.1037/pag0000421] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
We examined associations between personality traits measured in 1958 and both all-cause and cause-specific mortality assessed 45 years later in 2003. Participants were 1,862 middle-aged men employed by the Western Electric Company. Outcomes were days to death from all causes, coronary heart disease, stroke, cancer, and causes other than circulatory diseases, cancer, accidents/homicide/suicides, or injuries (other causes). Measures in 1958 included age, education, health behaviors, biomedical risk factors, and nine content factors identified in the Minnesota Multiphasic Personality Inventory (MMPI). Four content factors-neuroticism, cynicism, extraversion, and intellectual interests-were related to the five-factor model domains of neuroticism, agreeableness, extraversion, and openness, respectively. The remaining five-psychoticism, masculinity versus femininity, religious orthodoxy, somatic complaints, and inadequacy-corresponded to the five-factor model's facets and styles (combinations of two domains) or were unrelated to the five-factor model. In age-adjusted and fully adjusted models, cynicism was associated with greater all-cause and cancer mortality. In fully adjusted models, inadequacy was associated with lower all-cause mortality and lower mortality from other causes. In age-adjusted models, religious orthodoxy was associated with lower cancer mortality. Further analyses revealed that the association between cynicism and all-cause mortality waned over time. Exploratory analyses of death from any disease of the circulatory system revealed no further associations. These findings reveal the importance of cynicism (disagreeableness) as a mortality risk factor, show that associations between cynicism and all-cause mortality are limited to certain periods of the lifespan, and highlight the need to study personality styles or types, such as inadequacy, that involve high neuroticism, low extraversion, and low conscientiousness. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Collapse
Affiliation(s)
| | | | - Ian J Deary
- Centre for Cognitive Ageing and Cognitive Epidemiology
| | | | | |
Collapse
|
|
24
|
Manchia M, Comai S, Pinna M, Pinna F, Fanos V, Denovan-Wright E, Carpiniello B. Biomarkers in aggression. Adv Clin Chem 2019; 93:169-237. [PMID: 31655730 DOI: 10.1016/bs.acc.2019.07.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Aggressive behavior exerts an enormous impact on society remaining among the main causes of worldwide premature death. Effective primary interventions, relying on predictive models of aggression that show adequate sensitivity and specificity are currently lacking. One strategy to increase the accuracy and precision of prediction would be to include biological data in the predictive models. Clearly, to be included in such models, biological markers should be reliably associated with the specific trait under study (i.e., diagnostic biomarkers). Aggression, however, is phenotypically highly heterogeneous, an element that has hindered the identification of reliable biomarkers. However, current research is trying to overcome these challenges by focusing on more homogenous aggression subtypes and/or by studying large sample size of aggressive individuals. Further advance is coming by bioinformatics approaches that are allowing the integration of inter-species biological data as well as the development of predictive algorithms able to discriminate subjects on the basis of the propensity toward aggressive behavior. In this review we first present a brief summary of the available evidence on neuroimaging of aggression. We will then treat extensively the data on genetic determinants, including those from hypothesis-free genome-wide association studies (GWAS) and candidate gene studies. Transcriptomic and neurochemical biomarkers will then be reviewed, and we will dedicate a section on the role of metabolomics in aggression. Finally, we will discuss how biomarkers can inform the development of new pharmacological tools as well as increase the efficacy of preventive strategies.
Collapse
Affiliation(s)
- Mirko Manchia
- Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
| | - Stefano Comai
- San Raffaele Scientific Institute and Vita Salute University, Milano, Italy; Department of Psychiatry, McGill University, Montreal, QC, Canada.
| | - Martina Pinna
- Forensic Psychiatry Unit, Sardinia Health Agency, Cagliari, Italy
| | - Federica Pinna
- Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Vassilios Fanos
- Department of Surgical Sciences, University of Cagliari, Cagliari, Italy; Puericulture Institute and Neonatal Section, University Hospital Agency of Cagliari, Cagliari, Italy
| | | | - Bernardo Carpiniello
- Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| |
Collapse
|
|
25
|
Calkins SD, Dollar JM, Wideman L. Temperamental vulnerability to emotion dysregulation and risk for mental and physical health challenges. Dev Psychopathol 2019; 31:957-970. [PMID: 31097043 PMCID: PMC8186844 DOI: 10.1017/s0954579419000415] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Emotion dysregulation characterizes many forms of psychopathology. Patterns of dysregulation occur as a function of a developmental process in which normative and adaptive emotion regulation skills fail to become part of the child's behavioral repertoire due to biological, psychological, and contextual processes and experiences. Here we highlight the processes involved in the dysregulation of temperamental anger and frustration that become core features of externalizing problems and place children at risk for more serious forms of psychopathology. We imbed these processes in a larger self-regulatory framework, and we discuss how they influence mental as well as physical health, using data from our 20-year longitudinal study following a large cohort of children into young adulthood. Recommendations are made for future research involving the integration of biological systems with mental and physical health outcomes.
Collapse
Affiliation(s)
- Susan D. Calkins
- Department of Human Development and Family Studies, University of North Carolina at Greensboro, Greensboro, NC, USA
| | - Jessica M. Dollar
- Department of Human Development and Family Studies, University of North Carolina at Greensboro, Greensboro, NC, USA
| | - Laurie Wideman
- Department of Kinesiology, University of North Carolina at Greensboro, Greensboro, NC, USA
| |
Collapse
|
|
26
|
Novel Treatment Targets Based on Insights in the Etiology of Depression: Role of IL-6 Trans-Signaling and Stress-Induced Elevation of Glutamate and ATP. Pharmaceuticals (Basel) 2019; 12:ph12030113. [PMID: 31362361 PMCID: PMC6789839 DOI: 10.3390/ph12030113] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 07/10/2019] [Accepted: 07/26/2019] [Indexed: 12/11/2022] Open
Abstract
Inflammation and psychological stress are risk factors for major depression and suicide. Both increase central glutamate levels and activate the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Both factors also affect the function of the chloride transporters, Na-K-Cl-cotransporter-1 (NKCC1) and K-Cl-cotransporter-2 (KCC2), and provoke interleukin-6 (IL-6) trans-signaling. This leads to measurable increases in circulating corticosteroids, catecholamines, anxiety, somatic and psychological symptoms, and a decline in cognitive functions. Recognition of the sequence of pathological events allows the prediction of novel targets for therapeutic intervention. Amongst others, these include blockade of the big-K potassium channel, blockade of the P2X4 channel, TYK2-kinase inhibition, noradrenaline α2B-receptor antagonism, nicotinic α7-receptor stimulation, and the Sgp130Fc antibody. A better understanding of downstream processes evoked by inflammation and stress also allows suggestions for tentatively better biomarkers (e.g., SERPINA3N, MARCKS, or 13C-tryptophan metabolism).
Collapse
|
|
27
|
Zhang L, Hu XZ, Russell DW, Benedek DM, Fullerton CS, Naifeh JA, Li X, Chen Z, Wu H, Ng THH, Aliaga P, Kao TC, Yu T, Dohl J, Wynn G, Ursano RJ. Association between leukocyte telomere length and hostility in US army service members. Neurosci Lett 2019; 706:24-29. [PMID: 31039427 DOI: 10.1016/j.neulet.2019.04.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 03/22/2019] [Accepted: 04/08/2019] [Indexed: 10/26/2022]
Abstract
Hostility is a common form of emotionally charged anger which can lead to maladaptive and unhealthy behaviors. Significant association between shortened telomeres and greater levels of hostility has been observed in civilian populations, but has not yet been comprehensively studied in military populations. Our study investigates the relationship between hostility, post-traumatic stress disorder (PTSD), and leukocyte telomere length (LTL) in a sample of United States Army Special Operations personnel (n = 474) who deployed to Iraq and/or Afghanistan as part of combat operations. Hostility was measured with five items from the Brief Symptom Inventory (BSI). PTSD was determined using the PTSD Checklist (PCL) total score. The LTL was assessed using quantitative polymerase chain reaction methods and regression analyses were conducted to determine the association of hostility and telomere length. PTSD subjects reported higher hostility scores compared with those without PTSD. Among the participants with PTSD, those with medium or high level of hostility had shorter LTL than those with low level hostility (P < 0.01). Stepwise regression indicated that hostility level and age, but not gender and PTSD, were negatively correlated with LTL. Univariate regression showed that total hostility score was negatively associated with LTL (CI= -0.06 to -0.002, Beta= -0.095, p < 0.039) as well as a significant correlation between LTL and hostility impulses (HI) (CI= -0.108 to -0.009, Beta= -0.106, p < 0.021) and hostility controlling (HC) (CI= -0.071 to -0.002, Beta= -0.095, p < 0.004). Multiple regression analyses revealed that, while HC has no significant association with LTL, HI was still negatively correlated with LTL (p = 0.021). Our data indicates that LTL is associated with HI levels. Prevention and treatment efforts designed to reduce hostility may help mitigate risk for LTL shortening, a process of cellular aging, and thus slow accelerated aged-related health outcomes.
Collapse
Affiliation(s)
- Lei Zhang
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA.
| | - Xian-Zhang Hu
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - Dale W Russell
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - David M Benedek
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - Carol S Fullerton
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - James A Naifeh
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - Xiaoxia Li
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - Ze Chen
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - Hongyan Wu
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - Tsz Hin H Ng
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - Pablo Aliaga
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - Tzu-Cheg Kao
- Department of Preventive Medicine & Biostatistics, USUHS, USA
| | - Tianzheng Yu
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
| | - Jacob Dohl
- Consortium for Health and Military Performance, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
| | - Gary Wynn
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| | - Robert J Ursano
- Uniformed Services University of the Health Sciences, Department of Psychiatry, Center for the Study of Traumatic Stress, USA
| |
Collapse
|
|
28
|
The Association Between Neuropsychological Function with Serum Vitamins A, D, and E and hs-CRP Concentrations. J Mol Neurosci 2019; 68:243-250. [DOI: 10.1007/s12031-019-01288-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 02/28/2019] [Indexed: 10/27/2022]
|
|
29
|
Graham-Engeland JE, Sin NL, Smyth JM, Jones DR, Knight EL, Sliwinski MJ, Almeida DM, Katz MJ, Lipton RB, Engeland CG. Negative and positive affect as predictors of inflammation: Timing matters. Brain Behav Immun 2018; 74:222-230. [PMID: 30217538 PMCID: PMC6289783 DOI: 10.1016/j.bbi.2018.09.011] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Revised: 08/15/2018] [Accepted: 09/10/2018] [Indexed: 11/20/2022] Open
Abstract
Very little research has assessed how measures of negative and positive affect (NA and PA) derived from assessments at multiple time points per day (e.g., via ecological momentary assessment [EMA]), as opposed to questionnaires that rely on recall over a longer period, are related to levels of peripheral inflammation. We examined how different indicators of NA and PA predicted concentrations of C-reactive protein (CRP) and seven peripheral inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8, IL-4, IL-10, and IFN-γ) that were examined in the form of an inflammatory composite. A community-based sample of 220 adults (62% Black/African-American and 25% Hispanic/Latino; aged 25-65; 65% female) completed questionnaires at baseline (including recalled affect "over the past month") and then provided EMA reports 5x/day for 14 days. Blood was drawn from each participant after completion of EMA and used to determine plasma levels of CRP and cytokines. Analyses examined if indicators of affect predicted inflammation, controlling for age, gender, body mass index, education, health conditions, and statin use. Neither recalled NA or PA nor momentary NA or PA (aggregated across the 14 days of EMA) were significantly associated with the cytokine composite or CRP. Negative mood more proximal to the blood draw (i.e., aggregated momentary NA in week 2 of EMA) was associated with the cytokine composite but not CRP. Exploratory moderation analyses revealed that the cytokine composite was also associated with PA in week 2 for men only, and with recalled NA for those with lower education. Exploratory analyses around temporal dynamics suggested that the timing of NA measurement relative to the blood draw mattered: Specifically, there were stronger trends of association between momentary NA and inflammatory cytokines when NA was assessed closer in time to blood collection. Future investigation of the relevance of temporal proximity and other measurement details may improve understanding of how affect relates to inflammation.
Collapse
Affiliation(s)
- Jennifer E Graham-Engeland
- Department of Biobehavioral Health, The Pennsylvania State University, United States; The Center for Healthy Aging, The Pennsylvania State University, United States.
| | - Nancy L Sin
- Department of Biobehavioral Health, The Pennsylvania State University, United States; The Center for Healthy Aging, The Pennsylvania State University, United States
| | - Joshua M Smyth
- Department of Biobehavioral Health, The Pennsylvania State University, United States; The Center for Healthy Aging, The Pennsylvania State University, United States; Department of Medicine, The Pennsylvania State University, United States; Social Science Research Institute, The Pennsylvania State University, United States
| | - Dusti R Jones
- Department of Biobehavioral Health, The Pennsylvania State University, United States; The Center for Healthy Aging, The Pennsylvania State University, United States
| | - Erik L Knight
- Department of Biobehavioral Health, The Pennsylvania State University, United States; The Center for Healthy Aging, The Pennsylvania State University, United States
| | - Martin J Sliwinski
- The Center for Healthy Aging, The Pennsylvania State University, United States; Department of Human Development and Family Studies, The Pennsylvania State University, United States
| | - David M Almeida
- The Center for Healthy Aging, The Pennsylvania State University, United States; Department of Human Development and Family Studies, The Pennsylvania State University, United States
| | - Mindy J Katz
- Department of Neurology, Albert Einstein College of Medicine, United States
| | - Richard B Lipton
- Department of Neurology, Albert Einstein College of Medicine, United States; Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, United States; Department of and Epidemiology and Population Health, Albert Einstein College of Medicine, United States
| | - Christopher G Engeland
- Department of Biobehavioral Health, The Pennsylvania State University, United States; The Center for Healthy Aging, The Pennsylvania State University, United States; The College of Nursing, The Pennsylvania State University, United States
| |
Collapse
|
|
30
|
Coryell W, Wilcox H, Evans SJ, Pandey GN, Jones-Brando L, Dickerson F, Yolken R. Aggression, impulsivity and inflammatory markers as risk factors for suicidal behavior. J Psychiatr Res 2018; 106:38-42. [PMID: 30261413 DOI: 10.1016/j.jpsychires.2018.09.004] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 09/06/2018] [Accepted: 09/06/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Increased inflammatory markers have been linked to suicidal behavior in numerous studies. Measures of aggression and of impulsivity also comprise risks factors for suicidal behavior and there is evidence that inflammatory markers correlate with these traits. The following analyses compare suicide attempters and non-attempters to determine whether inflammatory markers mediate relationships between aggression or impulsivity and proclivities to suicidal behavior. METHODS Investigators at three academic centers recruited patients in major depressive episodes who had a history of two or more suicide attempts (n = 79), or who had no history of suicide attempts (n = 123). Analyses compared these groups by five inflammatory marker levels and by measures of aggression and of impulsivity. RESULTS These results did not confirm the hypotheses that cytokine levels would explain relationships between aggressive behavior and suicide attempt history. However, scores for aggressive behavior and for impulsivity were significantly higher among suicide attempters. One of five of the inflammatory markers, (IL-1β), distinguished the two groups with lower values in the suicide attempt group. IL-1β levels correlated inversely with measures of aggression but neither impulsivity or aggressive behavior appear to explain the association between IL-1β levels and suicide attempt status. CONCLUSION These results identify recent aggressive behavior, higher levels of impulsivity, and lower levels of IL-1β as risk factors for a history of multiple suicide attempts in a group suffering from major depressive episodes. These measures appear to be additive in their effects.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Robert Yolken
- Stanley Division of Developmental Neurovirology, USA
| |
Collapse
|
|
31
|
Munsterhjelm C, Nordgreen J, Aae F, Heinonen M, Valros A, Janczak AM. Sick and grumpy: Changes in social behaviour after a controlled immune stimulation in group-housed gilts. Physiol Behav 2018; 198:76-83. [PMID: 30290182 DOI: 10.1016/j.physbeh.2018.09.018] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 09/26/2018] [Accepted: 09/27/2018] [Indexed: 12/18/2022]
Abstract
Poor health is associated with an increased risk of tail biting outbreaks in pigs. We propose that this is because illness changes social dynamics either by changing the behaviour of the sick pig towards its penmates, the behaviour of the healthy penmates towards the sick pig, or both. We tested the effect of immune stimulation (lipopolysaccharide (LPS) injection: O111:B4; 1.5 μg kg-1 IV) on social behaviour in gilts housed in triplets in a cross-over experiment. Each pen was subjected to the control treatment (all three pigs injected with saline) and then LPS treatment (one pig injected with LPS, two injected with saline), or vice versa. LPS injected pigs had a shift in social motivation and performed more tail- and ear- directed behaviour than saline pigs two days after injection. They seemed to fit the description of 'sick and grumpy'. This change was seen about 40 h after the signs of acute illness dissipated and was not accompanied by a similar increase in activity. We discuss possible mechanisms for this behavioural change in light of changes in neurotransmitter levels at three days after LPS injection described in a previous experiment.
Collapse
Affiliation(s)
- Camilla Munsterhjelm
- Research Centre for Animal Welfare, Department of Production Animal Medicine, University of Helsinki, Finland.
| | - Janicke Nordgreen
- Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Oslo, Norway
| | - Frida Aae
- Animal Welfare Research Group, Department of Production Animal Clinical Science, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Oslo, Norway
| | - Mari Heinonen
- Research Centre for Animal Welfare, Department of Production Animal Medicine, University of Helsinki, Finland
| | - Anna Valros
- Research Centre for Animal Welfare, Department of Production Animal Medicine, University of Helsinki, Finland
| | - Andrew M Janczak
- Animal Welfare Research Group, Department of Production Animal Clinical Science, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Oslo, Norway
| |
Collapse
|
|
32
|
Takahashi A, Flanigan ME, McEwen BS, Russo SJ. Aggression, Social Stress, and the Immune System in Humans and Animal Models. Front Behav Neurosci 2018; 12:56. [PMID: 29623033 PMCID: PMC5874490 DOI: 10.3389/fnbeh.2018.00056] [Citation(s) in RCA: 136] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Accepted: 03/06/2018] [Indexed: 01/25/2023] Open
Abstract
Social stress can lead to the development of psychological problems ranging from exaggerated anxiety and depression to antisocial and violence-related behaviors. Increasing evidence suggests that the immune system is involved in responses to social stress in adulthood. For example, human studies show that individuals with high aggression traits display heightened inflammatory cytokine levels and dysregulated immune responses such as slower wound healing. Similar findings have been observed in patients with depression, and comorbidity of depression and aggression was correlated with stronger immune dysregulation. Therefore, dysregulation of the immune system may be one of the mediators of social stress that produces aggression and/or depression. Similar to humans, aggressive animals also show increased levels of several proinflammatory cytokines, however, unlike humans these animals are more protected from infectious organisms and have faster wound healing than animals with low aggression. On the other hand, subordinate animals that receive repeated social defeat stress have been shown to develop escalated and dysregulated immune responses such as glucocorticoid insensitivity in monocytes. In this review we synthesize the current evidence in humans, non-human primates, and rodents to show a role for the immune system in responses to social stress leading to psychiatric problems such as aggression or depression. We argue that while depression and aggression represent two fundamentally different behavioral and physiological responses to social stress, it is possible that some overlapped, as well as distinct, pattern of immune signaling may underlie both of them. We also argue the necessity of studying animal models of maladaptive aggression induced by social stress (i.e., social isolation) for understanding neuro-immune mechanism of aggression, which may be relevant to human aggression.
Collapse
Affiliation(s)
- Aki Takahashi
- Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Japan.,Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.,Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, United States
| | - Meghan E Flanigan
- Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Bruce S McEwen
- Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, United States
| | - Scott J Russo
- Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| |
Collapse
|
|
33
|
Montalvo-Ortiz JL, Zhang H, Chen C, Liu C, Coccaro EF. Genome-Wide DNA Methylation Changes Associated with Intermittent Explosive Disorder: A Gene-Based Functional Enrichment Analysis. Int J Neuropsychopharmacol 2018; 21:12-20. [PMID: 29106553 PMCID: PMC5789263 DOI: 10.1093/ijnp/pyx087] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Intermittent explosive disorder is defined as a recurrent, problematic, and impulsive aggression that affects 3% to 4% of the US population. While behavioral genetic studies report a substantial degree of genetic influence on aggression and impulsivity, epigenetic mechanisms underlying aggression and intermittent explosive disorder are not well known. METHODS The sample included 44 subjects (22 with a DSM-5 diagnosis of intermittent explosive disorder and 22 comparable subjects without intermittent explosive disorder). Peripheral blood DNA methylome was profiled using the Illumina Infinium HumanMethylation450 Beadchip. Intermittent explosive disorder-associated genome-wide DNA methylation changes were analyzed using the CpGassoc R package, with covariates age, sex, and race being adjusted. A gene-based functional enrichment analysis was performed to identify pathways that were overrepresented by genes harboring highly differentially methylated CpG sites. RESULTS A total of 27 CpG sites were differentially methylated in IED participants (P<5.0×10-5), but none reached genome-wide significant threshold. Functional enrichment analysis revealed that genes mapped by these CpG sites are involved in the inflammatory/immune system, the endocrine system, and neuronal differentiation. CONCLUSIONS Consistent with our previous studies showing an association of inflammatory response with aggressive behavior in intermittent explosive disorder subjects, our gene-based pathway analysis using differentially methylated CpG sites supports inflammatory response as an important mechanism involved in intermittent explosive disorder and reveals other novel biological processes possibly associated with intermittent explosive disorder.
Collapse
Affiliation(s)
| | - Huiping Zhang
- Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts
| | - Chao Chen
- State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China
| | - Chunyu Liu
- University of Illinois at Chicago, Chicago, Illinois
| | - Emil F Coccaro
- Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, University of Chicago, Chicago, Illinois
| |
Collapse
|
|
34
|
Munsterhjelm C, Nordgreen J, Aae F, Heinonen M, Olstad K, Aasmundstad T, Janczak AM, Valros A. To be blamed or pitied? The effect of illness on social behavior, cytokine levels and feed intake in undocked boars. Physiol Behav 2017; 179:298-307. [PMID: 28684135 DOI: 10.1016/j.physbeh.2017.06.024] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 05/29/2017] [Accepted: 06/30/2017] [Indexed: 01/07/2023]
Abstract
Tail biting is detrimental to animal welfare and has negative consequences for producer economy. Poor health is one of the risk factors for tail biting. The first aim of this study was therefore to test for links between health status and behavior related to tail biting at the individual level. The second aim of this study was to test whether variation in cytokines was related to variation in social behavior. These small molecules produced upon immune activation are known to influence behavior both in the direction of withdrawal and increased aggression. This could potentially increase non-functional social behavior and thereby the risk of a tail biting outbreak. To investigate this, we collected behavioral data, health data, feeding data and blood samples from undocked boars at a test station farm in Norway. We compared groups with three different diagnoses: osteochondrosis diagnosed by computer tomography scanning (OCSAN), osteochondrosis diagnosed by clinical examination (OCCLIN) and respiratory tract disease (RESP), with healthy controls (CTR). We tested whether the diagnoses were associated with feeding and growth, social behavior and cytokine levels. We then tested whether there were correlations between cytokine levels and social behavior. We also provide raw data on cytokine levels in the extended sample (N=305) as there are few publications on cytokine levels measured in pigs living under commercial conditions. OCCLIN pigs visited the feeder less, and fed longer compared to CTR pigs. Pigs diagnosed with RESP showed a large drop in growth the first week after filming, which corresponds to the week they were likely to have been diagnosed with illness, and a tendency to compensatory increase in the week after that. Social behavior differed between experimental groups with OCSCAN pigs receiving more social behavior (both aggressive and non-aggressive) compared to CTR, and RESP pigs tending to perform more ear- and tail-biting than controls. There were no differences in absolute levels of cytokines between categories. However IL1-ra and IL-12 showed correlations with several behaviors that have been shown by others to be associated with current or future tail biting activity. To our knowledge, this is the first published study indicating a role for illness in non-functional social behavior in pigs and the first showing a correlation between cytokine levels and social behavior.
Collapse
Affiliation(s)
- C Munsterhjelm
- Research Centre for Animal Welfare, Department of Production Animal Medicine, University of Helsinki, Finland
| | - J Nordgreen
- Animal Welfare Research Group, Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Oslo, Norway.
| | - F Aae
- Animal Welfare Research Group, Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Oslo, Norway
| | - M Heinonen
- Research Centre for Animal Welfare, Department of Production Animal Medicine, University of Helsinki, Finland
| | - K Olstad
- Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Oslo, Norway
| | | | - A M Janczak
- Animal Welfare Research Group, Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Oslo, Norway
| | - A Valros
- Research Centre for Animal Welfare, Department of Production Animal Medicine, University of Helsinki, Finland
| |
Collapse
|
|
35
|
Zhang Q, Hong W, Li H, Peng F, Wang F, Li N, Xiang H, Zhang Z, Su Y, Huang Y, Zhang S, Zhao G, Zhou R, Mao L, Lin Z, Cai W, Fang Y, Xie B, Zhao M. Increased ratio of high sensitivity C-reactive protein to interleukin-10 as a potential peripheral biomarker of schizophrenia and aggression. Int J Psychophysiol 2017; 114:9-15. [PMID: 28174109 DOI: 10.1016/j.ijpsycho.2017.02.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Revised: 12/11/2016] [Accepted: 02/03/2017] [Indexed: 01/18/2023]
Abstract
BACKGROUND Many studies have indicated that immune dysfunction might be involved in the physiopathology of schizophrenia and aggression. This study aimed to investigate the correlation between high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-10 and clinical characteristics, especially aggression, and to explore the potential role of hsCRP and IL-10 as plasma biomarkers of schizophrenia. METHODS Forty-one patients with schizophrenia and forty healthy individuals were enrolled. Psychopathological severity and aggression were assessed using the Positive and Negative Syndrome Scale (PANSS) and Modified Overt Aggression Scale (MOAS). Plasma concentrations of hsCRP and IL-10 were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS (1) Higher levels of hsCRP (p<0.001), lower levels of logIL-10 (p<0.001) and higher ratio of hsCRP to IL-10 (p<0.001) were observed in the plasma of patients with schizophrenia, compared to healthy controls; (2) ROC (receiver operating characteristic) curve analysis revealed that ratio of hsCRP/IL-10 (predictive value: 0.783, p<0.01; sensitivity: 85.4%; specificity: 67.5%) was more applicable as a biomarker to distinguish patients with schizophrenia from the control group than hsCRP and IL-10 alone (predictive value: 0.718, p<0.01; 0.275, p<0.001, respectively); (3) we found positive correlations between hsCRP and the total score and verbal aggression score of MOAS (r=0.654, p<0.01; r=0.678, p<0.05), and between hsCRP/IL-10 and the total score of MOAS (r=0.636, p<0.01). CONCLUSIONS Our results suggest the possible function of hsCRP and IL-10 in the pathogenesis of schizophrenia and the possible value of hsCRP/IL-10 as a potential peripheral biomarker of schizophrenia. This finding also suggests a relationship between hsCRP, IL-10 and their ratio with aggression in patients with schizophrenia.
Collapse
Affiliation(s)
- Qinting Zhang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Institute of Forensic Science, Ministry of Justice, Shanghai 200063, China; Collaborative Innovation Center for Brain Science, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Wu Hong
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
| | - Haozhe Li
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Institute of Forensic Science, Ministry of Justice, Shanghai 200063, China
| | - Fanglan Peng
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Fan Wang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Ningning Li
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Hui Xiang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Zongfeng Zhang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Yousong Su
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Yueqi Huang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Hangzhou Seventh People's Hospital, Hanzhou 310007, China
| | - Shengyu Zhang
- Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Institute of Forensic Science, Ministry of Justice, Shanghai 200063, China
| | - Guoqin Zhao
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Rubai Zhou
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Ling Mao
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; XuHui District Mental Health Center of Shanghai, Shanghai 200030, China
| | - Zhiguang Lin
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Weixiong Cai
- Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Service Platform, Institute of Forensic Science, Ministry of Justice, Shanghai 200063, China
| | - Yiru Fang
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Bin Xie
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Min Zhao
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Collaborative Innovation Center for Brain Science, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai, China.
| |
Collapse
|
|
36
|
Watkins LE, Harpaz-Rotem I, Sippel LM, Krystal JH, Southwick SM, Pietrzak RH. Hostility and telomere shortening among U.S. military veterans: Results from the National Health and Resilience in Veterans Study. Psychoneuroendocrinology 2016; 74:251-257. [PMID: 27689898 DOI: 10.1016/j.psyneuen.2016.09.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Revised: 08/12/2016] [Accepted: 09/12/2016] [Indexed: 01/08/2023]
Abstract
Chronic disorders of aging are critical concerns for the U.S. veteran population, which is, on average, two decades older than the non-veteran population. Characterization of risk factors that may accelerate biological aging is important in identifying targets for prevention and intervention. In the current study, we analyzed data from a contemporary, and nationally representative sample of U.S. veterans to evaluate the relationship between a broad range of sociodemographic, military, and clinical variables, and peripheral telomere length, which is an indicator of biological age and linked to risk for aging-related disorders and mortality. Data from 468U.S. military veterans who participated in the National Health and Resilience in Veterans Study were analyzed. Telomere length was assessed from cells isolated from saliva using quantitative polymerase chain reaction methods. A multivariable binary logistic regression analysis was conducted to evaluate the relations between hostility and telomere length, while controlling for sociodemographic, military, and clinical variables. Greater scores on a measure of hostility were independently associated with telomere shortening, even after adjustment for a broad range of other variables (odds ratio [OR]=1.58, 95% confidence interval [CI]=1.15-2.18). Secondary analyses revealed that this association was driven by difficulties controlling anger (OR=1.72, 95%CI=1.14-2.61), which reflect the external manifestation of hostility, rather than aggressive urges or impulses. Hostility, particularly difficulties controlling anger, is associated with peripheral telomere shortening in U.S. military veterans. Prevention and treatment efforts designed to reduce hostility may help mitigate risk for accelerated cellular aging in this growing segment of the U.S.
Collapse
Affiliation(s)
- Laura E Watkins
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
| | - Ilan Harpaz-Rotem
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Lauren M Sippel
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - John H Krystal
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Steven M Southwick
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Robert H Pietrzak
- U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| |
Collapse
|
|
37
|
Oshio A, Mieda T, Taku K. Younger people, and stronger effects of all-or-nothing thoughts on aggression: Moderating effects of age on the relationships between dichotomous thinking and aggression. COGENT PSYCHOLOGY 2016. [DOI: 10.1080/23311908.2016.1244874] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Affiliation(s)
- Atsushi Oshio
- Faculty of Letters, Arts, and Sciences, Waseda University, 1-24-1 Toyama, Shinjuku, Tokyo 162-8644, Japan
| | - Takahiro Mieda
- Graduate School of Letters, Arts, and Sciences, Waseda University, Tokyo, Japan
| | - Kanako Taku
- Department of Psychology, Oakland University, Rochester, Michigan, USA
| |
Collapse
|
|
38
|
Coccaro EF, Lee R, Fanning JR, Fuchs D, Goiny M, Erhardt S, Christensen K, Brundin L, Coussons-Read M. Tryptophan, kynurenine, and kynurenine metabolites: Relationship to lifetime aggression and inflammatory markers in human subjects. Psychoneuroendocrinology 2016; 71:189-96. [PMID: 27318828 PMCID: PMC5744870 DOI: 10.1016/j.psyneuen.2016.04.024] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 03/10/2016] [Accepted: 04/27/2016] [Indexed: 11/26/2022]
Abstract
Inflammatory proteins are thought to be causally involved in the generation of aggression, possibly due to direct effects of cytokines in the central nervous system and/or by generation of inflammatory metabolites along the tryptophan-kynurenine (TRP/KYN) pathway, including KYN and its active metabolites kynurenic acid (KA), quinolinic acid (QA), and picolinic acid (PA). We examined plasma levels of TRP, KYN, KA, QA, and PA in 172 medication-free, medically healthy, human subjects to determine if plasma levels of these substances are altered as a function of trait aggression, and if they correlate with current plasma levels of inflammatory markers. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble interleukin-1 receptor-II (sIL-1RII) protein were also available in these subjects. We found normal levels of TRP but reduced plasma levels of KYN (by 48%), QA (by 6%), and a QA/KA (by 5%) ratio in subjects with Intermittent Explosive Disorder (IED) compared to healthy controls and psychiatric controls. Moreover, the metabolites were not associated with any of the inflammatory markers studied. These data do not support the hypothesis that elevated levels of KYN metabolites would be present in plasma of subjects with IED, and associated with plasma inflammation. However, our data do point to a dysregulation of the KYN pathway metabolites in these subjects. Further work will be necessary to replicate these findings and to understand their role in inflammation and aggression in these subjects.
Collapse
Affiliation(s)
- Emil F. Coccaro
- Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States,Corresponding author at: Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, United States. (E.F. Coccaro)
| | - Royce Lee
- Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States
| | - Jennifer R. Fanning
- Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States
| | - Dietmar Fuchs
- Division of Biological Chemistry, Biocenter, Medical University, Innsbruck, Austria
| | - Michel Goiny
- Department of Physiology & Pharmacology, Karolinska Institute, Stockholm, Sweden
| | - Sophie Erhardt
- Department of Physiology & Pharmacology, Karolinska Institute, Stockholm, Sweden
| | - Kyle Christensen
- Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, United States,Laboratory of Behavioral Medicine, Van Andel Research Institute, Grand Rapids, MI, United States
| | - Lena Brundin
- Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, United States,Laboratory of Behavioral Medicine, Van Andel Research Institute, Grand Rapids, MI, United States
| | - Mary Coussons-Read
- Department of Psychology, University of Colorado, Colorado Springs, CO, United States
| |
Collapse
|
|
39
|
Affiliation(s)
- Monica Bucci
- Center for Youth Wellness, 3450 3rd Street, Building 2, Suite 201, San Francisco, CA 94124, USA
| | - Sara Silvério Marques
- Center for Youth Wellness, 3450 3rd Street, Building 2, Suite 201, San Francisco, CA 94124, USA.
| | - Debora Oh
- Center for Youth Wellness, 3450 3rd Street, Building 2, Suite 201, San Francisco, CA 94124, USA
| | - Nadine Burke Harris
- Center for Youth Wellness, 3450 3rd Street, Building 2, Suite 201, San Francisco, CA 94124, USA
| |
Collapse
|
|
40
|
Arnberg FK, Lekander M, Morey JN, Segerstrom SC. Self-rated health and interleukin-6: Longitudinal relationships in older adults. Brain Behav Immun 2016; 54:226-232. [PMID: 26872420 PMCID: PMC4828288 DOI: 10.1016/j.bbi.2016.02.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Revised: 02/08/2016] [Accepted: 02/08/2016] [Indexed: 10/22/2022] Open
Abstract
BACKGROUND Both self-rated health (SRH) and inflammation are implicated in chronic diseases and premature mortality. Better SRH is associated with lower proinflammatory cytokines, but there is little evidence about whether this relationship is more stable or dynamic. OBJECTIVE To study the between- and within-person associations between SRH and IL-6. METHODS Older adults (N=131; Mage=75 years) rated their health and provided blood samples for analysis of IL-6 at separate occasions every 6 months over a period up to 5 years. Age, sex, BMI, neuroticism, and statin use were examined as covariates in multilevel models. RESULTS In bivariate models, better SRH, lower BMI, younger age, and female sex correlated with lower IL-6. In multilevel models, stable SRH (between-person differences; p<.001) but not dynamic SRH (within-person changes; p=.93) correlated with IL-6. The stable relationship persisted with demographic and health covariates in the model. CONCLUSIONS Better stable SRH but not dynamic SRH was robustly associated with lower IL-6 among older adults, lending support to previous cross-sectional findings on the relation between inflammatory markers and SRH. The findings suggest that trait-like mechanisms, rather than changes over a time scale of 6-month waves, govern this association. To further investigate the mechanisms behind the SRH-IL-6 association, studies with different measurement frequencies, higher within-person variability, and experimental approaches are warranted.
Collapse
Affiliation(s)
- Filip K. Arnberg
- Stress Research Institute, Stockholm University, 106 91 Stockholm, Sweden
,Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden
| | - Mats Lekander
- Stress Research Institute, Stockholm University, 106 91 Stockholm, Sweden; Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden.
| | - Jennifer N. Morey
- Department of Psychology, University of Kentucky, 125 Kastle Hall, Lexington, KY, 40506-0044
| | - Suzanne C. Segerstrom
- Department of Psychology, University of Kentucky, 125 Kastle Hall, Lexington, KY, 40506-0044
| |
Collapse
|
|
41
|
Boylan JM, Lewis TT, Coe CL, Ryff CD. Educational Status, Anger, and Inflammation in the MIDUS National Sample: Does Race Matter? Ann Behav Med 2016; 49:570-8. [PMID: 25715901 DOI: 10.1007/s12160-015-9687-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Racial differences in anger frequency and expression styles have been found. Further, African Americans receive fewer health benefits from higher education than Whites. PURPOSE This study seeks to investigate racial differences in how anger moderates the association between education and inflammation. METHODS Midlife in the US participants (n = 1,200; 43.0 % male; 18.5 % African American) provided education and anger data via survey assessments. Interleukin-6 (IL-6) and fibrinogen were determined from a fasting blood sample following an overnight clinic visit. RESULTS African Americans reported higher anger-out, IL-6, and fibrinogen and lower anger-control than Whites. Anger-out predicted higher IL-6 and fibrinogen among African Americans with higher education; whereas, trait anger and anger-out predicted lower fibrinogen among Whites with higher education. Anger-out marginally predicted higher IL-6 in less educated Whites. CONCLUSIONS Findings underscore racial differences in the benefits and consequences of educational attainment, and how social inequities and anger are manifested in inflammatory physiology.
Collapse
Affiliation(s)
- Jennifer Morozink Boylan
- Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA,
| | | | | | | |
Collapse
|
|
42
|
Sanjuán P, Montalbetti T, Pérez-García AM, Bermúdez J, Arranz H, Castro A. A Randomised Trial of a Positive Intervention to Promote Well-Being in Cardiac Patients. Appl Psychol Health Well Being 2016; 8:64-84. [PMID: 26876425 DOI: 10.1111/aphw.12062] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Negative emotions are linked to the onset and development of coronary heart diseases (CHD), whereas positive emotions are associated with better health and lower mortality rates among patients with these diseases. The objective of this randomised trial was to improve cardiac patients' emotional states using a Programme to Improve Well-being (PIW) based exclusively on positive interventions (those that promote intentional behaviours and thoughts to improve well-being). METHODS Cardiac patients (n = 108) were randomly assigned to two parallel groups. In the control group, they participated in only a Cardiac Rehabilitation Programme (CRP group), whereas the intervention group also participated in the PIW (CRP+PIW group). Physical functional capacity, depressive symptoms, hostility, and negative and positive affect were assessed at T1 (baseline) and T2 (8 weeks later). RESULTS At T2, after controlling for functional capacity, the CRP+PIW group reported a significantly less negative affect than the CRP group. Moreover, the CRP group did not change from T1 to T2, whereas the CRP+PIW group reported more positive emotions and fewer negative emotions and hostility at T2 than at T1. CONCLUSIONS Positive interventions effectively improve the emotional state of cardiac patients. We suggest that specific modules should be included in the CRP to improve well-being.
Collapse
Affiliation(s)
- Pilar Sanjuán
- Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
| | | | | | - José Bermúdez
- Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain
| | | | | |
Collapse
|
|
43
|
de Baca TC, Wahl RA, Barnett MA, Figueredo AJ, Ellis BJ. Adversity, Adaptive Calibration, and Health: The Case of Disadvantaged Families. ADAPTIVE HUMAN BEHAVIOR AND PHYSIOLOGY 2016; 2:93-115. [PMID: 27175327 DOI: 10.1007/s40750-016-0042-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Epidemiologists and medical researchers often employ an allostatic load model that focuses on environmental and lifestyle factors, together with biological vulnerabilities, to explain the deterioration of human physiological systems and chronic degenerative disease. Although this perspective has informed medicine and public health, it is agnostic toward the functional significance of pathophysiology and health deterioration. Drawing on Life History (LH) theory, the current paper reviews the literature on disadvantaged families to serve as a conceptual model of stress-health relationships in which the allocation of reproductive effort is instantiated in the LH strategies of individuals and reflects the bioenergetic and material resource tradeoffs. We propose that researchers interested in health disparities reframe chronic degenerative diseases as outcomes resulting from strategic calibration of physiological systems to best adapt, survive, and reproduce in response to demands of specific developmental contexts. These effects of adversity on later-age degenerative disease are mediated, in part, by socioemotional and cognitive mechanisms expressed in different life history strategies.
Collapse
Affiliation(s)
- Tomás Cabeza de Baca
- Health Psychology, Department of Psychiatry, University of California, San Francisco
| | - Richard A Wahl
- Adolescent Medicine, Department of Pediatrics, College of Medicine, University of Arizona
| | - Melissa A Barnett
- Division of Family Studies and Human Development, Norton School of Family and Consumer Sciences, University of Arizona
| | - Aurelio José Figueredo
- Department of Psychology, School of Mind, Brain, and Behavior, College of Science, University of Arizona
| | - Bruce J Ellis
- Division of Family Studies and Human Development, Norton School of Family and Consumer Sciences, University of Arizona
| |
Collapse
|
|
44
|
Coccaro EF, Lee R, Gozal D. Elevated Plasma Oxidative Stress Markers in Individuals With Intermittent Explosive Disorder and Correlation With Aggression in Humans. Biol Psychiatry 2016; 79:127-35. [PMID: 24582164 DOI: 10.1016/j.biopsych.2014.01.014] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Revised: 01/09/2014] [Accepted: 01/10/2014] [Indexed: 01/15/2023]
Abstract
BACKGROUND Animal and clinical studies suggest a link between inflammation and oxidative stress. Because oxidative stress is an inherent part of inflammation, and inflammation is associated with behavioral aggression in lower mammals and humans, we hypothesized that markers of oxidative stress would be related to aggression in human subjects. In this case-control study, markers of oxidative stress and aggression were assessed in human subjects with histories of recurrent, problematic, impulsive aggressive behavior and in nonaggressive comparator subjects. METHODS Plasma levels of 8-hydroxy-2'-deoxyguanosine and 8-isoprostane were examined in the context of measures of aggression and impulsivity in physically healthy subjects with intermittent explosive disorder (n = 69), nonaggressive subjects with Axis I or II disorders (n = 61), and nonaggressive subjects with no history of Axis I or II disorders (n = 67). RESULTS Levels of plasma 8-hydroxy-2'-deoxyguanosine and 8-isoprostane were significantly higher in subjects with intermittent explosive disorder compared with psychiatric or normal control subjects. In addition, both oxidative stress markers correlated with a composite measure of aggression; more specifically, 8-hydroxy-2'-deoxyguanosine correlated with measures reflecting a history of actual aggressive behavior in all subjects. CONCLUSIONS These data suggest a positive relationship between plasma markers of oxidative stress and aggression in human subjects. This finding adds to the complex picture of the central neuromodulatory role of aggression in human subjects.
Collapse
Affiliation(s)
- Emil F Coccaro
- Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience.
| | - Royce Lee
- Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience
| | - David Gozal
- Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois
| |
Collapse
|
|
45
|
Golimbet VE, Alfimova MV, Korovaitseva GI, Lezheiko TV, Kondratyev NV, Krikova EV, Gabaeva MV, Kasparov SV, Kolesina NY. A study of the effect of the genes of inflammatory proteins on basic personality dimensions. Zh Nevrol Psikhiatr Im S S Korsakova 2016; 116:48-52. [DOI: 10.17116/jnevro20161166148-52] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
|
|
46
|
Barzilay R, Lobel T, Krivoy A, Shlosberg D, Weizman A, Katz N. Elevated C-reactive protein levels in schizophrenia inpatients is associated with aggressive behavior. Eur Psychiatry 2015; 31:8-12. [PMID: 26657596 DOI: 10.1016/j.eurpsy.2015.09.461] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 09/28/2015] [Accepted: 09/29/2015] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND An association between inflammation and behavioral domains of mental disorders is of growing interest. Recent studies reported an association between aggression and inflammation. In this study, we investigated the association between aggressive behavior and inflammatory markers in schizophrenia inpatients. METHODS Adult schizophrenia inpatients without affective symptoms (n=213) were retrospectively identified and categorized according to their C-reactive protein measurement at admission as either elevated (CRP>1 mg/dL; n=57) or normal (CRP<1 mg/dL; n=156). The following indicators of aggression were compared: PANSS excitement component (PANSS-EC), restraints and suicidal behavior during hospitalization. Univariate comparisons between elevated and normal CRP levels were performed and multivariate analysis was conducted to control for relevant covariates. RESULTS CRP levels significantly correlated with other laboratory markers indicating increased inflammation including leukocyte count and neutrophil to lymphocyte ratio (r=0.387, P<0.0001 and r=0.356, P<0.0001) respectively. Inpatients with elevated C-reactive protein displayed increased aggressive behavior compared to patients with normal CRP levels (<1 mg/dL). This was manifested by higher rates of restraint during hospitalization (χ(2)=5.22, P=0.031) and increased PANSS-EC score (U=5410.5, P=0.012). Elevated CRP levels were not associated with suicidal behavior. Multivariate analysis revealed that higher PANSS-EC score was associated with elevated CRP after controlling for the covariates age, sex, BMI and smoking. CONCLUSION This study identified a potential biological correlate (inflammation) of a specific behavioral endophenotype (aggression) in schizophrenia inpatients.
Collapse
Affiliation(s)
- R Barzilay
- Geha Mental Health Center, Sackler Faculty of Medicine, Tel Aviv University, 1 Helsinki St., 4910002 Petah-Tikva, Israel; Neurosciences laboratory, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Israel.
| | - T Lobel
- Geha Mental Health Center, Sackler Faculty of Medicine, Tel Aviv University, 1 Helsinki St., 4910002 Petah-Tikva, Israel
| | - A Krivoy
- Geha Mental Health Center, Sackler Faculty of Medicine, Tel Aviv University, 1 Helsinki St., 4910002 Petah-Tikva, Israel
| | - D Shlosberg
- Geha Mental Health Center, Sackler Faculty of Medicine, Tel Aviv University, 1 Helsinki St., 4910002 Petah-Tikva, Israel
| | - A Weizman
- Geha Mental Health Center, Sackler Faculty of Medicine, Tel Aviv University, 1 Helsinki St., 4910002 Petah-Tikva, Israel
| | - N Katz
- Geha Mental Health Center, Sackler Faculty of Medicine, Tel Aviv University, 1 Helsinki St., 4910002 Petah-Tikva, Israel
| |
Collapse
|
|
47
|
Inflammatory markers and chronic exposure to fluoxetine, divalproex, and placebo in intermittent explosive disorder. Psychiatry Res 2015; 229:844-9. [PMID: 26277033 PMCID: PMC4837655 DOI: 10.1016/j.psychres.2015.07.078] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Revised: 07/02/2015] [Accepted: 07/24/2015] [Indexed: 01/09/2023]
Abstract
Intermittent Explosive Disorder (IED) is a disorder of impulsive aggression affecting 4-7% of the U.S. population during some period of life. In addition to other biological correlates, elevations of plasma inflammatory markers have been reported in IED, compared with control, subjects. In this study we sought to explore if treatment exposure to anti-aggressive agents, compared with placebo, would be associated with a reduction in circulating levels of inflammatory markers. Thirty IED subjects, from a 12-week, double-blind, randomized, placebo-controlled trial of fluoxetine and divalproex, in which both pre- and post-treatment levels of C-Reactive Protein (CRP), interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α were obtained. Efficacy measures included the Overt Aggression Scale-Modified (OAS-M) score for Aggression and for Irritability, rate of Clinical Global Impression of Improvement (CGI-I), and rate of IED Remitters at study completion. As compared to placebo, neither fluoxetine nor divalproex reduced any of the measures of aggression. In addition, levels of CRP and pro- and anti-inflammatory cytokines showed no changes from pre- to post-treatment for any treatment condition. Correlations between pre- and post- treatment plasma CRP/cytokines were substantial (mean r=0.71, r(2)=0.50, p<0.001). Overall, circulating markers of inflammation markers were unaffected by treatment with fluoxetine or divalproex, consistent with the absence of change in measures of impulsive aggression.
Collapse
|
|
48
|
Fanning JR, Lee R, Gozal D, Coussons-Read M, Coccaro EF. Childhood trauma and parental style: Relationship with markers of inflammation, oxidative stress, and aggression in healthy and personality disordered subjects. Biol Psychol 2015; 112:56-65. [PMID: 26423894 DOI: 10.1016/j.biopsycho.2015.09.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 08/17/2015] [Accepted: 09/08/2015] [Indexed: 10/23/2022]
Abstract
Recent studies suggest that early life trauma is associated with elevations in circulating markers of inflammation in human subjects. History of aggression as a behavior, or aggression as a personality trait, is also associated with elevations of these inflammatory markers. Since early life trauma is associated with the development and maintenance of aggression in later life we examined the relationship of early life adversity, plasma inflammation markers (IL-6 and CRP) and oxidative stress markers (8-OH-DG and 8-ISO), and aggression in adult subjects with (n=79) and without (n=55) personality disorder. We used a series of mediated and moderated path models to test whether the effects of early adversity on later aggression may be mediated through markers of inflammation. Childhood abuse and parental control were associated with basal IL-6 and CRP concentrations. Path modeling suggested that childhood abuse was associated with aggression indirectly through CRP while parental control influenced aggression indirectly through IL-6 and CRP. Furthermore, these effects were independent of the effect of current depression. The results suggest that disruption of inflammatory processes represent one pathway by which early adversity influences aggression.
Collapse
Affiliation(s)
- Jennifer R Fanning
- Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, University of Chicago, Chicago, IL, United States
| | - Royce Lee
- Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, University of Chicago, Chicago, IL, United States
| | - David Gozal
- Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Chicago, IL, United States
| | - Mary Coussons-Read
- Department of Psychology, The University of Colorado, Colorado Springs, CO, United States
| | - Emil F Coccaro
- Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, University of Chicago, Chicago, IL, United States.
| |
Collapse
|
|
49
|
Provençal N, Booij L, Tremblay RE. The developmental origins of chronic physical aggression: biological pathways triggered by early life adversity. ACTA ACUST UNITED AC 2015; 218:123-33. [PMID: 25568459 DOI: 10.1242/jeb.111401] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Longitudinal epidemiological studies with birth cohorts have shown that physical aggression in humans does not appear suddenly in adolescence as commonly thought. In fact, physically aggressive behaviour is observed as early as 12 months after birth, its frequency peaks around 2-4 years of age and decreases in frequency until early adulthood. However, a minority of children (3-7%) maintain a high frequency of physical aggression from childhood to adolescence and develop serious social adjustment problems during adulthood. Genetic factors and early social experiences, as well as their interaction, have been shown to play an important role in the development of chronic aggressive behaviour. However, the biological mechanisms underlying these associations are just beginning to be uncovered. Recent evidence suggests that epigenetic mechanisms are responsive to adverse environments and could be involved in the development of chronic aggression. Using both gene candidate and genomic approaches, recent studies have identified epigenetic marks, such as DNA methylation alterations in genes involved in the stress response and the serotonin and immune systems to be partly responsible for the long-lasting effects of early adversity. Further longitudinal studies with biological, environmental and behavioural assessments from birth onwards are needed to elucidate the sequence of events that leads to these long-lasting epigenetic marks associated with early adversity and aggression.
Collapse
Affiliation(s)
- Nadine Provençal
- Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich 80804, Germany
| | - Linda Booij
- Ste-Justine Hospital Research Center, Montreal, QC H3T 1C5, Canada Department of Psychology and Psychiatry, Queen's University, Kingston, ON K7L 3N6, Canada Department of Psychiatry, University of Montreal, Montreal, QC H3T 1J4, Canada Department of Psychiatry, McGill University, Montreal, QC H3A 1A1, Canada
| | - Richard E Tremblay
- Ste-Justine Hospital Research Center, Montreal, QC H3T 1C5, Canada Department of Psychology and Pediatrics, University of Montreal, Montreal, QC H2V 2S9, Canada School of Public Health, Physiotherapy and Population Sciences, University College Dublin, Dublin 4, Ireland Institute of Genetic, Neurobiological, and Social Foundations of Child Development, Tomsk State University, Tomsk 634050, Russian Federation
| |
Collapse
|
|
50
|
Dermody SS, Wright AGC, Cheong J, Miller KG, Muldoon MF, Flory JD, Gianaros PJ, Marsland AL, Manuck SB. Personality Correlates of Midlife Cardiometabolic Risk: The Explanatory Role of Higher-Order Factors of the Five-Factor Model. J Pers 2015; 84:765-776. [PMID: 26249259 DOI: 10.1111/jopy.12216] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Varying associations are reported between Five-Factor Model (FFM) personality traits and cardiovascular disease risk. Here, we further examine dispositional correlates of cardiometabolic risk within a hierarchical model of personality that proposes higher-order traits of Stability (shared variance of Agreeableness, Conscientiousness, inverse Neuroticism) and Plasticity (Extraversion, Openness), and we test hypothesized mediation via biological and behavioral factors. In an observational study of 856 community volunteers aged 30-54 years (46% male, 86% Caucasian), latent variable FFM traits (using multiple-informant reports) and aggregated cardiometabolic risk (indicators: insulin resistance, dyslipidemia, blood pressure, adiposity) were estimated using confirmatory factor analysis (CFA). The cardiometabolic factor was regressed on each personality factor or higher-order trait. Cross-sectional indirect effects via systemic inflammation, cardiac autonomic control, and physical activity were tested. CFA models confirmed the Stability "meta-trait," but not Plasticity. Lower Stability was associated with heightened cardiometabolic risk. This association was accounted for by inflammation, autonomic function, and physical activity. Among FFM traits, only Openness was associated with risk over and above Stability, and, unlike Stability, this relationship was unexplained by the intervening variables. A Stability meta-trait covaries with midlife cardiometabolic risk, and this association is accounted for by three candidate biological and behavioral factors.
Collapse
|