Contents Part I Psychoneuroimmunology and Systems Biology Mechanisms 1 From Psychoneuroimmunology to Personalized, Systems, and Dynamical Medicine... 3 1.1 Psychoneuroimmunology (PNI) and Systems Biology... 3 1.2 Emotions, Stress, Inflammation, and Diseases... 4 1.3 The Dynamical Biopsychosocial Models on the Basis of PNI and Systems Biology... 5 1.4 Systemic PNI Profiles for Personalized, Systems, and Dynamical Medicine... 7 References... 8 2 Stress and Inflammation: Translational Implications in Mind Body Medicine... 11 2.1 Stress and Inflammation: A Systems Biology Perspective... 11 2.2 The PNI Networks, Systems-Based Biomarkers, and Mind Body Mechanisms... 12 2.3 The Stress Inflammation Disease Associations: Translational Implications of PNI... 13 2.4 Targeting the Stress and Inflammation-Associated Networks... 15 References... 15 3 Biological Rhythms and the HPA Axis in Psychoneuroimmunology... 19 3.1 The Rhythmic Patterns of the PNI Networks: Systems Biology Approaches... 19 3.2 Chronic Stress and the Dynamics of the HPA Axis... 20 3.2.1 The Rhythmic Patterns of the HPA Axis in Association with Stress Responses... 20 3.2.2 The Circadian and Homeostatic Mechanisms of the HPA Axis at Various Levels... 22 ix
x Contents 3.3 The Dynamics of the HPA Axis in Association with Diseases... 23 3.3.1 Depression and Cancer... 23 3.3.2 The Cholesterol Levels and Obesity... 24 References... 25 4 The Inflammatory Networks and Dynamical Patterns in Psychoneuroimmunology... 27 4.1 Inflammatory Networks and Systemic PNI Profiling... 27 4.2 IL-6 and Associated Networks... 28 4.3 TNF and Associated Networks... 29 4.4 NF-kB and Associated Networks... 30 4.5 BDNF and Associated Networks... 30 4.6 PPARs and Associated Networks... 32 References... 33 Part II Psychoneuroimmunology, Diseases, and Mind-Body Medicine 5 Sleep, Psychoneuroimmunology, and Mind Body Medicine... 39 5.1 Sleep Disturbances, Systemic Inflammation, and Mind Body Techniques... 39 5.2 Sleep Problems and Aging... 40 5.3 Psychosocial Stress, Poor Sleep Quality, and Obesity... 40 5.4 Mind Body Methods for Improving Sleep Quality... 41 References... 42 6 Psychoneuroimmunology of Depression... 43 6.1 PNI and the Biopsychosocial Models... 43 6.2 The PNI Implications in Personalized, Systems, and Dynamical Medicine... 44 6.3 Potential Systemic Biomarkers in Depression... 45 6.4 Stress Response and Inflammatory Pathways in Depression... 45 6.4.1 The Immune-Kynurenine Pathway... 45 6.4.2 The HPA Axis and Associated Pathways... 46 6.4.3 The ERK1/2 and MAPK Signaling Pathways... 47 6.4.4 The GSK3-Dependent TLR4 Signaling Pathways... 47 6.5 The Inflammatory Networks: The Links Between Depression and Other Diseases... 48 6.5.1 Cancer... 48 6.5.2 Cardiovascular Diseases... 49 6.5.3 Other Relevant Diseases... 50 References... 51 7 Psychoneuroimmunology of Schizophrenia... 53 7.1 The Stress Inflammation Associations and the Biopsychosocial Models... 53
Contents xi 7.2 The Interactions Among the Immune, Endocrine, Nervous Systems, and Cognition... 54 7.3 PNI and Potential Immunomodulation Strategies... 55 7.4 Stress Response and Inflammatory Pathways in Schizophrenia... 55 7.4.1 Metabolic and Inflammatory Pathways... 55 7.4.2 Important Cytokine Networks... 58 7.4.3 Neurotransmitters and Neuronal Signaling Pathways... 59 7.4.4 Multiple Signaling Pathways... 60 7.4.5 The HPA Axis and Associated Pathways... 62 References... 62 8 Obesity, Stress, Inflammation, and Psychoneuroimmunology... 65 8.1 Obesity, PNI, and the Biopsychosocial Models... 65 8.2 Psychological Stress, Obesity, and Associated Diseases... 66 8.3 Potential Stress and Inflammatory Biomarkers in Obesity... 67 8.4 Obesity-Associated Inflammatory Pathways... 69 8.5 Obesity and the HPA Axis... 70 8.6 Potential Therapeutic Targets in Association with Stress and Obesity... 71 References... 72 9 Psychoneuroimmunology of Aging... 75 9.1 Aging, PNI, and the Systems Biology Models... 75 9.2 The Stress Inflammation Correlations in Aging... 76 9.3 Inflammatory Pathways: The Links Among Stress, Aging, and Chronic Diseases... 77 9.3.1 Cardiovascular Aging and Diseases... 77 9.3.2 Brain Aging and Neuropsychiatric Symptoms... 79 9.3.3 The mtor Signaling Pathways, Alzheimer s Disease, and Autoimmune Disorders... 80 9.3.4 Melatonin-Associated Pathways and Age-Associated Neurodegenerative Disorders... 81 9.3.5 The Kidney Brain Axis and Chronic Kidney Disease (CKD)... 82 9.3.6 Bone Loss, Osteoporosis, and Muscle Dysfunctions... 82 9.3.7 Age-Related Macular Degeneration in the Eye... 83 9.3.8 Chronic Obstructive Pulmonary Disease (COPD)... 83 9.3.9 The Mitochondrial Signaling Pathways and Systemic Inflammation... 84 References... 84 10 Psychoneuroimmunology of Cardiovascular Diseases... 87 10.1 Psychological Stress, Depression, and Cardiovascular Diseases... 87 10.2 The Complex PNI Interactions and Inflammatory Biomarkers... 88
xii Contents 10.3 Inflammatory Pathways: The Links Between Stress and Cardiovascular Diseases... 89 10.3.1 Emotional Problems, Inflammation, and Atherosclerosis... 89 10.3.2 The IL-1 Family... 90 10.3.3 The Networks of Multiple Cytokines... 91 10.3.4 The Signaling Pathway of Toll-Like Receptors (TLR)... 92 10.3.5 The Kynurenine Pathway and Metabolic Networks... 92 10.3.6 The Complex Notch Signaling Pathway... 93 References... 94 11 Psychoneuroimmunology and Cancer... 97 11.1 The Systems-Based PNI Frameworks... 97 11.2 Inflammatory Pathways in Different Types of Cancer... 98 11.2.1 Pancreatic Cancer and the NFATc2-STAT3-GSK-3β Pathway... 98 11.2.2 Hepatocellular Carcinoma (HCC) and the β-catenin Signaling Pathway... 100 11.2.3 Squamous Cell Carcinoma (SCC) and the Pathways of Tgfbr2, p21... 100 11.2.4 Colorectal Cancer and the Signaling Pathways of TLRs and PPARδ... 101 11.2.5 Breast Cancer and Various Signaling Pathways... 101 11.3 The NF-kB- and p53-associated Pathways... 102 11.4 The Interleukin-1 (IL-1) Cytokine Family and Associated Pathways... 103 11.5 Inflammatory Pathways in the Microbiota... 103 11.6 Biobehavioral Pathways in Hematopoietic Stem Cell Transplant Patients... 104 11.7 The HPA Axis and the Roles of Melatonin... 105 11.8 Inflammatory Pathways Associated with Neuroendocrine (NE) Differentiation... 105 References... 106 12 Psychoneuroimmunology of Skin Diseases... 109 12.1 The PNI Mechanisms of Skin Disorders at Various Levels... 109 12.2 Emotional Tension and Immune Responses... 110 12.3 PNI of Atopic Dermatitis (AD) and Other Skin Diseases... 111 12.3.1 Atopic Dermatitis (AD)... 111 12.3.2 Other Relevant Skin Disorders... 112 12.4 Stress Response and Inflammatory Networks in Skin Disorders... 113 12.4.1 Stress and the Neurotrophin Nerve Growth Factor (NGF) Pathway... 113 12.4.2 Multiple Cytokine Networks and Skin Homeostasis... 115 12.4.3 Inflammatory Networks in Association with Various Skin Disorders... 116 References... 118
Contents xiii 13 The Translation of Psychoneuroimmunology into Mind Body Medicine... 121 13.1 From PNI to Mind Body Medicine... 121 13.2 The PNI Mechanisms of Meditation... 123 13.3 PNI and Nutrition... 124 13.3.1 Stress, Diets, and Inflammation... 124 13.3.2 Nutritional Interventions, Stress Responses, and Antiinflammatory Effects... 125 13.4 Mind Body Interventions for Cardiovascular Diseases... 126 13.5 Mind Body Interventions for Aging and Associated Disorders... 126 13.6 Incorporating Chronotherapy into Systems and Dynamical Medicine... 127 References... 128 Index... 131
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