스트레스와 질병 - 신경내분비, 신경해부학적 관점
TRANSCRIPT
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Psychological Stress on Neuroendocrine Bal-ance: Applications to
Human Diseases
Hyung Jin ChoiFunctional Neuroanatomy of Metabolism Regulation (FNMR) Lab
Department of Anatomy, Seoul National University College of Medicine
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Contents• What is Stress?• Mechanism
• Neuro-Anatomy of Stress• Neuro-Endocrine of Stress• Inflammation and Stress
• Stress and Disease• Stress and Food Addiction
• Stress and Central Regulation of Metabolism
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Contents• What is Stress?• Mechanism
• Neuro-Anatomy of Stress• Neuro-Endocrine of Stress• Inflammation and Stress
• Stress and Disease• Stress and Food Addiction
• Stress and Central Regulation of Metabolism
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고통을 회피하는 것과 쾌락을 원하는 것은 모든 행위의 두 가지 시동장치이다 .
Man can do what he wills, but he cannot will what he wills.
—Arthur Schopenhauer, On the Freedom of the Will
고통을 회피하는 것과 쾌락을 원하는 것은 모든 행위의 두 가지 시동장치이다 .- 베르나르 베르베르 “뇌”
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Pleasure Pain
Satiety
Libido
Hunger
Approach Avoid
Craving Fear
Anxiety
Appetite
Comfort PhysicalPain
LonelinessLove
Fear ofstarvation
Mania Depression
Anhedonia
Impulsive
Energy
Reproduction
Safety
Addiction Phobia
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Stress = Psychologic Pain
2011 Stress revisited- a critical evaluation of the stress concept
72015 Nature Neuroscience. Stress effects on the neural substrates of motivated behavior
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Pleasure-seeking vs. Pain-avoidance
Depression, chronic pain, anhe-donia
Impulsive behavior, schizophrenia2008 NRN A common neurobiology for pain and pleasure
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Contents• What is Stress?• Mechanism
• Neuro-Anatomy of Stress• Neuro-Endocrine of Stress• Inflammation and Stress
• Stress and Disease• Stress and Food Addiction
• Stress and Central Regulation of Metabolism
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Neuro-Anatomy of Stress
2012 Nature Neuroscience. Neurobiology of resilience
Prefrontal Cortex (PFC)Decision Making
AmygdalaEmotion
HypothalamusHomeostasis
HippocampusMemory
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Stress Weakens Prefrontal Networks
2015 Nature Neuroscience. Stress weakens prefrontal networks- molecular insults to higher cognition
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Physiological Needs Influence Behavior through Discrete Hypothalamic Circuits
2013 Neuron. Hypothalamic Survival Circuits- Blueprints for Purposive Behaviors
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Canonical Pathways that Regu-late Stress Responses and En-
ergy Balance
2014 Cell Metabolism. Neuroendocrine Circuits Governing Energy Balance and Stress Regulation- Functional Overlap and Therapeutic Implications
162015 NRN Stress-related synaptic plasticity in the hypothalamus
172013 Neuropeptide–Catecholamine Interactions in Stress
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Contents• What is Stress?• Mechanism
• Neuro-Anatomy of Stress• Neuro-Endocrine of Stress• Inflammation and Stress
• Stress and Disease• Stress and Food Addiction
• Stress and Central Regulation of Metabolism
192015 Stress, the stress system and the role of glucocorticoids
202013 Stress and excitatory synapses- From health to disease
212012 Neuron. Neural Mechanisms of Stress Resilience and Vulnerability
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Contents• What is Stress?• Mechanism
• Neuro-Anatomy of Stress• Neuro-Endocrine of Stress• Inflammation and Stress
• Stress and Disease• Stress and Food Addiction
• Stress and Central Regulation of Metabolism
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Stress-induced activation of the inflammatory re-
sponse
2009 BP Inflammation and its discontents- the role of cytokines in the pathophysiology of major depression
242015 NRGH Towards a systems view of IBS
Stress-Brain-Gut-Microbiota Axis
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Contents• What is Stress?• Mechanism
• Neuro-Anatomy of Stress• Neuro-Endocrine of Stress• Inflammation and Stress
• Stress and Disease• Stress and Food Addiction
• Stress and Central Regulation of Metabolism
262009 Nat Rev Endocrinol. Stress and disorders of the stress system
272015 Biological Psychiatry. Elevated Risk for Autoimmune Disorders in Iraq and Afghanistan Veterans with Posttraumatic Stress Disorder
Risk for Autoimmune Disorders with Posttraumatic Stress Disorder
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Prevalence of Autoimmune Disorderwith Posttraumatic Stress Disorder
2015 Biological Psychiatry. Elevated Risk for Autoimmune Disorders in Iraq and Afghanistan Veterans with Posttraumatic Stress Disorder
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Risk of Myocardial Infarc-tion
2012 Nature Reviews of Cardiology. Stress and cardiovascular disease
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Stress and Cardiovascular Disease
2012 Nature Reviews of Cardiology. Stress and cardiovascular disease
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Stress and Food Addcition
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Stress and Food Intake
2009 Trends in Endocrinology and Metabolism- Stress-induced obesity and the emotional nervous system
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Stress and addiction (substance or food)
2013 Stress as a Common Risk Factor for Obesity and Addiction
342013 Stress as a Common Risk Factor for Obesity and Addiction
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Model of insulin resistance, regional brain activation, and food craving in obese indi-viduals
2012 Diabetes Care. Neural Correlates of Stress- and Food- Cue-Induced Food Craving In Obesity
Viscous cycle driving weight gain
362009 Nat Rev Endocrinol. Stress and disorders of the stress system
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Contents• What is Stress?• Mechanism
• Neuro-Anatomy of Stress• Neuro-Endocrine of Stress• Inflammation and Stress
• Stress and Disease• Stress and Food Addiction
• Stress and Central Regulation of Metabolism
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Stress and Central Regulation of Metabolism
MetabolismMaster
Regulator
Pancreas
Gut MuscleLiver
FatBone
Adrenal
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Translational Stress Re-search
2015 Nature Neuroscience. Finding translation in stress research
설문지구분 설문지식욕 Visual Analogue Scale
식습관 Yale Food Addiction
식이행동질문지 -DEBQ
폭식행동척도 -BES
감정 긍정 / 부정정서 -PANAS
병원 불안 - 우울척도 -HADS
우울증 , 감정표현 불감증CDI,TAS-20K
성격 Temperament and Character Inventory(TCI)
특정 음식을 줄이거나 , 중단한 경우 , 그 음식에 대한 갈망이나 욕구가 증가하는 경험이 있다 .
뜻대로 일이 안되거나 잘못될 때 먹고 싶어집니까 ?
문제가 생기면 남에게 얘기하지 않고 혼자 간직하는 편이다
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Neurotherapeutic Strategies against Obesity and/or Eating Disorders
2015 Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity
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Objective
Neuromodulation Brain Activity Feeding Behavior
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Methods• Study Design
• Cross-over design• Real tDCS or sham tDCS
• Subjects• N=15• BMI > 28 kg/m2
• Brain Activity• Functional MRI with visual food cues
• Behavior Measurement• Visual analog scale: appetite, desire for food, mood
3
+
Food presentation max 4sec
Feedback 1sec
Fixation1~10sec
1 2 3 4 5 6 7
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Experimental Protocol
3
+
Food presentation max 4sec
Feedback 1sec
Fixation1~10sec
Tim
e
tDCS or sham stimula-tion
Visual task(food image rat -
ings)
Blood test/survey
Resting MRI
T1 structure MRI 5-6min
7min
5-6min
20min
Blood test/survey
Green Lines: orexigenic pathwaysRed lines: dopaminergic pathways
2013 The contribution of brain reward circuits to the obesity epidemic2014 Obesity – A neuropsychological disease- Systematic review and neuropsychological mode
A, amygdala; H, hypothalamus; NA, nucleus accumbens, PFC, prefrontal cortex; VTA, ventral tegmental area
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ConclusiontDCS Neuromodulation Controls Feeding Behavior via
Food Reward Activity and Connec-tivity
Neuromodulation Brain Activity Feeding Behavior
Brain Connectivity
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Multidimensional Architec-ture
Gene
Hormone
BrainPsychology
Behavior
Phenotype
Outcome
MetabolicDisease Vascular
Disease
Envi
ronm
ent
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