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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

8

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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