NEUROENDOCRINE

Dr dr Anwar Wardy W, SpS, DFM (K)

Dept.Neurology FK.UMJ

dept.neurology fk.umj

anwar wardy w

What is Response
NeuroEndocrine?
A physiologic response to a demand for
change
Fight or Flight response
General Adaptation Syndrome
Sympathetic
Nervous
system
Dominance

dept.neurology fk.umj

anwar wardy w

STRESS PHYSIOLOGY

Without stress, there would be no life

Stress = nonspecific response of the
body to any demand.

dept.neurology fk.umj

anwar wardy w

HOW CAN STRESS CAUSE SO

MUCH DAMAGE?
Selyes General Adaptation Syndrome
The 3 Stages of Stress

Arousal
Rapid increases in catecholamines (alarm molecules)
Slower increases of corticosteroids (stress steroids)
Adaptation
Characterized by sustained increased levels of
corticosteroids and alarm molecules
Altered glucose tolerance, blood pressure, thyroid
hormone and sex hormone metabolism
Exhaustion
Degenerative diseases characterized by the adverse
influence of corticosteroids and alarm molecules
dept.neurology fk.umj

anwar wardy w

STRESS versus THE

RELAXATION RESPONSE
RELAXATION RESPONSE
Parasympathetic State
Dec. Heart Rate
Dec. Blood Pressure
Dec. Respiratory Rate
Constricted Pupils
Muscle Relaxation
Enhances Digestion

dept.neurology fk.umj

FIGHT OR FLIGHT RESPONSE

Sympathetic State
Inc. Heart Rate
Inc. Blood Pressure
Inc. Respiratory Rate
Dilated Pupils
Muscle Tension
Inhibits Digestion

anwar wardy w

STRESS and
NEUROLOGIC Disease
The basis for human stress related
disease is the high percentage of time
spent in the sympathetic dominant
state.

dept.neurology fk.umj

anwar wardy w

SYMPATHETIC DOMINANCE:
LONG-TERM EFFECTS OF ELEVATED CORTISOL & CATECHOLAMINES

Cognitive impairment:
inability to concentrate, poor
memory
Neuromusculoskeletal
complaints: TMJ, bruxism,
trembling, nervous ticks,
back and muscle ache
Energy level: Fatigue of
unknown origin
Adrenal architecture
changes: Adrenal
hyperplasia burnout:
dryness of mouth, sweating,
salt cravings
Immune impairment:
increased susceptibility to
viral infections, autoimmune
disorders
dept.neurology fk.umj

GI distress: IBS, ulcers

Cardiovascular symptoms:
rapid pulse, pounding heart,
weakness, dizziness, chest
pain, high BP
Mood changes: general
irritability, floating anxiety,
depression, impulsive behavior,
nervous laughter, increase
startle response
Hyper-kinesis or excitation
Sleep disturbances:
nightmares, insomnia
Brain architecture changes:
Lower hippocampal volume
(inc cortisol)
anwar wardy w

STRESSAND ADRENAL
PROBLEM
Stress
triggers
neuroendocrine-immune
imbalances

dept.neurology fk.umj

psycho-

anwar wardy w

Emotional trauma Limbic system

Hypothalums
Locus Coenuleus Primary Afferent
Nociceptor Noxious Stimulus

dept.neurology fk.umj

anwar wardy w

Emotional trauma Limbic system

Hypothalums
Corticotrophin
Releasing Hormone
(CRH) Anterior
Norepinephine (NE)
Pitutiary
Sympathetic
Adrenocorticotrophin Nervous System
Adrenal
cortexCortisol

dept.neurology fk.umj

anwar wardy w

Cortisol
Increases with age and can elevate
blood glucose by up to 50%,
contributing to insulin resistance and
inflammation.

dept.neurology fk.umj

anwar wardy w

CORTISOL INFLUENCES
NEUROENDOCRINE FUNCTION
Inc. oxidative stress
Inc. inflammation
Inc. need for
detoxification
Impaired immunity
- Dec. Secretory IgA
- Inc. Antigen penetration
- Inc. IgG
- Dec. NK cell activity
- Dec. IL-2
- Inc. bone loss
dept.neurology fk.umj

Inc. Epinephrine (E) &

Norepinephrine
Inc. Cortisol
Inc. Insulin (due to inc.
glucose)
Inc. visceral fat
deposition
Dec. TSH, T4, T3
Dec. estrogen,
Testosterone,
Progesterone
Altered neurotransmitter
balance
anwar wardy w

Sympathetic Dominance Can Trigger

HPA Hypoactivation

Glucocorticoid receptor insensitivity or under production of cortisol

(adrenal insufficiency)
Symptoms and conditions
Fatigue/malaise
Risk of inflammatory conditions
Risk of autoimmune disease
Myocardial infarction
Unable to perform routine tasks
Inability to cope
Apathy
Anorexia
Weight loss
Restless sleep
Weakness
Chronic pain
Reduced libido

dept.neurology fk.umj

anwar wardy w

Sympathetic Dominance Can Trigger

HPA Hyperactivation

Impaired memory learning

Gastrointestinal disorders
Central obesity
Neurologic disorders
Loss of muscle tone
Decreased growth
Protein wasting
Bone loss
Skin disorders
Reduced immune defense
Poor injury/illness recovery
Reduced sex hormone levels
Reduced reproductive
function
Functional renal problems
dept.neurology fk.umj

Cortisol and catecholamine

excess and imbalance
Symptoms and conditions

Anxiety
Agitation/irritability
Restless sleep
Increased cholesterol
Increased triglyerides
Increased blood pressure
Insulin resistance
Reduced libido
Fatigue
Depression

anwar wardy w

Sympathetic Dominance
Can Trigger
HPA Hypoactivation
HPA hyperactivation
Adrenal Exhaustion adrenal gland
hyperplasia and failure to respond.

dept.neurology fk.umj

anwar wardy w

Stress Neuro_Physiology
Conditions Linked with Overproduction & Underproduction of
Cortisol
Underproduction

Seasonal depression
CFIDS
Fibromyalgia
Hypothyroidism
Tobacco withdrawal
Allergies/Asthma
Rheumatoid arthritis

B. McEwen. The End of Stress as We Know It.

2002, p.64

dept.neurology fk.umj

Overproduction
Cushings Syndrome
Depression & OCD
Diabetes
Sleep deprivation
Anorexia nervosa
Excessive exercise
Childhood abuse
Hyperthyroidism

anwar wardy w

RECOGNIZE SIGNS OF PHYSICAL

AND MENTAL STRESS
Insomnia (disturbed
sleep)
Relationship problems
(i.e. loss of sexual
desire)
Shortness of breath
Stiff neck
Upset stomach
Weight gain
Weight loss
Worrying
dept.neurology fk.umj

Anxiety
Back pain
Constipation
Diarrhea
Depression
Exhaustion
Fatigue
Headaches
High blood pressure
anwar wardy w

IDENTIFY NEURO_STRESS
AROUSAL TRIGGERS
METABOLIC STRESSORS
-Nutritional (need beyond
supply, supply beyond need)
-Oxidative
-Inflammatory
Physiological stressors
-Structural
-Traumatic
-Pain
-Excess exercise
-Poor sleep

dept.neurology fk.umj

PSYCHOLOGICAL STRESSORS
-Divorce
-Unemployment
-Death
-Children, etc.
-Self-esteem
Environmental Stressors
-Chemical/toxic
-Infection
-Endobiosis
-Noise
-Light
-Vibration
anwar wardy w

SUBCLINICAL
HYPOTHYROIDISM
Subclinical hypothyroidism is more common
than overt hypothyroid in elderly, especially
women
Subclinical hypothyroidism (inc. TSH in the
presence or normal T concentrations)
Increasing evidence to suggest a
predisposing factor for depression, cognitive
impairment and dementia
Davis JD et al: Current Psychiatry Reports (2003)S:384-390

dept.neurology fk.umj

anwar wardy w

Neuro-Stress & Immunity

Dynamic Balance = Health
Th1 dominance = tissue/organ specific autoimmune
disorders, delayed hypersensitivity reactions
Th2 dominance = allergic & atopic conditions,
systemic autoimmune disorders
Th3 imbalance = immunosuppression in allergies
and autoimmunity

dept.neurology fk.umj

anwar wardy w

OBESITY AND MOODS

Obesity is associated with an approximately
25% increase in odds of mood and anxiety
disorders and an approximately 25% decrease
in odds of substance use disorders. Variation
across demographic groups suggests that social
or cultural factors may moderate or mediate the
association between obesity and mood disorder.
Arch Gen Psychiatry. 2006;63:824-830
dept.neurology fk.umj

anwar wardy w

Manage Stress NaturallyCore Functional Approach

Eating habits
Diet
Specific nutrients
Plant adaptogens
Cognitive techniques to alter stress perception
Exercise

dept.neurology fk.umj

anwar wardy w

Food Improves Mood by

Buffering the Stress Response
Skipping meals, GI Dietlow blood
sugarHungry
brain=inc.
Cortisolinc. hepatic glucagon,
inc.
muscle
breakdowninc.
sugar, inc. insulin, inc. fats
dept.neurology fk.umj

anwar wardy w

Omega-3 fatty Acids and

Neuropsychiatric Disorders
decreased blood levels of omega-3 fatty
acids have been associated with several
neuropsychiatric
conditions,
including
Attention Deficit (Hyperactivity) disorder,
Alzheimers Disease, Schizophrenia and
Depression
Young, G et al: Reprod Nutr Dev. 2005 JanFeb:454(1);1-28

dept.neurology fk.umj

anwar wardy w

How Adaptogenic Herbs Buffer

Stress Molecules and Protect the
Nervous System
Non-toxic no change in normal
physiology
Helps the body adapt to stress
Normalizes body function

dept.neurology fk.umj

anwar wardy w

DISTURBED SLEEP &

MOOD
60 million Americans suffer from disturbed
sleep, characterized by functional
impairments during the day.
Today, the widespread practice of burning
the candle at both ends in western
industrialized societies has created so much
sleep deprivation that what is really
abnormal sleep is now almost the norm
dept.neurology fk.umj

anwar wardy w

NATURAL SLEEP CYCLE

Light sleep: Body movement decreases. Spontaneous
awakening may occur.
Stage 1: dec. serotonin
Intermediate sleep: Most of the night is spent in this stage.
Helps refresh the body.
Stage 2: dec. Melatonin
Deep sleep: Difficult to arouse. Most restorative stage,
lasting 30-40 minutes in first few cycles, less in later
cycles.
Stage 3 & 4: dec. Serotonin
REM: Dreaming occurs. Heart rate increases. Lasts about
10 minutes in first cycle, 20-30 minutes in later cycles
Stage 5: inc.Acetycholine, dec. GABA, dec. Dopamine
dept.neurology fk.umj

anwar wardy w

REM-NREM Balance

NREM=Restorative
Off line, Autistic
Internalized
Hypometabolic
Serotonergic and
GABAergic

dept.neurology fk.umj

REM=Ergotrophic
On-line, engaged
Externalized
Hypermetabolic
Cholinergic

anwar wardy w

Neurotransmitters Involved
in Sleep
Serotonin-NREM
Acetylcholine-REM
GABA-inhibits brain arousal centers,
reduces REM
Histamine-stimulates brain arousal
centers, wake promoting
neurotransmitter

dept.neurology fk.umj

anwar wardy w

HEALTHY SLEEP HYGIENE

Create A Relaxing Bedtime Routine:
Read a book
Listen to music
Practice a relaxation technique
Take a warm bath
Keep the temperature in your bedroom at a
comfortable level: extremes can disrupt your
sleep
Go to sleep and wake at the same time each
day helps to develop a sleep-wake rhythm that
encourages better sleep
dept.neurology fk.umj

anwar wardy w

MELATONIN
Reduced sleep onset
Increased REM sleep compared to
placebo
Effective in children and adolescents with
ADHD and insomnia
Improves tinnitus
Improvement in behavioral symptoms in
dementia patients
Cluster headaches
dept.neurology fk.umj

anwar wardy w

MELATONIN

Short half life (approx 1 hour)

Metabolized by P450 cytochromes
Physiologic range between 8 to 3 mg
Modest decrease in sleep latency
Melatonin has thermoregulatory effects
that assist in its sophoric effects, reduces
core body temperature
dept.neurology fk.umj

anwar wardy w

STRESS & RELAXATION

EVERYTHING to do with health

Worry is the most common effect
Type II stress is exhausting
80% serious illnesses preceded by high
stress levels in previous year
Animal research (Vernon Riley)

dept.neurology fk.umj

anwar wardy w

Breath & Back Pain

Patients suffering from chronic low back pain
improved significantly with breath therapy.
Changes in standard low back pain
measures of pain and disability were
comparable to those resulting from high
quality,
extended
physical
therapy.
Qualitative data suggested improved coping
skills and new insight into the effect of stress
on the body as a result of breath therapy.
Mehling WE, et al. RCT of Breath Therapy for Patients with chronic low back pain. Altern Ther
Health Med. 2005;11(4)44-52.

dept.neurology fk.umj

anwar wardy w

JAMA 2005:294;20102011
what we do agree on is reduction of risk factors for heart
disease and diabetes through lifestyle changes first, is
an appropriate treatment.

dept.neurology fk.umj

anwar wardy w

Wassalam, Maret 2015

Anwar Wardy W
Dept.Neurology FK UMJ

dept.neurology fk.umj

anwar wardy w