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Psychoneuroendocrinology

DR.KANAK SONI
3RD YEAR M.D.CLINICAL NATUROPATHY
SDM COLLEGE OF NATUROPATHY &
YOGIC SCIENCES ,
UJIRE .

The mind-body-hormones
connection is one of the hottest
topic in medicine today.
Documented by enormous
amounts of data regarding
hormone effect on the brain and
behaviour.
Lets see what is that !!!

Psychoneuroendocrinology
Psychoneuroendocrinology
emphasized
the importance of exploring the
inter-relationships between
mind, brain, and hormones.
It is the clinical study of
hormone fluctuations and their
relationship to human behaviour.

Comprehensively understand

Psychiatry

Neurology Endocrinology

To treat
Psychiatric illnesses
PNEC refers to structural and
functional relations between
hormonal and CNS and the behaviours
that modulate and arise from it.

Psycho-Neuroendocrinology
anxiety
stress
Stress

depression

conflict

bereavemen
t

personality

nervous system

Endocrine
system
HEALTH

immune system

Psychoneuroendocrinologic Investigation Path

1. Alterations in endogenous hormone


levels observed in primary
psychiatrics illness
2. Psychiatric concomitants or sequel of
hormonal deregulation in primary
endocrinologic illness
3. Behavioural effects of exogenously
administered hormones or hormone
antagonists.

Neuroendocrine
Interaction
between the
nervous system
and hormones
released by the
endocrine
glands
Fight or flight
response
HPA axis

The

sympathetic

nervous

system is responsible for upand down-regulating in many


homeostatic mechanisms in
living organisms
Best known for
mediating the neuronal and
hormonal stress
response commonly
known as the
fight-or-flight response

HPA Axis

STRESS, HPA AXIS AND


PSYCHOSIS

Chronic
Stress

Psycho
sis

The HPA axis is an innate system adept at


compensating for the detrimental effects of acute
stressors, reining the system back into equilibrium.
The system is meant to respond to an acute
stressor and then terminate that response via
negative feedback mechanisms.
However, chronic HPA stimulation due to ongoing
physical or emotional stress can lead to
unresponsiveness of hypothalamic
nuclei.
Additionally, if the adrenals maintain a high level of
activity to mobilize cortisol, epinephrine, and nor
epinephrine, the stores of these hormones may
become depleted.
Overall, the HPA axis receives input from a variety
of central and peripheral sources, and it is the
integration of these signals that allows this system
to produce the appropriate homeostatic response.
However, excessive stimulation of the HPA axis by
one or more of these inputs can disrupt its ability to
maintain homeostasis, which could then lead to a

Neuron
Contains the
nucleus and
cytoplasmic
organelles
The site of
protein
synthesis
and
processing,
including
synaptic
vesicles

Neuron
Hair-like
cytoplasmic
extension
of the
neuron
Conducts
electrical
impulses or
releases
chemical
messengers

How are Neurotransmitters made?

Monoamine
neurotransmitt
ers

Amino
acids
Ltrypt
opha
n

5HTP

Ltyros
ine

LDop
a

serotonin

dopa
mine

nor
epinephri
ne

epinephrin
e

ers are the


chemicals
within the
vesicles that
synoptically
separated
neurons utilize
for chemical
communication.

NTs help to control and regulate most


of your bodys functions including
Mood , memory , heart rate
Hunger ,cravings , pain
breathing ,hormonal ,breathing
Sleep, focus, body
temperature
Digestion ,B.P , weight
coordination ,concentration
Pleasure, arousal, addiction
Kidney functions
Behaviour

Neurotransmission

Neurotransmission
Synaptic
transmission, is the
process by which
signalling molecules
calledneurotransmit
tersare released by
aneuron(the pre
synaptic neuron),
and bind to and
activate
thereceptorsof
another neuron (the
postsynaptic
neuron).
Neurotransmission
is essential for the
process of
communication
between two
neurons

Activation of other neurons receptor

Neuronal organization
.

Normal ion flow in cell with presence of


neurotransmitter

Basic types of NTs


1.Inhibitory
neurotransmitters
slow down the flow of
information by
calming and reducing
activity of neurons
they help to bring
balance to the body.

2. Excitatory
neurotransmitters
generally increase the
flow of information. It is
the balance between the
inhibitory and excitatory
neurotransmitters that
has the greatest effect on
body functions.

Inhibitory
There are several inhibitory
NTs in the body, but the two
that are thought to have the
greatest and widest reaching
effects are serotonin and
GABA (gamma amino butyric
acid)

Serotonin

Serotonin is in relation to
mood and a class of drugs
known as selective
serotonin reuptake
inhibitors (SSRIs)
Approx 90% serotonin is
produced and found in the
intestine and remainders is
mostly found in the brain
and CNS.

How serotonin influence Us

Serotonin pathways are involved


with mood regulation.
It helps to regulate appetite,
sleep, memory ,learning,
temperature, mood, behaviour,
muscle contraction, cardiovascular
function, and hormone balance .

Recipe for serotonin


Ample dietary protein, specifically tryptophan.
Vitamin C, vitamin B6, and folic acid are cofactors in the
conversion of tryptophan to serotonin.
Magnesium is a cofactor for serotonin synthesis.
Vitamin B12 cofactor in neurotransmitter methyalation.
Vitamin D influences the metabolism of serotonin.
Food that contains slowly absorbed carbohydrates from
whole grain provides long-lasting serotonin.
(Conti.)

Conti.

Tryptophan found in protein such as turkey,

soybeans or milk

Vitamin C found in citrus fruits, tomatoes, kiwi,

broccoli and parsley

Vitamin B6 found in bananas, spinach and white

potatoes

Folic acid found in orange juice, lentils, chickpeas

and asparagus

Magnesium found in brown rice, hazelnuts and

Swiss chard

Carbohydrate found in whole grain such as

wheat, oats and quinoa

GABA
It reduce anxiety, calming the
mind and release tension.
Some anti-anxiety medications
like benzodiazepines and
barbiturates as well as many
sleep medications work
primarily by increasing the
amount of GABA released in a
neuron.

Nutritional Influences
Taurine and vitamin B6 boost the
production of GABA.
N-acetylcysteine (NAC) influences
GABA.
Calming herbs such as passionflower
and valerian promote GABA production.
L-theonine found in green tea and
oolong tea increases GABA.

Excitatory

Dopamine
Norepinephrine
Epinephrine
glutamate

Dopamine
Pleasure , focus, concentration,
memory, motivation, achieve
heightened arousal and do much of
our learning is done by dopamine .
Every type of reward increase the
level of dopamine transmission in
the brain
Cocaine, amphetamines act
directly on the dopamine
Disease: Parkinson, schizophrenia,
restless leg syndrome, ADD/ADHD.

Recipe for Dopamine

Tyrosine found in black beans, pumpkin seeds, sesame

seeds, avocado

Zinc found in oysters, wheat germ, cashews, cocoa

powder

Vitamin B6 found in bananas, spinach and white potatoes


Folic acid found in orange juice, lentils, chickpeas and

asparagus

Theanine found in green tea, black tea, plants

Norepinephrine
Made from Dopamine
This and epinephrine is
responsible for fight-or-flight
response to stress
Affects blood pressure, heart rate
Alertness, arousal, decision
making , attention, focus.
Medicines amphetamines ,
venlafaxine, duloxetine,
bupropion.

Epinephrine / Adrenaline
Responsible for fight-or-flight
response.
Regulate heart rate,
breathing ,blood pressure
Imbalance can lead to
adrenaline junkies= people
that seem to enjoy stress
and stressful activities.
Suffer from constant need for
urgency, have trouble
relaxing or sleeping .

Glutamate
Most abundant excitatory
neurotransmitter in the
human brain
Learning and memory like
cognitive functions
Imbalance in glutamate
levels are associated with
Alzheimer's disease, seizures
and autism.
Flavour enhancer in MSG.

Nutritional Influences
Mercury and other heavy metals increase
glutamate.
Homocysteine, aracadonic acid and
inflammatory cytokines all increase
glutamate.
Excessive sympathetic nervous system
activation (cortisol) increases glutamate.
Vitamin D blocks glutamate.
Taurine and Vitamin B6 convert
glutamate to GABA.

Anxiety
NT systems are partially
controlled by the serotonincatecholamine systems.
GABA-Glutamate NT system
is associated with control of
anxiety and panic attacks.
Some food rich in tryptophan
can help to treat anxiety
and/or panic attacks work on
GABA receptors.

Tryptophan-rich foods
Tryptophan is a routine
constituent of most protein-based
foods or dietary proteins.
It is particularly plentiful
inchocolate, oats, dried dates,
milk,yogurt,cottage cheese,red
meat, eggs,fish,poultry, sesame,
chickpeas, almonds, sunflower
seeds, pumpkin seeds,buck
wheat, spirulina, bananas, and
peanuts.
4mg per kilo of body weight

Bringing Back Balance

Turn up the voltage


The only way to increase NT
levels in the brain is to take amino
acids(along with cofactors) which
can cross the Blood Brain Barrier
where they can then be made into
NT.
Increasing NT level through the
neurons is analogous to
increasing the voltage in an
electric wire, where by turning up
the voltage you get more
electricity out the other end of the
wire.

Overcoming Nerve Damage


Even if 50%of the neurons in a nerve
bundle are damaged or destroyed , if
we give the remaining neurons more
amino acids(in the right dosages), the
remaining healthy neurons will
manufacture more NTs, effectively
alleviating symptoms and restoring
normal function.

Nervous system: neurotransmitters , control


Pituitary
Hormones

Thyroid
Metabolism

Adrenal
Stress

Immune system Chronic


infection

Causes of neurotransmitter
imbalances

High level of stress


or emotional
trauma
Dietary habits
Neurotoxins
Genetics

Hormone metabolism

How to Treat Hormone Imbalance


Take a History; Do an Exam; Test as
needed; Look for Cause
Treat the Matrix:
Brain
GUT
Detoxification Capacity
Mitochondrial Function/Oxidative
Stress
Immune Balance
Structural Imbalance
Mind-Body-Spirit
Hormone Imbalance

Selective serotonin reuptake inhibitors (SSRIs)

Imbalanced Neurotransmission
due to SSRIs

Integrative management of PNEC disorders


Purpos
e
Passio
n,
Pleasu
re

Exer
cise

Socia
l/
Spiri
tual
Mass
age

Diet

Envir
on.
Influ
ence
s

Arom
a
ther
apy

Integrative
Treatment
of PNEC
Diseases

Herb
al

Drug
s
Psyc
ho
logic
al

Slee
p

Hydr
othe
rapy

Naturopathy medicine
Nature
Cure Body
heals
itself
Health
Realization
Mind heals
itself

Natural life develops


proper physical body
perfectly abled mind
to progress
correct intellect
strong positive soul

mental /
Psychological
needs
Fulfillment of
physical needs
Love
Care and affection
Peace
Security and safety
Socialisation
Companion
Rest / Sleep

Satisfaction
Achievement
Motivation
Positivity
Faith and belief
Role model
Surrenderance
Leisure activity
Recognition
Social need

How does massage


help?

glucose

kinases

receptors

Our entire
toxins
organism is a
flowing
network of
energy and
information
What happens during Massage ?
nerves

blood

peptides

nutrients

chemicals
stem cells

dopamine

BDNF

hormones

oxygen

seratonin

mRNA

adipocytokines

glutamate

cytokines

synapses

macrophages

DNA

neuropeptides

ATP

University of Miami of Medicine


Touch Research Institute.
Miguel Diego and Tiffany Field
(2004) Moderate Pressure
Massage Increases Relaxation
Moderate pressure showed
shift towards the left frontal
lobe (positive emotive &
socialising aspects) and
decrease in heart rate during
and after massage

There are mixed results as to the


benefits of massage for immune
enhancement. Two studies have
noted increases in dopamine,
serotonin, NK cells and lymphocytes
in women with breast cancer after
thrice weekly massage for 5 weeks.
Depression, anxiety and anger were
also significantly reduced.
NK cells and lymphocytes increase in women with
BC following massage therapy. Hernandez-Reif
M, Field T, Ironson G et al. s.l.: Int J Neurosci
2005;115(4):495-510.
BC pts have improved immune and
neuroendocrine functions following massage
therapy. Hernandez-Reif M, Ironson G, Field T

et al. s.l.: J Psychosom Res 2004;57(1):45-52 .

Sleep
Good sleep is essential for physical and mental health.
There is strong evidence demonstrating that inadequate
sleep is associated with a multitude of health problems,
including cognitive impairment, mood disorders,
parasitical infections, cardiovascular diseases and
compromised immunity such as cancer.

Imeri L, Opp MR. How (and why) the immune system makes us sleep. s.l.: Nat Rev Neurosci
2009;10(3):199-210.
CA, Smyth. Evaluating sleep quality in older adults : the Pittsburgh Sleep Quality Index can be used to
detect sleep disturbances or deficits. s.l.: Am J Nurs 2008;108(5):42-50.
Meerlo P, Sgoifo A, Suchecki D. Restricted and disrupted sleep : effects on ANS function, neuroendocrine
stress systems and stress responsitivity. s.l.: Sleep Med Rev 2008;12(3):197-210.
Novati A, Roman V, Cetin T et al. Chronically restricted sleep leads to depression-like changes in NT
receptor sensitivity and neuroendocrine stress reactivity in rats. s.l.: Sleep 2008;31(11):1579-85.
Preston BT, Capellini I, McNamara P et al. Parasit resistance and the adaptive significance of sleep.
s.l.: BMC Evol Biol 2009;9:7.

Sleep
Melatonin is our natural sleep hormone and it is known to
decrease with increasing age. Recent studies have shown
that melatonin has an immune-modulating effect.
It stimulates the production of NK cells and CD4+ cells and
inhibiting CD8+ cells. It also stimulates the production of
granulocytes and macrophages, as well as the release of
various cytokines from NK cells and T-helper lymphocytes.
Cardinali DP, Esquifino AI, Srinivasan V et al. Melatonin and the
immune system in aging. s.l.: Neuroimmunomodulation 2008;15(46):272-8.

Acupuncture
Acupuncture has been used for centuries to
prevent and treat various conditions and to
simply maintain good health. In addition to its
known effects on the nervous system, emerging
evidence suggests that it may also effectively
modulate the innate immune system which
plays important roles in inflammation, pain,
metabolism, cell proliferation and apoptosis.
Acupuncture and immune modulation. Cabioglu MT, Cetin BE.
s.l.: Am J Chin Med 2008;36(1):25-36.
Acupuncture and innate immunity. G, Peng. s.l.: Zhen Ci Yan
Jiu 2008;33(1):49-52.
The messengers from PNS to CNS: involvement of
neurotrophins and cytokines in the mechanisms of A. J, Du.
s.l.: Zhen Ci Yan Jiu 2008;33(1):37-40.

Aromatherapy and
PNEC

Essential Oil and Psychological disordes


1) Alzheimer's Disease
28 older adults (including 17 people with Alzheimer's disease) used
aromatherapy (including use of lemon, rosemary, lavender, and
orange essential oils) for 28 days. Study results showed that
aromatherapy led to a significant improvement in certain measures
of cognitive function, especially among the Alzheimer's patients.
2) Anxiety
a 2004 study on rats determined that exposure to the odor of
lemon essential oil helped reduce levels of corticosterone (a type of
stress hormone). Published in Brain Research, the study also found
that lemon essential oil may possess anxiety-reducing and painrelieving properties.
# Breathing in the scent of orange essential oil may help alleviate
anxiety according to a small study published in Physiology &
Behavior in 2000.
3) Mood
Preliminary research indicates that lemon essential oil may
enhance mood. In a small study published in
Psychoneuroendocrinology in 2008, for instance, researchers found
that inhaling the aroma of lemon essential oil was more effective in
improving mood than aromatherapy involving the use of lavender
essential oil. The study involved 56 healthy men and women.

Nutrient Support in psycho-neuro-endocrinological


diseases
Immune System Function: vitamin A, vitamin E, zinc, folic
acid, vitamin B-6 , riboflavin, magnesium, selenium, vitamin
C
Nerve Impulses: sodium, potassium, magnesium, calcium,
vitamin B6, folic acid, B-12, copper, vitamin C
Tissue Repair and Formation: vitamin A, vitamin E, copper,
riboflavin, magnesium, vitamin B6, vitamin C
Metabolism: potassium, thiamin, niacin, vitamin B6,
magnesium, riboflavin, folic acid and vitamin C

Food is information
Food contains messages or
directions to the systems of the
body about function.
Function as single systems as well
as interconnected/interdependent
systems.
Focus should be on foods to
include rather than foods to
exclude.

Magnesium
Function
Needed for healthy bones
Initiates muscle release
Promotes healthy blood

vessels
May lower blood pressure
Involved in temperature
regulation
Needed for serotonin
production

Involved in nerve

transmission
Activates energy synthesis
Inhibits platelet
aggregation
Increases HDL cholesterol
Helps control blood sugar
Enhances immune function

Functional Nutrition
Looks for core underlying
imbalances.
Faulty digestion, impaired
detoxification, oxidative stress,
hormonal imbalances, altered
immunity and inflammation.
Dysfunction and disease arise
from diet, nutrient balance,
environment, trauma, stress,
attitude, beliefs, mind and spirit.

Integrative
Medical Model
Sur
ger
y
Che
mot
her
apy
Rad
ioth
era
Pharmaceuticals
py

Nutrients/Herbs

Conservative Interventions: Psychological/


Dietary Manipulation/Patient Education

Cognitive behaviour therapy

Group CBT training and psychotherapy for


women with breast cancer have also
resulted in improved immune parameters.
Attending group therapy may double
survival time and a self-perception of being
strong can also improve survival time.
A pilot RCT assessing the effects of autogenic training in early
stage cancer pts in relation to psychological status and
immune system responses. Hidderley M, Holt M. s.l.: Eur J
Oncol Nurs 2004;8(1):61-5.
An exploratory study into the effects of group psychotherapy
on CV and immunoreactivity to acute stress in breast ca pts.
vad der Pompe G, Antoni MH, Duivenvoorden HJ et al.
s.l.: Psychther Psychosom 2001;70(6):307-18.
Spiegel D, Bloom J, Kraemer H, Gottheil E. Effect of
psychosocial treatment on survival of patients with metastatic
breast cancer. Lancet 1989;2:888-891.
28. Hawks S, Hull M, Thalman R, Richins P. Review of spiritual
health: definition, role, and intervention strategies in health

Specific Dietary Programes


Gerson Diet
Use of specific foods, juices, supplements and coffee enemas

Gawler Foundation Diet


Raw, vegetarian food

Macrobiotic Diet
low fat, high fibre, mainly vegetarian diet emphasising whole grains and
vegetables and rich in phyto-oestogens from soy.

And so on

The Other Brain


The GI system contains about 100
million neurons, more than either the
spinal cord or the peripheral
nervous
system
95% of the bodies serotonin is in the
gut
SSRI medications can cause nausea,
diarrhea, and constipation. But, low
doses of SSRIs can be used to treat
nausea, diarrhea, and constipation.

Gut Brain Axis


A bidirectional communication system
between the brain and gastrointestinal
systems.
Communication occurs along immunologic,
neural, and biochemical pathways.
Gut microbiota can effect both brain
development and behavior.
Stress also can alter the composition of gut
microbiota.
Collins SM, Bercik P. The relationship between intestinal microbiota and the central nervous
system in normal gastrointestinal function and disease. Gastroenterology. 2009
May;136(6):2003-14. Epub 2009 May 7. Review.

Collins SM, Bercik P. The relationship between intestinal microbiota and the central nervous system in
normal gastrointestinal function and disease. Gastroenterology. 2009 May;136(6):2003-14. Epub 2009 May 7.

Pathways
involved in
bidirectional
communicatio
n between the
gut microbiota
and the brain.

John F. Cryan & Timothy G. Dinan


Nature Reviews
Neuroscience13,701712(October 2012)

Why Zebras Dont Get Ulcers

Robert Sapolsky, PhD

Stanford University - Stress Physiology

A
Stress occurs!

Yikes!!!!!

Whew
!

B
Stress response
begins in the brain
(lots of chemistry)

D
Stress response
ends and stress
hormones
dissipate

C
Fight or Flight
Figure 1.1
The normal stress response

Humans are not Zebras


and are not meant to harbor chronic
stressful situations
A
Stress occurs!

Yikes !!!

Yikes !!!

Stress response continues


and stress hormones lead to
tissue damage

E
Stress could lead to
health problems

Modern stressors
do not permit
Fight or Flight
Figure 1.2
The Type C personality (The HUMAN stress response)

SAME stress response


begins in the brain
(lots of chemistry)

Body Response to Stressful


situations
LowWHR

0.25

co rtiso l (u g /d l)

HighWHR
0.20

0.15

STRESS
0.10

50

100

Minutes (Session 1)

pel et al. Psychosom Med 2000;62(5):623-32

150

200

Cortisol

50

Norepinephrine

18

1400
1300

16

30

20

14

1200
1100

12

1000
900

NE(ng/l)

40

Cortisol(g/100ml)

ACTH(pg/ml)

ACTH

10
8

500

400

10
stress
0
10 10 30 50 70
Trier Social Stress Test
(public speaking &

800
700
600

300
200
stress

0
10 10 30 50 70

100

stress

0
10 10 30 50 70

M. Altemus, Cornell University.


Time(min)

Normal Diurnal Cortisol Rhythm

Cortisol Levels Throughout the Day


18
16
14
12
10
8
6
4
2
0
4AM

6AM

8AM

10AM Noon

2PM

4PM

6PM

8PM

10PM

Mid

2AM

Todays Health indicators


1980s = Cholesterol
Early 1990s = Free Radicals / Antioxidants
Later 1990s = Insulin / Blood Sugar
2000s = Cortisol

Just as high cholesterol, free radicals, and high blood


sugar are considered indicators of declining health,
there is increasing evidence that high cortisol is
emerging as a significant health indicator.

Scientific Evidence
The Relationship Between Elevated body responses to
everyday stresses and health

Cholesterol and
Mood: Whats the
Link?

The relationship between serum cholesterol and mood is


complex and research findings to date are inconsistent.
Research findings going back to the early 90s show that serum
cholesterol - especially the HDL fraction - is significantly lower in
many patients with major depressive disorder than in nondepressed individuals, and that clinical improvement following
antidepressant therapy is often associated with a significant
increase in serum total cholesterol. A review of 6 randomized
trials dating from the 1980s through the early 1990s found that
while lowering abnormally high serum cholesterol levels (below
150 mg/dL) decreased the number of deaths from coronary
heart disease, cholesterol lowering was actually associated with
increased mortality due to suicide or violence.

Busy lifestyles and weight


maintenance
High cortisol secretion
is associated with abdominal fat

Abdominal fat is most highly associated with a less


optimal health status:
High cortisol secretion may be a contributing factor to
the abnormal metabolism often seen in abdominal
obesity

1. Peeke PM, Chrousos GP. Ann NY Acad Sci 1995;771:665-76.


2. Bjorntorp P, Rosmond R. Nutrition 2000;16(10):924-36.

Abdominal fat & Stress-Related Cortisol


Stress-related cortisol

Abdominal Obesity
P<0.05

24

22.5
3.7

23
21.5
4.1

cm 22
21

0.34
0.5

0.4
nmol/L 0.3

20.6
2.2

0.15
0.6

0.2

20

0.1

19

<10

P<0.05

0.5

11-20

>21

Years in work

Rosmond, et al. Obes Res 2000;8:445-450.

0.04
0.3

<10

11-20

>21

Abdominal Fat Accumulation

Busy lifestyles / High Cortisol

Normal life / Normal Cortisol

Epel et al. found that purely psychological


intervention that reduces anxiety and cortisol
also reduces abdominal fat
Anxie
ty
Behavior?

r = .76

Abdominal fat

r = -.86

r = -.63Cortisol rhythmicity

Epel et al., Psychoneuroendocrine Workshops, 2000

Busy lifestyles and Appetite


Women with high cortisol response (compared to
women with low cortisol response):
consumed more calories
ate significantly more sweet foods
had more negative moods

High dietary restraint is associated with high urinary


cortisol excretion
Dietary Restraint = Consciously trying to limit food intake
to achieve or maintain a desired body weight

1. Epel ES, et al. Psychoneuroendocrinology 2001;26:37-49.


2. McLean JA, Barr SI, Prior JC. Am J Clin Nutr 2001;73:7-12.

Changes in Anxiety and Cortisol Rhythm

Change in diurnal rhythm magnitude

30

20

10

r = -.86, p < .01


-10
-30

-20

-10

10

Change in Trait Anxiety

Epel et al., Psychoneuroendocrine Workshops, 2000

Additional Research
Elevated Cortisol and Osteoporosis

High cortisol excretion associated with high dietary restraint


may cause long-term implications for bone health through
the effect on ovulatory function.

Elevated Cortisol and Depression


Fifty percent of women suffering from mood implications have high cortisol in
conjunction with HPA axis dysregulation.

Additional research has also focused on cardiovascularhealth status,


diabetes, mental function, and fatigue

1. McLean JA, Barr SI, Prior JC. Am J Clin Nutr 2001;73:7-12.


2. Sheline YI, et al. J Neuroscience 1999;19(12):5034-5043.

Osteoporosis and Oxidative Stress

How common is
the condition?
Prevalence of
insomnia- 6.5% in
Pre menopause,
56.6% in Peri
menopause,
50.7% in Post
menopause
Prevalence of Hot
Flashes

100%
50%
Perimenopause 79%
Postmenopause 39%
Premenopause 14%
0%

Decreased oxidative stress improves thyroid function


Peptides. 2004 Jun;25(6):1021-9.
Antigenicity and immunogenicity of the C-terminal
peptide of human thyroglobulin.
El Hassani RA, Estienne V, Blanchin S, Durand-Gorde JM, Mallet
B, De Micco C, Carayon P, Lalaoui K, Ruf J
Thyroglobulin (Tg) is cleaved into several peptides during
thyroid hormone synthesis, an oxidative process. P40, an
iodinated C-terminal peptide from human Tg, has a molecular
weight of about 40 kDa and contains two hormonogenic sites.
P40 is the smallest peptide that is still recognized by
monoclonal antibodies from mice immunized with human Tg
directed against its immunodominant region. Since P40 also
contains several T-cell epitopes, it is a good candidate for
studying the primary events involved in the process of
hormone synthesis leading to thyroid autoimmunity. The
present results show that P40 is recognized by Tg antibodies
from patients with thyroid disorders and induces Tg antibodies
in CBA mice. P40 may therefore be involved in the
autoimmune process, thus providing a useful tool for
diagnostic and therapeutic purposes.

Oxidative Stress
Positive Correlation with Chronic Disease and Aging

Hormone therapy and oxidative stress


J Obstet Gynaecol Res. 2012 Sep;38(9):1177-81. doi: 10.1111/j.14470756.2011.01842.x. Epub 2012 Apr 30.
Oxidative stress measured by carbonyl groups level in
postmenopausal women after oral and transdermal hormone
therapy.
Polac I, Borowiecka M, Wilamowska A, Nowak P.
Source
Department of Gynaecology and Menopausal Disorders, Polish Mother's
Memorial Hospital - Research Institute, Lodz, Poland. irekpolac@interia.pl
Menopause is associated with an increased risk of cardiovascular
disorders, which are accompanied by oxidative stress. Our study was
undertaken to determine whether oxidative stress in menopausal women
could be reduced after six months of oral or transdermal hormonal therapy.
Plasma protein carbonyl levels of postmenopausal women treated with oHT and t-HT for six months (o-HT: 1.785 0.31 nmol/mg; t-HT: 1.838
0.33 nmol/mg) were lower when compared with the control group (2.232
0.28 nmol/mg). There was no statistically significant difference in carbonyl
levels between women after oral and transdermal HT (P = 0.149).
CONCLUSION:
Hormonal therapy reduces the level of carbonyl protein, a marker of
oxidative stress, suggesting potential protective effect.

Adrenals and Oxidative Stress


Psychoneuroendocrinology.2013 Mar 9. pii: S0306-4530(13)00042-5. doi:
10.1016/j.psyneuen.2013.02.004. [Epub ahead of print]
Goodstress, badstressandoxidative stress: Insights from anticipatory cortisol
reactivity.
Aschbacher K,O'Donovan A,Wolkowitz OM,Dhabhar FS,Su Y,Epel E
Source
Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; The Institute for
Integrative Health, Baltimore, MD, USA.
Abstract

Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential
mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are
poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event
have the potential to either enhance or undermine psychobiological resilience to oxidativedamage, depending on the
body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, fortyeight post-menopausal women were recruited in a case-control design that matched women caring for spouses with
dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants
completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three
markers of oxidative damage were assessed: 8-iso-prostaglandin F2 (IsoP), lipid peroxidation, 8-hydroxyguanosine (8oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within
approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol
responses were measured. The increase from 0 to 30min was defined as "peak" cortisol reactivity, while the increase
from 0 to 15min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while
preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A
moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity
would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women
under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from
perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected
relations among chronically stressed participants (p.01) Intriguingly, among those with low chronic stress exposure,
moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage.
Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through
frequent and sustained activation of the hypothalamic-pituitary-adrenal axis. It also supports the less studied model of
'eustress' - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage.

Stress and your skin


Stress linked to skin problems in
50% of French women
Poli et al. J Eur Acad Dermatol Nov 2001 (3,305 women
aged 25-40 yrs)
Dermatology Service, Mondor Hospital, Creteil, France

Stress hormones => Stimulate oil


formation = skin problems
Zouboulis et al. Proc Natl Acad Sci, May 2002
Dept of Dermatology, Free University of Berlin, Germany

Adult female acne [is] a modern phenomenona


lot more common than 100 years ago
Richard Glogau, MD, Professor of Dermatology, Univ
California San Francisco (Allure, Aug 2002)

Adult acne [is] an epidemic [with] an exponential


increase in sufferers in the past ten years
Steven Grekin, MD, Clinical Professor of Dermatology,
Univ of Health Sciences, Des Moines (Allure, Aug
2002)

During stressful times - or any time the economy


is bad - we definitely see more acne
Debra Jaliman, MD, American Academy of Dermatology
(Allure, Aug 2002)

increaseinskinthickness(%baseline)

Acute stressful situations enhances a skin


response
control
stress

70
60
50
40
30
20
10
0

Time (days after challenge)


Dhabhar & McEwen, 1996, J. Immunology, 156, 2608-

increaseinskinthickness(%baseline)

Effect of Cortisol on Skin Response


acutecorticosterone

70

control
60

chroniccorticosterone

50

40

30

Too much
stress/cortisol makes
you thin-skinned!

20

10

Time(daysafterinduction)

Dhabhar&McEwen,1999,PNAS,96:1059.

Cortisol Levels Are Elevated In...


Chronic stressful situations
Sleep deprivation
Dieting / Restrained eating
Adults who need to control cortisol levels are
Frequently confronted with stressful situations
Getting less than 8 hours of sleep every night
Limiting caloric intake to lose weight

There is a strong scientific association


between chronically elevated cortisol levels
and stress-related body responses
Therefore, it is important for long-term health to control
your body responses to busy lifestyles

Example of

Health Benefits when


controlling cortisol levels
Enhances feelings of
wellbeing and control in
response to stressful situations
Improves performance and
increased vigor throughout the
day
Better mental concentration
and focus
Supports weight maintenance
efforts

You can control cortisol levels via:


Stress Management Techniques
Meditation, Coping strategies, etc
Exercise
Daily, moderate aerobic and strength training
Nutrition
Balance carbohydrates with protein
Maintain adequate hydration
Avoid caffeine
Supplements
Avoid ephedra and related stimulants
Cortisol-controlling supplements
(Phosphatidylserine, Beta-sitosterol...)
Relaxation supplements (Ashwagandha, Theanine)
...Evaluation (every month to see how you are doing)

Main Psychosomatic Diseases


linked with PNEC we treat :

Obesity
NIDDM
HTN
PCOS
PMS and Depression
Psoriasis
Hypo and Hyperthyroidism

Common Anti-Stress
Solutions
Valerian
Kava Kava
Melatonin
Tyrosine
None of these supplements directly address cortisol control

Endocrinology and Psychiatry


Storch M, Gaab J, Kttel Y,
Stssi AC, Fend H (Jul 2007).
"Psychoneuroendocrine
effects of resource-activating
stress management training".
Health Psychol 26 (4): 456
63. doi:10.1037/02786133.26.4.456. PMID
17605565

The American Psychiatric Press


Textbook of Psychiatry,
Washington, DC: American
Psychiatric Publishing, Inc., 2003
Stahl's Essential
Psychopharmacology:
Neuroscientific basis and
practical applications, New York:
Cambridge University Press,
2008

Storch M, Gaab J, Kttel Y, Stssi


AC, Fend H (Jul 2007).
"Psychoneuroendocrine effects of
resource-activating stress
management training". Health
Psychol 26 (4): 45663.
doi:10.1037/0278-6133.26.4.456.
PMID17605565.
Rohde A, Marneros A (1993).
"Postpartum Psychoses: Onset and
Long-Term Course".
Pscyhopathology 26: 203209.
doi:10.1159/000284823

REFERENCES
http://psycnet.apa.org/?&fa=main.doiLanding&doi=10.1037/02786133.26.4.456
http://blog.alanjacobsmd.com/
http://www.ncbi.nlm.nih.gov/pubmed/2654128
http://www.psyneuen-journal.com/article/S0306-4530(04)001209/abstract?cc=y=
http://www.sciencedirect.com/science/article/pii/S0306453003000982
http://www.sciencedirect.com/science/article/pii/S0306453000000214
http://www.sciencedirect.com/science/article/pii/S0306453002001464
http://www.bioxbio.com/if/html/PSYCHONEUROENDOCRINO.html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC284388/
http://www.sciencedirect.com/science/article/pii/S0306453003000994
http://www.ncbi.nlm.nih.gov/pubmed/6117245
http://www.sciencedirect.com/science/article/pii/S0306453003000969
http://www.ncbi.nlm.nih.gov/pubmed/2970959
http://www.sciencedirect.com/science/article/pii/S0306453000000214
http://www.ncbi.nlm.nih.gov/pubmed/2852463
http://www.ncbi.nlm.nih.gov/pubmed/1749461

Take home note


The important thing is to keep
looking upstream to find the
root imbalance so we can
achieve a lasting solution .

Thank you
BY
DR.KANAK