IFN-a

HPA AxisDecreased cortisol

Resistance to cortisolLoss of circadian

variation

ANSIncreased SNS

Decreased cholinergicReduced HRV

Raison et al. Trend Immun, 27:24-31, 2006

Chronic Stress, Depression and the Stress System

IFN-a

HPA AxisIncreased activity

Develop resistanceLoss of circadian

variation

ANSIncreased SNS

Decreased cholinergicReduced HRV

Raison et al. Trend Immun, 27:24-31, 2006

Pathways Linking Stress, Inflammation and Depression

HPA AxisIncreased activity

Develop resistanceLoss of circadian

variation

ANSIncreased SNS

Decreased cholinergicReduced HRV

Raison et al. Trend Immun, 27:24-31, 2006

Pathways Linking Stress, Inflammation and Depression

Increased Inflammation

Inflammation as a Link Between Stress, Depression and Illness

DIABETES CARDIOVASCULAR

CANCER DEMENTIA

SSRI Pretreatment Reduces IFN-alpha-Induced Depression

Weeks on IFN-alpha

Su

rviv

al F

ree

of

Maj

or

Dep

ress

ion

(%

)

0 2 4 6 8 10 120

20

40

60

80

100

Placebo

Musselman et al., New England Journal of Medicine, 344:961-966, 2001.

*-the majority of the depressed patients in this sample also endorsed significant early life stress as measured by the CTQ

Pace et al., Am J Psychiatry, 2006.

Pla

sma

IL-6

, p

g/

ml

0

1

2

3

4

5

6

-15 0 15 30

Major Depression (n = 14)

Control (n = 13)

TSST

*

*Between group comparison, p < 0.05

+Within group comparison vs. 0 min time pt, p < 0.05

Pla

sma

IL-6

, p

g/

ml

0

1

2

3

4

5

6

-15 0 15 30 45 60 75 90

Health Men WITH early trauma/neglect and major depression (n = 14)

Health Men WITHOUT early trauma/neglect or major depression (n = 13)

STRESS Time (min)

*Between group comparison, p < 0.05

+Within group comparison vs. 0 min time pt, p < 0.05

+ ++

+

*

+

+

*

Psychosocial Stress Activates Inflammation: Effect of Depression

Positive Social Connectivity Associated with Reduced Inflammation

Loucks EB et al. J Biosoc Sci 2006

Week 1 Developing Attention and Stability of MindIntroduction of basic meditation techniques for focusing attention for increasingly longer periods of time. These techniques are included in the practice of all subsequent compassion meditation components.

Week 2 Developing Compassion for Oneself through Mindfulness of Sensations,

Feelings and Emotions Introduction of techniques to develop awareness of how thoughts and actions contribute to subjective experiences of happiness or suffering, and techniques to increase identification of habitual, conditioned reactions.

Week 3 Cultivating Equanimity and AppreciationIntroducing practices designed to challenge unexamined thoughts and feelings determining categories of friend, enemy and stranger; introducing the perspective that all persons are all alike in wanting to be happy, and appreciating others for the ways they benefit us.

Week 4 Developing Affection and Empathy Techniques will be presented for developing undifferentiated affection for others, based on the many ways that others benefit us each day. The meditators will be introduced to the concept of empathy for others: identifying with their happiness and suffering alike.

Week 5 Wishing and Aspirational Compassion Using the concepts of appreciation and empathy as a starting point, the meditator will be guided toward the first stages of compassion: the wish that all beings might be happy and free of suffering, and the aspiration to help them achieve that.

Week 6 Active Compassion for OthersThe meditation training culminates in the generation of active compassion: practices introduced to develop a determination to work actively to alleviate the suffering of others. When this training is successful, this state of mind becomes ingrained and spontaneous.

Compassion Meditation Protocol Developed by LTN, PhD

FreshmanCollege Students

males/females

CompassionMeditation

Group

HealthDiscussion

ControlGroup

intervention

6 Weeks

intervention

Psychosocial Stress Test

Effect of Compassion Meditation on Inflammatory, Neuroendocrine and Behavioral Responses to Psychosocial Stress

STUDY HYPOTHESES:

Randomization to six weeks of training in compassion meditation will reduce interleukin (IL)-6, cortisol and behavioral distress responses to a standardized laboratory psychosocial stressor (Trier Social Stress Test [TSST]) in medically-healthy young adults when compared to randomizationto a health discussion control group.

1.

In participants randomized to compassion meditation training,amount of meditation practice during the study will be associated with inflammatory, neuroendocrine and behavioral responses to the TSST.

2.

Control

Compassion meditation

Time (min)TSST

0 15 30 45 60 75 90

a

pla

sma

cort

iso

l, µ

g/

dl

0

7.5

10.0

12.5

15.0

17.5

log

pla

sma

IL-6

, p

g/

ml

-1.5

-1.0

-0.5

0

0.5b

0 15 30 45 60 75 90

Time (min)TSST

Control

Compassion meditation

0 15 30 45 60 75 90

Time (min)TSST

PO

MS

- T

ota

l M

oo

d D

istr

ibu

tio

n S

core

-5

0

5

10

15c

Effect of Compassion Meditation on Inflammatory, Neuroendocrine and Behavioral Responses to Psychosocial Stress

Pace et al., PNE 2008

d

0

2

4

6

8

Av

era

ge

me

dit

ati

on

se

ss

ion

pe

r w

ee

k

Compassion Meditation Group (n = 33)

Distribution of Meditation Practice Exposure in Compassion Group

-2.0

-1.5

-1.0

-0.5

0

0.5

1.0

1.5

2.0

2 3 4 5 6 7

Average meditation sessions per week

Lo

g M

AX

IMA

L I

L-6

Po

st-s

tres

sor

8 91

PO

MS

- T

ota

l M

oo

d S

core

(p

ost

-str

esso

r)

-20

-15

-10

-5

0

5

10

15

20

25

30

2 3 4 5 6 7

Average meditation sessions per week

8 91

Evidence for a “Dose-Response” Relationship Between Amount of Meditation Practice and IL-6 and POMS Responses to the TSST

Pace et al., PNE 2008

rp = 0.46, p<0.01 rp = 0.39, p<0.05

TSST

log

pla

sma

IL

-6,

pg

/ m

l

Time (min)

-1.5

-1

-0.5

0

0.5

0 15 30 45 60 75 90

Control (n = 28)

Compassion meditation (n = 16)(high practice)

Compassion meditation (n = 17)(low practice)Compassion meditation (n = 33)

TSST

Incr

easi

ng

in

flam

mat

ion

Effect of Meditation Practice on IL-6 Responses to the TSST when Compared to Control Subjects

Incr

easi

ng

Dis

tres

s

-5

0

5

10

15

PO

MS

- T

ota

l Mo

od

Dis

trib

uti

on

Sco

re

-15 0 15 30

Time (min)

Compassion meditation (n = 16)(high practice)

Compassion meditation (n = 17)(low practice)

Control (n = 28)

STRESSOR

Effect of Meditation Practice on Distress Responses to the TSST when Compared to Control Subjects

Increased EngagementWith Meditation Practice

Reduced BehavioralAnd

Physiological StressResponses

Reduced BehavioralAnd

Physiological StressResponses

Increased EngagementWith Meditation Practice

Increased EngagementWith Meditation Practice

Reduced BehavioralAnd

Physiological StressResponses

Randomized toCompassionMeditation

6 Weeks

intervention

TSST

High Practice Time GroupPost-training TSST

Low Practice Time GroupPost-training TSST

Randomized toCompassionMeditation

TSST

6 Weeks

intervention

High Practice Time GroupPre-training TSST

Low Practice Time GroupPre-training TSST

TSST prior tomeditation training

TSST aftermeditation training

0.5

0

-0.5

-1.0

-1.50 30 6045 75 9015

TSST

0.5

0

-0.5

-1.0

-1.50 30 6045 75 9015

TSST

log

plas

ma

IL-6

, pg/

ml

log

plas

ma

IL-6

, pg/

ml

low practice

high practice

Time (min) Time (min)

18

12

10

8

00 30 6045 75 9015

TSST

16

14

18

12

10

8

00 30 6045 75 9015

TSST

16

14

pla

sma

cort

isol

, µg/

ml

pla

sma

cort

isol

, µg/

ml

Time (min) Time (min)

IL-6

Cortisol

25

10

5

0

-50 30 6045 75 9015

TSST

20

15

25

10

5

0

-50 30 6045 75 9015

TSST

20

15

PO

MS

- t

ota

l mo

od

d

istr

ibu

tio

n s

core

PO

MS

- t

ota

l mo

od

d

istr

ibu

tio

n s

core

Time (min) Time (min)

TSST prior tomeditation training

TSST aftermeditation training

POMSTotal

Distress