The 2 nd International Congress of International Prof. Dr. Alireza Yalda Academic Foundation in Medical Sciences 24-27 October 2011, Tehran, Iran The influence.

The 2nd International Congress of International Prof. Dr. Alireza Yalda Academic Foundation

in Medical Sciences 24-27 October 2011, Tehran, Iran

The influence of psyche on the immune system

,

President,Institute of Interventional

Allergology and Immunology,Cologne / Bonn, Germany

Prof. Alireza Ranjbar, MD,PhD

- In recent years one of the most rapidly advancing areas In recent years one of the most rapidly advancing areas

in medicine has been immunology and its interactions in medicine has been immunology and its interactions with various psychological states.with various psychological states.

- Considerable data indicate that psychological disorders Considerable data indicate that psychological disorders

may increase an organism's vulnerability to certain may increase an organism's vulnerability to certain diseases by means of exerting an immunosuppressive diseases by means of exerting an immunosuppressive effect, especially those diseases intimately associated effect, especially those diseases intimately associated with immunologic mechanisms, such as infection, with immunologic mechanisms, such as infection, malignancy, and autoimmune diseases. malignancy, and autoimmune diseases.

- Significant evidence suggests that the immune system is Significant evidence suggests that the immune system is capable of profoundly affecting central nervous system capable of profoundly affecting central nervous system (CNS).(CNS).

Inflammation and the pathogenesis of depressionInflammation and the pathogenesis of depression

Depression has been linked to a worse outcome in multiple medical disorders

Increasing amounts of data suggest that inflammatory responses have an important role in the pathophysiology of depression.

Depressed patients have higher levels of

- proinflammatory cytokines, - acute phase proteins, - chemokines and- cellular adhesion molecules.

Charles L. Raison, et al., Atlanta, USA, 2005


Proinflammatory cytokines interact with

- neurotransmitter metabolism, - neuroendocrine function, - synaptic plasticity and - behavior

that characterize depression.



Stress, which can precipitate depression, can also promote inflammatory responses through effects on sympathetic and parasympathetic nervous system pathways.

Depression might be a behavioralby product of early adaptive advantages conferred by genes that promote inflammation.

These findings suggest that targeting proinflammatory cytokines and their signaling pathways might represent a novel strategy to treat depression.


Psyche , CNS and Immune SystemPsyche , CNS and Immune System

Experimental and clinical trialsExperimental and clinical trials

The influence of CNS on Immune SystemThe influence of CNS on Immune System

Experimental studiesExperimental studies

In animal trials by directly stimulating the brain, In animal trials by directly stimulating the brain, different investigators have produced alterations different investigators have produced alterations in the immune response. in the immune response.

• Lesions in the dorsal hypothalamus of rabbits Lesions in the dorsal hypothalamus of rabbits

have been shown to suppress both humoral and have been shown to suppress both humoral and cellular immunity.cellular immunity.

(Korneva EA, Khai LM, (Korneva EA, Khai LM, Fiziol Zh SSSR, 49:42-48, 1963)Fiziol Zh SSSR, 49:42-48, 1963)

• Mesencephalic stimulation and electrical Mesencephalic stimulation and electrical stimulation of the lateral hypothalamus in rats stimulation of the lateral hypothalamus in rats enhance antibody responses.enhance antibody responses.

(Korneva EA, Khai LM, (Korneva EA, Khai LM, Fiziol Zh SSSR,Fiziol Zh SSSR,53:42-47, 196753:42-47, 1967 ) )

• Bilateral anterior hypothalamic lesions in guinea Bilateral anterior hypothalamic lesions in guinea pigs protect against lethal anaphylaxispigs protect against lethal anaphylaxis

(Freedman DX, Fenichel G, (Freedman DX, Fenichel G, Arch Neurol Psychiatr, 79:164-169, 1958; Arch Neurol Psychiatr, 79:164-169, 1958; Szentivanyi A, Filipp G Ann Allergy 16:143-151, 1958 ; Luparello TJ, Stein M, Szentivanyi A, Filipp G Ann Allergy 16:143-151, 1958 ; Luparello TJ, Stein M, Park DC:, Am J Physiol. 207:911-914, 1964Park DC:, Am J Physiol. 207:911-914, 1964 ) )

The influence of Immune System on CNSThe influence of Immune System on CNS

Experimental studiesExperimental studies

Corticotropin-releasing factor (CRF) and vasopressin Corticotropin-releasing factor (CRF) and vasopressin (VP) mRNA levels in adult rats after Injection with IL-1ß(VP) mRNA levels in adult rats after Injection with IL-1ß

Indomethacin reduces ACTH response to Indomethacin reduces ACTH response to iv. IL-1ßiv. IL-1ß

ACTH secretion in rats by IL-1ß Injection with and without ACTH secretion in rats by IL-1ß Injection with and without anti-CRF treatment anti-CRF treatment

Time course of the neurochemical Time course of the neurochemical Response to IL-1ß in miceResponse to IL-1ß in mice

Human studiesHuman studies

Clinical trialsClinical trials

Human studiesHuman studies

Example 1Example 1

Stress and Immune SystemStress and Immune System

- In a human study, bereavement was found to be In a human study, bereavement was found to be

associated with depressed lymphocyte function. In this associated with depressed lymphocyte function. In this study there was a 10-fold difference in T-cell function at study there was a 10-fold difference in T-cell function at 5 weeks between the 26 bereaved spouses and the 5 weeks between the 26 bereaved spouses and the controls.controls.

Human studiesHuman studies Example 2Example 2

Depression and CancerDepression and Cancer

Depressive Symptoms and Prospective Incidence of Depressive Symptoms and Prospective Incidence of

Colorectal Cancer in Women Colorectal Cancer in Women

- The authors examined depressive symptoms and prospective incidence of colorectal cancer and distal colorectal adenomas in 81,612 women without prior cancer from the Nurses' Health Study

- 400 cases of colorectal cancer and 680 distal colorectal adenomas accrued between 1992 and the year 2000.

- Depressive symptoms were assessed in 1992 and 1996 with the five-question Mental Health Index (MHI-5), a subscale of the Short-Form 36 health status survey.

C. H. Kroenke, G. BennettAmerican Journal of Epidemiology 2005 162(9):839-848



Scores ranged from 0 to 100, and women with scores between 0 and 52 were defined as having significant depressive

symptomatology.

The authors also created four categories across the range of Mental Health Index scores: 0–52, 53–75, 76–85, and 86–100 (referent).




Results:Women with the highest levels of depressive symptoms had an elevated risk of incident colorectal cancer (hazard ratio = 1.43, 95% confidence interval: 0.97, 2.11) compared with women with the lowest levels of symptoms (ptrend = 0.04).

Associations appeared stronger in overweight women. However, depressive symptoms were unrelated to risk of colorectal adenomas.

Associations are consistent with a possible role in late promotion of the disease.



Stress and Autoimmune DiseaseStress and Autoimmune Disease

Rheumatoid arthritis and depressionThe role of pro-inflammatory cytokine-induced SAPK/MAPK and JAK/STAT

Malemud CJ, Miller AH,Ohio 44106-5076, USAExpert Opin Ther Targets. 2008 Feb;12(2):171-83

Adult rheumatoid arthritis (RA) patients are frequently clinicallydepressed

Peripheral inflammation in RA may influence- neurotransmitter metabolism, - neuroendocrine function,- synaptic plasticity, as well as - growth factor production,

which can modify neural circuitry and contribute to depression.


Malemud CJ, Miller AH,Ohio 44106-5076, USAExpert Opin Ther Targets. 2008 Feb;12(2):171-83

A convergence between pro-inflammatory cytokine-inducedsynovial joint inflammation in RA and the effects of pro-inflammatory cytokines on the brain may occur through activation of the stress-activated/mitogen-activated protein kinases(SAPK/MAPK) and/or Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways.


Malemud CJ, Miller AH, Ohio 44106-5076, USAExpert Opin Ther Targets. 2008 Feb;12(2):171-83

Some novel anti-depression drugs that were employed in animal models of 'sickness behavior' and in human depression clinical trials suppressed clinical markers of inflammation, as well as SAPK/MAPK and/or JAK/STAT signaling in vitro.

Modifying pro-inflammatory cytokine signaling pathways in the brain with antidepressants may also be useful in ameliorating peripheral inflammation in RA


Depression and Infectious DiseaseDepression and Infectious Disease

Depressive symptoms and viral clearance in patients Depressive symptoms and viral clearance in patients receiving interferon-α and ribavirin for hepatitis C receiving interferon-α and ribavirin for hepatitis C

Interferon (IFN)-α plus ribavirin is an effective treatment for hepatitis C virus (HCV) infection, but is associated with a high rate of depression.

Therapeutic administration of the cytokine interferon-α leads to depression in up to 50% of patients.

Depression has been linked to a worse outcome in multiple medical disorders including viral illnesses.

The authors examined whether increased symptoms of depression during IFN-α/ribavirin therapy were associated with a reduced treatment response as assessed by clearance of HCV.

Charles L. Raisona, Sherry D. Broadwella, Andrey S. Borisova, et al., USA, 2004

Depressive symptoms and viral clearance in patients Depressive symptoms and viral clearance in patients

receiving interferon-α and ribavirin for hepatitis C receiving interferon-α and ribavirin for hepatitis C

Methods:

Depressive symptoms were evaluated in 102 HCV-infected patients at baseline and after 4, 8, 12, and 24 weeks of pegylated IFN-α-2b plus ribavirin therapy using the Zung self-rating depression scale (SDS).

Viral clearance was determined at 24 weeks by polymerase chain reaction (PCR).



Results:

- 34% of subjects (10 out of 29) with a 20-point or greater increase in SDS Index score were HCV PCR negative at 24 weeks,

- 59% (24 out of 41) of patients with a 10–19 point increase in SDS Index and

- 69% (22 out of 32) of patients with a less than 10 point increase (χ2=7.6, df=2, p<0.05).



Results:

- In addition, a 20-point or greater increase in SDS Index score during IFN-α/ribavirin therapy significantly predicted failure to clear virus when considered alone [crude odds ratio (OR), 3.2; 95% confidence interval (CI), 1.3–8.0; p<0.01] or when controlling for other factors that affected IFN-α treatment response (adjusted OR, 3.6; 95% CI, 1.3–9.5; p=0.01).

- These findings suggest that individuals who experience significant increases in depressive symptoms during IFN-α/ ribavirin therapy may be less likely to clear virus, highlighting the importance of identifying and treating depressive symptoms in this patient population.



Stress and Infectious DiseaseStress and Infectious Disease

Immune system, stress and Herpes infectionImmune system, stress and Herpes infection

Macrophage

Neutrophils

Lysozyme

LTB4fMLPC5a

IL-1IL-6

IL-8

TNF-alpha

GM-CSF

Myeloperoxidase

ElastaseCollagenase

Muraminidase

Oxygen free radicals

H2O2OHO2

-

--

Schematic outline of the role of Macrophage / Neutrophils in elimination of microorganisms ( A. Ranjbar )

Elimination of microorganisms

108,64

100

321,34

Ph

ag

ocyto

sis

-in

dex %

, m

ean

Phagocytosis-index of granulocytes under and without stress condition (n=26, 12m, 14 f)

50

50

without stress

stress

108,64

100

321,34

Ph

ag

ocyto

sis

-in

dex %

, m

ean

Phagocytosis-index of monocytes under and without stress condition(n=26, 12m, 14 f)

50

50

without stress

stress

72,8

100

321,34

0

Resp

irato

ry b

urs

t (P

MA

) %

,

mean

Respiratory burst of granulocytes after stimulation with PMA under and without stress condition(n=26, 12m,14 f)

50

50

without stress

with stress

72,8

100

321,34

0

Resp

irato

ry b

urs

t (P

MA

) %

,

mean

Respiratory burst of monocytes under and without stress condition(n=26, 12m, 14 f)

50

50

without stress

with stress

122

1250

1000

750

500

250

TN

F-a

lph

a l

evels

pg

/l,m

ean

TNF-alpha levels after stimulation with E.coli-derivedLPS plus rhIFN-gamma under and without stress condition

(n=26, 12m, 14 f)

52

p < 0.01

20

20with stress

without stress

Summary

There is a bidirectional relationship between the CNS / psychological states and the immune system.

Mental factors such as stress and depression have been shown to affect immune system functioning.

Stress and depression are associated with worse outcomes in immune-related disorders including cancer , autoimmune disorders and infectious diseases.

Summary

Conversely, immune system activation such as during infectious diseases, cancer, and autoimmune disorders is associated with the development of behavioral symptoms similar to those seen in the context of chronic stress or major depression.

These findings implicate a role for the immune system in the cause of behavioral disorders in a wide range of medical illnesses.

Finally, a paradigm is proposed in which abnormal functioning of either the hypothalamic-pituitary-adrenal (HPA) axis or the inflammatory response system disrupts feedback regulation of both neuroendocrine and immune systems contributing to the development of neuropsychiatric and immunologic disorders.

discoverd by Prof. Dr. Nossrat Peseschkian

by the year 1968in Wiesbaden, Germany

Positive Psychotherapy – A novel approach in Social

Psychotherapy with a

Transcultural Perspective

2000 : 1. Peseschkian-Ranjbar-Begegnung als2000 : 1. Peseschkian-Ranjbar-Begegnung als Referenten in einem Kongress in HamburgReferenten in einem Kongress in Hamburg

Success is

Success is

Success is

?

Success is

Teamwork!

Thank you for your attention

The 2 nd International Congress of International Prof. Dr. Alireza Yalda Academic Foundation in Medical Sciences 24-27 October 2011, Tehran, Iran The influence.

Documents

pathophysiology of depression

immune system psyche

immune response

phd slide

central nervous system

influence of cns

clinical trials experimental

influence of psyche