This document summarizes a presentation on the physical consequences of depression, stress, and anxiety. The presentation discusses how these mental health issues are associated with increased rates of cardiovascular disease, diabetes, obesity, and some cancers. Conditions like depression can also complicate the course of physical illnesses and impact mortality. Some of the main physical pathways discussed include inflammation, insulin resistance, and hypothalamic-pituitary-adrenal axis dysfunction.
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Physical and Mental Health Impacts of Depression
1. Psychiatry Below the Neck: The Physical
Consequences of Depression, Stress and
Anxiety
Richard G Petty MD, MSc, MRCP(UK), MRCPsych,
Promedica Research Center,
Georgia State University College of Health
Sciences,
Loganville, Georgia,
USA
rpettyus@aol.com
RichardGPettyMD.com
Sunday, July 26, 2009
2. Disclosure
Richard G. Petty, MD, MSc, MRCP(UK), MRCPsych
Consultant
• AstraZeneca; Eli Lilly and Company; Janssen Pharmaceuticals
Speaker’s Bureau
• Abbott Pharmaceuticals, Astra Zeneca; Janssen Pharmaceuticals
Grant Support
• British Diabetic Association; Bristol Meyers Squibb; British Heart
Foundation; Du Pont Merck, Inc.; Eli Lilly and Company; Janssen;
Medical Research Council (UK); National Institute of Mental
Health; Pfizer
Sunday, July 26, 2009
3. Objectives
1. Attendees will be able to list the main
cardiovascular, endocrine, metabolic,
immunological and oncological associations of
depression, stress and anxiety
2. Participants will be able to describe the impact of
depression, stress and anxiety on pre-existing
physical illnesses
3. Attendees will be able to screen for the physical
problems associated with depression, stress and
anxiety
Sunday, July 26, 2009
4. There Is a Serious Lack of Physical Well-being in Individuals
With Major Mental Illness: Not Only Schizophrenia, But Also
Bipolar Disorder and Major Depressive Disorder
Sunday, July 26, 2009
5. There Is a Serious Lack of Physical Well-being in Individuals
With Major Mental Illness: Not Only Schizophrenia, But Also
Bipolar Disorder and Major Depressive Disorder
Mortality rates: people die on average 10-20 years earlier than the
general population1-3
Sunday, July 26, 2009
6. There Is a Serious Lack of Physical Well-being in Individuals
With Major Mental Illness: Not Only Schizophrenia, But Also
Bipolar Disorder and Major Depressive Disorder
Mortality rates: people die on average 10-20 years earlier than the
general population1-3
In part because of suicide, but also:
Cardiovascular diseases
Coronary artery disease 4
Arrhythmias
Diabetes mellitus - Type II5
Obesity6
Some forms of cancer
Respiratory illness
Substance abuse7
1. Harris, E.C. and Barraclough, B. Br J Psychiatry 1998; 173: 11-53
2. Newman and Bland Can J Psychiatry 1991; 36: 239-245
3. Tabbane, K., R. Joober, et al. 1993; Encephale 19: 23-8
4. Allebeck, Schizophr Bull 1989; 15: 81-89
5. Dixon et al, J Nerv Ment Dis 1999; 187: 495-502
6. Allison, D., et al. J Clin Psychiatry 1999; 60: 215-220
7. Herran et al, Schizophr Res 2000; 41: 373-381
Sunday, July 26, 2009
7. Depression, Anxiety and Stress
Each may be associated with an array of
similar physical problems
These physical complications may have an
enormous impact on the health and well-
being of the patient
Depression, anxiety and stress may each
complicate physical illnesses and modulate
their course, severity and outcome
Sunday, July 26, 2009
9. Somatic Symptoms in People with Major Depressive
Disorder
Fatigue 86%* Chest pain 27%
Insomnia 79%* Sexual symptoms 23%
Nausea 51%* Pain in extremities 20%
Dyspnea 38% Dizziness 19%
Palpitations 38% Abdominal pain 18%
Back pain 36%* Tinnitus 18%
Diarrhea 29% Joint or limb pain 16%
Headache 28%
Patients presenting in a Psychosomatic Clinic assessed with Cornell Medical Index Questionnaire
*Significantly higher % in those with MDD
Nakao, M. et al, Psychopathology 2001: 34, 230-5
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10. Common Complicating Problems in
Depression
Smoking
Poor physical activity
Adherence to medical advice
Sleep disturbances
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11. Depressive Disorders in the
Physically Ill: Key Points
Depressive disorders are common in the
physically ill
Depressive disorders co-occurring with
physical illness complicate treatment of both
disorders
Depressive disorders and physical
illnesses must be treated in parallel
Sunday, July 26, 2009
12. Comorbid Depression Alters the
Outcome of Physical Illness
Depressed post-stroke patients
Less compliant with treatment, more irritable
and demanding1
Depressed patients following myocardial
infarction
Less compliant with rehabilitation programs,
longer recoveries and slower return to normal
functioning2
Are 2.7 times more likely to die3
Depressed diabetic patients
Poorer glucose control4
1. Ross, E.D. and Rush, A.J. Arch Gen Psychiatry 1981: 38, 1344-1354
2. Guiry, E., et al. Clin Cardiol 1987: 10, 256-260
3. Surtees, P.G. et al. Am J Psychiatry 2008: 165, 515-523
4. Lustman, PJ, et al. Diabetes Care 1988: 11, 605-612
Sunday, July 26, 2009
13. Increased Mortality Associated With
Depression and Physical Illness
Depressed patients have a significantly higher 4-
year mortality than non-depressed controls after
controlling for severity of physical illness1
Depression increased mortality in 211
hospitalized patients with a life-threatening illness
Depressed patients had significantly poorer outcome
over the 28 days following admission — 47% died or had
life-threatening complications vs 10% of the non-
depressed patients2
Murphy E, et al. Brit J Psych, 1988, 152:347-353.
Silverstone PH, J Psychosomatic Res. 1990, 34:6;651-657.
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14. Depressive Disorders and
Physical Illness: Possible Associations
Common cause for both
Physical illness “causing” depressive
disorder
Depressive disorder “causing” physical
illness
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15. The Major Physical Consequences of
Depression
Fatigue
Sleep disturbances
Inflammation
Carbohydrate and fat metabolism
Hypothalamic-pituitary-adrenal axis
Cardiovascular disease
Osteoporosis
The immune system
Sunday, July 26, 2009
16. Inflammation 1
A Missing Link Between:
Sleep deprivation1
Circadian rhythm disorders2-5
Stress6
Insulin resistance7-8
Abdominal obesity9
Diabetes mellitus10
1. Liu, H., Wang, G., Luan, G., and Liu, Q. J Thromb Thrombolysis 2008: July
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18597046
2. Shephard, R. J., and Shek, P. N. Can J Appl Physiol 1997; 22, 95-116
3. Dickerson, F., Stallings, C., Origoni, A., Boronow, J., and Yolken, R. Prog Neuropsychopharmacol Biol Psychiatry 2007: 31, 952-5
4. Huang, T. L., and Lin, F. C. Prog Neuropsychopharmacol Biol Psychiatry 2007: 31, 370-2
5. O'Brien, S. M., Scully, P., Scott, L. V., and Dinan, T. G. J Affect Disord 2006: 90, 263-7.
6. Hamer, M., and Stamatakis, E. Physiol Behav 2008: 94, 536-9
7. de Luca, C., and Olefsky, J. M. FEBS Lett 2008: 582, 97-105
8. Heilbronn, L. K., and Campbell, L. V. Curr Pharm Des 2008: 14, 1225-30
9. Nathan, C. Epidemic inflammation: pondering obesity. Mol Med 2008: 14, 485-92
10. Savoia, C., and Schiffrin, E. L. Clin Sci (Lond) 2007: 112, 375-84
Sunday, July 26, 2009
17. Inflammation 2
Chronic inflammation affects the photic response of the
suprachiasmatic nucleus1
Cox-2 inhibition appears promising in the treatment of
depression and schizophrenia2
Particulate air pollution is associated with systemic
inflammation3
Inflammation is associated with a reduction in heart rate
variability, a marker of depression and a major predictor of
death after myocardial infarction4
Physical exercise reduces inflammation and improves
heart rate variability and mood5
1. Palomba, M., and Bentivoglio, M. J Neuroimmunol 2008: 193, 24-
2. Muller, N., and Schwarz, M. J. Curr Pharm Des 2008: 14, 1452-65 7
3. Liu, L., Ruddy, T. D., Dalipaj, M., Szyszkowicz, M., You, H., Poon, R., Wheeler, A., and Dales, R. J Occup Environ Med 2007: 49, 258-65
4. von Kanel, R., Nelesen, R. A., Mills, P. J., Ziegler, M. G., and Dimsdale, J. E. Brain Behav Immun 2008: 22, 461-8
5. Thompson, A. M., Mikus, C. R., Rodarte, R. Q., Distefano, B., Priest, E. L., Sinclair, E., Earnest, C. P., Blair, S. N., and Church, T. S. Contemp Clin Trials 2008: 29, 418-27
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18. Inflammation, Sickness Behavior and
Depression
Inflammation and cytokines
Cytokine-induced sickness behavior:1
Weakness
Malaise
Listlessness
Disinterest
Poor concentration
Anorexia
Myers, J. S. Oncol Nurs Forum 2008: 35, 802-7
Sunday, July 26, 2009
21. What is Insulin Resistance?
Insulin resistance is defined as an impaired biological response to
insulin1
Insulin resistance is a primary defect in the majority of patients with
Type 2 diabetes2
In non-diabetic individuals, insulin resistance, in combination with
hyperinsulinemia, has a strong predictive value for the future
development of Type 2 diabetes3
1. American Diabetes Association. Diabetes Care 1998;21(2):310–314
2. Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–1721
3. Bloomgarden ZT. Clin Ther 1998;20(2):216–231
Sunday, July 26, 2009
22. What is Insulin Resistance?
Insulin resistance is defined as an impaired biological response to
insulin1
Insulin resistance is a primary defect in the majority of patients with
Type 2 diabetes2
In non-diabetic individuals, insulin resistance, in combination with
hyperinsulinemia, has a strong predictive value for the future
development of Type 2 diabetes3
Present in ~30-33% of the general population of the USA, but
with marked ethnic differences
1. American Diabetes Association. Diabetes Care 1998;21(2):310–314
2. Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–1721
3. Bloomgarden ZT. Clin Ther 1998;20(2):216–231
Sunday, July 26, 2009
24. The Metabolic Syndrome and the Insulin
Resistance Syndromes
Several sets of criteria
Most usually defined in the USA as the
presence of 3 or more of the following:
Abdominal obesity
(Waist circumference >40 inches in men; >35 inches in
women
Glucose intolerance (fasting glucose ≥110 mg/dL)
Blood pressure ≥130/85 mmHg
Triglycerides >150 mg/dL
Low HDL(Men: <40 mg/dL; women: <50 mg/dL)
NCEP ATP III. Circulation. 2002;106;3143.
Sunday, July 26, 2009
25. The Metabolic Syndrome and the Insulin
Resistance Syndromes
Several sets of criteria
Most usually defined in the USA as the
presence of 3 or more of the following:
Abdominal obesity
(Waist circumference >40 inches in men; >35 inches in
women
Glucose intolerance (fasting glucose ≥110 mg/dL)
Blood pressure ≥130/85 mmHg
Triglycerides >150 mg/dL
Low HDL(Men: <40 mg/dL; women: <50 mg/dL)
Present in ~22% of the general population of the USA, but with marked ethnic
variations
NCEP ATP III. Circulation. 2002;106;3143.
Sunday, July 26, 2009
37. The Physical Consequences of Depression:
Insulin Resistance
Insulin resistance is common in depression1 and anxiety2
Insulin resistance is associated with obesity, depression,
and chronic low-grade inflammation in women with
polycystic ovary syndrome3
Insulin resistance syndrome predisposes to the development
of depressive symptoms4
There is a complex relationship between antidepressants
and insulin resistance5,6
1. Timonen, M., Salmenkaita, I., Jokelainen, J., Laakso, M., Harkonen, P., Koskela, P., Meyer-Rochow, V. B., Peitso, A., and Keinanen-Kiukaanniemi, S.
Psychosom Med 2007: 69, 723-8
2. Narita, K., Murata, T., Hamada, T., Kosaka, H., Sudo, S., Mizukami, K., Yoshida, H., and Wada, Y. Psychoneuroendocrinology 2008: 33, 305-12
3. Benson, S., Janssen, O. E., Hahn, S., Tan, S., Dietz, T., Mann, K., Pleger, K., Schedlowski, M., Arck, P. C., and Elsenbruch, S. Brain Behav Immun 2008: 22,
177-84
4. Koponen, H., Jokelainen, J., Keinanen-Kiukaanniemi, S., Kumpusalo, E., and Vanhala, M. J Clin Psychiatry 2008: 69, 178-82
5. Chen, Y. C., Shen, Y. C., Hung, Y. J., Chou, C. H., Yeh, C. B., and Perng, C. H. J Affect Disord 2007: 103, 257-615.
6. Levkovitz, Y., Ben-Shushan, G., Hershkovitz, A., Isaac, R., Gil-Ad, I., Shvartsman, D., Ronen, D., Weizman, A., and Zick, Y. Mol Cell Neurosci 2007: 36, 305-12
Sunday, July 26, 2009
38. Intrapsychic or Environmental Stress Can Lead
to Increased Insulin Resistance
Basal Intra- Peripheral
Corticosteroid Abdominal Insulin
Insulin
Release Fat Levels
Resistance
Sunday, July 26, 2009
39. Intrapsychic or Environmental Stress Can Lead
to Increased Insulin Resistance
Stress
Basal Intra- Peripheral
Corticosteroid Abdominal Insulin
Insulin
Release Fat Levels
Resistance
Sunday, July 26, 2009
40. Intrapsychic or Environmental Stress Can Lead
to Increased Insulin Resistance
Stress
Basal Intra- Peripheral
Corticosteroid Abdominal Insulin
Insulin
Release Fat Levels
Resistance
Sunday, July 26, 2009
41. Intrapsychic or Environmental Stress Can Lead
to Increased Insulin Resistance
Stimulation
Release of Pancreatic
of FFA Insulin
and TG Release
+
Stress Reduced
Insulin
Breakdown
Basal Intra- Peripheral
Corticosteroid Abdominal Insulin
Insulin
Release Fat Levels
Resistance
Sunday, July 26, 2009
42. Intrapsychic or Environmental Stress Can Lead
to Increased Insulin Resistance
Stimulation
Release of Pancreatic
of FFA Insulin
and TG Release
+
Stress Reduced
Insulin
Breakdown
Basal Intra- Peripheral
Corticosteroid Abdominal Insulin
Insulin
Release Fat Levels
Resistance
Sunday, July 26, 2009
43. Intrapsychic or Environmental Stress Can Lead
to Increased Insulin Resistance
Stimulation
Release of Pancreatic
of FFA Insulin
and TG Release
+
Stress Reduced
Insulin
Breakdown
Basal Intra- Peripheral
Corticosteroid Abdominal Insulin
Insulin
Release Fat Levels
Resistance
Sunday, July 26, 2009
44. Depression With
Comorbid Diabetes
15% to 20% of patients with Type I or Type II
diabetes have major depression
Depression in diabetic patients is associated with
Poor compliance with diabetes regimen
Poor glycemic control
Increased risk for microvascular and macrovascular
complications
Lustman, P. J., Penckofer, S. M., and Clouse, R. E. Curr Diab Rep 2007: 7, 114-22
Sunday, July 26, 2009
45. Depression With Comorbid Diabetes
Fluoxetine, citalopram and nortriptyline are effective in
major depression with comorbid diabetes
Improvement in depression has an independent and
clinically relevant beneficial effect on glycemic control
There is increasing evidence that antidepressants
may worsen metabolic control1
1. Derijks, H. J., Meyboom, R. H., Heerdink, E. R., De Koning, F. H., Janknegt, R., Lindquist, M.,
and Egberts, A. C. Eur J Clin Pharmacol 2008: 64, 531-8
Sunday, July 26, 2009
46. The Physical Consequences of Depression:
Cardiovascular Disease
Coronary artery disease is more common in
depression, anxiety and stress disorders
Sunday, July 26, 2009
47. Depression and Physical Dysfunction from
Coronary Artery Disease (CAD)
Physical dysfunction secondary to CAD linked
with:
Number of main coronary vessels stenosed >70%
(p<0.03)
Depression (p=0.001)
After 1 year, physical function no longer
associated with number of arteries stenosed, but
still significantly associated with depression
(p<0.001)
Sullivan et al. Am J Med. 1997
Sunday, July 26, 2009
48. Depression and Myocardial Infarction
Patients with depression have 5-fold
increased risk of cardiac mortality1
New-onset depression after myocardial
infarction doubles mortality over eight
years2
The risk is reduced by:
Cardiac rehabilitation3
Some antidepressant medications4
1. Frasure-Smith, N. JAMA 1992: 268, 195
2. Dickens, C., McGowan, L., Percival, C., Tomenson, B., Cotter, L., Heagerty, A., and Creed, F. Psychosom Med 2008: 70, 450-5
3. Milani, R. V., and Lavie, C. J. Am J Med 2007: 120, 799-806
4. Jiang, W. Cleve Clin J Med 2008: 75 Suppl 2, S20-5
Sunday, July 26, 2009
49. Depression in the Medically Ill:
Cerebrovascular Accident
Multiple studies have shown an increased risk of
stroke in people with chronic depression1
Depression appears to be an independent risk
factor for stroke, though metabolic disturbances
and cerebral microvascular disease may yet prove
to be the “cause” of both
Surtees, P. G., Wainwright, N. W., Luben, R. N., Wareham, N. J., Bingham, S. A., and Khaw, K. T.
Neurology 2008 70, 788-94
Sunday, July 26, 2009
50. Depression and Stroke:
Fluoxetine vs. Maprotiline vs. Placebo
52 severely disabled hemiplegic subjects were
followed during 2 months of physical therapy1
Greatest improvements in functioning were observed in the
fluoxetine group
Fluoxetine yielded significantly larger number of patients with good
recovery compared to maprotiline and placebo
Subsequent studies have shown that successful
treatment with most SSRIs improve recovery after
stroke2
1. Dam M. Stroke. 1996;27:1211-1214
2. Bilge, C., Kocer, E., Kocer, A., and Turk Boru, U. Eur J Phys Rehabil Med 2008: 44, 13-8
Sunday, July 26, 2009
51. The Physical Consequences of Depression:
Osteoporosis
In depression:1
Reduced bone mineral density
Increased risk of fractures
It is unknown if anxiety or chronic stress decrease
bone mineral density
1. Mezuk, B., Eaton, W. W., and Golden, S. H. Osteoporos Int 2008: 19, 1-12
Sunday, July 26, 2009
52. The Physical Consequences of Depression:
Cancer
Clinical depression is the most common
psychiatric disorder among cancer patients and is
associated with significant functional impairment1
1. Hopko, D. R., Bell, J. L., Armento, M. E., Robertson, S. M., Hunt, M. K., Wolf, N. J., and Mullane, C. J
Psychosoc Oncol 2008: 26, 31-51
Sunday, July 26, 2009
53. Depression and Cancer
16
Fluoxetine Desipramine †
†
* *
Mean Change**
12
† †
* *
8 †
†
4 *
† *
†
0
HAM-D-17 HAM-A CGI-Severity FLIC
**Positive values are used to indicate improvement; *p<0.05 for analysis of change within drug treatment group
using Wilcoxon’s signed rank statistic with no allowance for investigator effects; †p<0.05 for analysis of change
within drug treatment group using Wilcoxon’s signed rank statistic after adjusting for investigator effects using
weighted means. Holland JC et al. Psycho-Oncology. 1998;7(4):291-300
Sunday, July 26, 2009
54. Effect of Psychosocial Treatment on Survival of
Patients with Metastatic Breast Cancer
1.0 Treatment (N=50)
Control (N=36)
0.8 Overlapping control and
treatment probabilities of survival
Probability of Survival
0.6 Some points represent more than 1 case
0.4
0.2
0.0
0 20 40 60 80 100 120 140
Months from Study Entry to Death
Spiegel et al. Lancet, 1989, II, 888-891
Sunday, July 26, 2009
55. Treating Depression in Cancer
Intervention-Depression Care for People with
Cancer:
Scotland, UK
Nurse-delivered complex intervention
200 patients, mean age 56.1 years
Reduced:
Depression
Anxiety
Fatigue
Cost-effective
Strong, V., Waters, R., Hibberd, C., Murray, G., Wall, L., Walker, J., McHugh, G., Walker, A., and Sharpe, M. Lancet 2008: 372,
40-8
Sunday, July 26, 2009
56. Major Depression and Medical Comorbidity
Evaluation
Consider all symptoms of major depression
despite another possible physical cause
Probe for loss of interest or pleasure or
psychological symptoms such as guilt or loss
of self-esteem
Evaluate medication regimen for drugs that
may cause depression
Sunday, July 26, 2009
57. Depressive Disorders In The Physically Ill:
Obstacles To Recognition
Attributing depressive symptoms to somatic illness
Denial of depressive experience
Similarity between depressive symptoms and
symptoms of other illnesses
Sunday, July 26, 2009
58. Risk Factors For Depressive
Disorders In Physical Illness
Female gender
Being unmarried
Living alone
Previous depressive episodes
Certain medical treatments
Severe forms of physical illness
Sunday, July 26, 2009
59. Diagnosing Depressive Disorders In
The Physically Ill: Patient’s And
Family’s Psychiatric History
Family history of depressive disorders/mania/
hypomania
Family history of suicide/suicide attempt(s)
Previous depressive episodes
Good response to antidepressants in past episodes
of mental disorder
Sunday, July 26, 2009
60. Diagnosing Depressive Disorders In The Physically
Ill: Patient’s And Family’s
Psychiatric History (cont’d)
Previous manic or hypomanic episodes
Previous suicide attempt(s)
History of alcoholism or alcohol abuse and/or
substance abuse disorders
Seasonal variation and/or diurnal variation of
depressive symptoms
Sunday, July 26, 2009
61. Treatment of Depression and Anxiety in
Physical Illness
Antidepressants cause improvement in
depression in patients with a wide range of
physical diseases significantly more frequently
than either placebo or no treatment
Antidepressants are reasonably well-tolerated
in patients with physical illness
Increasing evidence suggests that non-
pharmacological approaches to treatment are
also important
Gill D, Hatcher S. In: The Cochrane Library, Issue 2, 1999.
Sunday, July 26, 2009
62. Conclusions
Depression, anxiety and stress are all best
seen as systemic disorders with psychiatric
symptoms
It is essential to be alert to the possible
physical associations of each of these
disorders, and to screen and manage them
appropriately
Sunday, July 26, 2009
63. Suggested Evaluations and Investigations of People
with Depression, Stress and Anxiety Disorders
Evaluations:
Weight and height -> BMI
Measure waist and hips
Blood pressure and pulse - lying and standing
Signs of EPS or tardive dyskinesia
Investigations:
Fasting electrolytes, creatinine, glucose and lipids + measure insulin
resistance in high-risk patients
Liver function tests
Thyroid stimulating hormone: if equivocal consider free T3 and CK
Prolactin
Electrocardiogram
(Bone density measurement only if there are other high risk factors)
Despite the evident resource implications, suggest doing these at least
annually, and more often if:
Abnormal
There are clinical changes
There are other risk factors present
Sunday, July 26, 2009
64. Health Promotion Interventions
Female patients Male patients
Reinforce the need for: Reinforce the need for:
Breast self-exam Annual prostate exam
Does the patient know When, if ever, has he had
how to do a breast exam? a prostate exam?
Annual pap test Testicular self-exam
When was the last pap
smear? Does the patient know
how to do a self-exam?
Mammography
Has she ever had a
PSA, if indicated
mammogram? Has the patient ever had a
PSA?
Sunday, July 26, 2009
67. Concept of the Immune System
Adoptive IS Innate IS
AP-Cells Monocytes, ...
Complement
System
Th0-Cells
IFN-γ IL-4
IL-2 IL-10
IL-6 IL-6
Antibodies
Th1-Cells Th2-Cells B-Cells
Sunday, July 26, 2009
68. The Balance of Humoral and Cellular
Immune Response
Th1 cells Th2 cells
cellular immune response humoral
Sunday, July 26, 2009
69. Th1/Th2 in Major Depression
Markers of Th1/Th2 Responses in Major Depression
Site of cytokine Th1 Th2
expression
In-vitro production IFN-γ ↑ IL-6 ↑↑
Peripheral sIL-2R ↑↑ IL-6 ↑↑
IFN-γ ↑
IFN-γ ↑⇒ TRP↓
CSF sIL-2R ↑ IL-6↓
sIL-6R ↓
Hypothesis A Th1-serotonin-link in A Th2-dominance or an overactivation
suicidal MD? of monocyte/macrophage system in
non-suicidal MD?
Sunday, July 26, 2009
71. Interleukine 6 (IL6)
Marker of monocyte activation
Modulation of HPA axis
Elevation in depression
Sunday, July 26, 2009
72. Immune-Neurotransmitter Interaction in
Depression
T-cell Macrophage
activation activation
IFN-γ IL-1 TNF-α IL-6
Tryptophan
degradation 5-HT transporter 5-HT NE
?
PGE2
5-HT
Cortisol
Sunday, July 26, 2009
73. The Relationship Between the Th1 Cytokine
IFN-g and Serotonin Metabolism
Tryptophan
IFN-g + IDO
+
Kynurenine Serotonin
KYN-Hydrox.
Quinolinate 5-Hydroxyindole acetic acid
(IDO = indoleamine 2,3-dioxygenase;
KYN-Hydrox. = kynurenine hydroxylase)
Sunday, July 26, 2009
74. Possible Ways For Pro-inflammatory
Wichers & Maes, 2001
Sunday, July 26, 2009
75. Cytokine-Neurotransmitter Interaction of
Antidepressants
IL-10 IFN-γ IL-1 TNF-α IL-6
Antidepressants
5-HT transporter 5-HT NE
PGE2
Cortisol
Sunday, July 26, 2009
76. Inflammation, Prostaglandin E2 and Depression
IL-6 (PGE2↑) and TNF-α (COX-2 expression↑)
increased in a subgroup of depressive patients
Salivary concentration of PGE2 increased in major
depression (Ohishi et al, 1987; Nishino et al, 1988)
Increased PGE2 production in lymphocytes of major
depression (Song et al, 1998)
PGE2 reduces noradrenaline-release and stimulates
the HPA-axis in the CNS (Song & Leonard, 2000)
Antidepressants inhibit PGE2-synthesis (Mtabaji et al,
1977)
Sunday, July 26, 2009