Psychiatry Below the Neck

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

[email protected]

Sunday, July 26, 2009

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


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


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



Bipolar Disorder and Major Depressive Disorder Mortality rates: people die on average 10-20 years earlier than the

general population1-3



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: 11-532. Newman and Bland Can J Psychiatry 1991; 36: 239-2453. Tabbane, K., R. Joober, et al. 1993; Encephale 19: 23-84. Allebeck, Schizophr Bull 1989; 15: 81-895. Dixon et al, J Nerv Ment Dis 1999; 187: 495-5026. Allison, D., et al. J Clin Psychiatry 1999; 60: 215-2207. Herran et al, Schizophr Res 2000; 41: 373-381


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


The Physical Complications of Depressive Disorders


Somatic Symptoms in People with Major Depressive Disorder

Fatigue 86%* Insomnia 79%* Nausea 51%* Dyspnea 38% Palpitations 38% Back pain 36%* Diarrhea 29% Headache 28%

Chest pain 27% Sexual symptoms 23% Pain in extremities 20% Dizziness 19% Abdominal pain 18% Tinnitus 18% Joint or limb pain 16%

Patients presenting in a Psychosomatic Clinic assessed with Cornell Medical Index Questionnaire*Significantly higher % in those with MDDNakao, M. et al, Psychopathology 2001: 34, 230-5


Common Complicating Problems in Depression

Smoking Poor physical activity Adherence to medical advice Sleep disturbances


Depressive Disorders in thePhysically 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


1. Ross, E.D. and Rush, A.J. Arch Gen Psychiatry 1981: 38, 1344-13542. Guiry, E., et al. Clin Cardiol 1987: 10, 256-2603. Surtees, P.G. et al. Am J Psychiatry 2008: 165, 515-523 4. Lustman, PJ, et al. Diabetes Care 1988: 11, 605-612

Comorbid Depression Alters the Outcome of Physical Illness

Depressed post-stroke patientsLess compliant with treatment, more irritable

and demanding1

Depressed patients following myocardial infarctionLess compliant with rehabilitation programs,

longer recoveries and slower return to normal functioning2

Are 2.7 times more likely to die3

Depressed diabetic patientsPoorer glucose control4


Murphy E, et al. Brit J Psych, 1988, 152:347-353.Silverstone PH, J Psychosomatic Res. 1990, 34:6;651-657.

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


Depressive Disorders andPhysical Illness: Possible Associations

Common cause for both

Physical illness “causing” depressive disorder

Depressive disorder “causing” physical illness


The Major Physical Consequences of Depression

Fatigue Sleep disturbances Inflammation Carbohydrate and fat metabolism Hypothalamic-pituitary-adrenal axis Cardiovascular disease Osteoporosis The immune system


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: Julyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=185970462. Shephard, R. J., and Shek, P. N. Can J Appl Physiol 1997; 22, 95-1163. Dickerson, F., Stallings, C., Origoni, A., Boronow, J., and Yolken, R. Prog Neuropsychopharmacol Biol Psychiatry 2007: 31, 952-54. Huang, T. L., and Lin, F. C. Prog Neuropsychopharmacol Biol Psychiatry 2007: 31, 370-25. 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, 536-97. de Luca, C., and Olefsky, J. M. FEBS Lett 2008: 582, 97-1058. Heilbronn, L. K., and Campbell, L. V. Curr Pharm Des 2008: 14, 1225-309. Nathan, C. Epidemic inflammation: pondering obesity. Mol Med 2008: 14, 485-9210. Savoia, C., and Schiffrin, E. L. Clin Sci (Lond) 2007: 112, 375-84


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18597046

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18597046

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 73. Liu, L., Ruddy, T. D., Dalipaj, M., Szyszkowicz, M., You, H., Poon, R., Wheeler, A., and Dales, R. J Occup Environ Med 2007: 49, 258-654. von Kanel, R., Nelesen, R. A., Mills, P. J., Ziegler, M. G., and Dimsdale, J. E. Brain Behav Immun 2008: 22, 461-85. 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


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


The Physical Consequences of Depression: Insulin Resistance


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;94:1714–17213. Bloomgarden ZT. Clin Ther 1998;20(2):216–231



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;94:1714–17213. Bloomgarden ZT. Clin Ther 1998;20(2):216–231

Present in ~30-33% of the general population of the USA, but with marked ethnic differences


Insulin Resistance Syndrome

Synonyms Metabolic syndrome (Metabolic) Syndrome X Dysmetabolic syndrome Reaven’s syndrome Multiple metabolic syndrome


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.


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.

Present in ~22% of the general population of the USA, but with marked ethnic variations


Insulin Resistance


Insulin Resistance

Intra-Abdominal Obesity

Glucose Intolerance

CigaretteSmoking

Genetics

Aging

Medications

Fetal Malnutrition

Inactivity


Insulin Resistance

Type 2 Diabetes


Glucose Intolerance

CigaretteSmoking

Genetics

Aging

Medications

Fetal Malnutrition

Inactivity


Insulin Resistance

Type 2 Diabetes


Glucose Intolerance

CigaretteSmoking

Genetics

Aging

Medications

Fetal Malnutrition

Inactivity

Dyslipidemias

Polycystic Ovary

Syndrome

Endothelial Dysfunction

Hypertension

?CertainMalignancies

Microalbuminuria

Macrovascular Disease

Dysfibrinolysis

Other Metabolic Effects: e.g.

Hyperuricemia

QTcProlongation

Non Alcoholic Fatty Liver

Disease


Homeostatis Model Assessment (HOMA)

Normal: 100% β-cell function: Insulin resistance (R) =1

β-cell function (%): 20 x Insulin (µU/ml glucose (mmol) - 3.5

Insulin resistance: Insulin (µU/ml) x glucose (mmol) 22.5

Hafner et al. Diabetes Care 1996; 1138-1141Mathews DR, Hoskeer JP, et al. Diabetologia, 1985; 28:412-419


Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes



Insulin Resistance

CVD= Coronary vascular disease; PCOS = Polycystic ovarian syndrome; NAFLD = Non-alcoholic fatty liver diseaseAdapted from: ACE Position Statement on the Insulin Resistance Syndrome, Endocr Pract. 2003; 9, 240-252;Reaven GM. Diabetes 1988;37:1595–1607; Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–1721



Insulin Resistance

CompensatoryHyperinsulinemia

CVD


HypertensionStrokePCOS

NAFLD




Insulin Resistance

CompensatoryHyperinsulinemia

Inadequate Insulin Response + β-cell failure

Type 2 Diabetes Mellitus CVD


RetinopathyNephropathyNeuropathy

HypertensionStrokePCOS

NAFLD

Impaired Glucose Tolerance



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, 177-844. Koponen, H., Jokelainen, J., Keinanen-Kiukaanniemi, S., Kumpusalo, E., and Vanhala, M. J Clin Psychiatry 2008: 69, 178-825. 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


Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance

BasalCorticosteroid

Release

Intra-Abdominal

FatInsulin Levels

PeripheralInsulin

Resistance



Stress

BasalCorticosteroid

Release

Intra-Abdominal

FatInsulin Levels

PeripheralInsulin

Resistance



Stress

BasalCorticosteroid

Release

Intra-Abdominal

Fat

Release of FFA and TG

Stimulation of Pancreatic

Insulin Release

+

Reduced Insulin

Breakdown

Insulin Levels

PeripheralInsulin

Resistance


Lustman, P. J., Penckofer, S. M., and Clouse, R. E. Curr Diab Rep 2007: 7, 114-22

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 withPoor compliance with diabetes regimenPoor glycemic control Increased risk for microvascular and macrovascular

complications


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


The Physical Consequences of Depression: Cardiovascular Disease

Coronary artery disease is more common in depression, anxiety and stress disorders


Sullivan et al. Am J Med. 1997

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)


1. Frasure-Smith, N. JAMA 1992: 268, 1952. Dickens, C., McGowan, L., Percival, C., Tomenson, B., Cotter, L., Heagerty, A., and Creed, F. Psychosom Med 2008: 70, 450-53. 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

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


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


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;27:1211-12142. Bilge, C., Kocer, E., Kocer, A., and Turk Boru, U. Eur J Phys Rehabil Med 2008: 44, 13-8


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


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


Depression and Cancer

**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

0

4

8

12

16

HAM-D-17 HAM-A CGI-Severity FLIC

Fluoxetine Desipramine

Mea

n Ch

ange

** * ** *

* *

† †

† †

† †

††


Effect of Psychosocial Treatment on Survival of Patients with Metastatic Breast Cancer

Spiegel et al. Lancet, 1989, II, 888-891

0.0

0.2

0.4

0.6

0.8

1.0

0 20 40 60 80 100 120 140

Control (N=36)

Treatment (N=50)

Overlapping control andtreatment probabilities of survival

Some points represent more than 1 case

Months from Study Entry to Death

Pro

babi

lity

of S

urvi

val


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


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


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


Risk Factors For DepressiveDisorders In Physical Illness

Female gender Being unmarried Living alone Previous depressive episodes Certain medical treatments Severe forms of physical illness


Diagnosing Depressive Disorders InThe 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


Diagnosing Depressive Disorders In The Physically Ill: Patient’s And Family’sPsychiatric 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


Gill D, Hatcher S. In: The Cochrane Library, Issue 2, 1999.

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


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


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


Health Promotion Interventions

Female patients Reinforce the need for: Breast self-exam

Does the patient know how to do a breast exam?

Annual pap test When was the last pap

smear? Mammography

Has she ever had a mammogram?

Male patientsReinforce the need for: Annual prostate exam

When, if ever, has he had a prostate exam?

Testicular self-exam Does the patient know

how to do a self-exam? PSA, if indicated

Has the patient ever had a PSA?


Useful Addresses

Healia.com

www.richardgpettymd.com

[email protected]


Additional Data


Innate IS

Th0-Cells

IFN-γIL-2

IL-4IL-10IL-6 IL-6

Adoptive IS

B-CellsTh1-Cells Th2-Cells

AP-Cells

Antibodies

Concept of the Immune System

Monocytes, ...

Complement System


The Balance of Humoral and Cellular Immune Response

Th1 cells Th2 cells

cellular humoralimmune response


Markers of Th1/Th2 Responses in Major Depression

Site of cytokineexpression

Th1 Th2

In-vitro production IFN-γ ↑ IL-6 ↑↑

Peripheral sIL-2R ↑↑

IFN-γ ↑

IFN-γ ↑⇒ TRP↓

IL-6 ↑↑

CSF sIL-2R ↑ IL-6↓

sIL-6R ↓

Hypothesis A Th1-serotonin-link insuicidal MD?

A Th2-dominance or an overactivationof monocyte/macrophage system innon-suicidal MD?

Th1/Th2 in Major Depression


Immune Changes in Depression

T-cell activation

IFN-γ

Macrophage activation

Autoimmune response

Leucocyte number

CortisolAcute phase

proteins

TNF-α

IL-1ra IL-6R

IL-1 IL-6

Adapted from: Song, Leonard, 2000

PGE2


Interleukine 6 (IL6)

Marker of monocyte activation Modulation of HPA axis Elevation in depression


Immune-Neurotransmitter Interaction in Depression

T-cell activation

IFN-γ

Macrophage activation

Cortisol

TNF-αIL-1 IL-6

PGE2

Tryptophan degradation

5-HT

5-HT transporter

?

5-HT NE


Tryptophan

Serotonin

5-Hydroxyindole acetic acid

Kynurenine

IDO

Quinolinate

IFN-g +

KYN-Hydrox.

+

(IDO = indoleamine 2,3-dioxygenase; KYN-Hydrox. = kynurenine hydroxylase)

The Relationship Between the Th1 Cytokine IFN-g and Serotonin Metabolism


Possible Ways For Pro-inflammatory

Wichers & Maes, 2001


Cytokine-Neurotransmitter Interaction of Antidepressants

IFN-γ

Cortisol

TNF-αIL-1 IL-6

5-HT transporter 5-HT NE

Antidepressants

IL-10

PGE2


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)

TCA’s and SSRI’s inhibit cytokine-induced PGE2 production (Yaron et al, 1999)


Psychiatry Below the Neck

Health & Medicine

Transcript of Psychiatry Below the Neck