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Psychiatry Below the Neck
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Transcript of 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
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
Sunday, July 26, 2009
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
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
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
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: 11-532. 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
Sunday, July 26, 2009
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
The Physical Complications of Depressive Disorders
Sunday, July 26, 2009
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
Sunday, July 26, 2009
Common Complicating Problems in Depression
Smoking Poor physical activity Adherence to medical advice Sleep disturbances
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
Sunday, July 26, 2009
Depressive Disorders andPhysical Illness: Possible Associations
Common cause for both
Physical illness “causing” depressive disorder
Depressive disorder “causing” physical illness
Sunday, July 26, 2009
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
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
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
The Physical Consequences of Depression: Insulin Resistance
Sunday, July 26, 2009
What is Insulin Resistance?
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
Present in ~30-33% of the general population of the USA, but with marked ethnic differences
Sunday, July 26, 2009
Insulin Resistance Syndrome
Synonyms Metabolic syndrome (Metabolic) Syndrome X Dysmetabolic syndrome Reaven’s syndrome Multiple metabolic syndrome
Sunday, July 26, 2009
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
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
Sunday, July 26, 2009
Sunday, July 26, 2009
Insulin Resistance
Sunday, July 26, 2009
Insulin Resistance
Intra-Abdominal Obesity
Glucose Intolerance
CigaretteSmoking
Genetics
Aging
Medications
Fetal Malnutrition
Inactivity
Sunday, July 26, 2009
Insulin Resistance
Type 2 Diabetes
Intra-Abdominal Obesity
Glucose Intolerance
CigaretteSmoking
Genetics
Aging
Medications
Fetal Malnutrition
Inactivity
Sunday, July 26, 2009
Insulin Resistance
Type 2 Diabetes
Intra-Abdominal Obesity
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
Sunday, July 26, 2009
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
Sunday, July 26, 2009
Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes
Sunday, July 26, 2009
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
Sunday, July 26, 2009
Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes
Insulin Resistance
CompensatoryHyperinsulinemia
CVD
Insulin Resistance Syndrome
HypertensionStrokePCOS
NAFLD
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
Sunday, July 26, 2009
Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes
Insulin Resistance
CompensatoryHyperinsulinemia
Inadequate Insulin Response + β-cell failure
Type 2 Diabetes Mellitus CVD
Insulin Resistance Syndrome
RetinopathyNephropathyNeuropathy
HypertensionStrokePCOS
NAFLD
Impaired Glucose Tolerance
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
Sunday, July 26, 2009
Differentiation Between Insulin Resistance Syndrome and Type 2 Diabetes
Insulin Resistance
CompensatoryHyperinsulinemia
Inadequate Insulin Response + β-cell failure
Type 2 Diabetes Mellitus CVD
Insulin Resistance Syndrome
RetinopathyNephropathyNeuropathy
HypertensionStrokePCOS
NAFLD
Impaired Glucose Tolerance
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
Sunday, July 26, 2009
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
Sunday, July 26, 2009
Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance
BasalCorticosteroid
Release
Intra-Abdominal
FatInsulin Levels
PeripheralInsulin
Resistance
Sunday, July 26, 2009
Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance
Stress
BasalCorticosteroid
Release
Intra-Abdominal
FatInsulin Levels
PeripheralInsulin
Resistance
Sunday, July 26, 2009
Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance
Stress
BasalCorticosteroid
Release
Intra-Abdominal
FatInsulin Levels
PeripheralInsulin
Resistance
Sunday, July 26, 2009
Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance
Stress
BasalCorticosteroid
Release
Intra-Abdominal
Fat
Release of FFA and TG
Stimulation of Pancreatic
Insulin Release
+
Reduced Insulin
Breakdown
Insulin Levels
PeripheralInsulin
Resistance
Sunday, July 26, 2009
Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance
Stress
BasalCorticosteroid
Release
Intra-Abdominal
Fat
Release of FFA and TG
Stimulation of Pancreatic
Insulin Release
+
Reduced Insulin
Breakdown
Insulin Levels
PeripheralInsulin
Resistance
Sunday, July 26, 2009
Intrapsychic or Environmental Stress Can Lead to Increased Insulin Resistance
Stress
BasalCorticosteroid
Release
Intra-Abdominal
Fat
Release of FFA and TG
Stimulation of Pancreatic
Insulin Release
+
Reduced Insulin
Breakdown
Insulin Levels
PeripheralInsulin
Resistance
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
The Physical Consequences of Depression: Cardiovascular Disease
Coronary artery disease is more common in depression, anxiety and stress disorders
Sunday, July 26, 2009
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)
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
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
Sunday, July 26, 2009
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
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
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
** * ** *
* *
† †
† †
† †
††
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
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
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
Risk Factors For DepressiveDisorders In Physical Illness
Female gender Being unmarried Living alone Previous depressive episodes Certain medical treatments Severe forms of physical illness
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
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
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?
Sunday, July 26, 2009
Additional Data
Sunday, July 26, 2009
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
Sunday, July 26, 2009
The Balance of Humoral and Cellular Immune Response
Th1 cells Th2 cells
cellular humoralimmune response
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
Sunday, July 26, 2009
Interleukine 6 (IL6)
Marker of monocyte activation Modulation of HPA axis Elevation in depression
Sunday, July 26, 2009
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
Sunday, July 26, 2009
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
Sunday, July 26, 2009
Possible Ways For Pro-inflammatory
Wichers & Maes, 2001
Sunday, July 26, 2009
Cytokine-Neurotransmitter Interaction of Antidepressants
IFN-γ
Cortisol
TNF-αIL-1 IL-6
5-HT transporter 5-HT NE
Antidepressants
IL-10
PGE2
Sunday, July 26, 2009
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)
Sunday, July 26, 2009