1. April 15, 2013 1 Soma and Psyche A general introduction Nicole Vogelzangs Department of Psychiatry / EMGO+ Institute VU University Medical Center Amsterdam, The Netherlands n.vogelzangs@vumc.nl

2. Hippocrates ± 400 BC The physical and mental condition (the temperament) and disease symptoms can be explained from levels of 4 humors: Phlegm: calm temperament – brain, lungs Blood: optimistic, passionate temperament – liver Yellow bile: irritable temperament – spleen Black bile: depressive temperament – gall bladder Disbalance can be treated by diet April 15, 2013

3. Descartes ± 1600 Cogito ergo sum => Separation of body and mind => Still visible in modern medicine => But, Soma and Psyche, hot topic in medical research => Increasingly applied in medical practice April 15, 2013

4. 4 Examples?

5. April 15, 2013 5 Depression and incident morbidity Incident eventReference# studies# personsRR Overall mortalityCuijpers, 201325106 6281.81 Heart diseaseNicholson, 200621124 5091.81 HypertensionMeng, 2012922 3671.42 StrokeDong, 201217206 6411.34 DiabetesMezuk, 200813212 0191.60 AlzheimerGao, 201245 6561.66 ObesityLuppino, 201196 4361.58 CancerChida, 200825?1.29 Evidence from systematic reviews

6. April 15, 2013 6 Anxiety and medical illness Incident eventReference# studies# personsRR Heart diseaseRoest, 201020249 8461.26 COPDAtlantis, 20131628 7591.27 DiabetesSmith, 20131212 6261.25 ObesityGariepy, 201016?1.40 CancerRoy-Byrne, 20089?++

7. April 15, 2013 7 Medically unexplained symptoms Irritable bowel syndrome Chronic fatigue Fibromyalgia Chronic pain

8. April 15, 2013 8 2030Disease% DALYs* 1Depression9.6% 2Heart disease5.9% 3Alzheimer, dementia5.8% 4Alcohol use disorders4.7% 5Diabetes4.5% 6Stroke4.5% 7Hearing problems4.1% 8Lung cancer3.0% 9Osteoarthritis2.9% 10Lung disease2.5% Disease burden in western countries * DALYs = disability-adjusted life years = loss in life years + loss in quality of life WHO: Mathers et al. Plos Medicine 2006

9. April 15, 2013 9 Disease burden in the Netherlands * According to life years lived in health (RIVM, Nationaal Kompas Volksgezondheid) 1Heart disease 2Anxiety disorders 3Stroke 4Depression 5Lung disease 6Diabetes 7Lung cancer 8Alcohol dependence 9Artrosis 10Dementia

10. April 15, 2013 10 Mechanisms linking  ???

11. April 15, 2013 11 Mechanisms linking soma  psyche association = causality Unhealthy lifestyle Decreased (self)care Poorer psychosocial profile Pathophysiology association ≠ causality Depressive/anxiety symptoms = (early) sign of (severity of) disease depressive/anxiety symptoms Third factor somatic disease

12. April 15, 2013 - Nicole Vogelzangs 12

13. April 15, 2013 13 Unhealthy lifestyle Controls n=524 Remitted MDD n=774 Current MDD n=1075 p Physical activity - low - moderate - high 12.8% 37.2% 50.0% 15.2% 37.3% 47.5% 21.1% 36.3% 42.6%.001 Alcohol dependence1.4%5.2%9.1%<.001 Smoking26.5%39.5%45.2%<.001 Body Mass Index25.125.625.9.01

14. April 15, 2013 14 Decreased (self) care Depressive patients: Poorer adherence to life style advice Less therapy compliant Receive less adequate (somatic) care DiMatteo et al. Arch Int Med 2000: meta-analysis: Depressed persons are 3 times less compliant to therapy than non- depressed persons

15. April 15, 2013 15 Poorer psychosocial profile Depressive patients: Less support from close contacts Lower social economical situation Less adequate coping

16. April 15, 2013 16 Mechanisms linking soma  psyche association = causality Unhealthy lifestyle Decreased (self)care Poorer psychosocial profile Pathophysiology association ≠ causality Depressive/anxiety symptoms = (early) sign of (severity of) disease depressive/anxiety symptoms Third factor somatic disease

17. April 15, 2013 17 (Early) disease signs: “reverse causality” Depressive/anxiety symptoms are first signs of a preclinical disease status Time Preclinical disease status Depressive/anxiety symptoms Clinical somatic diagnosis Depressive/anxiety symptoms reflect severity of somatic disease

18. April 15, 2013 18 “pseudo association” Depression/ anxiety Somatic disease Genetics Other disease processes + physiology SES

19. April 15, 2013 19 Mechanisms linking soma  psyche association = causality Unhealthy lifestyle Decreased (self)care Poorer psychosocial profile Pathophysiology association ≠ causality Depressive/anxiety symptoms = (early) sign of (severity of) disease depressive/anxiety symptoms Third factor somatic disease

20. April 15, 2013 20 Depression/anxiety Somatic disease Biological black box

21. April 15, 2013 21 HPA Depression/anxiety Somatic disease Metabolic syndrome ANS

22. April 15, 2013 22 Metabolic syndrome ≥ 3 of the following 5: Waist circumference > 102 cm (men) > 88 cm (women) Triglycerides ≥ 150 mg/dl HDL cholesterol < 40 mg/dl (men) < 50 mg/dl (women) Blood pressure ≥ 130/85 mmHg or medication Fasting glucose ≥ 110 mg/dl or medication

23. April 15, 2013 23 Depression and metabolic syndrome Reference# studies # personsORComponent Pan, 201229155 3331.42waist, HDL, TRI Xu, 20111534 8321.38waist Metabolic syndrome

24. April 15, 2013 24 Meta-analyses: inflammation in depression Howren et al., Psychosomatic Medicine, 2009 Dowlati et al., Biological Psychiatry, 2010 Marker # studies Effect size / MD p95%CI CRP490.15.0010.10-0.21 IL-6610.25<.0010.18-0.31 IL-1140.35.030.03-0.67 TNF133.97 pg/ml<.0012.24-5.71

25. April 15, 2013 25 Meta-analyses: ANS in depression Reference# studies # personseffectDysregulation Rottenberg, 200713686--HRV Kemp, 201014726--HRV Licht, 201011533noHRV

26. April 15, 2013 26 Meta-analyses: HPA in depression Reference# studies # personseffectDysregulation Stetler, 201135418374++cortisol Knorr, 2010202318++cortisol

27. April 15, 2013 27 But… …large heterogeneity

28. Depression = container concept nerveus manisch Melancholy No energy Nervous Manic Atypical depression April 15, 2013

29. 29 Cognitive versus somatic symptoms N=2861CRPIL-6TNF-α Somatic β=.078 p<.001 β=.054 p=.005 β=.045 p=.02 Cognitive β=.021 p=.27 β=.028 p=.13 β=.035 p=.07 * Adjusted for sociodemographics and health factors Depressive symptoms within NESDA Duivis et al. Psychoneuroendocrinology 2013

30. April 15, 2013 30 Atypical versus melancholic depression Cortisol awakening curve ControlMelan cholic Atypicalp CRP1.18 (1.05) 1.05 (1.12) 1.67 (1.12).005 IL-60.75 (1.04) 0.69 (1.10) 1.00 (1.09).003 TNF-α0.84 (1.03) 0.77 (1.07) 1.02 (1.06).003 Adjusted mean (SE) inflammation levels Lamers et al. Molecular Psychiatry 2013

31. April 15, 2013 31 CRP, mg/l n=193 n=96 n=100 n=68 n=62 n=35 Age of depressive disorder onset Men only p=.03 TNF-α, pg/ml n=193 n=96 n=100 n=68 n=62 n=35 Age of depressive disorder onset p=.03 Adjusted mean inflammation levels across age of onset in currently depressed men Vogelzangs et al. Translational Psychiatry 2012 p=.03

32. April 15, 2013 32 Take home message Thight link between soma and psyche Research on mechanisms is expanding Mechanisms overlap across disorders and diseases More consideration should be given to heterogeneity => Personalized medicine considering both physical and mental health!

33. April 15, 2013 33 Questions?