A Long Shadow over the Soul:                                  Molecular and Quantum Approaches to Psychopathology         ...
Summary•   Burden of chronic non communicable diseases•   Alliances for NCD•   A pathological approach•   NCD Common Soils...
Leading causes of attributable global mortality and  burden of disease, 2004 (Lancet 2009; 374:973-4)        Attributable ...
The burden of chronic Non Communicable Disease - NCDMajor chronic non-communicable diseases (NCDs)—primarily cardiovascula...
European prevalence of Neurological Disorders-ND :(in millions) H.U. Witchen, F. Jacobi et alii European Neuropsychopharma...
European prevalence rates of Mental Disorders – MD(H.U. Witchen, F. Jacobi et alii European Neuropsychopharmacology 2011; ...
The size and burden of Mental Disorders and otherDisorders of the Brain in Europe 2010(H.U.   Witchen, F. Jacobi et alii E...
Numbers in comparisonH.U. Witchen, F. Jacobi et alii European Neuropsychopharmacology 2011; 21, 655–6792010 report by Alzh...
Summary•   Burden of chronic non communicable diseases•   Alliances for NCD•   A pathological approach•   NCD Common Soils...
UN High-LevelMeeting on NCDs19 -20 September 2011                        …36 million deaths every year                    ...
UN High-Level Meeting on NCDs:    Politic al Declarations   16 September and 15 September 2011              Political Decl...
Question how much in the mentioned alliances there was a participation of the experts on psychopathology?  how much of the...
Summary•   Burden of chronic non communicable diseases•   Alliances for NCD•   A pathological approach•   NCD Common Soils...
INTERHEART StudyLarge case control study toexamine the importance of 9 IHDrisk factors : > 29.000 peoplein 52 countries.Wo...
Figure 1INTERSTROKE Study Martin J ODonnell et alii , Risk factors for ischaemic and intracerebral haemorrhagic stroke in ...
Figure 2 INTERSTROKE Study         Martin J ODonnell et alii , Risk factors for ischaemic and intracerebral haemorrhagic s...
Integrated Biomarkers: atherosclerosisInfarction of the brain : by arterial thrombosis or embolism.                       ...
Integrated Biomarkers: atherosclerosisInfarction of the brain : by arterial thrombosis or embolism.Intermediate infarct of...
Integrated Biomarkers: atherosclerosisInfarction of the brain   The neurons are the most sensitive cells   to anoxic injur...
Integrated Biomarkers: atherosclerosisStenosis of the common carotid Artery         by Thomas Hatsukami - Seattle 2008    ...
Integrated Biomarkers: atherosclerosisMagnetic Resonance Imaging  MRI provides non-invasive, in vivo    characterization o...
Integrated Biomarkers: atherosclerosisHistological Validation of MRI Findings    left carotid endarterectomy              ...
Integrated Biomarkers: atherosclerosisAcute Stroke Biomarkers                                                 ICAM-1Cytoki...
Integrated Biomarkers: atherosclerosisAcute Stroke Biomarkers: Main Characteristics…   Cytokines Expression   Neutrophil R...
Integrated Biomarkers: atherosclerosis Acute Stroke Biomarkers: Main Characteristics…   Cytokines Expression    Neutrophil...
Summary•   Burden of chronic non communicable diseases•   Alliances for NCD•   A pathological approach•   NCD Common Soils...
Scenarios Non communicable diseases: diabetes, obesity, cardiovascular disease,    COPD Crossroads or a common soil ? : mi...
Integrated Biomarkers: atherosclerosisCoronary artery with thrombosis: occlusion of the lumen and consequentlyacute corona...
Acute Coronary SyndromeBiomarkers constellation                                           cTnT, cTnI,                     ...
Ischemic StrokeInfarction of the brain: by arterial thrombosis or embolism.                                               ...
Ischemic Strokemultiaxis framework                                                              apoB/apoAI,              M...
ObesityAbdominal adiposity                      32
Obesity-Diabetes- CVD riskVisceral obesity and cardiovascular risk         BP, Ang II, RAGE, Alb/Crt               apoB/ap...
The mitochondrial respiratory chainis the main source of ROS that increase damage to deoxyribonucleic acid(DNA), proteins,...
Categories of SIRT1Targets for Deacetylation and Their Associated Diseases.                                         The pr...
Potential mechanisms of action of SIRT6 on longevity        Lombard DB, Miller RA: Ageing Soting out the the sirtuins. Nat...
...NCDs no longer by a silos approach, but ratherwith a common effort of allied stakeholders... NCD have many patho-mechan...
...and what about NDs?                         38
Summary•   Burden of chronic non communicable diseases•   Alliances for NCD•   A pathological approach•   NCD Common Soils...
ModelsHow much is it known on metabolic dysfunctions in NDs such as, e.g.,Alzheimers Disease-AD and Vascular Dementia-VD, ...
legenda Mitochondrial metabolic constellation: some pathways for medical exploration interplay of major mitochondrial func...
Summary•   Burden of chronic non communicable diseases•   Alliances for NCD•   A pathological approach•   NCD Common Soils...
QuestionsHow much can the combination of the studies on the matter and on the  soul, help to better manage the NCD patient...
Συμπάσχει η ψυχή τω σώματι νοσούντι και τεμνομένω, το δε  σώμα τη ψυχήThe soul suffers when the body is diseased or trauma...
“We will now observe a moment of silence         to check our BlackBerrys.”                                           45
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  • Risk of stroke associated with number of cigarettes smoked for all stroke, ischaemic stroke, and intracerebral haemorrhagic stroke Data are adjusted for age, sex, and region.
  • Risk of all stroke associated with body-mass index and waist-to-hip ratio T=tertile.
  • .
  • A growing body of evidence, indicates that inflammatory mechanisms contribute to (secondary) neuronal injury after acute cerebral ischemia. This inflammatory response is characterized by the local expression of cytokines such as IL-1, TNF-a and IL-6, resulting in chemotactic cytokine release and adhesion molecules upregulation. This cytokines work in concert to activate leukocyte migration to the ischemic region. This white cells are leukocytes, almost plugging the microvessels, where they cause tissue injury by generation of oxygen free radicals, or Matrix Metalloproteinases release, both of which may disrupt the BBB, contributing to infarct growing.
  • Figure 2. Categories of SIRT1 Targets for Deacetylation and Their Associated Diseases. The protein targets of SIRT1, a sirtuin that has been shown to regulate metabolism and stress response, include transcription factors and cofactors, histones and other chromatin proteins, and components of DNA repair machinery. The depictions of the associations between SIRT1 targets and the diseases that are affected are graphical, since the exact mechanisms of most of these associations are not known.
  • Figure 2. Categories of SIRT1 Targets for Deacetylation and Their Associated Diseases. The protein targets of SIRT1, a sirtuin that has been shown to regulate metabolism and stress response, include transcription factors and cofactors, histones and other chromatin proteins, and components of DNA repair machinery. The depictions of the associations between SIRT1 targets and the diseases that are affected are graphical, since the exact mechanisms of most of these associations are not known.
  • Andrea Peracino

    1. 1. A Long Shadow over the Soul: Molecular and Quantum Approaches to Psychopathology An Interdisciplinary Dialog with Psychiatrists Fano, Italy 29, 30, 31 March 2012How much is the matter far away from the soul? Andrea Peracino, MD, PhD Vice President of the Giovanni Lorenzini Medical Science Foundation, Milan­-I, Houston­-TX andrea.peracino@lorenzinifoundation.org 1
    2. 2. Summary• Burden of chronic non communicable diseases• Alliances for NCD• A pathological approach• NCD Common Soils• Models• Questions 2
    3. 3. Leading causes of attributable global mortality and burden of disease, 2004 (Lancet 2009; 374:973-4) Attributable Mortality Attributable DALYs % %2. High blood pressure 12.8 • Childhood underweight 5.93. Tobacco use 8.7 • Unsafe sex 4.64. High blood glucose 5.8 • Alcohol use 4.55. Physical inactivity 5.5 • Unsafe water, sanit. hygiene 4.26. Overweight and obesity 4.8 • High blood pressure 3.77. High cholesterol 4.5 • Tobacco use 3.78. Unsafe sex 4.0 • Suboptimal breastfeeding 2.99. Alcohol use 3.8 • High blood glucose 2.710. Childhood underweight 3.8 • Indoor smoke from solid fuels 2.711. Indoor smoke from solid fuels 3.3 • Overweight and obesity 2.359 million total global deaths 1.5 billion total global DALYs 3
    4. 4. The burden of chronic Non Communicable Disease - NCDMajor chronic non-communicable diseases (NCDs)—primarily cardiovasculardisease (CVD), cancer, chronic obstructive pulmonary disease (COPD),and diabetes—are responsible for 85% of the deaths and 70% of the burdenof disease in Europe.Atherosclerosis Supplements 2009; 10: 1-30The Disorders of the Brain -BD in Europe are responsible for around 15,8 million DALYs (26,6% of global DALYs) aged > 15 age: 7,3 million for men (23,4%), 8,5 million for women (30,1%).H.U. Witchen, F. Jacobi et alii European Neuropsychopharmacology 2011; 21: 655–679. 4
    5. 5. European prevalence of Neurological Disorders-ND :(in millions) H.U. Witchen, F. Jacobi et alii European Neuropsychopharmacology 2011; 21: 655–679 Diagnosis Mio individuals Headache 152,8 Sleep apnoea 12,5 Stroke 8,24 Dementias 6,34 Traumatic brain injury 3,75 Epilepsy 2,64 Parkinson’s disease 1,25 Multiple slcerosis 0,54 Neuromuscolar disorders 0,26 Brain dsorders 0,24 5
    6. 6. European prevalence rates of Mental Disorders – MD(H.U. Witchen, F. Jacobi et alii European Neuropsychopharmacology 2011; 21, 655–679)Diagnosis Yearly prevalence Mio individuals/yearAlcohol dependance % 3,4 14,6Cannabis dependence 1,0 1,5Psychotic disorders 1,2 5,0Panic disorders 1,8 7,9Personality disorder 1.3 4,3Major depression 6,9 30.3Insomnia 3,5 14,6Anxiety disorders 14.0 61,5ADHD/Hypercin disorders 5,0 6,3Dementias 5,4 6,3Somatoform disorder 4,9 20,4Eating disorders 0,9 1,5Any mental disorder 38.2 164.8 6
    7. 7. The size and burden of Mental Disorders and otherDisorders of the Brain in Europe 2010(H.U. Witchen, F. Jacobi et alii European Neuropsychopharmacology 2011; 21: 655–679) 7
    8. 8. Numbers in comparisonH.U. Witchen, F. Jacobi et alii European Neuropsychopharmacology 2011; 21, 655–6792010 report by Alzheimers Disease Internationalhttp://www.europarl.europa.eu/sides/getDoc.do?type=TA&language=EN&reference=P7-TA-2011-0016European CVD diseases Feb 2008 EU EU EU EU Deaths /y suffering DALYs Costs BD 164.9 mio 16.0 mio (26%) € 300 bio 53% w Dementia 6.3 - 9.9 mio 5 (8%) Stroke 0.5 mio 3,7 (6%) 57% w CVD 2.0 mio 12.0 mio (19 %) € 200 bio 54% w People worldwide worldwide worldwide suffering 2010 2030 2050 Dementia 35.6 mio 65.7 mio 115.4 mio 8
    9. 9. Summary• Burden of chronic non communicable diseases• Alliances for NCD• A pathological approach• NCD Common Soils• Models• Questions 9
    10. 10. UN High-LevelMeeting on NCDs19 -20 September 2011 …36 million deaths every year for NCD are demanding a global commitment among the decision makes world wide… 10
    11. 11. UN High-Level Meeting on NCDs: Politic al Declarations 16 September and 15 September 2011 Political Declaration of the High-level Meeting of the General Assembly on the Prevention and Control of Non- communicable Diseases (http://www.who.int/ nmh/events/un_ncd_summit2011/en/index.html) EU position and commitment in advance of the UN high-level meeting on the prevention and control of non- communicable diseases. http://www.europarl.europa.eu/sides/getDoc.do? pubRef=//EP//NONSGML+PV+20110915+SIT+ DOC+PDF+V0//EN&language=EN. 11
    12. 12. Question how much in the mentioned alliances there was a participation of the experts on psychopathology? how much of the probable, but not clearly defined and decided in term of budget, will be allocated to support studies on how to combine matter and soul in approaching the huge amount of subjects suffering by NDDs ? http://whqlibdoc.who.int/publications/2009/9789241597418_eng.pdf 12
    13. 13. Summary• Burden of chronic non communicable diseases• Alliances for NCD• A pathological approach• NCD Common Soils• Models• Questions 13
    14. 14. INTERHEART StudyLarge case control study toexamine the importance of 9 IHDrisk factors : > 29.000 peoplein 52 countries.Worldwide, the 9 factorscollectively predicted> 90% of the risk of MI.The presence of all 9 riskfactors was associated withan OR >256 . Yusuf S et al. Effect of potentially modifiable risk factors with myocardial infarction in 52 countries (the INTERHEART study). Lancet 2004;364: 937-52. 14
    15. 15. Figure 1INTERSTROKE Study Martin J ODonnell et alii , Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the) INTERSTROKE study : a case-control study. Lancet 2010;376:112-23 15
    16. 16. Figure 2 INTERSTROKE Study Martin J ODonnell et alii , Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the) INTERSTROKE study : a case-control study. Lancet 2010;376:112-23Source 16
    17. 17. Integrated Biomarkers: atherosclerosisInfarction of the brain : by arterial thrombosis or embolism. 17
    18. 18. Integrated Biomarkers: atherosclerosisInfarction of the brain : by arterial thrombosis or embolism.Intermediate infarct of the frontal lobe.magnetic resonance imaging scan Microscopic aspect revealing marked edema (the pale areas) 18
    19. 19. Integrated Biomarkers: atherosclerosisInfarction of the brain The neurons are the most sensitive cells to anoxic injury. Seen here are red neurons which are dying as a result of hypoxia. Cerebral infarction demonstrates the presence of many macrophages at the right which are cleaning up the lipid debris from the liquefactive necrosis 19
    20. 20. Integrated Biomarkers: atherosclerosisStenosis of the common carotid Artery by Thomas Hatsukami - Seattle 2008 20
    21. 21. Integrated Biomarkers: atherosclerosisMagnetic Resonance Imaging MRI provides non-invasive, in vivo characterization of human IC atherosclerosis A ECA – Histologically validated – Reproducible MRI findings predictive of more rapid progression and increased likelihood of future ischemic events Plaqueby Thomas Hatsukami - Seattle 2008 CCA CCA = common carotid artery ; ICA = internal carotid artery; ECA = external carotid artery 21
    22. 22. Integrated Biomarkers: atherosclerosisHistological Validation of MRI Findings left carotid endarterectomy carotid plaque specimen by Thomas Hatsukami - Seattle 2008 22
    23. 23. Integrated Biomarkers: atherosclerosisAcute Stroke Biomarkers ICAM-1Cytokines Expression IL-6 IL-8 Neutrophil Recruitment Proteases Release IL-1 BBB destruction Neuron & Glia damage Infarct Growth Montaner, Integrated Biomarkers, Lugano 2005 23
    24. 24. Integrated Biomarkers: atherosclerosisAcute Stroke Biomarkers: Main Characteristics… Cytokines Expression Neutrophil Recruitment Proteases Release BBB destruction Neuron & Glia damage Infarct GrowthMontaner, Integrated Biomarkers, Lugano 2005 24
    25. 25. Integrated Biomarkers: atherosclerosis Acute Stroke Biomarkers: Main Characteristics… Cytokines Expression Neutrophil Recruitment Proteases Release BBB destruction Neuron & Glia damage Infarct GrowthMontaner, Integrated Biomarkers, Lugano 2005 25
    26. 26. Summary• Burden of chronic non communicable diseases• Alliances for NCD• A pathological approach• NCD Common Soils• Models• Questions 26
    27. 27. Scenarios Non communicable diseases: diabetes, obesity, cardiovascular disease, COPD Crossroads or a common soil ? : mithocondria, metabolic fuel, insulin resistance, inflammation, endothelial dysfunction, neurohormones…. …and what about NDs ? astrocytes activation, BBB damage, apoptosis deregulation, neurodegeneration, and metabolic disorders 27
    28. 28. Integrated Biomarkers: atherosclerosisCoronary artery with thrombosis: occlusion of the lumen and consequentlyacute coronary syndrome with ischemia and/or infarction of themyocardium. 28
    29. 29. Acute Coronary SyndromeBiomarkers constellation cTnT, cTnI, Myo, FABP apoB/apoAI, IMA, uFFA, BNP Lp (a), HDL, LDL, LOX index, Trg BNP, NE, Copeptin IL-6, hs-CRP, Ox LDL MCP-1, MPO, IL-18 PAI-1, sCD40L vWF, D-dimer sICAM, pSelectin, cIMT? MMP’s, sCD40L, PLGF, ICAM, V-CAM Integrated Biomarkers: Lugano-2005, Berlin-2007, Seattle-2008 29
    30. 30. Ischemic StrokeInfarction of the brain: by arterial thrombosis or embolism. 30
    31. 31. Ischemic Strokemultiaxis framework apoB/apoAI, MMP-9, S100-ß Lp (a), HDL, LDL, S100-ß IL-6, hs-CRP, Ox LDL, MCP-1, MPO, IL-18 BNP, NE, Copeptin Fibrinogen, Fibrin, D-dimer, tPA, PAI-1, VIIc, Plasminogen , TAFI IMA, uFFA, BNP (modified fromBraunwald, Circ 1998:98:2219) 31
    32. 32. ObesityAbdominal adiposity 32
    33. 33. Obesity-Diabetes- CVD riskVisceral obesity and cardiovascular risk BP, Ang II, RAGE, Alb/Crt apoB/apoAI, Lp (a) HDL, LDL, Trg hs-CRP, Ox LDL, TNFa IFG/IGT, HbA1c MCP-1, MPO, IL18 FFA, Resistin, Adiponectin, Leptin, W/H HOMA-IR Vessel reactivity sICAM, pSelectin, cIMT cIMT? 33
    34. 34. The mitochondrial respiratory chainis the main source of ROS that increase damage to deoxyribonucleic acid(DNA), proteins, or lipids accumulates with age progression, and impair cellularfunction. •Mitochondrial dysfunction, mitochondrial loss •ROS • insulin resistance •aging. Telomere length is a sensitive indicator of oxidative stress and is implicated in senescence and apoptotic signaling. Telomere length was reduced up to 30% in cardiomyocytes of old (normal-weight and obese) and young obese subjects. 34
    35. 35. Categories of SIRT1Targets for Deacetylation and Their Associated Diseases. The protein targets of SIRT1, that has been shown to regulate metabolism and stress response, include transcription factors and cofactors, histones and other chromatin proteins, and components of DNA repair machinery. Guarente L. N Engl J Med 2011;364:2235-2244. 35
    36. 36. Potential mechanisms of action of SIRT6 on longevity Lombard DB, Miller RA: Ageing Soting out the the sirtuins. Nature 2012 483: 166-67. 36
    37. 37. ...NCDs no longer by a silos approach, but ratherwith a common effort of allied stakeholders... NCD have many patho-mechanisms in common, and havecommon genetic and environmental antecedents they would spring from a “common soil”. 37
    38. 38. ...and what about NDs? 38
    39. 39. Summary• Burden of chronic non communicable diseases• Alliances for NCD• A pathological approach• NCD Common Soils• Models• Questions 39
    40. 40. ModelsHow much is it known on metabolic dysfunctions in NDs such as, e.g.,Alzheimers Disease-AD and Vascular Dementia-VD, or Depression? 40
    41. 41. legenda Mitochondrial metabolic constellation: some pathways for medical exploration interplay of major mitochondrial functions with cell and tissue pathological changesAß: ß amyloid OLGs: oligodendrocytesATP: adenosine-5-triphosphate OPCs: oligodendrocyte precursor cellsBP: Blood pressure PAMPs: pathogen-associated molecular patternsCHI: closed head injury PPARα : peroxisome proliferator-activated receptors αCRH: corticotropin-releasing hormone PPARs: peroxisome proliferator-activated receptorsDAMPs: danger-associated molecular patterns PGC1α: peroxisome proliferator-activated receptor γIL-6: Interleukin-6 co-activator 1αLCFA: long chain fatty acides RC: respiratory chainmtDNA: mitochondrial deoxyribo-nucleic –acid ROS: reactive oxygen speciesMMP-9: matrix metalloproteinase-9 TNFα: Tumor necrosis factor alphaNLRP3: NLR family, pyrin domain-containing 3 UCP: Uncoupling proteinsNO: nitric oxide VEGF-A: Vascular endothelial growth factorOXPHOS: oxidative phosphorylation WMLs: White matter lesions 41
    42. 42. Summary• Burden of chronic non communicable diseases• Alliances for NCD• A pathological approach• NCD Common Soils• Models• Questions 42
    43. 43. QuestionsHow much can the combination of the studies on the matter and on the soul, help to better manage the NCD patients?How much can the psychopathologists help the physicians of the matter to reduce the affliction of the soul? 43
    44. 44. Συμπάσχει η ψυχή τω σώματι νοσούντι και τεμνομένω, το δε σώμα τη ψυχήThe soul suffers when the body is diseased or traumatized, while the body suffers when the soul is ailing Aristotle 44
    45. 45. “We will now observe a moment of silence to check our BlackBerrys.” 45

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