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Charting Neural Pathways in Schizophrenia and BPD-Chicago Conference 2016 - Sanjoy Sanyal

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This was presented by Dr. Sanjoy Sanyal, Professor, Surgeon, Neuroscientist, Informatician, at 2nd International Conference on Brain Disorders and Therapeutics, Chicago, USA, October 26-28, 2016
Types of Schizophrenia
Types of Bipolar Disorder (BPD)
DTI Findings in Schizophrenia / BPD
Videos of White Matter Affected in Psychosis
Brain Network Concepts
Basal Forebrain Components and VTA
Videos of Meso-limbic / Meso-cortical Tracts
Receptors in Psychotic Disorders
Videos of Pathophysiology in Schizophrenia 1 and 2 – Rx Principles
Future Research Possibilities
Summary and Conclusion
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Charting Neural Pathways in Schizophrenia and BPD-Chicago Conference 2016 - Sanjoy Sanyal

  1. 1. Charting the Neural Pathways on a Dissected Human Brain to Elucidate the Commonality of Abnormal Networks in Schizophrenia and Bipolar Disorder Dr. Sanjoy Sanyal MBBS, MS (Surgery), MSc (Royal College Surgeons of Edinburgh), ADPHA Texila American University, Goedverwagting, East Coast Demerara, Guyana, South America 2nd International Conference on Brain Disorders and Therapeutics, Chicago, USA, October 26-28, 2016
  2. 2. Roadmap of Presentation 1. Types of Schizophrenia 2. Types of Bipolar Disorder (BPD) 3. DTI Findings in Schizophrenia / BPD 4. Videos of White Matter Affected in Psychosis 5. Brain Network Concepts 6. Basal Forebrain Components and VTA 7. Videos of Meso-limbic / Meso-cortical Tracts 8. Receptors in Psychotic Disorders 9. Videos of Pathophysiology in Schizophrenia 1 and 2 – Rx Principles 10.Future Research Possibilities 11.Summary and Conclusion
  3. 3. Video 1 – Introduction • Introduction: https://www.youtube.com/watch?v=jHmPYFJLt 00
  4. 4. Schizophrenia Type 1 Type 1: Positive symptoms • Hallucinations • Delusions • Bizarre behavior • Confused thinking Pathophysiology: ?Problems with Dopamine neurotransmission Rx: Responds well to Anti-psychotic medication (D2 Blockers)
  5. 5. Schizophrenia Type 2 Type 2: Negative Symptoms • Poverty of speech • Emotional unresponsiveness • Seclusiveness • Impaired attention • Blunted affect Pathophysiology: ?Structural brain abnormality (1957 Flu epidemic, Helsinki) Rx: Unresponsive to Anti-psychotic medication; 5-HT 2 or D4 Blockers used
  6. 6. BPD Criteria and Subtypes Bipolar I Disorder: >1 Manic episode necessary to make diagnosis • Depressive episodes are common but are unnecessary for diagnosis Bipolar II Disorder: No Manic episodes • >1 Hypomanic episodes • > 1 Major Depressive episodes
  7. 7. DTI Findings – Differences • BPD have increased radial diffusion rather than axial diffusion along the orientation of fiber tracts • Schizophrenia have increased diffusion along white matter tracts with alterations in both radial and axial diffusivity
  8. 8. DTI Findings 1 – Similarities • Shared white-matter dysconnectivity between the 2 Psychotic disorders • DTI showed 5 clusters with reduced Fractional Anisotropy (FA) in Psychosis • Corpus Callosum* (Commissural Fibers) • Posterior Thalamic Radiation* (Projection) • Optic Tracts • Para-limbic • Fronto-occipital Fasciculus* (Association)
  9. 9. DTI Findings 2 – Similarities • BPD patients showed lower FA in the – Cingulum (Subcortical white matter of Cingulate Gyrus) – Internal Capsule – Posterior Corpus Callosum* – Tapetum – Posterior Thalamic Radiation* – Inferior Fronto-occipital Fasciculus* / Inferior Longitudinal Fasciculus FA: Fractional Anisotropy Diffusion of H2O -Thickness -Density -Myelination
  10. 10. Video 2 – White Matter Affected in Psychosis • C-P-A Fibers – DTI – White Matter Affected in Psychosis: https://www.youtube.com/watch?v=cwyJkgpLN sg
  11. 11. Brain Network Concepts • Brain Network is composed of Brain Regions that function together • Responsible for activities of the mind – Motivation – Emotion – Cognition (memory, attention, planning) • Networks interact with each other • Various behaviors are likely related to these interactions
  12. 12. Network Abnormalities in Schizophrenia and BPD • Schizophrenia: Decreased interaction between 2 Networks compared to Normal • BPD: Increased interactions between 2 other Networks compared to Normal • 2 Networks have decreased interactions in both Schizophrenia and BPD • Networks that are out of balance in both illnesses possibly cause Psychotic symptoms seen in both, viz. Delusions
  13. 13. Brain Dissection Procedure • On this platform of existing knowledge we sagittally divided a formalinized human brain • Located Basal Forebrain components, Ventral Tegmental Area (VTA), and Medial Forebrain Bundle (MFB) • Charted 2 Neural Pathways • Related this to the Pathophysiology of Schizophrenia and possibly BPD • Suggested Rx principles
  14. 14. Basal Forebrain – Partly • Nucleus Accumbens (Ventral Striatum of Basal Forebrain) • Medial Forebrain Bundle (MFB) • Ventral Tegmental Area (VTA) Image courtesy: G2COnline
  15. 15. Video 3 – Ventral Tegmental Area • VTA: https://www.youtube.com/watch?v=wolhO- MkJQE
  16. 16. Brain Dissection Procedure • The Meso-limbic and Meso-cortical pathways were charted out on the Brain Model • Preliminary feedback from viewers of this model has been very positive
  17. 17. Video 4: Meso-limbic Tract • Mesolimbic Tract: https://www.youtube.com/watch?v=0t0S0wkFFjI
  18. 18. Video 5 – Mesocortical Tract • Mesocortical Tract: https://www.youtube.com/watch?v=87dWMKhxwxg
  19. 19. Receptors in Psychotic Disorders – Human Studies 1. Psycho-stimulants and Dopamine system sensitization produces Psychosis 2. NMDA Receptor antagonism produces Psychosis 3. Antipsychotics (D2 blockers) act by antagonizing NMDA Receptor antagonists 4. This supports hypothesis of confluence of both systems 5. 5-HT 2 Receptor blockers secondarily enhance Dopamine release
  20. 20. Brain Dissection Procedures Based on this background knowledge… • Most probable locations of pathology in Type-1 and 2 Schizophrenia were pinpointed in these Pathways • Their treatment principles were highlighted on these Pathways
  21. 21. Video 6 – Negative Schizophrenia & Rx Principles • Mesocortical Tract Lesion –ve Schizophrenia Rx: https://www.youtube.com/watch?v=JZG95BxslLQ
  22. 22. Video 7 – Positive Schizophrenia & Rx Principles • Mesolimbic Lesion +ve Schizophrenia Rx: https://www.youtube.com/watch?v=rE26sMaaRds -Mood-stabilizing Antipsychotics: Risperidone OR Olanzapine -Anti-depressant Antipsychotics: Fluoxetine PLUS Olanzapine
  23. 23. Future Possibilities This Model (although clearly speculative): • Enables to envisage Pathophysiology of Schizophrenia and BPD in a tangible way • Provides location of Antipsychotic Rx for Schizophrenia and possibly BPD • Suggests lines of future Experiments • Paves the way for focused Imaging Studies (For more accurate localization of pathological Brain Networks in both conditions)
  24. 24. Video 8 – Summary and Conclusion • Summary and Conclusion: https://www.youtube.com/watch?v=0- Rl7t1OF2w
  25. 25. References • Kumar J; et al. Shared white-matter dysconnectivity in schizophrenia and bipolar disorder with psychosis. Psychological Medicine, ISSN: 1469-8978, 2015 Mar; Vol. 45 (4), pp. 759-70; Publisher: Cambridge University Press; PMID: 25089761 • Lu LH; et al. White matter microstructure in untreated first episode bipolar disorder with psychosis: comparison with schizophrenia. Bipolar Disorders, ISSN: 1399-5618, 2011 Nov- Dec; Vol. 13 (7-8), pp. 604-13; Publisher: Wiley- Blackwell Munksgaard; PMID: 22085473
  26. 26. References • Rubin, E. Bipolar Disorder and Schizophrenia— Similar and Different https://www.psychologytoday.com/blog/demystifyi ng-psychiatry/201303/bipolar-disorder-and- schizophrenia-similar-and-different • Duncan GE, et al. An integrated view of pathophysiological models of schizophrenia. Brain Res Rev. 1999 Apr;29(2-3):250-64 http://www.ncbi.nlm.nih.gov/pubmed/10209235 • http://homepage.psy.utexas.edu/homepage/class/ Psy301/Salinas/sec3.2/Abnormal/12.html

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