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 Thank you for watching.

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. 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. Video 1 – Introduction
• Introduction:
https://www.youtube.com/watch?v=jHmPYFJLt
00

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Basal Forebrain – Partly
• Nucleus Accumbens (Ventral
Striatum of Basal Forebrain)
• Medial Forebrain Bundle (MFB)
• Ventral Tegmental Area (VTA)
Image courtesy: G2COnline

15. Video 3 – Ventral Tegmental Area
• VTA: https://www.youtube.com/watch?v=wolhO-
MkJQE

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. Video 4: Meso-limbic Tract
• Mesolimbic Tract:
https://www.youtube.com/watch?v=0t0S0wkFFjI

18. Video 5 – Mesocortical Tract
• Mesocortical Tract:
https://www.youtube.com/watch?v=87dWMKhxwxg

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. 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. Video 6 – Negative Schizophrenia
& Rx Principles
• Mesocortical Tract Lesion –ve Schizophrenia Rx:
https://www.youtube.com/watch?v=JZG95BxslLQ

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. 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. Video 8 – Summary and
Conclusion
• Summary and Conclusion:
https://www.youtube.com/watch?v=0-
Rl7t1OF2w

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. 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