Neurochemical & Neuropathological Similarities in Autism & Schizophrenia

1. Specific Neurological Similarities in Autism & Schizophrenia Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion PHM142 Fall 2014 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson Neurochemical & Neuropathological Similarities in Autism & Schizophrenia Prince Nagra, Andrew Kuo, Alexandra Kourkounakis, Miles Luke October 14, 2014

2. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Overview • Introduction • Neuropathological Similarities • Neurochemical Similarities • Common Medications • Conclusion

3. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Autism • A neurodevelopmental disorder that hinders a child’s interactive and communicative capabilities. • Categorized under the Autism Spectrum Disorder (ASD) ‘umbrella’ • Symptoms: • Varying degrees of severity • Social impairments • Repetitive actions • Speech/Communication delays http://etec.ctlt.ubc.ca/510wiki/File:Umbie2.jpg

4. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Autism • Causes: • Genetic BasisCandidate Genes ImplicatedMultigene Interaction • Epigenetic 15q11-13 duplication7q imprinting • Environmental Factors • Risk Factors: • Sex of Child • Family History • Preterm infants • Age of Parents • Rett Syndrome and Fragile X Syndrome (Comorbidities)

5. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Schizophrenia A disabling mental disorder that distorts a person’s ability to behave, act, and discern the difference between reality and delusion. Symptoms

6. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Schizophrenia • Risk Factors: • Family History • Age of Father • Prenatal Exposure to Toxins and Viruses • Hypersensitive immune system • Causes: • Genetic Basismultigene interactions • Environmental Factors • Substance Usetoxic/induced psychosis

7. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Prenatal Infection • The fetal brain is extremely susceptible to developmental disruption caused during pregnancy • Increased risk of autism and schizophrenia associated with prenatal maternal infection http://www.womancarehealth.com/363269/2012/02/06/prenatal-infection-prevention-month-gbs-facts.html

8. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Prenatal Infection • This suggests that commonalities between the immune responses to these pathogens may be involved in the etiology of autism and schizophrenia Berg, J. M., Tymoczko, J. L., and Stryer, L. (2012) Biochemistry, 7th Ed.

9. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Prenatal Infection • Pro-inflammatory cytokine IL-6 of particular interest • Abnormal behaviours and brain gene expression • Disruption of the GH/IGF-I axis https://www.bioscience.org/1996/v1/d/keller2/htmls/3.htm

10. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Lower Grey Matter Volumes Posterior Cingulate Parahippocampal Gyrus http://en.wikipedia.org/wiki/Parahippocampal_gyrus#mediaviewer/File:Gray727_parahippocampal_gyrus.png

11. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Lower Grey Matter Volumes Thalamus Putamen http://en.wikipedia.org/wiki/Putamen#mediaviewer/File:BrainCaudatePutamen.svg

12. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Lower Grey Matter Volumes Insula http://en.wikipedia.org/wiki/Insular_cortex#mediaviewer/File:Gray743.png

13. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Summary: Lower Grey Matter Volumes (Autism Spectrum Disorders) Cheung et al., 2010

14. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Basal Ganglia Loop Disruption • Disruption within the basal ganglia loop systems is thought to explain impaired sensorimotor gating

15. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Neurotransmitters • Serotonin • Regulate development of serotonergic neurons and target tissues • Lose serotonin terminals & neuronal development • Hyperserotonemia & animal research • Dopamine • Cognition, motor function.... • Hyperactivity of dopamine transmission • Dopaminergic neurons overactive • Repetitive, stereotyped behaviour, ↑activity, aggression

16. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Neurotransmitters • GABA • Inhibitory transmitter • Glutamate • Excitatory transmitter

17. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Neurotransmitters • exitotoxicity • aberrant neuronal • development http://www.heartfixer.com/AMRI-Nutrigenomics.htm

18. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Hormones • Oxytocin • Neurohypophysial hormone (hypothalamus)  PPG • Neuroanatomy of intimacy • Various behaviours • Orgasm, social recognition, anxiety • Repetitive behaviour

19. Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Common Medications • Antipsychotics (improves social cognition) • Risperidone & Aripiprazole • Hyperactivity, aggression, stereotyped behaviour • Neurohormonal neuromodulator oxytocin (improves social cognition, decreased repetitive behaviours, psychosis) Risperidone Aripiprazole http://www.ramdevchem.com/Aripiprazole.asp http://commons.wikimedia.org/wiki/File:Risperidone.svg

20. Future Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Thank You For Your Time

21. Future Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Summary Slide • Introduction • Autism is a neurodevelopmental disorder that hinders a child’s interactive and communicative capabilities, classified as ASD. • Schizophrenia is disabling mental disorder that distorts a person’s ability to behave, act, and discern the difference between reality and delusion. Has positive and negative symptoms. • Prenatal Infection Linked to Schizophrenia and Autism • Maternal prenatal infection increases risk of autism and schizophrenia in offspring • Increased risk is not pathogen specific, so etiology is in common immune response • Cytokines are small proteins involved in immune response that also affect neurodevelopment Neuropathological Similarities between Schizophrenia and Autism • Lower grey matter volumes within limbic-striato-thalamic circuitry • Specifically, the right parahippocampal gyrus, posterior cingulate, putamen, left thalamus and insula show lower grey matter volumes • Disruption within the basal ganglia loop systems is also thought to explain impaired sensorimotor gating • Neurochemical Similarities between Schizophrenia and Autism • Neurotransmitters Serotonin, Dopamine, Glutamate increases • Neurotransmitters GABA decreases • Hormone Oxytocin decreases • Common Medications include antipsychotics (dopamine blockers) and oxytocin

22. Future Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion Reference Slide Berg, J. M., Tymoczko, J. L., and Stryer, L. (2012) Biochemistry, 7th Ed. New York: W. H. Freeman and Company. Cheung, C. et al. (2010). Autistic Disorders and Schizophrenia: Related or Remote? An Anatomical Likelihood Estimation. PLoS ONE5, e12233. Deveman, B. E. and Patterson, P. H. (2009). Cytokines and CNS development. Neuron. 64: pp. 61-78 Frago, L. M and Chowen, J. A. (2005). “Basic Physiology of the Growth Hormone/Insulin-Like Growth Factor (IGF)-Axis”. The Growth Hormone/Insulin-Like Growth Factor Axis During Development. Ed. Varela-Nieto, I. and. Chowen, J. A. New York: Springer. Advances in Medicine and Biology. 567: pp. 1-26 Mescher, A. L. (2010). Junqueira’s Basic Histology: Text & Atlas, 12th Ed. New York: McGraw-Hill Medical Meyer, U., Feldon, J., and Dammann, O. (2011). Schizophrenia and autism: both shared and disorder-specific pathogensis via perinatal inflammation. Pediatr Res. 69(5): pp. 26R-33R. Patterson, P. H. (2011). Maternal infection and immune involvement in autism. Trends Mol Med. 17(7): pp. 389-394. Radeloff, D. et al. (2014). Structural Alterations of the Social Brain: A Comparison between Schizophrenia and Autism. PLoS ONE 9, e106539. Ho, BC. et al. (2000). Untreated initial psychosis: its relation to quality of life and symptom remission in first-episode schizophrenia . Am J Psychiatry 158(6): pp 986 Simic, M. et al. (2004). Autistic spectrum disorder associated with partial duplication of chromosome 15; three case reports. Eur Child Adolesc Psychiatry 6, 389-93