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Specific Neurological Similarities in Autism & Schizophrenia

Neurochemical & Neuropathological Similarities in Autism & Schizophrenia

Prince Nagra, Andrew Kuo,Alexandra Kourkounakis, Miles Luke

October 14, 2014

Specific Neurological Similarities in Autism & SchizophreniaIntroduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

PHM142 Fall 2014Coordinator: Dr. Jeffrey HendersonInstructor: Dr. David Hampson

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Specific Neurological Similarities in Autism & Schizophrenia

• Introduction

• Neuropathological Similarities

• Neurochemical Similarities

• Common Medications

• Conclusion

Overview

Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

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Specific Neurological Similarities in Autism & Schizophrenia

•A neurodevelopmental disorder that hinders a child’s interactive and communicative capabilities.•Categorized under the Autism Spectrum Disorder (ASD) ‘umbrella’

Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

Symptoms: •Varying degrees of severity•Social impairments •Repetitive actions •Speech/Communication delays

http://etec.ctlt.ubc.ca/510wiki/File:Umbie2.jpg

Autism

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Specific Neurological Similarities in Autism & SchizophreniaIntroduction 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)

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Specific Neurological Similarities in Autism & Schizophrenia

A disabling mental disorder that distorts a person’s ability to behave, act, and discern the difference between reality and delusion.

Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

Positive Negative

Delusions Emotionless

Hallucinations Lack motivation

Disorganized speech/thoughts Loss of Interest

Symptoms

Schizophrenia

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Specific Neurological Similarities in Autism & SchizophreniaIntroduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

Schizophrenia

Causes: •Genetic Basismultigene interactions

•Environmental Factors•Substance Usetoxic/induced psychosis

Risk Factors:•Family History •Age of Father •Prenatal Exposure to Toxins and Viruses •Hypersensitive immune system

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• 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

Prenatal Infection

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Specific Neurological Similarities in Autism & SchizophreniaIntroduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

• 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.

Prenatal Infection

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Specific Neurological Similarities in Autism & SchizophreniaIntroduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

• 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

Prenatal Infection

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Lower Grey Matter Volumes

Parahippocampal Gyrus

Posterior Cingulate

http://en.wikipedia.org/wiki/Parahippocampal_gyrus#mediaviewer/File:Gray727_parahippocampal_gyrus.png

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Lower Grey Matter Volumes

Putamen

Thalamus

http://en.wikipedia.org/wiki/Putamen#mediaviewer/File:BrainCaudatePutamen.svg

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Insula

Introduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

Lower Grey Matter Volumes

http://en.wikipedia.org/wiki/Insular_cortex#mediaviewer/File:Gray743.png

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Specific Neurological Similarities in Autism & Schizophrenia

(Autism Spectrum Disorders)

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Cheung et al., 2010

Summary: Lower Grey Matter Volumes

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Specific Neurological Similarities in Autism & SchizophreniaIntroduction 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

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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

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Specific Neurological Similarities in Autism & SchizophreniaIntroduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

• GABA– Inhibitory transmitter

• Glutamate– Excitatory transmitter

Neurotransmitters

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Neurotransmitters

• exitotoxicity

aberrant neuronal

development

http://www.heartfixer.com/AMRI-Nutrigenomics.htm

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• Oxytocin– Neurohypophysial hormone (hypothalamus)

PPG– Neuroanatomy of intimacy– Various behaviours

• Orgasm, social recognition, anxiety

– Repetitive behaviour

Hormones

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Common Medications• Antipsychotics (improves social cognition)

– Risperidone & Aripiprazole– Hyperactivity, aggression, stereotyped behaviour

• Neurohormonal neuromodulator oxytocin (improves social cognition, decreased repetitive behaviours, psychosis)

http://commons.wikimedia.org/wiki/File:Risperidone.svg http://www.ramdevchem.com/Aripiprazole.asp

Risperidone Aripiprazole

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Thank You For Your Time

FutureIntroduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

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Specific Neurological Similarities in Autism & Schizophrenia

FutureIntroduction Neuropathological Similarities Neurochemical Similarities Common Medications Conclusion

Summary SlideIntroduction•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

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Reference Slide1. Berg, J. M., Tymoczko, J. L., and Stryer, L. (2012) Biochemistry, 7th Ed. New York: W. H. Freeman and

Company.

2. Cheung, C. et al. (2010). Autistic Disorders and Schizophrenia: Related or Remote? An Anatomical Likelihood Estimation. PLoS ONE 5, e12233.

3. Deveman, B. E. and Patterson, P. H. (2009). Cytokines and CNS development. Neuron. 64: pp. 61-78

4. 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

5. Mescher, A. L. (2010). Junqueira’s Basic Histology: Text & Atlas, 12th Ed. New York: McGraw-Hill Medical

6. 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.

7. Patterson, P. H. (2011). Maternal infection and immune involvement in autism. Trends Mol Med. 17(7): pp. 389-394.

8. Radeloff, D. et al. (2014). Structural Alterations of the Social Brain: A Comparison between Schizophrenia and Autism. PLoS ONE 9, e106539.

9. 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

10. 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