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Yolken webinar
 

Yolken webinar

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presentation made by Dr. Robert Yolken on the 13th of November, 2012, at the Schizophrenia Research Forum (www.schizophreniaforum.org) live webinar.

presentation made by Dr. Robert Yolken on the 13th of November, 2012, at the Schizophrenia Research Forum (www.schizophreniaforum.org) live webinar.

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    Yolken webinar Yolken webinar Presentation Transcript

    • Neurotropic Infectious Agents and Cognitive Impairment in Schizophrenia Robert H Yolken Johns Hopkins School of Medicine Vishwajit Nimgaonkar University of Pittsburgh
    • Outline of the webinarThis presentation, R Yolken:Biology of schizophrenia and infectious agentsPresentation 2, K.Prasad:‘Epidiagnostic’ risk for cognitive impairmentPresentation 3, V. Nimgaonkar:Role of host genetic variationPresentation 4, M. Pletnikov:Effects of Toxoplasma gondii infection in rodentmodels of cognition
    • Schizophrenia in the Human Population Aspects Not Consistent with Gene-Only Effects Events during pregnancy and birth  Seasonality (Increased rates during winter)  Urban birth  Maternal Fever/Infection/Pre-eclampsia  Famine  Migration Discordance among monozygotic twins Common occurrence of disorders in individuals without an affected first degree relative Increased levels of antibodies to infectious agents and food antigens Evolutionary persistence of a trait associated with low rates of reproduction (Torrey and Yolken, Scz Bulletin, 2010)
    • Microbial agents in Psychiatric Disorders Likely Biological characteristics Capable of long term persistence within the CNS Associated with cognitive impairments Biological effects on brain cell functioning  Dopamine metabolism  Ion channels  Immune system activation Capable of interaction with host genes  Genetic susceptibility (HLA, Micb)  Epigenetic modifications  Cross species infections Possible relationship to known neurotropic agents:  Similar  Variant strains  Novel agents 4
    • Infections and Schizophrenia-Associations with infectious agents and inflammatory factors Perinatal Associations  Rubella Brown et al, 2001; Odds Ratio (OR)~3.5  Enteroviruses Jones et al, 1998; OR~4  Herpesvirus type 2 Buka et al 2001; OR~4  Toxoplasma gondii Brown, Mortensen; 2005/7; OR~3 )  Fever in Pregnancy Torrey et al 2000; OR~3  Pre-eclampsia Dalman et al, 1999; OR~2.5  Antibodies to food antigens Karlsson et al 2012; OR~2 Adult Associations  Toxoplasma gondii Torrey and Yolken 2012; OR ~2.5  Endogenous Retroviruses Karlsson et al 2001; OR~2  Circulating Immune Complexes Severance et al 2012; OR~3  Antibodies to food antigens Dickerson et al 2011; OR~3
    • Toxoplasma Gondii and Schizophrenia Forest plot of 23 previous and 15 new studies and their combination. Torrey E F et al. Schizophr Bull 2012;38:642-647© The Author 2012. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    • Toxoplasma Life cycle Cats are theAll other animals definitiveare dead-end host, where sexualhosts. The life reproduction cancycle can only be take placecompleted bygetting back into acat Having 2 methods of transmission makes Toxoplasma a highly successful parasite
    • T gondii Contains Genes which May Generate Dopamine in Infected BrainsToxoDB Thanvi and Treadwell Postgrad Med J 2004 Prandovszky et al, Plos One, 2011
    • Infectious Agents and Animal Behavior Mechanisms that increase transmission Malaria/Leishmania Listlessness Increased insect exposure Rabies Virus Increased aggression Transmission by biting Respiratory viruses Coughing Droplet transmission Herpesviruses/Retroviruses Cognitive impairment Sexual transmissionMany agents which have not yet been characterized in humans
    • Evolutionary Genetics of Human Psychiatric Diseases-Conclusionso Human psychiatric disorders are diseases involving multiple genomes.o Genomes involved include: o Human genome o Replicating zoonotic protozoa capable of altering neurotransmission o Viruses persisting in the braino The prevention of these infections may result in a dramatic decrease in the massive personal, social and economic impact of these disorders.
    • Perinatal Infections and Schizophrenia Collaborators  Johns Hopkins University  Brown University  Lorraine Jones-Brando  Steve Buka  J-C Xiao  UCLA  Flora Leister  Ty Cannon  Shuojia Yang  Ann Cusic  University of Aarhaus  Emily Severence  Preben Mortensen  Emese O”Donnell  University of London  Stanley Medical Research  Joanne Webster Institute  University of Leeds  E Fuller Torrey  Gerald McConkey  Sheppard Pratt Hospital  Faith DickersonThis work was supported by the Stanley Medical Research Institute