Neurotropic Infectious Agents and    Cognitive Impairment in         Schizophrenia            Robert H Yolken   Johns Hopk...
Outline of the webinarThis presentation, R Yolken:Biology of schizophrenia and infectious agentsPresentation 2, K.Prasad:‘...
Schizophrenia in the Human Population       Aspects Not Consistent with Gene-Only Effects Events during pregnancy and bir...
Microbial agents in Psychiatric Disorders                 Likely Biological characteristics Capable of long term persiste...
Infections and Schizophrenia-Associations with         infectious agents and inflammatory factors Perinatal Associations ...
Toxoplasma Gondii and Schizophrenia                          Forest plot of 23 previous and 15 new studies and their combi...
Toxoplasma Life cycle                                                                       Cats are theAll other animals ...
T gondii Contains Genes which May Generate                  Dopamine in Infected BrainsToxoDB                             ...
Infectious Agents and Animal Behavior          Mechanisms that increase transmission Malaria/Leishmania    Listlessness ...
Evolutionary Genetics of Human Psychiatric           Diseases-Conclusionso Human psychiatric disorders are diseases involv...
Perinatal Infections and Schizophrenia                              Collaborators    Johns Hopkins University            ...
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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.

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Yolken webinar

  1. 1. Neurotropic Infectious Agents and Cognitive Impairment in Schizophrenia Robert H Yolken Johns Hopkins School of Medicine Vishwajit Nimgaonkar University of Pittsburgh
  2. 2. 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
  3. 3. 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)
  4. 4. 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
  5. 5. 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
  6. 6. 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.
  7. 7. 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
  8. 8. T gondii Contains Genes which May Generate Dopamine in Infected BrainsToxoDB Thanvi and Treadwell Postgrad Med J 2004 Prandovszky et al, Plos One, 2011
  9. 9. 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
  10. 10. 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.
  11. 11. 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
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