VULNERABILITY MARKERS IN PRODROMAL SCHIZOPHRENIA

Summary

Principal Investigator: K S Cadenhead
Affiliation: University of California
Country: USA
Abstract: In the renewal application/Vulnerability Markers in Prodromal Schizophrenia," the first specific aim is to identify vulnerability markers for psychosis that are present in the prodromal phase and first episode of schizophrenia using 1) clinical, 2) neurophysiological, and 3) neurocognitive measures. Other aims are to increase our understanding of neurodevelopmental processes in individuals in the early stages of schizophrenia, to better understand pre-psychotic symptomatology and to determine the validity and efficiency of vulnerability markers in predicting evolution of psychosis and functional outcome. Increased knowledge regarding the onset of psychosis may help to better identify individuals who are at-risk for psychosis and provide insight into the neurodevelopmental processes that occur in this stage. Additional aims include assessment of at-risk individuals who do not make the transition to psychosis to better understand potential protective factors, decrease the rate of false positives, and decrease disability. Major hypotheses: 1) The at-risk and first episode groups will demonstrate abnormalities when compared to normals on measures of prepulse inhibition; visual masking; P50 gating; and neurocognition; 2) The trait- related deficits will be stable over time; and 3) The clinical and information processing measures will be differentially correlated with each other and one or more factors will predict psychotic conversion and functional outcome in the at-risk sample. The current proposal is unique in that it combines the current knowledge of clinical and demographic risk factors for schizophrenia with the rapidly emerging data on vulnerability markers, or endophenotypes, that are associated with schizophrenia. The use of brain-based vulnerability markers may help to identify neurobiologically and clinically meaningful subgroups within this heterogeneous population in the early stages of schizophrenia and determine which subjects would benefit from early treatment. Greater knowledge regarding protective factors and early indicators of functional outcome may also lead to targeted treatments in the early phase of the illness. Appropriate intervention at this early stage could possibly prevent or delay the development of a psychotic illness along with clinical and functional deterioration. The disruption of social networks, education and occupational activity and the high incidence of suicide and crime that often accompany psychosis might be reduced or averted.
Funding Period: 1999-12-01 - 2011-04-30
more information: NIH RePORT

Top Publications

  1. ncbi Premorbid functional development and conversion to psychosis in clinical high-risk youths
    Sarah I Tarbox
    Yale University School of Medicine
    Dev Psychopathol 25:1171-86. 2013
  2. pmc Risk factors for psychosis: impaired social and role functioning
    Barbara A Cornblatt
    Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore Long Island Jewish Health System, 75 59 263rd Street, Glen Oaks, NY 11004, USA
    Schizophr Bull 38:1247-57. 2012
  3. pmc Treatment implications of the schizophrenia prodrome
    Tejal Kaur
    Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA
    Curr Top Behav Neurosci 4:97-121. 2010
  4. pmc Treatment history in the psychosis prodrome: characteristics of the North American Prodrome Longitudinal Study Cohort
    Kristin S Cadenhead
    Department of Psychiatry and Biobehavioral Sciences, UCSD, San Diego, California 92093 0810, USA
    Early Interv Psychiatry 4:220-6. 2010
  5. pmc Visual information processing dysfunction across the developmental course of early psychosis
    V B Perez
    University of California, San Francisco UCSF, CA, USA
    Psychol Med 42:2167-79. 2012
  6. pmc A developmental look at the attentional system in the at risk and first episode of psychosis: age related changes in attention along the psychosis spectrum
    Heline Mirzakhanian
    Department of Psychiatry, University of California, San Diego, CA 92093 0810, USA
    Cogn Neuropsychiatry 18:26-43. 2013
  7. pmc The relation of antipsychotic and antidepressant medication with baseline symptoms and symptom progression: a naturalistic study of the North American Prodrome Longitudinal Sample
    Elaine F Walker
    Department of Psychology, Emory University, Atlanta, GA 30322, USA
    Schizophr Res 115:50-7. 2009
  8. pmc North American Prodrome Longitudinal Study (NAPLS 2): overview and recruitment
    Jean Addington
    Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
    Schizophr Res 142:77-82. 2012
  9. pmc Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America
    Tyrone D Cannon
    Department of Psychology, University of California, Los Angeles, 1285 Franz Hall, Los Angeles, CA 90095
    Arch Gen Psychiatry 65:28-37. 2008
  10. pmc Sexual dimorphisms and prediction of conversion in the NAPLS psychosis prodrome
    Deborah J Walder
    Brooklyn College, The City University of New York, United States The Graduate Center, The City University of New York, United States
    Schizophr Res 144:43-50. 2013

Scientific Experts

  • K S Cadenhead
  • Jean Addington
  • Robert Heaton
  • Larry Seidman
  • Scott Woods
  • Danijela Piskulic
  • Elaine F Walker
  • Tyrone D Cannon
  • Thomas H McGlashan
  • Diana O Perkins
  • Barbara A Cornblatt
  • Robert Heinssen
  • Ming T Tsuang
  • Sarah I Tarbox
  • Jacob S Ballon
  • Fiza Singh
  • Tejal Kaur
  • Katherine Seeber
  • Majid M Saleem
  • Sandra Weintraub
  • Heline Mirzakhanian
  • Deborah J Walder
  • V B Perez
  • C Jahshan
  • Isabel Domingues
  • Ming Tsuang
  • Barbara Cornblatt
  • Carol Jahshan
  • Karin Kristensen
  • A D Eastvold
  • Nasra Haroun
  • Jacqueline Stowkowy
  • Beth Borosh
  • JOANNE A DEOCAMPO
  • Jennifer L Beaumont
  • Daniel H Mathalon
  • Nathan A Fox
  • Emmeline Edwards
  • Kevin Conway
  • David S Tulsky
  • Jacob E Anderson
  • Carrie W Holtzman
  • Dan Mungas
  • Cindy J Nowinski
  • Philip D Zelazo
  • Sureyya S Dikmen
  • Jennifer J Manly
  • Kathleen M Shafer
  • Noelle E Carlozzi
  • Patricia J Bauer
  • Jonathan W King
  • Hanan D Trotman
  • Brad D Pearce
  • David Blitz
  • Richard Havlik
  • Kathleen Wallner-Allen
  • Richard C Gershon
  • Jennifer Richler
  • Jerry Slotkin
  • Lisa Freund
  • Claudia Moy
  • Ellen Witt
  • Todd Lencz
  • TYRONNE D CANNON
  • D L Braff
  • K Kirihara
  • A J Rissling
  • K M Shafer
  • G A Light
  • Ricardo E CarriĆ³n
  • Jaime Pineda
  • Tracy Alderman
  • Shahrokh Golshan
  • Thomas McGlashan
  • Katherine A Dean
  • Diana Perkins
  • Elaine Walker
  • Iliana I Marks
  • Ansar Haroun
  • Laura Dunn

Detail Information

Publications33

  1. ncbi Premorbid functional development and conversion to psychosis in clinical high-risk youths
    Sarah I Tarbox
    Yale University School of Medicine
    Dev Psychopathol 25:1171-86. 2013
    ..As such, it may be a good candidate for inclusion in prediction algorithms and could represent an advantageous target for early intervention. ..
  2. pmc Risk factors for psychosis: impaired social and role functioning
    Barbara A Cornblatt
    Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore Long Island Jewish Health System, 75 59 263rd Street, Glen Oaks, NY 11004, USA
    Schizophr Bull 38:1247-57. 2012
    ..Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors...
  3. pmc Treatment implications of the schizophrenia prodrome
    Tejal Kaur
    Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA
    Curr Top Behav Neurosci 4:97-121. 2010
    ..Treatment algorithms can then be tailored to presenting symptoms, number of risk factors present, and evidence of progression of the illness, to assure appropriate, safe and effective interventions in the early stages of psychosis...
  4. pmc Treatment history in the psychosis prodrome: characteristics of the North American Prodrome Longitudinal Study Cohort
    Kristin S Cadenhead
    Department of Psychiatry and Biobehavioral Sciences, UCSD, San Diego, California 92093 0810, USA
    Early Interv Psychiatry 4:220-6. 2010
    ..The primary aim of this manuscript is to describe the treatment histories of a large cohort of individuals who entered into one of seven prodromal research programs in a North American Prodrome Longitudinal Study consortium...
  5. pmc Visual information processing dysfunction across the developmental course of early psychosis
    V B Perez
    University of California, San Francisco UCSF, CA, USA
    Psychol Med 42:2167-79. 2012
    ..It has been suggested that VM impairments may be a vulnerability marker in individuals at risk for developing psychosis...
  6. pmc A developmental look at the attentional system in the at risk and first episode of psychosis: age related changes in attention along the psychosis spectrum
    Heline Mirzakhanian
    Department of Psychiatry, University of California, San Diego, CA 92093 0810, USA
    Cogn Neuropsychiatry 18:26-43. 2013
    ....
  7. pmc The relation of antipsychotic and antidepressant medication with baseline symptoms and symptom progression: a naturalistic study of the North American Prodrome Longitudinal Sample
    Elaine F Walker
    Department of Psychology, Emory University, Atlanta, GA 30322, USA
    Schizophr Res 115:50-7. 2009
    ..The results are discussed in light of the relative risks and benefits of preventive interventions, both medication and cognitive therapies, and the importance of future clinical trials...
  8. pmc North American Prodrome Longitudinal Study (NAPLS 2): overview and recruitment
    Jean Addington
    Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
    Schizophr Res 142:77-82. 2012
    ..This paper describes the overall methodology of the NAPLS-2 project and reports on the ascertainment and demographics at the midway point of the study with (360 CHR) and 180 controls...
  9. pmc Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America
    Tyrone D Cannon
    Department of Psychology, University of California, Los Angeles, 1285 Franz Hall, Los Angeles, CA 90095
    Arch Gen Psychiatry 65:28-37. 2008
    ....
  10. pmc Sexual dimorphisms and prediction of conversion in the NAPLS psychosis prodrome
    Deborah J Walder
    Brooklyn College, The City University of New York, United States The Graduate Center, The City University of New York, United States
    Schizophr Res 144:43-50. 2013
    ..2012) across a temporally sensitive neurodevelopmental trajectory towards conferring risk...
  11. pmc Cognition assessment using the NIH Toolbox
    Sandra Weintraub
    Cognitive Neurology and Alzheimer s Disease Center, Northwestern Feinberg School of Medicine, Chicago, IL, USA
    Neurology 80:S54-64. 2013
    ..With a computerized format and national standardization, this battery will provide a "common currency" among researchers for comparisons across a wide range of studies and populations...
  12. pmc Cortisol levels and risk for psychosis: initial findings from the North American prodrome longitudinal study
    Elaine F Walker
    Department of Psychology, Emory University, Atlanta, GA 30322, USA
    Biol Psychiatry 74:410-7. 2013
    ..It was hypothesized that cortisol levels would be 1) elevated in the CHR group relative to control subjects, 2) positively correlated with symptom severity, and 3) most elevated in CHR patients who transition to psychotic level severity...
  13. pmc Perceived discrimination in those at clinical high risk for psychosis
    Majid M Saleem
    Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
    Early Interv Psychiatry 8:77-81. 2014
    ..The aim of this study was to determine the prevalence of perceived discrimination in a CHR sample and its possible relationship to attenuated positive symptoms and negative self-beliefs...
  14. pmc North American Prodrome Longitudinal Study: a collaborative multisite approach to prodromal schizophrenia research
    Jean Addington
    Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
    Schizophr Bull 33:665-72. 2007
    ....
  15. pmc Psychotropic medication use in youth at high risk for psychosis: comparison of baseline data from two research cohorts 1998-2005 and 2008-2011
    Scott W Woods
    Department of Psychiatry, Yale University, New Haven, CT, United States
    Schizophr Res 148:99-104. 2013
    ..Antipsychotic medication use rates have generally been rising among youth with psychiatric disorders, but little is known about use rates of antipsychotics or other psychotropic medications in patients at high risk for psychosis...
  16. pmc Functional development in clinical high risk youth: prediction of schizophrenia versus other psychotic disorders
    Sarah I Tarbox
    Yale University School of Medicine, Department of Psychiatry, 34 Park Street, 38D, New Haven, CT 06519, USA Electronic address
    Psychiatry Res 215:52-60. 2014
    ....
  17. pmc Automatic sensory information processing abnormalities across the illness course of schizophrenia
    C Jahshan
    Mental Illness Research, Education and Clinical Center, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA
    Psychol Med 42:85-97. 2012
    ..However, MMN and P3a have not been sufficiently studied early in the course of psychotic illness. The present study aimed to investigate MMN, P3a and reorienting negativity (RON) across the course of schizophrenia...
  18. pmc Negative symptoms in individuals at clinical high risk of psychosis
    Danijela Piskulic
    Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
    Psychiatry Res 196:220-4. 2012
    ..Thus, early and persistent negative symptoms may represent a vulnerability for risk of developing psychosis...
  19. pmc Strategies for effective recruitment of individuals at risk for developing psychosis
    Isabel Domingues
    Department of Psychiatry and Biobehavioral Sciences, University of California San Diego, San Diego, California, USA
    Early Interv Psychiatry 5:233-41. 2011
    ..The development of an extensive community outreach and education campaign is essential for programmes that aim to identify and treat individuals in the early stages of psychotic illness...
  20. pmc Startle reactivity and prepulse inhibition in prodromal and early psychosis: effects of age, antipsychotics, tobacco and cannabis in a vulnerable population
    Kristin S Cadenhead
    Department of Psychiatry, 0810, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0810, USA
    Psychiatry Res 188:208-16. 2011
    ....
  21. pmc Association of impaired EEG mu wave suppression, negative symptoms and social functioning in biological motion processing in first episode of psychosis
    Fiza Singh
    Department of Psychiatry, University of California at San Diego, La Jolla, CA 92093 0810, United States
    Schizophr Res 130:182-6. 2011
    ..And since social adaptation problems are common in schizophrenia, the authors designed a study to test mu wave suppression in a first episode of psychosis population...
  22. pmc At clinical high risk for psychosis: outcome for nonconverters
    Jean Addington
    Centre for Mental Health Research and Education, University of Calgary, 3280 Hospital Dr, NW, Calgary, Alberta T2N 4Z6
    Am J Psychiatry 168:800-5. 2011
    ..Less is known about the outcome among this group, referred to as false positive individuals...
  23. pmc HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study
    R K Heaton
    University of California, San Diego, USA
    Neurology 75:2087-96. 2010
    ....
  24. pmc Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis
    Larry J Seidman
    Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Arch Gen Psychiatry 67:578-88. 2010
    ..Early detection and prospective evaluation of clinical high-risk (CHR) individuals who may develop schizophrenia or other psychotic disorders is critical for predicting psychosis onset and for testing preventive interventions...
  25. ncbi P50 suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment
    Kristin S Cadenhead
    Department of Psychiatry, University of California San Diego, La Jolla, California 92093 0810, USA
    Biol Psychiatry 57:1504-9. 2005
    ..The aim of the present study was to determine whether individuals "at risk" for schizophrenia have deficits in P50 suppression, a preattentive measure of sensory gating...
  26. pmc Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research
    Nasra Haroun
    University of California, San Diego, USA
    Schizophr Bull 32:166-78. 2006
    ..Finally, our data strengthen the evidence base available to inform the discussion of ethical issues relevant to this important research area...
  27. pmc Cannabis abuse and risk for psychosis in a prodromal sample
    Karin Kristensen
    Department of Psychiatry, 0810, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0810, USA
    Psychiatry Res 151:151-4. 2007
    ....
  28. pmc Social functioning in young people at risk for schizophrenia
    Jacob S Ballon
    University of California, San Diego, Department of Psychiatry, San Diego, CA 92093 0810, USA
    Psychiatry Res 151:29-35. 2007
    ..Individuals at risk for schizophrenia have significant functional deficits which may be potential indicators of increased vulnerability for psychosis...
  29. pmc Neurocognitive deficits in the (putative) prodrome and first episode of psychosis
    A D Eastvold
    University of Utah, USA
    Schizophr Res 93:266-77. 2007
    ..The identification of brain based neurocognitive vulnerability markers for schizophrenia may contribute to the development of an at risk algorithm with greater predictive accuracy...
  30. pmc Obstetrical complications in people at risk for developing schizophrenia
    Jacob S Ballon
    Department of Psychiatry, 0810, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0810, United States
    Schizophr Res 98:307-11. 2008
    ..Obstetrical complications may be an important risk factor in identifying vulnerable subjects and ultimately may, along with other risk factors, be part of an algorithm for determining likelihood of developing schizophrenia...
  31. pmc Validity of the prodromal risk syndrome for first psychosis: findings from the North American Prodrome Longitudinal Study
    Scott W Woods
    PRIME Prodromal Research Clinic, Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06519, USA
    Schizophr Bull 35:894-908. 2009
    ..The strong evidence of diagnostic validity for the prodromal risk syndrome for first psychosis raises the question of its evaluation for inclusion in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition)...
  32. pmc Course of neurocognitive deficits in the prodrome and first episode of schizophrenia
    Carol Jahshan
    Joint Doctoral Program in Clinical Psychology, San Diego State University University of California, San Diego, USA
    Neuropsychology 24:109-20. 2010
    ....
  33. ncbi How does studying schizotypal personality disorder inform us about the prodrome of schizophrenia?
    Katherine Seeber
    Department of Psychiatry, 0810, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Curr Psychiatry Rep 7:41-50. 2005
    ..The current review details a strategy for researching the schizophrenia prodrome by using information gained from research in schizotypal personality disorder...