In most schizophrenic patients, a prodromal phase is evident from less than a year to several years before psychosis onset, characterized by attenuated psychotic symptoms and deterioration in social, academic, and occupational function. Research on the schizophrenia prodrome has increased in recent years for at least two reasons. First, while electrophysiolgical (e.g., N100, mismatch negativity, P300, error-related negativity components of the event-related potential;ERP) and functional magnetic resonance imaging (fMRI) measures of neurocognitive dysfunction (e.g., sensory processing, attention, working memory, performance monitoring) in schizophrenia are generally assumed to predate the onset of psychosis, reflecting a genetic vulnerability and/or a neurodevelopmental insult, this critical pathophysiological hypothesis remains largely untested. Second, evidence that a longer duration of untreated psychosis after illness onset predicts a poor clinical outcome has led to the hypothesis that earlier antipsychotic treatment may improve clinical outcomes by slowing or attenuating a progressive pathophysiological process. An extension of this hypothesis, namely that antipsychotic treatment of prodromal symptoms may delay or even prevent the onset of psychosis, has already received preliminary support in two recent placebo-controlled clinical trials. However, while current clinical criteria for diagnosing the prodromal syndrome show promising predictive validity, with estimated 12-month psychosis conversion rates ranging from 20 to 60%, this still leaves 40 to 80% of patients identified as prodromal who are not at imminent risk for psychosis onset and who, therefore, may not require or benefit from early antipsychotic treatment or other interventions. Thus, enhancing the predictive validity of prodromal criteria by incorporation of neurobiological measures is a major research imperative. These considerations motivate the current study, which has three major objectives: 1) To examine whether ERP and fMRI measures of neurocognitive function, which are known to be abnormal in schizophrenia, are present in prodromal patients prior to the onset of psychosis, 2) to determine whether these abnormalities, if present, are equivalent or attenuated in severity relative to early illness schizophrenic patients, and 3) to assess whether these neurobiological abnormalities are predictive of conversion to psychosis in prodromal patients followed monthly for 24 months.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
3R01MH076989-05S1
Application #
8804052
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Rumsey, Judith M
Project Start
2007-05-21
Project End
2014-09-30
Budget Start
2014-02-01
Budget End
2014-09-30
Support Year
5
Fiscal Year
2014
Total Cost
$102,276
Indirect Cost
$35,560
Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Fulford, Daniel; Pearson, Rahel; Stuart, Barbara K et al. (2014) Symptom assessment in early psychosis: the use of well-established rating scales in clinical high-risk and recent-onset populations. Psychiatry Res 220:1077-83
Perez, Veronica B; Woods, Scott W; Roach, Brian J et al. (2014) Automatic auditory processing deficits in schizophrenia and clinical high-risk patients: forecasting psychosis risk with mismatch negativity. Biol Psychiatry 75:459-69
Fulford, Daniel; Niendam, Tara A; Floyd, Erin G et al. (2013) Symptom dimensions and functional impairment in early psychosis: more to the story than just negative symptoms. Schizophr Res 147:125-31
Whitford, Thomas J; Ford, Judith M; Mathalon, Daniel H et al. (2012) Schizophrenia, myelination, and delayed corollary discharges: a hypothesis. Schizophr Bull 38:486-94
Turner, Jessica A; Chen, Hongji; Mathalon, Daniel H et al. (2012) Reliability of the amplitude of low-frequency fluctuations in resting state fMRI in chronic schizophrenia. Psychiatry Res 201:253-5
Perez, Veronica B; Ford, Judith M; Roach, Brian J et al. (2012) Error monitoring dysfunction across the illness course of schizophrenia. J Abnorm Psychol 121:372-87
Luck, Steven J; Mathalon, Daniel H; O'Donnell, Brian F et al. (2011) A roadmap for the development and validation of event-related potential biomarkers in schizophrenia research. Biol Psychiatry 70:28-34
Whitford, T J; Mathalon, D H; Shenton, M E et al. (2011) Electrophysiological and diffusion tensor imaging evidence of delayed corollary discharges in patients with schizophrenia. Psychol Med 41:959-69
Mathalon, Daniel H; Ford, Judith M (2008) Divergent approaches converge on frontal lobe dysfunction in schizophrenia. Am J Psychiatry 165:944-8