Olfactory function is disturbed in schizophrenia, as identified by behavioral markers (smell identification and odor threshold) and olfactory event-related potentials (OERPs). These disturbances are also present in unaffected family members, which make them good candidates as potential biomarkers of schizophrenia risk. Smell identification deficits were found to discriminate who among high-risk cases will actually develop schizophrenia. Little is, however, known about the underlying pathophysiology of emerging psychosis during the prodromal period. This R21 application brings together clinical researchers doing prodromal studies and investigators with expertise in cognitive and electrophysiologic studies in schizophrenia. The proposed study will use improved methods for ERP analyses and for identifying at-risk young people so as to evaluate in cross-section behavioral and electrophysiological measures of olfactory function in prodromal patients, and their association with symptom features and measures of social and cognition function. If olfactory ERPs are found to be abnormal in prodromal patients, we will then apply for an R01 to evaluate whether olfactory ERPs in a prodromal cohort may be a biomarker of conversion to schizophrenia. ERPs and behavioral detection responses will be measured in 30 prodromal patients and 30 matched healthy controls to three concentrations of hydrogen sulfide during a detection task. This will take advantage of existing methods for precise control of olfactory stimuli (olfactometer) and also new data analytic techniques in the electrophysiologic domain. Current source density (CSD;surface Laplacian) and temporal principal components analysis (PCA) are combined to yield reference-free measures of radial current flow corresponding to meaningful olfactory ERP components. Auditory ERPs will also be measured during a novelty oddball detection task so as to begin to examine the modality specificity of olfactory ERP deficits. Interviewer-based and self-ratings of psychopathology, measures of social function, facial emotion recognition, and cognitive function will be used to examine the relation of ERP and behavioral olfactory deficits in patients to prodromal symptoms, social function, and cognition.

Public Health Relevance

From a clinical perspective, the study of prodromal patients is of importance not only for discovering markers for predicting conversion to schizophrenia but also for the potential development of treatments that would precede the onset of psychosis. Identification of a risk biomarker could lead to a lower rate of false positives in prodromal research and perhaps protect young people against unnecessary medication exposure.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Kozak, Michael J
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New York State Psychiatric Institute
New York
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Choi, Jimmy; Corcoran, Cheryl M; Fiszdon, Joanna M et al. (2017) Pupillometer-based neurofeedback cognitive training to improve processing speed and social functioning in individuals at clinical high risk for psychosis. Psychiatr Rehabil J 40:33-42
Vadhan, Nehal P; Corcoran, Cheryl M; Bedi, Gill et al. (2017) Acute effects of smoked marijuana in marijuana smokers at clinical high-risk for psychosis: A preliminary study. Psychiatry Res 257:372-374
Colibazzi, Tiziano; Yang, Zhen; Horga, Guillermo et al. (2017) Aberrant Temporal Connectivity in Persons at Clinical High Risk for Psychosis. Biol Psychiatry Cogn Neurosci Neuroimaging 2:696-705
Gill, Kelly E; Cressman, Victoria; Poe, Sarah Lucy et al. (2016) Social inference in individuals at clinical high risk for psychosis. Early Interv Psychiatry 10:77-80
Colibazzi, Tiziano; Horga, Guillermo; Wang, Zhishun et al. (2016) Neural Dysfunction in Cognitive Control Circuits in Persons at Clinical High-Risk for Psychosis. Neuropsychopharmacology 41:1241-50
Gill, Kelly E; Poe, Lucy; Azimov, Neyra et al. (2015) Reasons for cannabis use among youths at ultra high risk for psychosis. Early Interv Psychiatry 9:207-10
Bedi, Gillinder; Carrillo, Facundo; Cecchi, Guillermo A et al. (2015) Automated analysis of free speech predicts psychosis onset in high-risk youths. NPJ Schizophr 1:15030
Corcoran, C M; Keilp, J G; Kayser, J et al. (2015) Emotion recognition deficits as predictors of transition in individuals at clinical high risk for schizophrenia: a neurodevelopmental perspective. Psychol Med 45:2959-73
Ben-David, Shelly; Birnbaum, Michael L; Eilenberg, Mara E et al. (2014) The subjective experience of youths at clinically high risk of psychosis: a qualitative study. Psychiatr Serv 65:1499-501
Kayser, J├╝rgen; Tenke, Craig E; Kroppmann, Christopher J et al. (2014) Auditory event-related potentials and ? oscillations in the psychosis prodrome: neuronal generator patterns during a novelty oddball task. Int J Psychophysiol 91:104-20

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