Olfaction in the psychosis prodrome: Electrophysiological and behavioral measures of odor detection

• We studied olfactory processing in clinical high-risk patients and healthy controls.
• We recorded olfactory ERPs during odor detection of hydrogen sulfide and blank air.
• ERPs reflected odor intensity and detection more strongly in controls than patients.
• Negative symptoms correlated with reduced ERPs, detection, and Sniffin' Sticks score.
• Three patients who developed psychosis had markedly reduced N1, P2, and thresholds.

Smell identification deficits (SIDs) are relatively specific to schizophrenia and its negative symptoms, and may predict transition to psychosis in clinical high-risk (CHR) individuals. Moreover, event-related potentials (ERPs) to odors are reduced in schizophrenia. This study examined whether CHR patients show SIDs and abnormal olfactory N1 and P2 potentials. ERPs (49 channels) were recorded from 21 CHR and 20 healthy participants (13 males/group; ages 13–27 years) during an odor detection task using three concentrations of hydrogen sulfide (H2S) or blank air presented unilaterally by a constant-flow olfactometer. Neuronal generator patterns underlying olfactory ERPs were identified and measured by principal components analysis (unrestricted Varimax) of reference-free current source densities (CSD). Replicating previous findings, CSD waveforms to H2S stimuli were characterized by an early N1 sink (345 ms, lateral–temporal) and a late P2 source (600 ms, mid-frontocentroparietal). N1 and P2 varied monotonically with odor intensity (strong > medium > weak) and did not differ across groups. Patients and controls also showed comparable odor detection and had normal odor identification and thresholds (Sniffin' Sticks). However, olfactory ERPs strongly reflected differences in odor intensity and detection in controls, but these associations were substantially weaker in patients. Moreover, severity of negative symptoms in patients was associated with reduced olfactory ERPs and poorer odor detection, identification and thresholds. Three patients who developed psychosis had poorer odor detection and thresholds, and marked reductions of N1 and P2. Thus, despite the lack of overall group differences, olfactory measures may be of utility in predicting transition to psychosis among CHR patients.

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