IEPA 11

Susanna L. Fryer1,2, Peter Bachman3, Aysenil Belger4, Ricardo Carrión5, Erica Duncan6, Jason Johannesen7, Margaret Niznikiewicz8, Brian Roach2, Jean Addington9, Kristin Cadenhead10, NAPLS Consortium, Daniel H. Mathalon1,2; 1University of California, San Francisco, 2San Francisco VA Healthcare System, 3University of Pittsburgh, 4University of North Carolina, 5Zucker Hillside Hospital, 6Emory University, 7Yale University, 8Harvard Medical School, 9University of Calgary, 10University of California, San Diego
           
The mismatch negativity (MMN) event-related potential (ERP) is an auditory prediction error signal elicited by the violation of the expectation that a standard, frequent sound will repeat.  Repetitions of standards strengthen this prediction signal, and produce an increasing electrophysiological signature, the “repetition positivity” (RP).  The RP reflects strengthening of experience-dependent short-term plasticity.  Here, we examine the RP elicited by a MMN paradigm in youth at clinical high risk for psychosis (CHR; n=450) and healthy controls (HC; n=241) from the North American Prodromal Longitudinal Study-2.  After 24 months of clinical follow-up, CHR participants (n=244) were categorized by clinical outcome status into subgroups that:  i) transitioned to psychosis (CHR-Transition, n = 54), ii) did not transition but remained symptomatic (CHR-Symptomatic, n = 112), and iii) did not transition and reached symptom remission (CHR-Remission, n = 78).  The RP (100-200 ms post-stimulus) to successive standards (2, 3, 4-5, 6-7, 8-10, >10 repetitions) was assessed at baseline.  Significant group differences in RP amplitude were detected based on clinical outcome (Group*Standard interaction, p <.001).  Follow-up tests revealed CHR-Transition had significantly smaller baseline RPs to late standards (>10 repetitions), relative to HC and CHR-Remission participants, who did not differ from each other.  Similarly, the CHR-Symptomatic group, which did not differ from the CHR-Transition group, had smaller baseline RPs to late standards relative to HC and CHR-Remission groups (all follow-up p’s <.05, FDR-corrected for multiple comparisons).  These results implicate deficits in short-term auditory cortex plasticity as a risk factor for psychosis that is sensitive to clinical outcome.