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Background People with schizophrenia have clear impairments in early auditory processing. Mismatch negativity (MMN) is an auditory event-related potential that has been studied extensively in schizophrenia. MMN is elicited when an unexpected, low probability deviant auditory stimulus is presented after a repeated train of standard stimuli. The roving standard MMN paradigm is a modified version of MMN in which a series of standards is presented followed by a deviant, as in a typical (i.e. non-roving) MMN. However, the first appearance of the deviant stimulus is repeated over successive trials, so it becomes the new standard. This type of MMN varies the number of times the standard is presented. Exploration of predictive coding features of the MMN and its constituent components (i.e. repetition positivity, deviant negativity) can be optimized using a roving standard MMN paradigm. Methods This presentation will cover three studies from our laboratory using MMN in people with schizophrenia. Study 1 compared roving standard MMN in 43 people with schizophrenia and 30 healthy comparison subjects over a two-week follow-up period. Study 2 compared roving standard MMN in 16 people with schizophrenia with recent auditory hallucinations, 14 without recent auditory hallucinations, and 20 healthy comparison subjects. Study 3 investigated non-roving MMN in 99 people with schizophrenia participating in a 12-week randomized control trial comparing two types of computerized cognitive remediation. Results In the first study, we found that people with schizophrenia showed reduced MMN amplitude [F(1,66.62)=4.14, p=0.05] due to reduced deviant negativity [F(1,70.86)=4.39, p=0.04], but had normal repetition positivity [F(1,73.12)=0.06, p=0.81]. Hence, they could establish a memory trace for the standards, but had abnormal prediction error signaling. In the second study, we found that schizophrenia patients with auditory hallucinations (but not non-hallucinators) failed to show an increase in negativity as the number of standards increased, indicating abnormalities in prediction error signaling are associated with hallucinations [F(2,27)=3.98, p=0.03]. In the third study, MMN amplitude was associated with overall cognitive performance at the baseline assessment [r=-0.22, p=0.03]. Moreover, changes in MMN amplitude after 6 weeks of training predicted treatment effects on selected cognitive domains (e.g. verbal learning, reasoning / problem solving) after 12 weeks of training [r's>-0.38, p's<0.05]. Conclusions Overall, these studies show the value of two versions of MMN for understanding clinical symptoms and treatment effects in schizophrenia. [ABSTRACT FROM AUTHOR]

Background Tardive dyskinesia (TD) is a persistent and debilitating movement disorder associated with prolonged antipsychotic use. Valbenazine (VBZ), a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults, has been evaluated in 2 prior long-term studies (KINECT 3 extension, KINECT 4). Participants who completed KINECT 3 or KINECT 4 were eligible to participate in the current rollover study (NCT02736955). Data from this study were analyzed to evaluate the long-term safety and effectiveness of once-daily VBZ in adults with schizophrenia or schizoaffective disorder (SCHZ subgroup). Methods Key eligibility criteria included: age 18 to 85 years; completion of KINECT 3 extension or KINECT 4; maintenance medications for psychiatric disorders at stable doses; Brief Psychiatric Rating Scale score <50; and without high risk of active suicidal ideation or behavior. Following washout of prior VBZ treatment, participants were re-initiated at 40 mg for 4 weeks and escalated to 80 mg based on the investigator's assessments of safety/tolerability and clinical assessment of TD; a subsequent reduction to 40 mg was allowed if 80 mg was not tolerated (80/40 mg group). Participants received open-label VBZ for up to 72 weeks or until VBZ became commercially available. Assessments included the Clinical Global Impression of Severity-TD (CGIS-TD: range, 1 [normal/not at all ill] to 7 [extremely ill]) and Patient Satisfaction Questionnaire (PSQ: range, 1 [very satisfied] to 5 [very dissatisfied]). Treatment-emergent adverse events (TEAEs) were monitored for safety. Outcomes were analyzed descriptively in the SCHZ subgroup. Results Of 160 participants in the analyses, 104 were in the SCHZ subgroup (40 mg, n=23; 80 mg, n=75; 80/40 mg, n=6). Approximately one-third of these participants reached the Week 48 visit (n=34). Only 1 participant reached Week 60, and none reached Week 72 because VBZ became commercially available during the study. In SCHZ participants, mean CGIS-TD score changes from baseline to Week 48 indicated sustained global improvement (40 mg, -1.1; 80 mg, -1.3; 80/40 mg, -2.0). The percentage of participants with a CGIS-TD score ≤2 increased from baseline (40 mg, 8.7%; 80 mg, 14.7%; 80/40 mg, 0%) to Week 48 (40 mg, 37.5%; 80 mg, 60.9%; 80/40 mg, 66.7%). At baseline, almost all SCHZ participants had a PSQ score ≤2 (99.0%), indicating satisfaction with their prior VBZ experience in KINECT 3 or KINECT 4. At Week 48, this subgroup continued to express satisfaction with treatment (97.1%). During the study, 51.0% of participants in the SCHZ subgroup had ≥1 TEAE; 6.7% discontinued due to a TEAE. Discussion Similar to the overall population in this study, VBZ was generally well tolerated and no new safety signals were observed, even in participants with a dose reduction. Clinician-based assessments indicated ongoing and meaningful TD improvements in participants with schizophrenia/schizoaffective disorder who received long-term VBZ treatment (80 or 40 mg) in the current study following up to 48 weeks of treatment in previous VBZ studies. Patient satisfaction rates with VBZ remained high in this subgroup. [ABSTRACT FROM AUTHOR]