Gregory A. Light

Background: Computerized auditory training (AT) modestly improves symptoms, cognition, and functioning in schizophrenia. We assessed whether d-amphetamine (AMPH) or memantine (MEM) can enhance gains from 30-h of AT. Methods: Antipsychotic-medicated individuals with chronic psychosis (n = 68; mean age 47.03y; M:F = 39:29) completed up to 30 AT sessions (2-3/week; n = 50 completed 30 sessions) in 3 groups: “AMPH group” (AMPH (5 mg po) 1-h before each AT session); “MEM group” (titrated to 10 mg MEM bid and maintained that dose throughout training); “PBO group” (PBO dosed identically to either AMPH or MEM). Primary (PANSS total, MCCB Composite, WHODAS) and secondary (PANSS positive, PANSS negative, YMRS, PHQ-9, PSYRATS) outcome measures were acquired at baseline, after 10, 20, and 30 AT sessions, and 12 weeks post-training. Pill identity (active/PBO) was blind to subjects and staff. Results: Marginally significant between-group gains for AMPH vs PBO were detected for one of three primary outcomes (WHODAS, P =.050; but not PANSS total or MCCB Composite), and for 3 of 5 secondary clinical outcomes (PANSS positive, YMRS, PSYRATS, P’s≤.027–.049). Within-subject gains over time were detected for primary and secondary clinical measures for AMPH (P’s≤.014–.004) and MEM (P’s≤.02–.001) groups; some of these would not survive conservative correction for multiple comparisons. No measures detected symptom worsening; treatment satisfaction exceeded subjects’ expectations. Conclusions: Results are mixed; drug-associated gains in several measures vs PBO suggest that these regimens may augment AT-induced functional and clinical improvement in psychosis patients, independent of changes in neurocognition. Assessment in larger samples seems warranted.

In studies of event‐related brain potentials (ERPs), it is common practice to exclude participants for having too few trials for analysis to ensure adequate score reliability (i.e., internal consistency). However, in research involving clinical samples, the impact of increasingly rigorous reliability standards on factors such as sample generalizability, patient versus control effect sizes, and effect sizes for within‐group correlations with external variables is unclear. This study systematically evaluated whether different ERP reliability cutoffs impacted these factors in psychosis. Error‐related negativity (ERN) and error positivity (Pe) were assessed during a modified flanker task in 97 patients with psychosis and 104 healthy comparison participants, who also completed measures of cognition and psychiatric symptoms. ERP reliability cutoffs had notably different effects on the factors considered. A recommended reliability cutoff of 0.80 resulted in sample bias due to systematic exclusion of patients with relatively few task errors, lower reported psychiatric symptoms, and higher levels of cognitive functioning. ERP score reliability lower than 0.80 resulted in generally smaller between‐ and within‐group effect sizes, likely misrepresenting effect sizes. Imposing rigorous ERP reliability standards in studies of psychotic disorders might exclude high‐functioning patients, which raises important considerations for the generalizability of clinical ERP research. Moving forward, we recommend examining characteristics of excluded participants, optimizing paradigms and processing pipelines for use in clinical samples, justifying reliability thresholds, and routinely reporting score reliability of all measurements, ERP or otherwise, used to examine individual differences, especially in clinical research.