Objective: The disentangling of early sensory information processing deficits and examination of their relationships to demographic and clinical factors are important steps for the validation of potential biomarkers and/or endophenotypes of schizophrenia. The aims of the present study were to characterize commonly used sensory event-related potential deficits, to determine whether they are (1) distinct from one another and (2) independently associated with important clinical characteristics. Methods: MMN, P3a and RON event-related potentials (ERP) were recorded from schizophrenia patients (SZ; n=429) and nonpsychiatric comparison subjects (NCS; n=286). Subgroup analyses on demographic and clinical variables were performed. Results: Schizophrenia patients exhibited robust ERP deficits at frontocentral electrodes (MMN: d=1.10; P3a: d=0.87; RON: d=0.77), consistent with previous studies. Each ERP component uniquely accounted for variance in amplitude and schizophrenia deficits. Amplitude reductions occurred with increasing age in both NCS and SZ patients. A small subset of patients prescribed combinations of 1st and 2nd generation antipsychotics exhibited significantly reduced MMN amplitude relative to other medication-defined subgroups. Conclusions: MMN, P3a, and RON are dissociable deficits with distinct relationships to age and medication status in schizophrenia patients, potentially reflecting divergent pathophysiological processes. Reduced MMN in patients taking multiple antipsychotic medications appear to be attributable to greater severity of symptoms and functional impairments, rather than a medication effect. Significance: Independent information processing deficits in schizophrenia patients may differentially contribute to the commonly observed deficits in neurocognitive and psychosocial functioning.
Bibliographical noteFunding Information:
This work was supported by the National Alliance for Research on Schizophrenia and Depression , and grants from the Department of Veteran Affairs (VISN 22 Mental Illness Research, Education, and Clinical Center) and National Institute of Mental Health ( MH079777 , MH042228 and MH065571 ). The authors wish to Richard Sharp for his assistance.
- Event related potentials
- Mismatch negativity
- Reorienting negativity