Abstract
Patients with schizophrenia have impairments in early auditory system functioning that relate to clinical, cognitive, and psychosocial functioning. Some neurophysiological biomarkers of auditory information processing are sensitive to and predictive of clinically relevant outcomes following auditory-based targeted cognitive training (TCT) in schizophrenia. It is not known, however, whether schizophrenia patients show abnormalities at the earliest stage of sensory processing reflecting the integrity of the ascending auditory pathway at the level of the brainstem, or whether such abnormalities can serve as biomarkers. This study aimed to determine whether click-evoked auditory brainstem responses (click ABRs) are 1) abnormal in schizophrenia patients relative to healthy comparison subjects (HCS), 2) acutely sensitive to or predictive of TCT response, and 3) associated with clinically relevant symptoms. We also sought to determine whether 4) click ABRs show adequate psychometric reliability. Click ABRs were examined in 52 patients with schizophrenia and 32 HCS. Patients were randomized to either TCT ( n = 30), which comprised 30 h of training, or treatment as usual (TAU; n = 23). Patients showed intact click ABRs relative to HCS and click ABRs did not change significantly after 1 or 30 h of TCT. Exploratory analyses revealed modest relationships between click ABRs and baseline measures of positive symptoms and speech-in-noise perception; acute changes in ABRs were modestly related to improvements on measures of cognition independent of treatment. ABR measurements showed adequate internal consistency indicating their suitability for cross-sectional studies of individual differences, but poor test-retest reliability indicating poor suitability for clinical trials. In contrast to a growing literature demonstrating the utility of later cortical neurophysiological measures for translational research, the present findings indicate that brainstem-mediated responses are intact in schizophrenia and are not sensitive to or predictive of clinical changes in the context of TCT. These data provide guidance for establishing future neurophysiology-guided interventions in schizophrenia.
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