David A Parker1, Jordan P Hamm2, Jennifer E McDowell3, Sarah K Keedy4, Elliot S Gershon5, Elena I Ivleva6, Godfrey D Pearlson7, Matcheri S Keshavan8, Carol A Tamminga9, John A Sweeney10, Brett A Clementz11. 1. Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens, GA, United States. Electronic address: daparker@uga.edu. 2. Neuroscience Institute, Georgia State University, Atlanta, GA, United States. Electronic address: jhamm1@gsu.edu. 3. Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens, GA, United States. Electronic address: jemcd@uga.edu. 4. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, United States. Electronic address: skeedy@bsd.uchicago.edu. 5. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, United States. Electronic address: egershon@yoda.bsd.uchicago.edu. 6. Department of Psychiatry, UT-Southwestern Medical Center, Dallas, TX, United States. Electronic address: Elena.Ivleva@utsouthwestern.edu. 7. Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, CT, United States; Institute of Living, Hartford Hospital, Hartford, CT, United States. Electronic address: godfrey.pearlson@hhchealth.org. 8. Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States. Electronic address: mkeshava@bidmc.harvard.edu. 9. Department of Psychiatry, UT-Southwestern Medical Center, Dallas, TX, United States. Electronic address: Carol.Tamminga@utsouthwestern.edu. 10. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, United States. Electronic address: John.Sweeney@utsouthwestern.edu. 11. Departments of Psychology and Neuroscience, Bio-Imaging Research Center, University of Georgia, Athens, GA, United States. Electronic address: clementz@uga.edu.
Abstract
Deviant auditory steady-state responses (aSSRs) in the gamma range (30-90 Hz) may be translational biomarkers for schizophrenia (SZ). This study tests whether aSSR deviations are (i) specific to SZ across the psychosis dimension, (ii) specific to particular frequency bands, and (iii) present in bipolar I disorder without psychosis (BDNP). METHODS: Beta (20-), low- (40-), and high-gamma (80-Hz) aSSRs were measured with EEG and compared across 113 SZ, 105 schizoaffective disorder (SAD), 99 bipolar disorder with psychosis (BDP), 68 BDNP, and 137 healthy comparison subjects (HC). Standard aSSR measures (single-trial power [STP] and inter-trial phase coherence [ITC]), as well as evoked responses to stimulus onsets/offsets and pre-stimulus power, were quantified. Multivariate canonical discriminant analysis was used to summarize variables that efficiently and maximally differentiated groups. RESULTS: (i) Psychosis groups showed reduced responses on ITC 20 Hz, STP/ITC 40 Hz, STP/ITC 80 Hz, indicating dimensional reductions in aSSR across the psychosis spectrum not specific to aSSR frequency. For the 40- and 80-Hz ITCs there was greater reduction in SZ compared to SAD, possibly indexing cortical disruptions linked to psychosis without mood symptoms. (ii) All probands had elevated pre-stimulus power, possibly compromising neural entrainment to the steady-state stimuli. (iii) Onset/Offset and 80 Hz ITC responses were most important for group discrimination and showed dimensional reduction across the schizo-bipolar spectrum. CONCLUSIONS: Deviant aSSRs were found across the schizo-bipolar spectrum at multiple frequencies with psychosis status and severity linked to greatest reductions at low and high gamma.
Deviant auditory steady-state responses (aSSRs) in the gamma range (30-90 Hz) may be translational biomarkers for schizophrenia (SZ). This study tests whether aSSR deviations are (i) specific to SZ across the psychosis dimension, (ii) specific to particular frequency bands, and (iii) present in bipolar I disorder without psychosis (BDNP). METHODS: Beta (20-), low- (40-), and high-gamma (80-Hz) aSSRs were measured with EEG and compared across 113 SZ, 105 schizoaffective disorder (SAD), 99 bipolar disorder with psychosis (BDP), 68 BDNP, and 137 healthy comparison subjects (HC). Standard aSSR measures (single-trial power [STP] and inter-trial phase coherence [ITC]), as well as evoked responses to stimulus onsets/offsets and pre-stimulus power, were quantified. Multivariate canonical discriminant analysis was used to summarize variables that efficiently and maximally differentiated groups. RESULTS: (i) Psychosis groups showed reduced responses on ITC 20 Hz, STP/ITC 40 Hz, STP/ITC 80 Hz, indicating dimensional reductions in aSSR across the psychosis spectrum not specific to aSSR frequency. For the 40- and 80-Hz ITCs there was greater reduction in SZ compared to SAD, possibly indexing cortical disruptions linked to psychosis without mood symptoms. (ii) All probands had elevated pre-stimulus power, possibly compromising neural entrainment to the steady-state stimuli. (iii) Onset/Offset and 80 Hz ITC responses were most important for group discrimination and showed dimensional reduction across the schizo-bipolar spectrum. CONCLUSIONS: Deviant aSSRs were found across the schizo-bipolar spectrum at multiple frequencies with psychosis status and severity linked to greatest reductions at low and high gamma.
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