Smooth Pursuit Eye Movement, Prepulse Inhibition, and Auditory Paired Stimuli Processing Endophenotypes Across the Schizophrenia-Bipolar Disorder Psychosis Dimension

Abstract

Background: This study examined smooth pursuit eye movement (SPEM), prepulse inhibition (PPI), and auditory event-related potentials (ERP) to paired stimuli as putative endophenotypes of psychosis across the schizophrenia-bipolar disorder dimension. Methods: Sixty-four schizophrenia probands (SZP), 40 psychotic bipolar I disorder probands (BDP), 31 relatives of SZP (SZR), 26 relatives of BDP (BDR), and 53 healthy controls (HC) were tested. Standard clinical characterization, SPEM, PPI, and ERP measures were administered. Results: There were no differences between either SZP and BDP or SZR and BDR on any of the SPEM, PPI, or ERP measure. Compared with HC, SZP and BDP had lower SPEM maintenance and predictive pursuit gain and ERP theta/ alpha and beta magnitudes to the initial stimulus. PPI did not differ between the psychosis probands and HC. Compared with HC, SZR and BDR had lower predictive pursuit gain and ERP theta/alpha and beta magnitudes to the first stimulus with differences ranging from a significant to a trend level. Neither active symptoms severity nor concomitant medications were associated with neurophysiological outcomes. SPEM, PPI, and ERP scores had low intercorrelations. Conclusion: These findings support SPEM predictive pursuit and lower frequency auditory ERP activity in a paired stimuli paradigm as putative endophenotypes of psychosis common to SZ and BD probands and relatives. PPI did not differ between the psychosis probands and HC. Future studies in larger scale psychosis family samples targeting putative psychosis endophenotypes and underlying molecular and genetic mediators may aid in the development of biology-based diagnostic definitions.

Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia

“…PPI reflects the coordination of sensorimotor gating in the CNS, and its diminution may predict aspects of schizophrenic phenotype (Ivleva et al, 2013; Kohl et al, 2013). We found that when assessed at 6 months of age – the latest time-point at which the C57Bl/6 background strain of our rag1 −/− mice can be reliably assessed, since these mice suffer premature auditory loss which might otherwise diminish auditory PPI – that mice engrafted with SCZ hGPCs exhibited significantly diminished auditory prepulse inhibition (Figure 6A), and did so at all volumes of pre-pulse.…”

Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology

“…SPEM impairments occur with a higher frequency in subjects with high schizotypal scores or schizotypal disorders (Siever et al 1984(Siever et al , 1990. In contrast, impaired SPEM do not seem to be associated with other psychiatric disorders, except for the bipolar affective disorders where the impairment is not so consistent (Ivleva et al 2014). SPEM abnormalities have been shown to be stable over time and mostly independent of symptom state (Lee and Williams 2000;Nkam et al 2001) and, with some exceptions, independent of medication (Campion et al 1992;Hutton et al 2001).…”

Oculomotor Prediction: A Window into the Psychotic Mind

“…Moreover, CD abnormalities should be associated with other disorders with prominent psychotic symptoms. Consistent with this notion, CD abnormalities have been observed in individuals with bipolar disorder who have a history of psychotic symptoms [45, 46] and in healthy individuals with schizophrenia-like traits [47, 48]. Although there is some evidence for a relationship between psychotic symptom severity and CD alterations in schizophrenia [29, 35, 39], these relationships are inconsistent across studies.…”