Deficits in smooth pursuit eye movements are an established phenotype for schizophrenia (SZ) and are being investigated as a potential liability marker for bipolar disorder. Although the molecular determinants of this deficit are still unclear, research has verified deficits in predictive pursuit mechanisms in SZ. Because predictive pursuit might depend on the working memory system, we have hypothesized a relationship between the two in healthy control subjects (HC) and SZ and here examine whether it extends to psychotic bipolar disorder (BDP).
Volunteers with SZ (n = 38), BDP (n = 31), and HC (n = 32) performed a novel eye movement task to assess predictive pursuit as well as a standard visuospatial measure of working memory.
Individuals with SZ and BDP both showed reduced predictive pursuit gain compared with HC (p < .05). Moreover, each patient group showed worse performance in visuospatial working memory compared with control subjects (p < .05). A strong correlation (r = .53, p = .007) was found between predictive pursuit gain and working memory in HC, a relationship that showed a trend correlation within the BDP group but not among SZ.
Individuals with SZ and BDP showed similar deficits in predictive pursuit, suggesting that this alteration could be a characteristic trait of the psychosis domain. The correlation between predictive pursuit and working memory in HC supports the assumption that working memory is related to predictive pursuit eye movements; however, the degradation of working memory in people with psychosis disrupts its association with eye-tracking behavior.
"The results were found for a group of healthy control subjects, as well as for schizophrenic patients, although the eye velocities of the patients were slower. Hong et al.  and Moates et al.  reported similar findings using a related method involving retinally stabilized targets. They found that both the healthy control subjects and the schizophrenic patients pursued the stabilized targets in patterns that resembled the motion patterns of the unstabilized targets that were pursued in the immediately previous trials, as if the pursuit response reflected the prediction that the patterns of motion seen in the recent past would continue into the future. "
[Show abstract][Hide abstract] ABSTRACT: Smooth pursuit eye movements are important for vision because they maintain the line of sight on targets that move smoothly within the visual field. Smooth pursuit is driven by neural representations of motion, including a surprisingly strong influence of high-level signals representing expected motion. We studied anticipatory smooth eye movements (defined as smooth eye movements in the direction of expected future motion) produced by salient visual cues in a group of high-functioning observers with Autism Spectrum Disorder (ASD), a condition that has been associated with difficulties in either generating predictions, or translating predictions into effective motor commands. Eye movements were recorded while participants pursued the motion of a disc that moved within an outline drawing of an inverted Y-shaped tube. The cue to the motion path was a visual barrier that blocked the untraveled branch (right or left) of the tube. ASD participants showed strong anticipatory smooth eye movements whose velocity was the same as that of a group of neurotypical participants. Anticipatory smooth eye movements appeared on the very first cued trial, indicating that trial-by-trial learning was not responsible for the responses. These results are significant because they show that anticipatory capacities are intact in high-functioning ASD in cases where the cue to the motion path is highly salient and unambiguous. Once the ability to generate anticipatory pursuit is demonstrated, the study of the anticipatory responses with a variety of types of cues provides a window into the perceptual or cognitive processes that underlie the interpretation of events in natural environments or social situations.
PLoS ONE 12/2013; 8(12):e83230. DOI:10.1371/journal.pone.0083230 · 3.23 Impact Factor
[Show abstract][Hide abstract] 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: This review examines the history of psychiatric nosology, with particular reference to the nineteenth-century origins of the concepts of manic-depressive illness and schizophrenia as distinct clinical syndromes and their evolution and diagnostic refinement over time. I document how the terminology applied to these entities has generated controversy, and discuss the ways in which the resulting diagnostic entities as defined by pure phenomenological symptom descriptors fail to capture discrete diagnostic distinctions, leading some researchers to posit an illness continuum rather than separate disorders. Furthermore, the two syndromes overlap substantially on multiple biologic measures, and clarity is lacking as to the underlying etiology and pathology necessary to move from descriptions of clinical syndromes to diseases. I next examine how biologically based classifications agnostic to conventional diagnostic schemes may be useful and how these are being implemented in practice, and conclude by summarizing where such approaches are likely to lead. Expected final online publication date for the Annual Review of Clinical Psychology Volume 11 is March 28, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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