Calkins ME, Iacono WG. Eye movement dysfunction in schizophrenia: a heritable characteristic for enhancing phenotype definition. Am J Med Genet 97: 72-76

Clinical Science and Psychopathology Research Traing Program , University of Minnesota, MN 55455-0344l, USA.
American Journal of Medical Genetics (Impact Factor: 3.23). 02/2000; 97(1):72-6. DOI: 10.1002/(SICI)1096-8628(200021)97:1<72::AID-AJMG10>3.0.CO;2-L
Source: PubMed

ABSTRACT The occurrence of ocular motor dysfunction in schizophrenia patients and their first-degree biological relatives is remarkably consistent, suggesting that abnormal smooth pursuit and saccadic oculomotion are heritable characteristics that can be used to identify gene carriers for schizophrenia. Saccadic system dysfunction probably reflects a generalized deficit in prefrontal cortical functioning, rather than a specific deficit in saccade system functioning. Although abnormal smooth pursuit has also been associated with impaired frontal functioning, it is unclear whether these two types of dysfunction arise from the same neural pathology. Therefore, deviant smooth pursuit and saccadic oculomotion may constitute unrelated factors identifying two different types of genetic risk. Alternatively, they may derive from a single risk factor that causes (a) both types of deficits to be expressed together or (b) each type to be expressed separately as pleiotropic manifestations of the underlying genotype. Although a full complement of pursuit and saccade measures has not been examined together in family studies of schizophrenia, there is obvious value in determining how these measures relate to one another in schizophrenia families and whether they can be used in combination to enhance phenotype definition to facilitate the search for schizophrenia susceptibility genes.

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    • "It has been suggested that the analysis of a weighted combination of these electrophysiological features may provide greater diagnostic power than any single endophenotype alone.83 For instance, Price et al84 compared and contrasted four electrophysiological components, analyzing their covariance on a single cohort of schizophrenic patients, family members, and controls. "
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    ABSTRACT: The relapse rate for many psychiatric disorders is staggeringly high, indicating that treatment methods combining psychotherapy with neuropharmacological interventions are not entirely effective. Therefore, in psychiatry, there is a current push to develop alternatives to psychotherapy and medication-based approaches. Cognitive deficits have gained considerable importance in the field as critical features of mental illness, and it is now believed that they might represent valid therapeutic targets. Indeed, an increase in cognitive skills has been shown to have a long-lasting, positive impact on the patients' quality of life and their clinical symptoms. We hereby present four principal arguments supporting the use of event-related potentials (ERP) that are derived from electroencephalography, which allow the identification of specific neurocognitive deficiencies in patients. These arguments could assist psychiatrists in the development of individualized, targeted therapy, as well as a follow-up and rehabilitation plan specific to each patient's deficit. Furthermore, they can be used as a tool to assess the possible benefits of combination therapy, consisting of medication, psychotherapy, and "ERP-oriented cognitive rehabilitation". Using this strategy, specific cognitive interventions could be planned based on each patient's needs, for an "individualized" or "personalized" therapy, which may have the potential to reduce relapse rates for many psychiatric disorders. The implementation of such a combined approach would require intense collaboration between psychiatry departments, clinical neurophysiology laboratories, and neuropsychological rehabilitation centers.
    Neuropsychiatric Disease and Treatment 11/2013; 9:1835-1845. DOI:10.2147/NDT.S53687 · 1.74 Impact Factor
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    • "Stabilized patients have repeatedly demonstrated deficits in attention allocation (Amado et al., 2009; Kebir, Ben Azouz, Amado, & Tabbane, 2008; Posner, Early, Reiman, Pardo, & Dhawan, 1988) supporting the notion of a proposed schizophrenic 'pseudo-hemineglect' (Cavezian et al., 2007; Posner et al., 1988). Impaired visuo-spatial functioning has been observed in spatial delayed-response tasks (Keefe et al., 1995; Park & Holzman, 1992), including memory-guided saccade paradigms (Calkins & Iacono, 2000; Gooding & Basso, 2008; Landgraf, Amado, Bourdel, Leonardi, & Krebs, 2008) and spatial span tasks (Cannon et al., 2000; Perry et al., 2001). Chronic patients also display deficits in motor agency (Franck et al., 2001), with an altered ability to model others' behavior. "
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    ABSTRACT: Psychotic symptoms in schizophrenia patients encompass the difficulty to distinguish between the respective points of view of self and others. The capacity to adopt and switch between different perspectives is, however, fundamental for ego- and allocentric spatial referencing. We tested whether schizophrenia patients are able to adopt and maintain a non-egocentric point of view in a complex visual environment. Twenty-four chronic schizophrenic outpatients (11 females) and 25 controls matched for age, gender, years of education and handedness were recruited from a population-based sample. In a virtual environment, participants had to make a decision as to which of two trash cans was closest to themselves (viewer-centered, egocentric), to a ball (object-centered, unstable allocentric), or to a palace (landmark-centered, stable allocentric). Main outcome measures were reaction time, error rate, learning rate and local task switch cost. While egocentric reaction time was preserved, patients showed an increased reaction time in both allocentric referencing conditions (stable and unstable) and an overall increased error rate. Switch cost was diminished in patients when changing from the egocentric to the landmark-centered condition and elevated when changing from the landmark-centered to the egocentric condition. The results imply that schizophrenia patients' adoption of an egocentric perspective is preserved. However, adopting an allocentric point of view and switching between egocentric and landmark-centered perspectives are impaired. Perturbations in non-egocentric referencing and transferring efficiently between different referential systems might contribute to altered personal and social world comprehension in schizophrenia.
    Neuropsychologia 08/2010; 48(10):2922-30. DOI:10.1016/j.neuropsychologia.2010.05.034 · 3.30 Impact Factor
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    • "For genetic studies, useful endophenotypes should be heritable, frequently expressed in probands, and stable over time (Gottesman and Gould, 2003). Deficits in smooth pursuit eye movement (SPEM) are some of the most established markers in schizophrenia (Holzman, 2000; Hong et al., 2006b; Thaker et al., 1998; Calkins and Iacono, 2000). SPEM deficits are also present in unaffected relatives of schizophrenia patients (i.e., relatives without DSM-IV schizophrenia), suggesting that they may reflect underlying genetic liabilities for schizophrenia (Karoumi et al., 2001). "
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    ABSTRACT: Smooth pursuit eye movement (SPEM) deficit is an established schizophrenia endophenotype with a similar neurocognitive construct to working memory. Frontal eye field (FEF) neurons controlling SPEM maintain firing when visual sensory information is removed, and their firing rates directly correlate with SPEM velocity. We previously demonstrated a paradoxical association between a functional polymorphism of dopamine signaling (COMT gene) and SPEM. Recent evidence implicates the dopamine transporter gene (DAT1) in modulating cortical dopamine and associated neurocognitive functions. We hypothesized that DAT1 10/10 genotype, which reduces dopamine transporter expression and increases extracellular dopamine, would affect SPEM. We examined the effects of DAT1 genotype on: Clinical diagnosis in the study sample (n = 418; 190 with schizophrenia), SPEM measures in a subgroup with completed oculomotor measures (n = 200; 87 schizophrenia), and DAT1 gene expression in FEF tissue obtained from postmortem brain samples (n = 32; 16 schizophrenia). DAT1 genotype was not associated with schizophrenia. DAT1 10/10 genotype was associated with better SPEM in healthy controls, intermediate SPEM in unaffected first-degree relatives of schizophrenia subjects, and worse SPEM in schizophrenia subjects. In the gene expression study, DAT1 10/10 genotype was associated with significantly reduced DAT1 mRNA transcript in FEF tissue from healthy control donors (P < 0.05), but higher expression in schizophrenia donors. Findings suggest regulatory effects of another gene(s) or etiological factor in schizophrenia, which modulate DAT1 gene function.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2009; 150B(2):282-9. DOI:10.1002/ajmg.b.30811 · 3.42 Impact Factor
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