Exploratory eye movement dysfunction as a discriminator for schizophrenia : a large sample study using a newly developed digital computerized system.
ABSTRACT In our previous studies, we identified that exploratory eye movement (EEM) dysfunction appears to be specific to schizophrenia. The availability of a biological marker specific to schizophrenia would be useful for clinical diagnosis of schizophrenia. Consequently, we performed the discriminant analysis between schizophrenics and non-schizophrenics on a large sample using the EEM test data and examined an application of the EEM for clinical diagnosis of schizophrenia. EEM performances were recorded in 251 schizophrenics and 389 non-schizophrenics (111 patients with mood disorders, 28 patients with neurotic disorders and 250 normal controls). The patients were recruited from eight university hospitals and three affiliated hospitals. For this study with a large sample, we developed a new digital computerized version of the EEM test, which automatically handled large amounts of data. We measured four parameters: number of eye fixations (NEF), total eye scanning length (TESL), mean eye scanning length (MESL) and responsive search score (RSS). These parameters of schizophrenics differed significantly from those of the other three groups. The stepwise regression analysis selected the TESL and the RSS as the valid parameters for discriminating between schizophrenics and non-schizophrenics. In the discriminant analysis using the RSS and TESL as prediction parameters, 184 of the 251 clinically diagnosed schizophrenics were discriminated as having schizophrenia (sensitivity 73.3%); and 308 of the 389 clinically diagnosed non-schizophrenic subjects were discriminated as non-schizophrenics (specificity 79.2%). Based on our findings we believe that the EEM measures may be useful for the clinical diagnosis of schizophrenia.
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ABSTRACT: Schizophrenia may have etiological heterogeneity, and may reflect common symptomatology caused by many genetic and environmental factors. In this review, we show the potential existence of heterogeneity in schizophrenia based on the results of our previous studies. In our study of the NOTCH4 gene, there were no significant associations between any single nucleotide polymorphisms (SNPs) of NOTCH4 and schizophrenia. However, exploratory analyses suggested that the SNP, rs3134928 may be associated with early-onset schizophrenia, and that rs387071 may be associated with schizophrenia characterized by negative symptoms. In our highly familial schizophrenia study, the African-American cohort without environmental exposure showed a possible linkage at marker 8p23.1 in the dominant model and in the European-American cohort, a marker at 22q13.32 showed a probable linkage in the recessive model. In the less familial schizophrenia families, these linkages were not shown. Based on our eye movement study, a putative subtype of schizophrenia with severe symptoms related to excitement/hostility, negative symptoms and disorganization may be associated with chromosome 22q11. We consider that a sample stratification approach may clarify the heterogeneity of schizophrenia. Therefore, this approach may lead to a more straightforward way of identifying susceptibility genes of schizophrenia. © 2013 Wiley Periodicals, Inc.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2013; 162(7):648-52. DOI:10.1002/ajmg.b.32161 · 3.27 Impact Factor
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ABSTRACT: Eye-movement abnormalities in schizophrenia are a well-established phenomenon that has been observed in many studies. In such studies, visual targets are usually presented in the center of the visual field, and the subject's head remains fixed. However, in every-day life, targets may also appear in the periphery. This study is among the first to investigate eye and head movements in schizophrenia by presenting targets in the periphery of the visual field. Two different visual recognition tasks, color recognition and Landolt orientation tasks, were presented at the periphery (at a visual angle of 55° from the center of the field of view). Each subject viewed 96 trials, and all eye and head movements were simultaneously recorded using video-based oculography and magnetic motion tracking of the head. Data from 14 patients with schizophrenia and 14 controls were considered. The patients had similar saccadic latencies in both tasks, whereas controls had shorter saccadic latencies in the Landolt task. Patients performed more head movements, and had increased eye-head offsets during combined eye-head shifts than controls. Patients with schizophrenia may not be able to adapt to the two different tasks to the same extent as controls, as seen by the former's task-specific saccadic latency pattern. This can be interpreted as a specific oculomotoric attentional dysfunction and may support the hypothesis that schizophrenia patients have difficulties determining the relevance of stimuli. Patients may also show an uneconomic over-performance of head-movements, which is possibly caused by alterations in frontal executive function that impair the inhibition of head shifts. In addition, a model was created explaining 93% of the variance of the response times as a function of eye and head amplitude, which was only observed in the controls, indicating abnormal eye-head coordination in patients with schizophrenia.PLoS ONE 09/2013; 8(9):e74845. DOI:10.1371/journal.pone.0074845 · 3.53 Impact Factor
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ABSTRACT: Impaired eye movements have a long history in schizophrenia research and meet the criteria of a reliable biomarker. However, the effects of cognitive load and task difficulty on saccadic latencies (SL) are less understood. Recent studies showed that SL are strongly task dependent: SL are decreased in tasks with higher cognitive demand, and increased in tasks with lower cognitive demand. The present study investigates SL modulation in patients with schizophrenia and their first-degree relatives. A group of 13 patients suffering from ICD-10 schizophrenia, 10 first-degree relatives, and 24 control subjects performed two different types of visual tasks: a color task and a Landolt ring orientation task. We used video-based oculography to measure SL. We found that patients exhibited a similar unspe-cific SL pattern in the two different tasks, whereas controls and relatives exhibited 20–26% shorter average latencies in the orientation task (higher cognitive demand) compared to the color task (lower cognitive demand). Also, classification performance using support vector machines suggests that relatives should be assigned to the healthy controls and not to the patient group. Therefore, visual processing of different content does not modulate SL in patients with schizophrenia, but modulates SL in the relatives and healthy controls. The results reflect a specific oculomotor attentional dysfunction in patients with schizophrenia that is a potential state marker, possibly caused by impaired top-down disinhibition of the superior colliculus by frontal/prefrontal areas such as the frontal eye fields.Frontiers in Behavioral Neuroscience 02/2015; 9(44):1-7. DOI:10.3389/fnbeh.2015.00044 · 4.16 Impact Factor