The heterogeneity theory of schizophrenia is generally accepted but identification of subtypes, which is crucial for genetic research, has been difficult. Deficit syndrome schizophrenia has been proposed as a valid subtype and is characterized by patients who exhibit primary enduring negative symptoms. High concordance of deficit schizophrenia in families suggests a shared genetic and/or environmental etiology. This proposed study represents the first effort (to our knowledge) to systematically determine neurobiological markers for deficit schizophrenia by studying their non-psychotic family members. Non-ill relatives may carry smaller numbers of susceptibility genes that do not result in psychosis, but may result in abnormalities that can be detected by neurobiological tests such as eye movements. Identification of heritable cognitive and electrophysiological abnormalities in deficit syndrome will help demarcate the boundary of the disorder and provide alternative phenotypes in genetic studies. Neurobiological abnormalities identified only in deficit patients and their family members may be marking the liability of deficit schizophrenia. In our preliminary study with small sample sizes that examined components of the smooth pursuit eye movement response, we found that impaired smooth pursuit initiation was specifically associated with deficit probands and their relatives, whereas predictive smooth pursuit was equally impaired in patients with and without deficit schizophrenia and in their relatives. This supports the validity of our research approach. In this proposed study, we aim to determine whether pursuit initiation is impaired only in relatives of deficit probands by using a modified initiation task in which predictive factors are minimized. We will also include memory saccade task, antisaccade tasks, and a version of the CPT with degraded presentations. These tasks are chosen because they have shown evidence of association with schizophrenia or deficit syndrome. These tasks will be administered to 30 relatives of deficit probands, 30 relatives of nondeficit probands, and 30 normal controls. Testing in relatives rather than patients will serve to eliminate differences in secondary effects of psychosis and medications. We plan to use the preliminary data collected from this grant support to guide our full-scale search for phenotypic markers specifically associated with the liability for deficit schizophrenia and subsequent molecular genetic studies. ? ?
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| Hong, L Elliot; Turano, Kathleen A; O'Neill, Hugh B et al. (2009) Is motion perception deficit in schizophrenia a consequence of eye-tracking abnormality? Biol Psychiatry 65:1079-85 |
| Hong, L Elliot; Turano, Kathleen A; O'Neill, Hugh et al. (2008) Refining the predictive pursuit endophenotype in schizophrenia. Biol Psychiatry 63:458-64 |
| Hong, L Elliot; Wonodi, Ikwunga; Lewis, Jada et al. (2008) Nicotine effect on prepulse inhibition and prepulse facilitation in schizophrenia patients. Neuropsychopharmacology 33:2167-74 |
| Hong, L Elliot; Wonodi, Ikwunga; Stine, O Colin et al. (2008) Evidence of missense mutations on the neuregulin 1 gene affecting function of prepulse inhibition. Biol Psychiatry 63:17-23 |
| Hong, L Elliot; Summerfelt, Ann; Mitchell, Braxton D et al. (2008) Sensory gating endophenotype based on its neural oscillatory pattern and heritability estimate. Arch Gen Psychiatry 65:1008-16 |
| Wonodi, Ikwunga; Reeves, Gloria; Carmichael, Dana et al. (2007) Tardive dyskinesia in children treated with atypical antipsychotic medications. Mov Disord 22:1777-82 |
| Hong, L Elliot; Summerfelt, Ann; Wonodi, Ikwunga et al. (2007) Independent domains of inhibitory gating in schizophrenia and the effect of stimulus interval. Am J Psychiatry 164:61-5 |
| Hong, L Elliot; Mitchell, Braxton D; Avila, Matthew T et al. (2006) Familial aggregation of eye-tracking endophenotypes in families of schizophrenic patients. Arch Gen Psychiatry 63:259-64 |
| Hong, L Elliot; Avila, Matithew T; Wonodi, Ikwunga et al. (2005) Reliability of a portable head-mounted eye tracking instrument for schizophrenia research. Behav Res Methods 37:133-8 |
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