Kazuo Yara

Significant linkage to chromosome 22q for exploratory eye movement dysfunction in schizophrenia

A genome‐wide scan for a locus responsible for exploratory eye movement (EEM), which is quantitative and can be disturbed in association with schizophrenia, was performed. A 10‐cM resolution genome‐wide linkage analysis of the EEM disturbance with 358 highly polymorphic microsatellite markers in 38 nuclear families with 122 members (38 probands, 47 sibs, and 37 parents) including 58 sib‐pairs yielded the suggestive linkage to the GCT10C10 marker on chromosome 22q11.2 (LOD = 2.48). Dense mapping with additional markers around the GCT10C10 marker yielded evidence for significant linkage between EEM disturbance and markers D22S429 and D22S310 on chromosome 22q12.1 (LOD score of 4.63) with suggestive evidence for the chromosome region 22q11.2–q12.1. Our findings suggest that a relatively small number of loci may control the schizophrenia‐related quantitative EEM trait. We believe that identifying gene(s) on chromosome 22q associated with the EEM phenotype may forward our understanding of the etiology of schizophrenia.

Family-based association study of the NOTCH4 gene in schizophrenia using Japanese and Chinese samples

BACKGROUND A family based association study in a British sample found the NOTCH4 gene to be associated with schizophrenia; however, all six replication studies failed to confirm the finding. METHODS We performed a family based association study of NOTCH4 and schizophrenia in 123 trios (16 Japanese and 107 Chinese). In addition to the original studys polymorphisms, we examined four new single nucleotide polymorphisms (SNPs)--SNPs_A, B, C and D--around SNP1 of the original study. We genotyped all samples for SNPs_A-D and for SNP1 and (CTG)n of the original study. RESULTS We found no significant associations between NOTCH4 and schizophrenia or its subtypes for all polymorphisms, regardless of gender. The finding remained negative when the Chinese sample was analyzed separately. Exploratory analyses suggested that SNP_A may be associated with early-onset schizophrenia and that SNP1 may be associated with schizophrenia characterized by numerous negative symptoms. CONCLUSIONS NOTCH4 is not a significant susceptibility gene for schizophrenia when clinical heterogeneity is ignored; however, NOTCH4 may be associated with early-onset schizophrenia or schizophrenia with many negative symptoms, but these findings should be interpreted cautiously.

Impairment of exploratory eye movement in schizophrenia patients and their siblings

Aims:  Previous family, adoption and twin studies of schizophrenia have shown that genetic factors contribute significantly to the risk of schizophrenia. The aim of the present study was therefore to investigate whether exploratory eye movement (EEM) abnormalities are related to the genetic markers linked to schizophrenia.

Age at onset of schizophrenia: gender differences and influence of temporal socioeconomic change.

This study was undertaken to examine whether males develop schizophrenia at a younger age than females, and whether temporal socioeconomic change affects the age at onset of schizophrenia. The subjects were 848 ICD‐9 schizophrenics who were admitted to Nihon University Hospital, Tokyo, Japan, during the period of 1955–64 (n = 468 (214 males and 254 females), group A) or during the period of 1982–91 (n = 380 (220 males and 160 females), group B). Schizophrenic males showed an earlier age at onset than schizophrenic females. However, the mean age at onset of schizophrenia did not differ significantly between group A and group B. These results indicate that the gender difference in age at onset of schizophrenia has not been influenced by temporal socioeconomic change.

Patients with systemic lupus erythematosus show a normal responsive search score in exploratory eye movement analysis: comparison with schizophrenia

Objective: To assess whether a difference in psychiatric vulnerability exists between patients with systemic lupus erythematosus (SLE) and those with schizophrenia. Methods: Twenty women with SLE underwent exploratory eye movement analysis, and a responsive search score (RSS) was obtained, two months after the onset of the disease. Fifteen women with schizophrenia in remission also underwent this analysis. Exploratory eye movement was recorded by an eye mark recorder, which detects corneal reflection of infrared light. The number of eye fixations (instance of more than 0.2 seconds of eye fixation time) was recorded, and the RSS was calculated from eye fixation analysis. Results: Mean (SD) RSS differed significantly between patients with SLE and those with schizophrenia (9.85 (1.87) v 7.27 (1.58) points, respectively, p<0.0001), whereas no difference in mean RSS was found between patients with SLE and 19 normal women. No difference in mean RSS was found between patients with active SLE and those with inactive SLE (9.51 (1.87) v 10.0 (1.77) points). Conclusion: The psychiatric vulnerability in patients with SLE, measured by the RSS, differs from that in patients with schizophrenia.

Exploratory Eye Movements as a Trait Marker of Schizophrenia

To clarify a genetic factor in the development of schizophrenia from a psychophysiological point of view, the exploratory eye movements that we have shown to be specific to schizophrenia in healthy families of schizophrenics were investigated. Eye movements of parents, siblings, and healthy cotwins of monozygotic discordant pairs were examined while they looked at S-shaped figures. The responsive search scores (RSSs) of both parents and siblings were similar to those of schizophrenics. In the RSS, there was a relationship between each pair in discordant twins. These results suggest that RSS shown in schizophrenics may be a trait marker for schizophrenia. Furthermore, eye movements of schizophrenics with schizophrenic family members in their first-degree relatives were measured. As the number of schizophrenic family members of schizophrenics increased, their RSS became lower. This result also indicates that RSS can be related to the genetic factors of schizophrenia.

Prolonged polysomnography in a case with recurrent hypersomnia

Abstract An 18‐year‐old male patient with recurrent hypersomnia (RH) was evaluated using prolonged polysomnography (PSG). During symptomatic period (SMP), the patient showed both ‘dissociated stage REM’ (DREM), REM sleep without muscle atonia and ‘dissociated stage 1’ (DSt‐1), and stage 1 sleep with rapid eye movement. These stages were observed in the morning or following daytime record. They decreased during asymptomatic period (ASMP). It has been said that RH is caused by dysfunction of the hypothalamus and midbrain limbic system. The present result suggests also that RH involves dysfunction of the brain stem.