Expression Profiles and Neurocognitive/Social Functions as a Predictive Biomarker of Schizophrenia

Poster A120, Thursday, October 20, 11:30 am - 1:00 pm, Le Baron

Yuko Okahisa1, Shinji Sakamoto1, Makiko Kishimoto1, Manabu Takaki1, Norihito Yamada1; 1Okayama University Hospital

Individuals with schizophrenia or other psychotic disorders experience a prodromal period characterized by non-specific psychiatric symptoms. Several studies reported that the treatment during this prodromal period could result in attenuation, delay or even prevention of the onset of schizophrenia and other psychotic disorders. However, rate of the conversion to psychosis is not 100%, estimated to be 30-40% over 2-3 years. In this study, to identify the biomarker which can distinguish future conversion of schizophrenia, we conducted a transcriptomic study of RNA extracted at a prodromal period and assessed social function, comparing schizophrenia and non-psychosis samples diagnosed after one-year follow-up. Subjects comprised six individuals who met criteria by using the comprehensive assessment of the at risk mental state (CAARMS). We evaluated the symptoms of these six individuals for one year and divided them into groups, “schizophrenia” and “non-psychosis” samples. RNA was extracted from whole blood at the first visit. Microarray analysis was performed on the Affymetrix Human Genome U133 Plus 2.0 arrays. We examined cognitive function using the Brief Assessment of Cognition in Schizophrenia in a Japanese-language version (BACS-J) and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery in a Japanese-language version (MCCB-J). The Japanese version of UCSD Performance-based Skills Assessment Brief (UPSA-B Japanese version) was administered to assess social function. Expression profiles of three samples from patients with schizophrenia were compared to three samples from patients with non-psychosis. Our data did not detect an association with a genome-wide significance level, although some susceptibility genes were suggested. The top-ranked were the GCLC (glutamate-cysteine ligase, catalytic subunit) gene (P = 3.7 × 10(-5)) in chromosome 6p12, the TMX4 (thioredoxin-related transmembrane protein 4) gene (P = 3.8 × 10(-5)) in chromosome 20p12, and the TRIP11 (thyroid hormone receptor interactor 11) gene (P = 4.2 × 10(-5)) in chromosome 14q31-q32, although none of the genes remained significant after correction of multiple testing. Patients with schizophrenia showed a tendency of working memory deficits compared to non-psychotics. The most significant gene were detected around the GCLC gene (P = 3.7 × 10(-5)) in chromosome 6p12, although none of the genes remained significant after correction of multiple testing. Previous studies have implicated that oxidative stress and glutathione (GSH) deficits may be involved in the pathogenesis of schizophrenia and lower GCLC protein expression among schizophrenic patients was reported. The present study provides clues about a predictive biomarker of schizophrenia at a prodromal period. A larger sample should be investigated in further studies.

Topic Area: Genetics

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