title: Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients.
abstract: Reelin, a secretory protease that plays major roles in neurodevelopment and synaptic plasticity, may also play a role in the pathogenesis of schizophrenia. The present study was undertaken to examine whether the expression of two receptors for reelin, very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor type 2 (ApoER2), were abnormal in peripheral blood lymphocytes of schizophrenic patients. In this study, we measured the mRNA levels of VLDLR and ApoER2 in blood lymphocytes from patients with schizophrenia (drug-naive patients (n=20) and medicated patients (n=20)) and age-and gender-matched healthy controls (n=40) using quantitative real-time RT-PCR. Furthermore, we examined the correlation between mRNA levels and clinical variables in patients. Levels of VLDLR mRNA in drug-naive, unmedicated patients with schizophrenia were significantly lower than those of controls. In contrast, levels of ApoER2 mRNA in drug-naive patients did not differ from those of controls, although the levels of ApoER2 mRNA in medicated patients were significantly lower than those of controls. Interestingly, levels of VLDLR mRNA in drug-naive patients showed significant increases with respect to baseline after six months of antipsychotic treatment, whereas levels of ApoER2 mRNA were significantly lower than baseline after six months of treatment. In all patients, there was a negative correlation between VLDLR mRNA levels and the severity of clinical symptoms. Our findings suggest that peripheral VLDLR mRNA levels may serve as a reliable peripheral biological marker of schizophrenia, and that the reelin-VLDLR/ApoER2 signaling pathway plays a role in the pathophysiology of schizophrenia.
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kawai
authors.forename: Genichi
authors.initials: G
authors.lastname: Sugihara
authors.forename: Kenji J
authors.initials: KJ
authors.lastname: Tsuchiya
authors.forename: Shiro
authors.initials: S
authors.lastname: Suda
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Nori
authors.initials: N
authors.lastname: Takei
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D010054:Brief Psychiatric Rating Scale; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D026502:LDL-Receptor Related Proteins; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D018110:Receptors, Lipoprotein / Q000235:genetics* / Q000378:metabolism; D000091042:Reelin Protein; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D012737:Sex Factors
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D026502:LDL-Receptor Related Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C469363:reelin receptor; C000717127:RELN protein, human