GENE EXPRESSION ANALYSIS OF THE POSTMORTEM BRAINS AND LYMPHOBLASTS IN BIPOLAR DISORDER

Tadafumi

Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute,

We

performed gene expression analysis in 60 postmortem prefrontal cortices of the

Stanley Foundation Brain Collection.  Down-regulation (HTR2C, CACNA1A, GRM1,

GRIK1) or up-regulation (LIM) of genes related to intracellular

calcium signaling systems was of particular interest.  Genes encoding stress

response proteins or molecular chaperons were up-regulated in bipolar disorder (HSP27,

HSPF1).  We also found the altered expression of LIM and HSPF1

in the lymphoblastoid cells in bipolar disorder.  These genes would be novel

candidate genes for bipolar disorder.  We also performed gene expression

analysis in lymphoblastoid cells derived from two pairs of monozygotic twins

discordant for bipolar disorder and found that two genes related to endoplasmic

reticulum (ER) stress response pathway, XBP1 and HSPA5.  We found

that a single nucleotide polymorphism in the promoter of XBP1 gene losing the

positive feedback regulation activity of XBP1 was significantly associated with

bipolar disorder in Japanese patients and NIMH samples.  Impaired XBP1 loop was

improved by Valproate but not by lithium.  These findings suggested that the