GENE  EXPRESSION ANALYSIS IN SCHIZOPHRENIA

offer opportunities to investigate gene expression in complex Neuropsychiatric

disorders on a large scale. We screened a custom-made candidate gene cDNA array

comprising 300 genes. The genes chosen have been implicated in schizophrenia,

make conceptual sense in the light of the current understanding of the disease,

or are located on known high-susceptibility chromosome locations.  The

array screen using prefrontal cortex tissue from 10 schizophrenia and 10 control

brains revealed robust upregulation of apolipoprotein L1 (apo L1) by

2.6-fold.  This finding was cross-validated in a blinded quantitative PCR

study using prefrontal cortex tissue from the Stanley Foundation Brain

Collection.  This collection consists of 15 schizophrenia, 15 bipolar

disorder, 15 major depression and 15 control individuals, all 60 brains being

well-matched on conventional parameters, with anti-psychotic drug exposure in

the schizophrenia and bipolar disorder groups.  Significant upregulation of

apo L1 gene expression in schizophrenia was confirmed.  Using quantitative

PCR, expression profiles of other members of the apo L family (apo L2 – apo L6)

were investigated showing that apo L2 and apo L4 were highly significantly

upregulated in schizophrenia.  Results were then confirmed in an

independent set of 20 schizophrenia and 20 control brains from Japan and New

Zealand.  Apo L proteins belong to the group of high density lipoproteins (HDA),

with all 6 apo L genes located in close proximity to each other on chromosome

22q12.  This chromosome region is a confirmed high susceptibility locus for

schizophrenia and close to the region associated with the Velo-Cardio-Facial