Microarray technology: a review of new strategies to discover candidate vulnerability genes in psychiatric disorders.
OBJECTIVE
An international effort is in progress to discover candidate genes and pathways associated with psychiatric disorders, including two of the most serious diseases, schizophrenia and mood disorders, through the use of new technology-microarrays. Instead of studying one gene at a time, microarrays provide the opportunity to analyze thousands of genes at once.


METHODS
This article reviews the steps in this discovery process, including the acquisition and characterization of high-quality postmortem brain tissue, RNA extraction, and preparation and use of microarray technology. Two alternative microarray methods and factors affecting the quality of array data are reviewed.


RESULTS
New analytical strategies are being developed to process the massive data sets generated by microarray studies and to define the significance of implicated genes. Array results must be validated by other methods, including in situ hybridization and real-time polymerase chain reaction. Identified genes can also be evaluated in terms of their chromosomal locations and possible overlap with regions of suggestive linkage or association identified with genome-wide linkage analysis in psychiatry and in terms of overlap with genes identified by microarray studies in animals administered psychoactive drugs. Microarray studies are only the first major step in the process. Further efforts in the investigation involve multiple strategies for studying function and gene structure, including transgenic and knockout animal studies.


CONCLUSIONS
Microarrays present a methodology that can identify genes or pathways for new and unique potential drug targets, determine premorbid diagnosis, predict drug responsiveness for individual patients, and, eventually, initiate gene therapy and prevention strategies.
Bunney
William E
WE
Department of Psychiatry, University of California, Irvine 92697, USA. webunney@uci.edu
Bunney
Blynn G
BG
Vawter
Marquis P
MP
Tomita
Hiroaki
H
Li
Jun
J
Evans
Simon J
SJ
Choudary
Prabhakara V
PV
Myers
Richard M
RM
Jones
Edward G
EG
Watson
Stanley J
SJ
Akil
Huda
H
D001923:Brain Chemistry / Q000235:genetics; D005796:Genes / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D012333:RNA, Messenger