The use of microarrays to characterize neuropsychiatric disorders: postmortem studies of substance abuse and schizophrenia.
Neuropsychiatric disorders are generally diagnosed based on a classification of behavioral and, in some cases, specific neurological deficits. The lack of distinct quantitative and qualitative biological descriptors at the anatomical and cellular level complicates the search for and understanding of the neurobiology of these disorders. The advent of microarray technology has enabled large-scale profiling of transcriptional activity, allowing a comprehensive characterization of transcriptional patterns relating to the pathophysiology of neuropsychiatric disorders. We review some of the unique methodological constraints related to the use of human postmortem brain tissue in addition to the generally applicable requirements for microarray experiments. Microarray studies undertaken in neuropsychiatric disorders such as schizophrenia and substance abuse by the use of postmortem brain tissue indicate that transcriptional changes relating to synaptic function and plasticity, cytoskeletal function, energy metabolism, oligodendrocytes, and distinct intracellular signaling pathways are generally present. These have been supported by microarray studies in experimental models, and have produced multiple avenues to be explored at the functional level. The quality and specificity of information obtained from human postmortem tissue is rapidly increasing with the maturation and refinement of array-related methodologies and analysis tools, and with the use of focused cell populations. The development of experimental models of gene regulation in these disorders will serve as the initial step towards a comprehensive genome-linked analysis of the brain and associated disorders, and help characterize the integration and coordinate regulation of complex functions within the CNS.
Lehrmann
E
E
Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH/DHHS, Baltimore, MD 21224, USA. elehrman@intra.nida.nih.gov
Hyde
T M
TM
Vawter
M P
MP
Becker
K G
KG
Kleinman
J E
JE
Freed
W J
WJ
D020869:Gene Expression Profiling; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D019966:Substance-Related Disorders / Q000235:genetics* / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
D012313:RNA