The F1 approach is depicted on the figure as proceeding from right to left in an attempt to capitalize on current knowledge of the pathophysiology of the illness. The comprehensiveness of the previously described positional cloning approach contrasts with the directness of the candidate gene approach. Neurotransmitter-related genes are often considered the leading candidate genes to be examined for evidence of linkage or linkage disequilibrium with psychiatric disorders. Genes for neurotransmitter receptors and proteins involved in transmitter biosynthesis, storage, release, transduction of message, transport, metabolism, termination of action, and breakdown may all be candidates. When selecting a marker to assay for evidence of association with illness, it is preferable to select a marker within the etiological candidate gene, optimally a marker whose alternative forms (alleles) have a demonstrable pathophysiological difference, e.g., amount of activity or binding affinity.