A major problem for investigators in the field of schizophrenia research is the difficulty of producing unambiguous results because, at least in part, of schizophrenia being a syndrome comprising of a number of disorders, which all present clinically with similar clusters of symptoms. The symptoms of schizophrenia can be categorized into three clusters: 1) positive symptoms (an excess or distortion of normal functions), 2) negative symptoms (the diminution or loss of normal functions) and 3) cognitive symptoms (deficits in attention, concentration and memory) (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders 2000). The heterogeneity of the schizophrenia syndrome ordains that studies on the disorder generate data that have a ‘decreased signal to noise ratio’ (Hallmayer et al. Am J Hum Genet 2005, 77 468–476). That is to say, studying the biochemical indexes of a group of disorders gives a less clear outcome than would be obtained by studying a single disorder. It has now been shown that investigating specific phenotypes in the schizophrenia syndrome and comparing results across phenotypes within the syndrome, as well as to those from control subjects, enhances the potential of identifying specific pathogenetic mechanisms (Hallmayer et al. Am J Hum Genet 2005, 77 468–476). We now use this approach of using endophenotypes to increase the capacity of our postmortem research to detect the biological abnormalities that underlie the schizophrenia syndrome.
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