Epidemiological and clinical research as a guide in the search for risk factors and biological markers.

One of the major events in psychiatric research in the last decade has been the firm establishment of the concept of biological markers and risk factors as legitimate signposts in the search for causes and pathogenetic mechanisms in mental disorders. However, to date, no single variable and no group of variables have been unequivocally identified as markers or risk factors, as far as the functional psychoses, or personality and neurotic disorders are concerned. The reasons for this state of affairs lie in the multifactorial nature of "idiopathic" psychiatric disorders, in persisting differences between the diagnostic criteria employed by various "schools", in the low statistical power of most research designs in biological psychiatry and in the lack of a general theory of cerebral and mental functioning which can yield testable hypotheses. Epidemiological methods, which had produced spectacular results in the past, are now rarely applied to narrow down the field of investigation where disease markers are most likely to be found. There are obvious similarities between the epidemiological strategy of risk factor identification and the biological strategy of disease marker research. A combination of these two strategies is more likely to advance the field than continued use of each singly. Schizophrenia research is an example of an area presenting interesting opportunities in this respect. The following priorities are suggested: development of a research classification of schizophrenia proceeding from well-defined sub-divisions of the phenotype; studies of the schizophrenia spectrum of disorders; search for populations with extremely high or extremely low incidence; studies of large pedigrees; further attempts to clarify the phenomenon of seasonal distribution of births of schizophrenia patients; studies on the occurrence of schizophrenic syndromes in association with other, well-defined diseases; search for early developmental precursors of the disorder; and subtyping of schizophrenia according to therapeutic response.