Progress in defining the biological causes of schizophrenia

Schizophrenia is a common mental illness resulting from a complex interplay of genetic and environmental risk factors. Establishing its primary molecular and cellular aetiopathologies has proved difficult. However, this is a vital step towards the rational development of useful disease biomarkers and new therapeutic strategies. The advent and large-scale application of genomic, transcriptomic, proteomic and metabolomic technologies are generating data sets required to achieve this goal. This discovery phase, typified by its objective and hypothesis-free approach, is described in the first part of the review. The accumulating biological information, when viewed as a whole, reveals a number of biological process and subcellular locations that contribute to schizophrenia causation. The data also show that each technique targets different aspects of central nervous system function in the disease state. In the second part of the review, key schizophrenia candidate genes are discussed more fully. Two higher-order processes - adult neurogenesis and inflammation - that appear to have pathological relevance are also described in detail. Finally, three areas where progress would have a large impact on schizophrenia biology are discussed: deducing the causes of schizophrenia in the individual, explaining the phenomenon of cross-disorder risk factors, and distinguishing causative disease factors from those that are reactive or compensatory.