The tools of modern neuroscience, drawing from neuroanatomy, neurophysiology, brain imaging, genetic analysis, and psychopharmacology, promise to provide a host of new insights into the etiology and treatment of schizophrenia. Increasing knowledge of pathophysiology and better characterization of genotype–phenotype relationships may lay the way toward rational drug design and the identification of environmental factors that pose risks for individuals. Conversely, our abilities to identify high-risk individuals will contribute to realistic preventive measures.
Current data suggest that schizophrenia may represent a spectrum of phenotypic consequences that overlie a group of disorders whose etiopathogenesis involves the interplay of complex polygenic influences and environmental risk factors operating on brain maturational processes. Clearly, the complexity of these potential gene–environment–development interactions presents a tremendous challenge for the clinical elaboration of mechanisms operative in schizophrenia. The endgame in uncovering the etiology of complex, polygenic disorders will depend on clarification of allele function in health and illness. In the coming decade, we may see the first reports of studies that examine precisely measured genetic and environmental causes of schizophrenia for a given population (131). We will also have to take into account the dynamic interplay between genes and environment in utero. Animal models of schizophrenia that focus on developmental events will be crucial for assessment of neurobiological processes that occur early in the illness (39). Hypothesis-independent approaches, such as linkage and gene expression profiling may simplify gene identification.
Structural and functional brain imaging suggests both global and regional abnormalities as well as disconnections of specific cortical-subcortical circuits (132). New approaches to study brain activity in vivo may give leads as to where to look for abnormalities, and could provide an objective index that reflects vulnerability, clinical state, and prognosis of schizophrenia (122). Imaging measurements also promise to unite pathophysiological, genetic, and etiological research efforts (122). Furthermore, the usefulness of fMRI in monitoring and evaluating neurobiological responses to psychosocial therapies must also be thoroughly explored. Recent developments in profiling gene expression (e.g., gene chips) may allow rapid screening of novel antipsychotic drugs and the pharmacogenetic ramifications of their side effects. Future research must also consider events upstream as well as downstream to receptors, and attention must be directed to the complete range of neurotransmitters, including acetylcholine, GABA, neuropeptides, and neurosteroids.
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