Genetics and Developmental Neurobiology of Major Psychoses

Curtis Deutsch

Findings from our laboratory suggest that both schizophrenia and bipolar affective disorder arise from pathogenic forces that begin early on, even during fetal development. A primary area of phenotyping in our laboratory involves craniofacial abnormality (“dysmorphology”), which provides a window into neural development. How might abnormal features of the head and face relate to brain development? It turns out the both the brain and face derive from common embryonic primordial and shaped simultaneously by shared forces. Thus, abnormal genes or environmental influences could affect not only brain development but also the features of the head and face. Indeed, patterns of craniofacial abnormality can delineate areas of brain involvement. First, we utilize objective, reliable measures of dysmorphology diagnosis using quantitative techniques. Second, rather than study individual anomalies, which are of limited theoretical interest, we study combinations of anomalies that describe classes of biologically interpretable factors (e.g., timing of maldevelopment, types of abnormalities, areas of dysmorphogenesis). We have applied this approach to the study of brain abnormalities in schizophrenia, testing our developmental hypotheses. Also, we have studied patterns of transmission of these craniofacial abnormalities in the families of individuals with major psychoses in conjunction with McLean Hospital and the Harvard Neuroscience Laboratory, with the goal
of identifying specific genes for these disorders.