Neurobiological endophenotypes of psychosis and schizophrenia: Are there biological markers of illness onset?

Introduction In this chapter, we describe neuropsychological, psychophysiological and brain imaging findings in the early stages of psychosis and schizophrenia, with a particular focus on the recent high-risk studies, and consider whether the evidence supports these as potential endophenotypic markers of illness. We argue that few potential markers meet criteria to be considered true endophenotypes of schizophrenia. Rather, the evidence supports the notion that there are a number of processes relevant to the onset of psychosis, which influence the phenotypic expression of the disorder at its different illness stages. Further, potential markers are non-specific and actively changing as the psychosis evolves and the illness progresses. Concurrently, these same potential indices are also dynamically changing as part of normal maturation during the adolescent and early adult period. Consequently, we suggest that these potential markers are not stable attributes of schizophrenia, nor psychosis more generally. A more parsimonious model needs to take account of the dynamic changes occurring in the brain (especially in frontal and temporal cortices) during adolescence - the period of life during which the illness typically manifests itself. Studies have not taken account of such changes, particularly in assessing the stability of proposed endophenotypes. We suggest that there is an interaction of genetic and environmental aetiological factors with stage of brain maturation at illness onset, leading to the phenotypic characteristics of the illness. Accordingly, we assert that the current conceptualizations of ‘endophenotypes’ for schizophrenia may need to be reconsidered in the context of ‘early’ versus ‘late’ brain maturational processes.