The neurodevelopmental model of schizophrenia: update 2005.

Neurodevelopmental models of schizophrenia that identify longitudinal precursors of illness have been of great heuristic importance focusing most etiologic research over the past two decades. These models have varied considerably with respect to specificity and timing of hypothesized genetic and environmental 'hits', but have largely focused on insults to prenatal brain development. With heritability around 80%, nongenetic factors impairing development must also be part of the model, and any model must also account for the wide range of age of onset. In recent years, longitudinal brain imaging studies of both early and adult (to distinguish from late ie elderly) onset populations indicate that progressive brain changes are more dynamic than previously thought, with gray matter volume loss particularly striking in adolescence and appearing to be an exaggeration of the normal developmental pattern. This supports an extended time period of abnormal neurodevelopment in schizophrenia in addition to earlier 'lesions'. Many subtle cognitive, motor, and behavioral deviations are seen years before illness onset, and these are more prominent in early onset cases. Moreover, schizophrenia susceptibility genes and chromosomal abnormalities, particularly as examined for early onset populations (ie GAD1, 22q11DS), are associated with premorbid neurodevelopmental abnormalities. Several candidate genes for schizophrenia (eg dysbindin) are associated with lower cognitive abilities in both schizophrenic and other pediatric populations more generally. Postmortem human brain and developmental animal studies document multiple and diverse effects of developmental genes (including schizophrenia susceptibility genes), at sequential stages of brain development. These may underlie the broad array of premorbid cognitive and behavioral abnormalities seen in schizophrenia, and neurodevelopmental disorders more generally. Increased specificity for the most relevant environmental risk factors such as exposure to prenatal infection, and their interaction with susceptibility genes and/or action through phase-specific altered gene expression now both strengthen and modify the neurodevelopmental theory of schizophrenia.

Enhanced nutrition of offspring as a crucial factor for the evolution of intelligence on land.

Whilst life in the sea is undoubtedly an ancient process organisms with an exclusively marine lineage have not evolved the degree of intelligence demonstrated by the most advanced terrestrial species. Among the differences between terrestrial and marine environments which may begin to account for this is the instability of the terrestrial environment in comparison to the ocean. Unlike the ocean, terrestrial environments are not buffered against rapid changes in temperature, available water and other environmental extremes. This represents a challenge for the vulnerable offspring of terrestrial species. Evolutionary adaptation to this challenge has included greater transfer of resources from adult to offspring, as demonstrated by terrestrial vertebrates. However the evolution of mechanisms allowing enhanced transfer of resources between generations also creates conditions whereby offspring can be born with larger and more costly brains, developed and nourished from the outset even when they are not likely to prove useful until later life. As nutrition of offspring on land improved through natural selection better brains may thereby have been facilitated, with subsequent evolution driven by proximate selective pressures. The culmination of this process may be seen in the enormous transfer of resources from parents to offspring characteristic of humans and the advanced intelligence associated with them. Medical implications of this theory include the possible impact on the maternal brain of increased transfer of resources to the developing brain during pregnancy and lactation. This could help to account for the observed association between mental illness and the puerperium.