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. Author manuscript; available in PMC: 2010 Sep 1.
Published in final edited form as: Trends Neurosci. 2009 Aug 26;32(9):485–495. doi: 10.1016/j.tins.2009.05.007

Figure 1. Long-term neurodevelopmental processes, which are disturbed in schizophrenia (SZ).

Figure 1

The upper part depicts normal corticogenesis: radial migration of the neural progenitor cells from the subventricular zone towards the cortical plate to form the well defined cortical layers and elimination of connections in adolescence. The lower part shows details of the processes that might go wrong in SZ. SZ is primarily an adult psychiatric disorder in which disturbances elicited by susceptibility genes and environmental insults (risks/insults) during early development (indicated by three pink stars in the left side) disturb postnatal brain maturation. These factors, including genetic (e.g., Neuregulin-1/ErbB4 and DISC1) and environmental factors (e.g., birth hypoxia and congenital infection), are likely to impair some of the crucial processes in early development, including progenitor cell proliferation, neuronal migration, and dendritic arborization and outgrowth. Independent of such initial risks/insults, disease-associated intrinsic factors may also directly affect postnatal brain maturation (indicated by two pink central stars). The accumulation of such deleterious insults results in overall disturbance of proper postnatal brain maturation, which includes maturation of interneurons and dopaminergic projections, pruning of glutamate synapses, and myelination. Therefore, it is crucial to understand the mechanisms that underlie the long-term progression to the full disease manifestation in young adulthood to enable development of novel etiology-based therapeutic strategies. In this figure, interneuron maturation is plotted by an increased response of interneurons to dopamine D2 agonists in the prefrontal cortex [26], whereas mesocortical dopaminergic projection is based on the levels of tyrosine hydroxylase [34]. The relative amount/level of glutamatergic synapse density and myelination are depicted according to the previous publications [38, 47]. Molecular cascades involving NRG1/ErbB4 and DISC1 in each developmental stage (indicated by rectangles) are described in Figure 2. CP, cortical plate; SVZ, subventricular zone.