ing sheath of myelin, which promotes the rapid and efficient conduction of electrical impulses. In humans, myelination progresses rapidly from 1 to 2 months prior to birth through the first 1 to 2 years of life, but it also continues through adolescence and into adulthood (Levitt, 2003; Paus, Collins, et al., 2001; Yakovlev and Lecours, 1967). This timing is similar to the developmental timing of dendritic elaboration and synapse formation.

The survival of cells and synapses requires their ongoing neural activity, suggesting that external stimuli and environmental conditions, including relative deprivation, can have important long-term influences on brain development. These influences have been demonstrated in animal models, from rodents to nonhuman primates (Sanchez, Ladd, and Plotsky, 2001). Their demonstration in humans has been more indirect. It includes evidence that differences in cognitive and psychosocial stimulation are associated with modest differences in cognitive development (Gottlieb and Blair, 2004; Santos, Assis, et al., 2008; Walker, Wachs, et al., 2007), and that the more severe environmental deprivation that occurs with institutionalized infants reduces head size and overall physical growth and impairs emotional and social responsiveness, attentional abilities, and cognitive development (Smyke, Koga, et al., 2007).

Pathological synaptic pruning in particular may contribute to the genesis of at least some MEB disorders, although in the absence of direct longitudinal data, this hypothesis has not yet been confirmed (Levitt, 2003; Rakic, 2002). Disturbances in synaptic pruning that occur during adolescence are hypothesized to underlie many of the anatomical and functional disturbances seen in brain imaging of persons with schizophrenia (Lewis and Levitt, 2002; McGlashan and Hoffman, 2000). Longitudinal studies have reported exaggerated rates of cortical thinning in the dorsal prefrontal, parietal, and temporal cortices compared with healthy developing controls (Mathalon, Sullivan, et al., 2001; Thompson, Vidal, et al., 2001). Nevertheless, the cellular bases for this cortical thinning, as well as the mechanism whereby exaggerated cortical thinning would produce psychotic symptoms, are unknown.

Continuing Development and Mechanisms of Change

As noted, many developmental processes in the brain continue into childhood, adolescence, and young adulthood. This appears to be true of the frontal lobe in particular. In fact, several large human imaging studies have reported a progressive reduction in the thickness or volume of gray matter (regions containing neuronal cell bodies) in the cerebral cortex that begins in childhood and continues through young adulthood, particularly in areas of the frontal and parietal cortices (Giedd, Blumenthal, et al.,



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