Non‐human primate models of childhood psychopathology: the promise and the limitations

Abstract

Although non-human primate models have been used previously to investigate the neurobiology of several sensory and cognitive developmental pathologies, they have been employed only sparingly to study the etiology of childhood psychopathologies for which deficits in social behavior and emotion regulation are major symptoms. Previous investigations of both adult human and non-human primates have indicated that primate social behavior and emotion are regulated by a complex neural network, in which the amygdala and orbital frontal cortex play major roles. Therefore, this review will provide information generated from the study of macaque monkeys regarding the timing of normal social and emotional behavior development, the normal pattern of anatomical and functional maturation of the amygdala and orbital frontal cortex, as well as information regarding the neural and behavioral effects of early perturbations of these two neural structures. We will also highlight 'critical periods' of macaque development, during which major refinements in the behavioral repertoire appear to coincide with significant neural maturation of the amygdala and/or orbital frontal cortex. The identification of these 'critical periods' may allow one to better predict the specific behavioral impairments likely to appear after neonatal damage to one or both of these neural areas at different time points during development. This experimental approach may provide a new and important way to inform and stimulate research on childhood psychopathologies, such as autism, schizophrenia and Williams syndrome, in which the development of normal social skills and emotional regulation is severely perturbed. Finally, the promise and limitations inherent to the use of non-human primate models of childhood psychopathology will be discussed.

Cell proliferation in the striatum during postnatal development: preferential distribution in subregions of the ventral striatum

“…Animals are weaned, begin peer interactions, and develop appropriate social responses (C. J. Machado and J. Bachevalier, 2003). Our results show that, during this time period, there is profuse striatal, NG2 + cell proliferation.…”

Preliminary evidence for persistent abnormalities in amygdala volumes in adolescents and young adults with bipolar disorder

“…However, studies earlier in childhood are needed to determine precisely when in ontogeny these abnormalities arise and whether indeed they are present at the time of onset of the illness or whether instead they are consequences of either chronic or recurrent illness (38) or of medication exposure. The presence of abnormalities in the amygdala during adolescence, a period of intense dynamic development of the orbitofrontal cortices and other regions connected to the amygdala that have been implicated in the pathophysiology of BD (39)(40)(41)(42)(43)(44), raises the possibility that targeting those abnormalities with treatments could help in preventing the progression of abnormalities in cortico-limbic circuits (37). We did not detect medication effects on amygdala volumes, although this may be attributable to insufficient statistical power.…”

Effects of neonatal amygdala or hippocampus lesions on resting brain metabolism in the macaque monkey: A microPET imaging study

“…For example, nonhuman primates have been commonly used to investigate the behavioral consequences of neonatal brain damage through multiple stages of development (Goldman-Rakic, 1987, Alvarado and Bachevalier, 2000, Machado and Bachevalier, 2003, Bauman and Amaral, 2007. However, brain injury in developing individuals yields morphological and neurochemical reorganization that may, along with the lesion, either exacerbate or mitigate behavioral deficits.…”