The experience-dependent maturation of a regulatory system in the orbital prefrontal cortex and the origin of developmental psychopathology

The maturation of corticolimbic systems that neurobiologically mediate essential affective and social regulatory functions is experience dependent. During the first and second years of life, the infant's affective experiences, especially those embedded in the relationship with the primary caregiver, elicit patterns of psychobiological alterations that influence the activity of subcortically produced trophic bioamines, peptides, and steroids that regulate the critical period growth and organization of the developing neocortex. Interactive attachment experiences of psychobiological attunement, stressful misattunement, and stress-regulating repair and reattunement that maximize positive and minimize negative affect are imprinted into the orbitofrontal cortex-the hierarchical apex of the limbic system that is expanded in the early developing right hemisphere. During the critical period of maturation of this system, prolonged episodes of intense and unregulated interactive stress are manifest in disorganizing experiences of heightened negative affect and altered levels of stress hormones, and this chaotic biochemical alteration of the internal environment triggers an extensive apoptotic parcellation of corticolimbic circuitries. In this manner less than optimal affect-regulating experiences with the primary caregiver are imprinted into the circuits of this frontolimbic system that is instrumental to attachment functions, thereby producing orbitofrontal organizations that neurobiologically express different patterns of insecure attachments. Such pathomorphogenetic outcomes result in structurally defective systems that, under stress, inefficiently regulate subcortical mechanisms that mediate the physiological processes that underlie emotion. The functional impairments of the cortical-subcortical circuitries of this prefrontal system are implicated in an enduring vulnerability to and the pathophysiology of various later forming psychiatric disorders.