Neuronal-immune interactions in mediating stress effects in the etiology and course of schizophrenia: Role of the amygdala in developmental co-ordination

Stress, in its many forms, is long associated with the etiology and course of schizophrenia. The mechanisms mediating the impacts of stress are not fully elucidated. Here it is proposed that stress induced cortisol alters kynurenic acid (KA) and quinolinic acid (QA) in the cortex and amygdala/striatum, respectively. These effects are significantly modulated by BAG-1 (bcl-2 associated anthanogene) and involve ROS, IL-18, and the induction of IDO (indoleamine 2,3-dioxygenase). The kynurenine pathway (KP) products response to stress seems to mediate both prenatal etiology and symptom course in adulthood. It is suggested that the effects of cortisol and quinolinic acid in the amygdala, coupled to an increase in dopamine efflux, mediate amygdala driven developmental changes in the cortex and VTA/N.Accumbens junction. This change in patterned brain activity co-ordinates alterations in motivated behaviour and thought outputs. Such developmental alterations determine changes in sensory-amygdala interactions, readily allowing developmental links to changes in lateral inhibition and pre-pulse inhibition. Decreases in vitamin D3 and melatonin further potentiate such stress induced changes. The likely involvement of glia in mediating increases in the KP products suggests that adaptation to stress is driven by neuronal activity as a form of glia to glia communication.