Corticotrophin releasing factor--a peptide link between stress and psychopathology associated with epilepsy?

This selective review considers the contribution of recent investigations of corticotropin releasing factor (CRF) to our understanding of the link between stress and psychopathology associated with limbic epilepsy. Data are reviewed which clearly indicate that CRF does not play a simple modulatory role in behaviour. On the one hand, it is clear that CRF reproduces many of the central effects initiated by environmental stressors. One primary effect of limbic and locus coeruleus CRF systems, at least, seems to be to modulate neural circuitry involved in anxiety. On the other hand, its functioning as a modulator of animal anxiety can vary from anxiogenic, to neutral to anxiolytic, depending on the prior experience of the animal. Handling stress eliminates the anxiogenic action of CRF, and repeated limbic seizures change CRF into an anxiolytic. All of these findings suggest that CRF is an important link between stress and affective disturbance, but the nature of that link is complex and poorly understood. Chronic stress and epileptic disorders probably modify CRF functioning itself, as well as neurotransmitter systems with which CRF interacts. Nevertheless, the data suggest a novel hypothesis regarding the relationship between stress and mood in epileptics and the role of CRF in that relationship.