Corticotropin Releasing Factor, the Amygdaloid Complex, and Depression: A Hypothetical Interrelationship

Abstract

The neurochemical basis of the pathogenesis and pharmacotherapy of affective disorders has been the subject of much speculation and theorization. The early biogenic amine theories postulated a critical role for norepinephrine and serotonin in the etiology of depression (Schildkraut 1965; Jesberger and Richardson 1985) and the mechanism of action of antidepressant (Sulser et al. 1978; de Montigny and Aghajanian 1978). More recently, the concept of a peptidergic basis of depression has received considerable investigative attention (Nemeroff and Bissette 1986) with the majority of interest focused on the 41 amino acid neuropeptide corticotropin releasing factor (CRF; Nemeroff 1990). This discussion attempts to expand the involvement of CRF in depressive disorders to include specific actions in the amygdaloid complex, an integral component of the limbic system. To this end, a brief discussion of the evidence implicating CRF in depression is presented, followed by a review of evidence linking the amygdaloid complex and depressive disorders, and, finally, the case for a role of CRF as a neurotransmitter or neuromodulator in the amygdaloid complex is presented. The causal relationships proposed result from our contention that the amygdaloid nuclear complex represents a common anatomical substrate for a seemingly diverse group of psychiatric disorders (e.g., schizophrenia, depression, anxiety) which utilize distinct amygdaloid neurotransmitter systems as elements of neutral circuits mediating affected behaviors.