Vasopressin-neurophysin and bipolar depression

Abstract

Vasopressin-neurophysin is a part of the precursor molecule for the active nonapeptide vasopressin (antidiuretic hormone, AVP). In humans, this neurophysin has a marked anodal electrophoretic migration and is therefore named neurophysin-I (hNpI) (Legros and Louis 1973) (see review of the precursor in lvell et al. 1983). AVP and hNpI are released simultaneously by exocytosis of neurosecretory granules in the peripheral circulation and in the cerebrospinal fluid (CSF): modifications of hNrI concentrations therefore reflect the ~uctuations of AVP release in different physiological and pathological conditions. Moreover, as hNpI is more stable than AVP, its blood and CSF levels might better reflect long-term vasopressinergic function than isolated AVP assays (see discussion in Legros 197.5). Since the pioneer work of de Wied (1965). there has arisen a growing evidence that vasopressin has a central activating action (mood, memory, selective attention) in animals and humans (de Wied 1977; Legros et al. 1978; Kovaks et al. 1979; Weingartner et al. 1981: Legros and Lancranjan 1984). The recent discovery of hippocampal receptors for AVP and the close correlation between the in vitro binding affinity and the in vivo behavioral power of different vasopressin analogs or derivatives (Audigier and Barberis 1985) reinforce the psychophysiological meaning of this peptide action on the brain. Based on this activity. Gold et al. (1978) postulated that vasopressin release can be aitered in some psychopathological conditions, and more p~icul~ly, in depression and mania. However, basal plasma levels did not differ in the different groups of patients, whereas sophisticated challenge tests (hypertonic saline infusion) revealed decreased release during the depressive phase and increased response during the manic phase (Gold et al. 1983a). We have also previously described an increase of CSF neurophysins in bipolar as compared to unipolar depressed patients (Legros et al. 1983; Linkowski et al. 1984). We therefore decided to investigate basal and apomorphine-stimulated neurophysin serum levels in different psychopathological conditions. In the course of that study, we recently had an opportunity to test one bipolar patient who had never been treated with lithium, during consecutive depressive and manic episodes while remaining completely unmedicated.