Depression has been hypothesized to be related to the reduced biosynthesis
of neurotransmitters such as serotonin, noradrenalin and dopamine. Much pas
t research has also been devoted to dysregulation of the hypothalamic-pitui
tary-adrenal (HPA) axis in depression. The present article reviews the evid
ence linking tetrahydrobiopterin, a co-factor in the biosynthesis of neurot
ransmitters, and nitric oxide, an apparent neuroendocrine modulator of the
HPA axis, to the immune system and to neuronal control within affective dis
order and stress. On the basis of this review, it is suggested that future
psychoneuroimmunological research should more fully explore the possible ro
le of tetrahydrobiopterin and nitric oxide in depressive disorders. (C) 199
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