ABSTRACT
That one of the three distinguished neuroscientists in receipt of the 2000 Nobel Prize for Medicine, Arvid Carlsson, was the progenitor (1) of the still prevailing (2) dopamine (DA) receptor blockade hypothesis of antipsychotic drug action is gratifying for the field. Yet this recognition is timely at another level: it occurs in juxtaposition to the first material body of evidence, after essentially 40 years, that DAergic function may be heightened in schizophrenia itself (3; see also Laruelle et al., this volume). This confluence of events usefully prompts reconsideration of a number fundamental issues: (a) Given the vicissitudes that have characterized attempts over this 40-year period, to what extent are we currently able to generalize not only from this mechanism of antipsychotic drug action to a pathobiology of psychosis, but also vice versa? (b) What are the temporal origins and trajectory of pathobiology in relation to emergence of psychosis in young adulthood and subsequent course of chronic illness? (c) Do such concepts relate specifically to schizophrenia, or generalize to other forms of psychotic illness, particularly bipolar disorder? The present analysis elaborates recently published reviews on aspects thereof (2, 4).
