Pre-Emptive Intervention in Psychosis: Agnostic Rather than Diagnostic

and Anderson (this issue p.509–514) reprise the tenacious question of the validity of psychiatric diagnosis and the relationship between clinical phenotypes and putative underlying ‘ processes ’ . Having spent most of the 1980s immersed in this issue myself, trapped in a maze of historical literature and beguiled by the ghosts of schizophrenia past, I read this paper with a real sense of nostalgia. The novel angle here though is the contention that the fortunes of the early intervention paradigm, and specifi cally prodromal or pre-psychotic intervention, depend on an adherence to a narrow 19th-century disease model of psychiatry, which rigidly equates syndromes with underlying disease entities: a model which, although fatally fl awed, dies very hard. The crux of the authors ’ argument is that ‘ prodromal diagnosis ’ as they characterize it, is an invalid extension of an invalid model. They assert that a hypothetical, heavily deterministic and as yet undiscovered ‘ process ’ is seen by proponents of pre-psychotic treatment as a necessary target for interventions aimed at reducing risk of progression to a more serious stage. The authors ’ concerns are similar to those which led Alison Yung and I to eschew at the outset the prodromal label for this pre-psychotic or sub-threshold stage and to coin the new term ‘ at-risk mental state ’ (ARMS) [1] and later the ‘ ultra-high risk ’ (UHR) state [2,3]. This was intended to capture the high level of risk for progression conferred by the phenotype we described and validated in prediction studies, but on the other hand to underscore that progression was by no means inevitable, or even the most common outcome, and there were many false positives. At the time, most clinicians believed in a highly deterministic model in which ‘ a trace of schizophrenia is schizophrenia ’ and that once the ‘ process ’ started it rarely if ever receded or stopped. Some still do. This was unreconstructed Kraepelin, and a model that I sought at the outset of my career to challenge [4,5]. I suspect that Rosenman and Anderson are very much in sympathy with this. We subsequently have elaborated a broader ‘ clinical staging ’ model [6,7] which acknowledges the fl uidity of the clinical phenotype, recognizes that it evolves over time and will have a variable and as yet unclear relationship with underlying biomarkers and any putative ‘ processes ’ . The latter term is a very loaded one in psychiatry, and is perhaps better avoided, since it contains so many assumptions and connotations. A more scientifi c approach would seek to separate biomarkers which refl ect prior and underlying vulnerability (endophenotypes) from those which indicate either the ‘ substrates ’ and possibly drivers of emerging symptoms, or the secondary consequences of progressive illness. A clinical staging model enables this to be carried out systematically. All of these biomarkers cross current syndromal diagnostic boundaries to varying degrees, so syndromes and stages form a two-dimensional matrix. The clinical staging model proposes an arbitrary series of categorical stages linked to the degree of clarity, specifi city and extension of the clinical phenotype. It imposes structure on what are obviously dimensional phenomena but from a perspective orthogonal to the traditional diagnostic categories. The model allows us to explore the relationship between elements of the clinical phenotype (putative core symptoms versus ‘ noise ’ ) at each stage and the prediction of remission or progression to a more severe stage. The relationship of the clinical phenotype with biomarkers within each stage and their role in prediction can also be understood and the strength and topography of underlying neurobiological changes ( ‘ process ’ ) may be better