When the paradigms languish.

Craddock and Owen start their cogent, thought-provoking analysis and bold vision of the future of psychiatric classification of major psychoses by inserting, not surprisingly, a Kuhnian reminder of the fate of theoretical constructs in science (1). It is, indeed, impressive that the "dichotomous view", underlining the apparent clinical independence between schizophrenia and bipolar disorders, has survived for almost a century. On the other hand, it seems evident that DSM-III and DSMIV have contributed decisively to the advances that substantiate the authors' proposals. The progress in research, particularly on molecular genetics, has now set the stage for the development of a new classification. It will have to offer clear validators that, according to the authors, "should allow us to identify the biological systems that are involved in disease pathogenesis". The debates in the field of psychiatric diagnosis are among the most lively and productive, both theoretically and heuristically. It is rather predictable that they will continue for years and decades to come. The etiological insufficiencies are echoed by phenomenological insufficiencies. The categorical versus dimensional debate thrives in the realm of terminological ambiguities, gray areas in the clinical ambit, or the impact of demographic variables, developmental cycles, comorbidities, and cultural variations (2). Nowadays, with DSM-V in the horizon, there is no question that the dimensional view will gain ground, and that genetic concepts will have a stronger impact. Yet, issues such as a multiaxial approach, physical concomitants, disability, quality of life or sociocultural environment will have to be considered as well. Therefore, a purely neurobiological approach to psychiatric diagnosis would still be incomplete. The complexity of human beings suffering from mental illnesses surpasses the lofty aspirations of clinicians and researchers. The authors suggest - and rightly so - that family, twin linkage and association studies have demonstrated the shortcomings of the dichotomous classification. Bipolar disorder and schizophrenia are but two components of a spectrum that apparently can be more carefully and elegantly delineated on the basis of genes, loci and haplotypes, coding specific susceptibilities, or explaining unique clinical characteristics. A big part of the argument is the existence of "mixed features" in many patients. Polypharmacy, in the treatment of not only major psychoses but practically all types of psychiatric conditions, is a contemporary phenomenon that deserves more studies. Craddock and Owen stop short of suggesting that practically all those conditions, and not only the "major" psychiatric disorders, should be included in a "mixed" space. And this is one of the most fascinating features of their work. Schizoaffective disorder was the first American contribution to psychiatric nosology (3). It embodied a bold break from the hierarchical principle sponsored by Jaspers as a perpetuation of the Kraepelinian creed. In turn, the schizoaffective disorder is one vivid example of the trials and tribulations of psychiatric nosologies. Its existence as a valid diagnostic entity is questioned even by Craddock and Owen. They advocate a finer phenomenological approach to detect clinical nuances that can justify not only the use of the term, but the validity of the concept. This goes beyond the "mood incongruent delusions" model (4), the exclusion of depressive states in established schizophrenia, or the mood incongruence "explainable" in the context of a bipolar mood psychosis (5). Yet, some would still rather readily embrace the idea that schizoaffective disorder represents a "heterogeneous collection of interforms" (6). It may be wishful thinking to consider it as a "lifetime diagnosis", particularly considering its well-known instability (7). We all want new psychiatric classifications possessing all the advantages that Craddock and Owen postulate. Presumably, they agree with the resurgence of concepts such as endophenotype (8). More explicitly, they agree with concepts such as spectrum, syndrome, or even dimensions. By the same token, they recognize the value of a descriptiveclassificatory approach, as they used it to develop their Bipolar Affective Disorder Dimension Scale (BADDS). Would it not be more conceptually sound and clinically pragmatic to think of a behavioral continuum going from being "just different" to the most severe psychotic pictures? That is, essentially, a Popperian approach (9), opposite to Kuhn's life and death of paradigms. This eclectic view would tell us that, together with "unraveling the biological basis of disorders," we should accept, like Craddock and Owen state in their paper, that there may be "syndromes" with a discrete biological basis, but also conditions that are better conceptualized on a continuum. Paradigms die, but they don't die acute deaths, they languish. It is rather a long-term, step-by-step process. Comprehensiveness, balance, and harmony are essential ingredients of a good psychiatric (and medical) diagnosis. Clinical usefulness requires not only biological validity. From Kandel (10), we have learned that genetic expressiveness can be changed by external factors, such as psychotherapy. From Eisenberg (11), we know that learning more about biology will hopefully allow more specific non-biological interventions. From Kendler (12), that there is something called "explanatory pluralism". And, from Popper, we know that a continuous search for the truth, away from dogmas, is the only guarantee of individual and collective freedom.