The question of the nosological status of schizoaffective disorders remains one of the most controversial issues of clinical psychiatry. There are, in fact, at least five different hypotheses about the nature of these disorders: • that they are always variants of schizophrenia, • that they are always variants of major affective disorders, • that they represent a “third psychosis” distinct from both schizophrenia and manic-depressive illness, • that they find their place in the intermediate position of a “continuum” whose poles are represented by the typical forms of schizophrenia and manic-depressive illness, • that they result from the simultaneous occurrence of a true schizophrenia and a true manic-depressive illness in the same patient. The last of these hypotheses can hardly be accepted, since it would predict an annual frequency of schizoaffective disorders of about 2 per 108, compared to the actual frequency of 2 per 105. Of the remaining four hypotheses, the first two are consistent with the Kraepelinian “dichotomic” paradigm, whereas the third and the fourth contradict this paradigm. The results of empirical investigations (that is, of family studies, outcome studies and studies on response to drug treatments in schizoaffective patients) do not provide a full support to any of the above hypotheses. What empirical evidence seems to show, instead, is that schizoaffective disorders represent a heterogeneous group of syndromes. Part of these disorders can be interpreted, upon close scrutiny, as variants of either of the major psychoses (for instance, bipolar schizoaffective States appear to be closely allied to major affective disorders). There seems to be, however, a subpopulation of schizoaffective patients which escapes the Kraepelinian dichotomic model.

The author has reviewed evidence generated during the past decade at the University of Tennessee and other affective disorders research units in support of a psychobiologic understanding of affective disorders as the final common pathway of various psychologic and biologic factors that impinge on midbrain centers of reward, circadian rhythms, and psychomotor function. In this model, inherited temperamental instability, based on a persistent diencephalic abnormality, provides the fertile soil for the development of major affective episodes. The pathogenesis of full-blown affective episodes is then the product of multiple factors, none of which alone is a necessary or sufficient cause. It is submitted that this unified theory, in bridging psychosocial and biologic factors, provides the most comprehensive etiologic understanding of depressive illness permitted by current data. Clinical implications of the theory are discussed.