More than 100 years ago Kraepelin proposed a very practical and persuasive solution to a long-standing problem in clinical psychiatry. He proposed to reduce heterogeneity by splitting the perplexing variety of psychopathological signs and symptoms, of patterns of deviant behavior and experiences, of short- and long-term course and outcome of functional disturbances into two major groups: schizophrenia (dementia praecox) and affective disorders (manic-depressive illness) (1). In this way, he created the so-called ‘Kraepelinian dichotomy’, which turned out to be clinically useful for subsequent decades. However, he himself got skeptical subsequently (2) if this simplistic solution really worked in practice as the number of ‘cases in-between’ were too numerous.
About 70 years ago, the concept of schizoaffective disorders emerged from difficulties in practicing Kraepelin's dichotomy by separating schizophrenia and affective disorders. In 1933, Kasanin first coined this term (3). Although originally related to ‘reactive psychoses’ in the Scandinavian tradition (4), the term became transformed to indicate the intraindividual co-occurrence of both severe affective as well as severe psychotic syndromes, which did not fit in either of Kraepelin's categories.
The widespread use of this term reflected the clinical need to consider border-cases separately. Many clinicians are probably motivated to use this category because of implications on the course of illness. However, qualitative inter-class differences cannot be detected: the most recent outcome study (5) saw a less poor outcome in schizoaffective disorders compared with schizophrenia, but it was difficult to distinguish schizoaffective and mood disorders with psychotic symptoms; a progressively worsening intermediate course was reported for both diagnostic groups. Thus, a dimensional view of schizoaffective outcome is recommended.
In contrast to its clinical popularity, research investigations in this diagnostic category – although operational definitions became available – remained relatively rare as it becomes evident from a PubMed search (search terms in titles: schizoaffective disorder = 230 citations; schizophrenia = 13.297; bipolar disorder = 2.355; during a 10-year period 1995–2005). If this category became a research topic at all, it was a border-category of schizophrenia and/or affective disorders. Thus, the biological basis and the nature of this category ‘in-between’ remained obscure. Several reasons might account for this fact.
An unequivocal definition of schizoaffective disorder was never attained. For example, the concepts of ICD-10 and DSM-IV strongly differ by the criterion of simultaneity or temporal contiguity. The available diagnostic definitions include so complex criteria that the reliability is relatively low (6). Thus, it does not come as a surprise that most cases with a schizoaffective episode change this diagnosis in subsequent episodes (7). Furthermore, both most widely used diagnostic manuals propose criteria which are fully different from the clinical conventions. This is now demonstrated by a careful diagnostic re-evaluation of a representative Danish in-patient sample (n = 59) with the diagnosis of schizoaffective disorder by Vollmer-Larsen et al. (8): not a single patient fulfilled either the DSM-IV or the ICD-10 criteria (full criteria) for schizoaffective disorder. The vast majority of cases were allocated either to schizophrenia or to affective disorders (ICD-10), both by the rater of the clinical records or by an automatic OPCRIT algorithm.
This observation is important because the basic assumption for proposing the diagnostic entity of schizoaffective disorders is losing its validity. At the starting point for this diagnostic category ‘in-between’ schizophrenia and bipolar affective disorders were assumed to be due to two distinct disease processes. Doubts in this unproven hypothesis emerged already in the 1970s. Thus, the relationship between depression and schizophrenia has been studied in a variety of contexts in the past. For example, it was recognized that (i) postpsychotic depression was a common phenomenon, and (ii) postpsychotic depression was often preceded by depression, already at the beginning of the psychotic episode but overseen by the clinician [e.g. (9)]. Very recently, a most carefully conducted retrospective epidemiological study reported depressive symptoms and syndromes to be very common precursors of the first negative and psychotic symptoms in subjects developing schizophrenia later-on (10); it was convincingly concluded that depression presents an integral part or even the basic fundament of schizophrenia (10). In this perspective, schizoaffective disorders cannot be considered as a distinct disease entity between the two extremes of Kraepelin's dichotomy. This conclusion also goes together with recent family studies. In a huge case-register in Denmark schizoaffective disorders did not ‘breed true’, and a family history of schizoaffective disorders did not only increase the risk for schizoaffective disorder, but also for schizophrenia and affective disorder by a similar magnitude (11).
An increasing number of family and twin studies report that intrafamilial cosegregation and concordance of schizophrenia and affective disorders are more common than expected by chance and point at shared genetic basis (12). Thus, on a clinical level the overlap between the syndromes of schizophrenia and affective disorders are too broad to be captured by the intermediate diagnosis of schizoaffective disorders.
It might be argued that clinical phenomenology is too unspecific to clearly differentiate disease processes on a pathophysiological or molecular level. Can the prototypes schizophrenia and affective disorders be clearly distinguished on a neurobiological basis? Yet, they cannot! (13). Multiple neuropathological, biochemical and genetic communalities between schizophrenia and affective disorders (especially bipolar) were also recently detected, which add to the symptomatic overlap. Recently, common susceptibility genes such as NRG1, G72/G30 or DISC1 were detected to impact on schizophrenia, affective disorders as well as schizoaffective disorders (14). In addition to these communalities, both disorders also reveal diagnosis-specific etiological factors (as the susceptibility gene DTNBP1 for schizophrenia). Taken together, there is growing evidence that a substantial proportion of etiological factors is shared between schizophrenia and bipolar disorder; the contribution of these common determinants is particularly strong in the symptomatic interface, especially in schizoaffective disorders. In this perspective, schizoaffective disorders reflect a quantitative variation in the common etiological and pathophysiological underground of schizophrenia and affective disorders.
In summary, the historical starting point of the concept of schizoaffective disorders is not valid any more. The diagnosis ‘schizoaffective disorder’ has not yet been unequivocally defined after more than 70 years, the available concurrent diagnostic definitions are not reliable. The most recommended diagnostic definitions in ICD-10 and DSM-IV even lack face validity because they do not fit with clinical conventions.
Do we need this category any more? Is it more appropriate to broaden the concepts of schizophrenia and bipolar disorder even more and concede that etiological communalities might come up as symptomatic overlaps? Or is it even more appropriate to discard categorical diagnostic concepts and substitute them by dimensions: a psychotic, a manic and a depressive one, which allow graduations and overlaps?
Currently, these questions are open to discussion. The task forces for new versions of the DSM- and ICD-diagnostic systems and manuals have to consider these recent insights and developments. They would be badly advised if they would just continue the historical and current concepts of schizoaffective disorders into the future.