Is Schizoaffective Disorder Really a Distinct Illness?

The understanding of schizoaffective disorder can be organized into five different theories. One approach holds that schizoaffective disorder is its own illness, separate from others, as appears to be the case superficially from its separate diagnostic criteria in DSM-IV. A second model holds that schizoaffective disorder represents a middle clinical picture on a psychotic continuum extending from bipolar disorder to schizophrenia — in other words, this model rejects the Kraepelinian dichotomy of bipolar disorder and schizophrenia. A third model argues that schizoaffective disorder represents the comorbidity of affective disorders and schizophrenia, thereby maintaining the Kraepelinian dichotomy and explaining overlapping symptoms as chance co-occurrence. A fourth theory views schizoaffective disorder as essentially a variant of bipolar disorder, and a fifth sees it as a variant of schizophrenia.Nassir Ghaemi, MDMany clinicians unconsciously take the first approach. They assume that because “schizoaffective disorder” is written as two words on a page — especially within DSM criteria — those two words must represent a “real” thing: a real illness in the real world, separate and apart from other illnesses. This is a common human inference, flowing from the assumption that naming something makes it exist. Of course, we name many things that do not exist — sometimes fantasies, sometimes mere falsehoods. This text has discussed the rationale for why many DSM labels do not correspond to “real” diseases or illnesses, but rather represent social constructs of the American psychiatric profession. Separate from that point, we should keep in mind that any diagnostic label represents, first and foremost, only a clinical picture. Whether that clinical picture reflects a different disease from another clinical picture is a separate question. Readers should therefore understand that we’re discussing a clinical picture: patients who present with a mixture of delusions or hallucinations alongside mood symptoms. What that clinical picture means — whether it constitutes a separate illness or not — is the question this article addresses.Figure 1. The five candidate models of schizoaffective disorder.Table 1. The Five Models of Schizoaffective DisorderModelDescription1. Separate illness Its own distinct disease, as DSM criteria imply 2. Single psychotic continuum A midpoint between bipolar disorder and schizophrenia; rejects the Kraepelinian dichotomy 3. Comorbidity Chance co-occurrence of affective illness and schizophrenia, maintaining the Kraepelinian dichotomy 4. Variant of bipolar disorder A more severe form of bipolar illness 5. Variant of schizophrenia A milder form of schizophrenia Phenomenology At the level of observation, the term “schizoaffective” simply applies to individuals with continuous psychotic and mood symptoms. Unlike mood disorders, psychotic symptoms here are not brief; and unlike schizophrenia, mood symptoms are not absent. Clinically, many patients seem to fall into this overlap region. In fact, the original paper describing such patients was published in 1933. Kraepelin himself observed that a good number of patients showed this overlap of manic-depressive and dementia praecox symptoms. The occurrence of such overlap is thus almost universally accepted, even by Kraepelin, who originated the very idea that mood and psychotic disorders differ. By itself, the presence of overlap does not invalidate the diagnoses of schizophrenia and manic-depressive illness. This is partly because phenomenology is only one of four diagnostic validators, alongside genetics, course of illness, and treatment effects or biological markers. It is also partly because a difference in symptoms is not an all-or-nothing phenomenon. To say that schizophrenia and mood disorders differ in symptoms is not to say that they never overlap, only that they usually do not. Indeed, some well-done symptom-prevalence studies have shown that patients with mood and psychotic symptoms tend to separate into two large groups, one with predominantly mood symptoms and one with predominantly psychotic symptoms, with some overlap between them (Figure 2).Figure 2. Schizoaffective illness as an overlap condition between schizophrenia and mood disorders. It is sometimes argued that the mere existence of schizoaffective disorder is a counterexample to the Kraepelinian dichotomy of schizophrenia and affective illness. As the considerations above make clear, this is not the case: Some overlap is expected, and symptoms are only one aspect of diagnostic validation. To refute the Kraepelinian diagnostic schema, one would also need to examine the data pertaining to genetics, illness course, and treatment response. Genetics If schizoaffective disorder were a separate illness in its own right, one would expect it to breed true in families. Almost all genetic studies, however, are consistent in showing that it does not. Schizoaffective disorder is not found mainly in families of persons with schizoaffective disorder; rather, various studies suggest a different pattern. In families of persons with bipolar disorder, there is an increased prevalence of schizoaffective disorder, bipolar type. In families of persons with schizophrenia, there is an increased prevalence of schizoaffective disorder, depressed type. And in a number of well-executed studies comparing both groups, schizoaffective disorder is more prevalent in families of persons with schizophrenia or bipolar disorder than in control populations, or than in families of persons with schizoaffective disorder itself. These results are consistent with several possibilities. In some persons, schizoaffective disorder, bipolar type, appears to be a more severe variant of bipolar disorder. In others, schizoaffective disorder, depressed type, appears to be a less severe variant of schizophrenia. Because the condition seems to run in families of persons with both schizophrenia and bipolar disorder, two further explanations remain possible:Either there is in fact no dichotomy between bipolar disorder and schizophrenia, and no meaningful distinction can be drawn among psychotic disorders, which should instead be seen as one continuum; orSchizoaffective disorder simply represents the comorbidity of having, by chance, both schizophrenia and bipolar disorder (or unipolar depression) at the same time — much as one might have diabetes and asthma at the same time.The genetics of schizoaffective disorder argue against the concept of a separate illness, while the four other possibilities remain open. Illness Course Studies of the course of schizoaffective disorder are fairly consistent: The illness runs a course more severe than bipolar disorder but less severe than schizophrenia. Further, schizoaffective disorder, depressed type, shows less recovery than schizoaffective disorder, bipolar type. These findings, again, are consistent with the four remaining models. If there is a single continuum of psychotic illness, bipolar disorder may lie at the less severe end, schizophrenia at the more severe end, and schizoaffective disorder in between — which would explain its intermediate course. Alternatively, if schizoaffective disorder represents comorbidity, the more severe outcome of schizophrenia might be leavened by the coexistence of bipolar disorder, again producing an intermediate outcome. Further, if the bipolar type is a variant of bipolar disorder, it would be expected to have a worse outcome than bipolar disorder but a better one than schizophrenia. And if the depressed type is a variant of schizophrenia, one would expect a better outcome than schizophrenia, given the more treatment-responsive affective component. In sum, the course studies, like the genetic studies, support all the models except the concept of a separate illness. Treatment Response Treatment response is the least specific diagnostic validator, but it remains useful. There are few dedicated treatment studies of schizoaffective disorder, but it is generally thought that these patients require long-term treatment with antipsychotic agents, as in schizophrenia, together with long-term treatment with either mood stabilizers (bipolar type) or antidepressants (depressed type), as in the corresponding affective disorders. This treatment pattern, again, is consistent with all four models except the separate-illness model.Table 2. Diagnostic Validators Applied to Schizoaffective DisorderValidatorKey findingModel(s) weakenedGenetics Does not breed true; elevated in families of bipolar probands (bipolar type) and schizophrenia probands (depressed type) Separate illness Illness course Intermediate severity between bipolar disorder and schizophrenia; depressed type shows less recovery than bipolar type Separate illness Treatment response Requires long-term antipsychotics plus mood stabilizers or antidepressants, mirroring both parent conditions Separate illness Phenomenology and prevalence Symptom-based studies broadly separate into two groups along Kraepelinian lines; prevalence under 0.5%, far below either parent condition Separate illness; single psychotic continuum (weakened) And the Answer Is… It appears clear that — its appearance in DSM-III through DSM-5 notwithstanding — there is no evidence that schizoaffective disorder represents a separate illness distinct from schizophrenia and bipolar disorder. Studies of symptomatology vary, but some important, well-done studies find a difference in symptoms between psychotic and affective populations that more or less follows Kraepelin’s dichotomy of schizophrenia and affective disorders. While overlap areas exist, such overlap is empirically expected in any real-world population. Studies of phenomenology can therefore be read as leaning against the single-psychosis-continuum model. If schizoaffective disorder represents a comorbidity of schizophrenia and bipolar disorder, one would expect an epidemiologic prevalence significantly lower than either parent condition — because chance comorbidity should not be overly frequent. Clinical impressions notwithstanding, epidemiologic prevalence studies do indeed show that schizoaffective disorder is very infrequently diagnosed in the general community, at a level of less than 0.5% — much lower than the accepted prevalence rates for schizophrenia (about 1%) and bipolar disorder (about 2%-4%). Table 3. Epidemiologic PrevalenceConditionApproximate prevalenceSchizophrenia About 1% Bipolar disorder About 2%-4% Schizoaffective disorder Less than 0.5% Three Final Models These considerations suggest that the remaining three models are the ones consistent with the available diagnostic research (Figure 3). Some persons experience mainly bipolar mood symptoms, with only some excess of psychosis. These persons are diagnosable with schizoaffective disorder, bipolar type, seen as a severe variant of bipolar disorder. By and large, they need aggressive mood-stabilizer treatment and somewhat less aggressive antipsychotic treatment. They have a relatively good prognosis. Some persons experience mainly psychotic symptoms, with only some excess of unipolar depressive symptoms. These persons are diagnosable with schizoaffective disorder, depressed type, seen as a somewhat less severe variant of schizophrenia. By and large, they need aggressive antipsychotic treatment and somewhat less aggressive antidepressant treatment. Their prognosis, though better than in schizophrenia, is usually only fair. Some persons appear to be truly schizoaffective: They experience psychotic and affective symptoms in more or less equal amounts. This group represents the true comorbidity of schizophrenia and affective disorders; has an intermediate outcome; and requires aggressive, persistent, long-term treatment with both antipsychotic agents and either mood stabilizers or antidepressants. If clinicians attempt to differentiate apparently schizoaffective patients along these lines, they will find that these three groupings account for most of what they observe.Figure 3. Three clinically observed varieties of schizoaffective illness. Table 4. The Three Surviving Subtypes in Clinical PracticeSubtypeSymptom balanceInterpretationTreatment emphasisPrognosisSchizoaffective, bipolar type Mainly bipolar mood symptoms, some excess psychosis Severe variant of bipolar disorder Aggressive mood stabilizer; less aggressive antipsychotic Relatively good Schizoaffective, depressed type Mainly psychotic symptoms, some excess unipolar depression Milder variant of schizophrenia Aggressive antipsychotic; less aggressive antidepressant Usually only fair True schizoaffective (comorbid) Roughly equal psychotic and affective symptoms True comorbidity of schizophrenia and affective illness Aggressive, persistent, long-term treatment with both antipsychotics and mood stabilizers/antidepressants Intermediate Nassir Ghaemi, MD, MPH, is founder of Psychiatry Letter, and a lecturer on psychiatry at Harvard Medical School, Cambridge Health Alliance, in Boston. Dr Ghaemi is also an employee at Bristol Myers Squibb. The views presented here are his own and do not necessarily reflect those of his employers.