Frederick K. Goodwin, MD, is with the Center for Neuroscience, Medical Progress, and Society; Department of Psychiatry, The George Washington University Medical Center, Washington, DC. S. Nassir Ghaemi, MD, is with the Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston.
Dr. Goodwin and Dr. Gaemi have disclosed no relevant financial relationships.
Our understanding of schizoaffective disorder can be organized in five different models (see Sidebar, page 170). One approach holds that schizoaffective disorder is its own illness, separate from others, as appears to be the case superficially by its separate diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV).1 A second model holds that schizoaffective disorder represents a middle clinical picture on a psychotic continuum that extends from bipolar disorder to schizophrenia; in other words, this model rejects the Kraepelinian dichotomy of bipolar disorder and schizophrenia.2,3 A third model argues that schizoaffective disorder represents the comorbidity of affective disorders and schizophrenia, thereby maintaining the Kraepelinian dichotomy and explaining overlap symptoms as chance co-occurrence.4 A fourth theory views schizoaffective disorder as basically a variant of bipolar disorder,5 and a fifth sees schizoaffective disorder as a variant of schizophrenia.6
Five Models of Schizoaffective Disorder
A separate illness
An intermediate form on the continuum of psychosis
Comorbidity of schizophrenia and affective disorders
A more severe variant of bipolar disorder
A less severe variant of schizophrenia
Phenomenology of Schizoaffective Disorder
This is the aspect of the schizoaffective category that receives the most attention from clinicians. From this perspective, the term “schizoaffective” simply applies to those individuals with continuous psychotic and mood symptoms. Unlike mood disorders, psychotic symptoms are not brief or confined to the severe stages of either mania or depression. Unlike schizophrenia, mood symptoms remain prominent. Clinically, many patients seem to fall into this overlap region. Indeed, Kraepelin himself observed that many patients had such overlap of manic-depressive and dementia praecox symptoms.7,8 Hence, the fact that such overlap occurs is almost universally accepted, even by Kraepelin, who originated the idea that mood and psychotic disorders differ.
By itself, the presence of overlap does not invalidate the diagnoses of schizophrenia and mood disorders. This is partly because phenomenology is only one of four diagnostic validators.9 This is also partly because a difference in symptoms is not an all-or-nothing phenomenon. In other words, to say that schizophrenia and mood disorders differ in symptoms is not to say that they never overlap.10 It only means that they usually do not overlap. Indeed, some well-conducted symptom prevalence studies4 have shown that patients with mood and psychotic symptoms tend to differentiate into two big groups, one with mainly mood symptoms and one with mainly psychotic symptoms, although there is some overlap.
It is sometimes argued that the mere existence of schizoaffective disorder is counter to the Kraepelinian dichotomy of schizophrenia and mood disorders.11 As should be clear from the above considerations, this is not the case. Some overlap is expected, and symptoms are only one aspect of diagnostic validation.10 To refute the Kraepelinian diagnostic schema, one would also need to look at genetic, course, and treatment response data.9
Schizoaffective disorder is not found mainly in families of people with schizoaffective disorder.12 Rather, various studies suggest a unique pattern. In some studies of families of people with bipolar disorder, there is an increased prevalence of schizoaffective disorder, bipolar type.5 In some family studies of schizophrenia, there is an increased prevalence of schizoaffective disorder, depressed type.6,13 In a number of well-executed studies comparing both major groups, schizoaffective disorder is more prevalent in families of people with bipolar disorder or schizophrenia than in control populations or in families of people with schizoaffective disorder.12,14
These results are consistent with a number of possibilities. In some people, 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. In still others, because it seems to run in families of people with both schizophrenia and bipolar disorder, only two explanations seem possible: 1) Schizoaffective disorder may indeed exist as part of one continuum rather than separate diagnostic entities; or 2) schizoaffective disorder may simply represent the incidental co-occurrence of schizophrenia and bipolar disorder (or unipolar depression) at the same time, just as one might have diabetes and asthma at the same time.4 Therefore, the genetics of schizoaffective disorder mainly argues against the concept of a separate illness, but the four other possibilities remain open.
These findings again are consistent with the four remaining models. If there is only one continuum of psychotic illness, bipolar disorder may lie at the less extreme end, schizophrenia at the more extreme end, and schizoaffective disorder in between. Therefore, schizoaffective disorder might have an intermediate course.15–18 On the other hand, if it represents a comorbidity, it may be that the more severe outcome of schizophrenia is leavened by the coexistence of bipolar disorder so that an intermediate outcome would be observed in schizoaffective disorder.16–19 Further, if the bipolar type of schizoaffective disorder is a variant of bipolar disorder, it would be expected to have a worse outcome than bipolar disorder but better than schizophrenia.15,20 Also, if the unipolar depressed type of schizoaffective disorder is a variant of schizophrenia, one would expect a better outcome than schizophrenia, given the more responsive affective illness factor.21,22
In summary, the course studies are similar to the genetic studies in supporting all of the models, except the concept of a separate illness.
This is the least-specific diagnostic validator, and, indeed, it has become even less specific since the advent of the atypical antipsychotics, which combine effects on mood regulation with their antipsychotic profile and which are effective therapeutic agents in both bipolar disorder and schizophrenia. There are few studies of treatment of schizoaffective disorder, but it is generally thought that these patients require long-term treatment with antipsychotic agents, as in schizophrenia, and long-term treatment with either mood stabilizers (bipolar type) or antidepressants (unipolar depressed type) as in the corresponding affective disorders.23–27 Again, this treatment response pattern is consistent with all four models except the separate illness model.
What are we to conclude? What appears most clear is that, its appearance in DSM-IV notwithstanding, there is no evidence that schizoaffective disorder represents a separate illness distinct from schizophrenia and bipolar disorder. Studies of symptomatology vary. However, some important and well-conducted studies tend to find a difference in symptoms in psychotic and affective populations that more or less fall along the lines of Kraepelin’s dichotomy of schizophrenia and affective disorders. Although there are overlapping areas, such overlap is empirically expected in a real-world population of individual patients. Therefore, studies of phenomenology can be interpreted as leaning against the single-psychosis continuum model.
If schizoaffective disorder represents a comorbidity of schizophrenia and bipolar disorder, one would expect an epidemiological prevalence that is significantly lower than the other two. Indeed, epidemiological prevalence studies find that only 0.5% of the population meets diagnostic criteria for schizoaffective disorder, a prevalence much lower than that of schizophrenia (1%) or bipolar disorder (1.2%–1.5%).
Clinicians frequently use the schizoaffective diagnosis to describe psychotic symptoms in bipolar patients or, less commonly, mood symptoms in schizophrenic patients. This overly broad use of the term schizoaffective was illustrated in a patient referred to one of us as schizoaffective. However, his manic and depressive episodes, both of which included periods of florid psychosis, responded prophylactically to a combination of lithium and valproate, plus occasional short-term use of an atypical antipsychotic. After three stable decades on the lithium-valproate combination, he developed renal complications requiring progressive reduction in his lithium dose. When the lithium dose fell below 75 mg/day, psychotic symptoms recurred for the first time in years; when lithium was reestablished at only 75 mg, the psychotic symptoms disappeared. Clearly, this patient is not schizoaffective but rather has severe psychotic symptoms integral to bipolar illness.
How might we integrate this vast and complex literature with our own clinical experience?
Some patients experience predominantly bipolar mood symptoms, with psychotic symptoms occasionally persisting beyond the mood episode. Such patients 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, perhaps, somewhat less aggressive antipsychotic treatment. They have a relatively good prognosis.
Some patients experience mainly psychotic symptoms, with some excess of major depressive symptoms. These people 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 perhaps somewhat less aggressive antidepressant treatment. Their prognosis, although better than in schizophrenia, is usually only fair. This group is to be distinguished from schizophrenia with comorbid major depressive episodes. In the latter case, a patient may experience one or two or only a few depressive episodes that are brief, spaced apart, and often psychosocially triggered. In schizoaffective disorder, depressed type, depressive symptoms are more frequent and more persistent, although still less persistent than the psychotic symptoms.
Some people 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.
In dealing with a patient with more or less persistent mood and psychotic symptoms, we feel it will be helpful for the clinician to categorize the patient in one of these three groupings as a way of organizing one’s thinking about rational treatment approaches.
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- Craddock N, O’Donovan MC, Owen MJ. Psychosis genetics: modeling the relationship between schizophrenia, bipolar disorder, and mixed (or “schizoaffective”) psychoses. Schizophr Bull. 2009;35(3):482–490. doi:10.1093/schbul/sbp020 [CrossRef]
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- Maj M, Starace F, Pirozzi R. A family study of DSM-III-R schizoaffective disorder, depressive type, compared with schizophrenia and psychotic and nonpsychotic major depression. Am J Psychiatry. 1991;148(5):612–616.
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- Trede K, Salvatore P, Baethge C, Gerhard A, Maggini C, Baldessarini RJ. Manic-depressive illness: evolution in Kraepelin’s Textbook, 1883–1926. Harv Rev Psychiatry. 2005;13(3):155–178. doi:10.1080/10673220500174833 [CrossRef]
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