Is Schizoaffective Disorder a Useful Diagnosis?

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Is Schizoaffective Disorder a

Useful Diagnosis?

Stephan Heckers, MD

Corresponding author Stephan Heckers, MD

Vanderbilt University Psychiatric Hospital, 1601 23rd Avenue South, Room 3060, Nashville, TN 37212, USA.

A diagnosis of schizoaffective disorder is frequently used to describe a psychotic person with signifi cant symptoms of depression and/or mania. The word schizoaffective was introduced by Jacob Kasanin in 1933 and has appeared in all editions of the DSM since 1952. However, the current DSM-IV-TR diagnosis of schizoaffective disorder is not reliable and is of limited clinical utility. The validity is built primarily on the prediction of course and outcome and on emerging fi ndings from genetic and neuro-biological studies. This review of the current status of schizoaffective disorder concludes with several suggestions for a revision of the diagnosis within a categorical or dimensional nosology of psychotic and affective disorders.

Introduction

Kasanin [1] introduced the term acute schizoaffective psychoses to describe nine patients who were initially diagnosed with dementia praecox but who achieved full recovery after several weeks of acute psychosis and affec-tive symptoms. All editions of the DSM have included the term schizoaffective, but the diagnostic concept changed over time, especially with the introduction of diagnostic criteria in the DSM-III-R.

Many clinicians and patients consider schizoaffective disorder to be an adequate diagnostic label for a person who is struggling with signifi cant psychotic and affective symptoms. However, there are serious concerns about the reliability, clinical utility, and validity of the diag-nosis. Should we continue or discontinue schizoaffective disorder as a diagnostic category? This review evaluates the current concept of schizoaffective disorder, explores recent literature, and proposes options for a revision of the diagnosis.

Schizoaffective Disorder in the DSM-IV-TR

There are four diagnostic criteria (A–D) for the diagnosis schizoaffective disorder in the DSM-IV-TR (Table 1). Let us review how a clinician or researcher makes the diagno-sis of schizoaffective disorder (after an organic etiology has been excluded, usually with a thorough physical and neurological examination, a review of the medical history, and a set of laboratory tests).

First, the diagnosis will only be considered if a person has prominent psychotic and affective symptoms. The psychosis has to be severe enough to meet criterion A for schizophrenia, and the person needs to have signifi cant affective symptoms during the same period of psychosis. This requires suffi cient clinical data for a period of at least 1 month. This fi rst step in the diagnostic process has thus far identifi ed a person with an affective psychosis.

Second, schizoaffective disorder needs to be distin-guished from a primary mood disorder with psychotic symptoms. This is achieved via criterion B, which can be rephrased as follows: if a period of nonaffective psycho-sis lasting at least 2 weeks (during the same time period considered for criterion A) can be identifi ed, then the diagnosis of a primary mood disorder can be excluded, and schizoaffective disorder should be considered. With criterion B, the DSM-IV-TR limits the diagnosis of schizoaffective disorder to the sequential type and pro-vides a clear demarcation from severe psychotic bipolar disorder. In contrast, ICD-10 also recognizes the concur-rent type of schizoaffective disorder [2].

Finally, the DSM defi nition of schizoaffective disorder goes one step beyond the exclusion of psychotic mood dis-orders. It also excludes cases that fulfi ll criteria A and B but do not have prominent mood symptoms. For example, a person with a 20-year history of schizophrenia and only two clear episodes of major depression will be excluded, as the mood symptoms did not occupy a substantial por-tion of the total illness durapor-tion.

It is important to realize that the proper diagnosis of schizoaffective disorder requires access to longitudinal clinical data. This is different from many other DSM diagnoses, which are based on the evaluation of the here-and-now or brief periods of time (eg, 1 week for manic episode, 2 weeks for major depressive episode). Such lon-gitudinal clinical data need to be assessed for temporal overlap (criterion B) and relative distribution over time

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(criterion C). What does this mean for the diagnostic pro-cess? Most clinical and research settings do not allow for the direct observation of 4 or 6 weeks, but the diagnosis of schizoaffective disorder requires 1 month of data for criterion A and 2 weeks for criterion B. Therefore, most diagnoses of schizoaffective disorder must rely on accurate autobiographic memory of the patient, collateral infor-mation, or access to medical and mental health records. However, even if such data can be obtained and criteria A and B are met, it is diffi cult to accurately gauge the correct portion of illness with prominent mood symptoms. This is particularly challenging in patients who have suffered from a psychotic illness for many years. Finally, criterion C does not include a quantitative threshold and leaves it to the clinician to judge what constitutes a “substantial portion” of the illness duration.

The History of Schizoaffective Disorder

in the DSM

The authors of the DSM have wrestled with the clinical challenge of accurately diagnosing patients with an affec-tive psychosis. In the process, the diagnostic concept of schizoaffective disorder has evolved throughout the four editions and two revisions of the DSM.

The DSM-I does not use the diagnosis of schizophre-nia. Instead, it refers to schizophrenic reaction. One of the subtypes is schizophrenic reaction, schizoaffective type, about which the authors state the following [3]:

This category is intended for those cases show-ing signifi cant admixtures of schizophrenic and affective reactions. The mental content may be pre-dominantly schizophrenic, with prolonged elation or depression. Cases may show predominantly affective changes with schizophrenic-like thinking or bizarre behavior … On prolonged observation, such cases usually prove to be basically schizophrenic in nature.

This sets the stage for the current concept of schizoaf-fective disorder as a schizophrenia-like illness.

The DSM-II does use the diagnostic label schizophrenia and includes two subtypes: 1) schizophrenia, schizoaffec-tive type, excited, and 2) schizophrenia, schizoaffecschizoaffec-tive

type, depressed. It holds on to the notion that this “cat-egory is for patients showing a mixture of schizophrenic symptoms and pronounced elation or depression” [4].

The DSM-III introduces the term schizoaffective dis-order but does not propose any diagnostic criteria. The authors anticipate the still-ongoing debate about schizoaf-fective disorder [5]:

Future research is needed to determine whether there is a need for this category and if so, how it should be defi ned and what its relationship is to schizophrenia and affective disorder. The category is retained in this manual without diagnostic cri-teria for those instances in which the clinician is unable to make a differential diagnosis with any degree of certainty between affective disorder and either schizophreniform disorder or schizophrenia.

It appears that the fi rst three editions of the DSM simply addressed the clinical need to provide a diagnostic term for patients who did not fi t into either schizophrenia or bipolar disorder.

The DSM-III-R operationalized for the fi rst time the diagnostic criteria and separated two subtypes: bipolar and depressive type. The manual captures the history and diagnostic challenges well [6]:

The term schizoaffective disorder has been used in many different ways since it was fi rst introduced as a subtype of schizophrenia, and rep-resents one of the most confusing and controversial concepts in psychiatric nosology. The approach taken in this manual emphasizes the temporal rela-tionship of schizophrenic and mood symptoms.

As noted above, this defi nes the sequential subtype of schizoaffective disorder. The authors offer the follow-ing justifi cation for the inclusion of the diagnosis and the defi nition of criteria: “… this description of schizoaf-fective disorder appears to have tentative validity from prognostic, treatment, and family studies as delimiting an entity …” [6]. The three validators mentioned are a chronic course, a prognosis that is “somewhat better than schizophrenia,” and a familial pattern of “increased risk

Table 1. DSM-IV-TR criteria for schizoaffective disorder (abbreviated)

A. An uninterrupted period of illness during which, at some time, there is either a major depressive episode, a manic episode, or a mixed episode concurrent with symptoms that meet criterion A for schizophrenia (ie, at least 2 of 5 symptoms [delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms], each present for a signifi cant portion of time during a 1-mo period).

B. During the same period of illness, there have been delusions or hallucinations for at least 2 wk in the absence of prominent mood symptoms.

C. Symptoms that meet criteria for a mood episode are present for a substantial portion of the total duration of the active and residual periods of the illness.

D. The disturbance is not due to the direct physiologic effects of a substance (eg, a drug of abuse, a medication) or a general medical condition.

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of schizophrenia in fi rst-degree biologic relatives with [schizoaffective disorder].” The DSM-IV introduced the current text to defi ne schizoaffective disorder (Table 1) and included a mixed form of the bipolar subtype but did not change the diagnostic criteria established in the DSM-III-R [7]. There were no further changes in the DSM-IV-TR [8].

Despite listing the “somewhat better” prognosis of schizoaffective disorder in the DSM-III-R as a potential validator, the DSM never embraced Kasanin’s notion of schizoaffective disorder. Clinical features such as phasic course, interepisode recovery, and good outcome were not included as diagnostic criteria. Kasanin’s concept of schizoaf-fective seems to be more in line with bouffée délirante, a French diagnosis of the 19th century, and the current ICD diagnosis of “acute and transient psychotic disorder.”

In summary, the authors of the DSM always acknowl-edged that the borderland of psychotic and affective disorders is more complex than the simple dichotomy of schizophrenia and mood disorder makes us believe, but how does the schizoaffective disorder diagnosis address this complexity?

Reliability and Clinical Utility

Reliability and clinical utility are conditiones sine qua non for the validity and ultimate value of a diagnosis [9•]. First, any psychiatric diagnosis is noisy and subject to potential error. It would be ideal if a patient always received the same diagnosis (by the same rater over time and by differ-ent raters at the same time), but this is usually not the case. Therefore, a diagnostic criterion that minimizes noise in the diagnostic process and increases intra- and interrater reliability is of great value. The introduction of operational-ized criteria in the DSM-III-R and the subsequent increase in reliability are generally considered to be major achieve-ments in recent psychiatric nosology.

Second, criteria need to be practical. A criterion may ensure a highly reliable diagnosis, but it is of limited clini-cal utility if the necessary cliniclini-cal information is diffi cult to obtain. For example, if longitudinal data need to be collected, then the reliability of the diagnosis will depend more on the consistent availability of information over time rather than the reliability of the diagnostic procedure at one point in time.

The DSM-IV fi eld trials provided promising data on the reliability of the criteria for schizoaffective dis-order. A total of 165 patients were studied at different sites, and the interrater (0.48–0.66) and test–retest (0.48–0.56) reliability were deemed to be in the fair to good range [10]. These estimates are at odds with several reports in the literature that have seriously challenged the reliability and clinical utility of the diagnosis of schizoaffective disorder. Nurnberger et al. [11] reported excellent reliabilities for several psychiatric disorders using the algorithms of the Diagnostic Interview for Genetic Studies, except in the case of schizoaffective

disorder, “for which disagreement on estimates of dura-tion of mood syndromes relative to psychosis reduced reliability.” This led to an explicit threshold in the third edition of the Diagnostic Interview for Genetic Studies: mood symptoms needed to be present for at least 30% of the total duration of psychosis to make the diagnosis of schizoaffective disorder. Maj et al. [12] reported low reliability scores for criteria A, B, and C for schizoaffec-tive disorder, with the lowest being 0.29 (Cohen’s !) for criterion C.

The temporal stability of the schizoaffective disorder diagnosis is low. Schwartz et al. [13] reported 6- and 24-month follow-up assessments after an initial assessment at fi rst admission to a psychiatric inpatient facility and found that the diagnoses were stable in 92% of cases for schizophrenia, 83% for bipolar disorder, and 74% for major depression, but only 36% for schizoaffective dis-order. Salvatore et al. [14•] observed 500 fi rst-episode psychotic disorder patients for 2 years and reported a change in the categorical diagnoses in 22.4% of all cases. The major change was an increase in the schizoaffective disorder diagnosis from 0.2% to 12.2% of all cases, pri-marily due to the emergence of newly perceived affective features among those initially diagnosed with a nonaffec-tive psychosis.

Finally, the clinical utility has been questioned. When 59 patients with a discharge diagnosis of schizoaf-fective disorder given by a clinician were re-evaluated by a research team, none of them were found to meet the DSM-IV criteria [15]. Taken together, the sequential nature (criterion B) and the estimation of the duration of mood symptoms over the entire duration of the ill-ness (criterion C) make the DSM-IV-TR defi nition of schizoaffective disorder a challenge even for the most skilled diagnostician.

Validity

The history of the diagnosis of schizoaffective disorder illustrates the different concepts of validity of a psychiatric diagnosis [16,17••,18,19•]. Here I focus on two aspects: course/outcome and genetic/neural mechanisms.

Course and outcome

Patients diagnosed with schizoaffective disorder tend to have a better outcome than patients diagnosed with schizophrenia [20] and a worse outcome compared with those diagnosed with bipolar disorder [21]. A lon-gitudinal 15-year follow-up of schizoaffective disorder patients revealed that at the time of fi rst hospitalization, schizoaffective disorders were distinguishable from both schizophrenia and affective disorders, but long-term out-come of schizoaffective disorder was similar to that of affective disorders [22]. However, course and outcome are not diagnostic criteria for schizoaffective disorder in the DSM. This could explain some of the appeal of schizoaffective disorder in clinical practice, as it avoids a

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prediction of poor outcome and the bias associated with it. This implicit poor-to-good outcome gradient in the DSM (schizophrenia > schizoaffective disorder > affective disorder) is in contrast to the diagnostic system developed by Leonhard [23], which makes explicit and strong out-come predictions for affective psychoses.

Genetic and neural mechanisms

Studies of probands with schizophrenia have revealed an increased risk for schizoaffective disorder in fi rst-degree relatives [19•]. At the same time, studies of probands with schizoaffective disorder have revealed an increased risk for schizophrenia, bipolar disorder, and schizoaffective disorder [24]. This has led some to conclude that schizoaffective disorder is not sim-ply a subgroup of bipolar disorder or schizophrenia but rather a genetic intermediate form. There is now increasing evidence for shared genetic mechanisms of schizophrenia and bipolar disorder. This includes linkage to loci on chromosomes 1q42, 6q22, 8p21, 9q31, 13q32, and 15q14 and the identifi cation of posi-tional candidate genes G72/G30, NRG1, and DISC1, conferring an increased risk for both disorders [19•]. Genome-wide linkage scans in patients with the diag-nosis of schizoaffective disorder have reported signals at 1q42, 22q11, and 19p13 [25]. This has been inter-preted as evidence that some susceptibility genes have specifi city to schizophrenia, others to bipolar disorder, and that some confer risk across the spectrum.

A growing number of studies have identifi ed similari-ties and differences between schizophrenia and bipolar disorder with regard to brain structure, brain function, and cognition. Many of these studies have included schizoaffective disorder diagnoses, often grouped together with schizophrenia. Convergent fi ndings include struc-tural abnormalities of the cerebral cortex [26], abnormal function of "-aminobutyric acid–positive interneurons [27], and impaired cognition [28].

With all this taken together, the diagnosis of schizoaffective disorder has frequent clinical usage as an intermediate between schizophrenia and affective disor-der without compelling validation by outcome, genetic, or neuroscientifi c studies. Where can we go from here? Before we explore options for the DSM-V, we need to review how the diagnosis fi ts into the current nosology of psychotic disorders.

The Major Theoretical Models of Psychosis

Schizoaffective disorder is the result of the Kraepelinian dementia praecox/manic depressive illness dichotomy. According to Kraepelin [29], the two diagnoses are vali-dated by outcome (poor vs good), clinical picture (defi cits of volition, cognition, and affect vs depressive and/or manic episodes with interepisode recovery), and pathology (cor-tical lesion vs unknown or no lesion). However, many clinicians have found it diffi cult to assign a signifi cant

number of patients to either schizophrenia or one of the two major mood disorders. After his retirement, even Krae-pelin [30] himself expressed doubts about whether patients with an affective psychosis could be grouped accurately into either schizophrenia or manic depressive illness. Over the years, there have been three approaches to addressing this nosological challenge.

First, psychotic and affective disorders are dichoto-mous categories. This includes Kraepelin’s original strong position and many variants, giving rise to subtypes such as schizoaffective disorder and defi cit/nondefi cit schizo-phrenia [31] and even more detailed groupings derived from latent-class analysis [32].

Second, psychotic and affective disorders are a con-tinuum. This unitary psychosis model predates Kraepelin and continues to attract interest today. Proponents of this model argue that 1) there is no point of rarity to distin-guish psychotic from affective patients and 2) there are no clear validators such as outcome or disease mecha-nism. Therefore, dimensions (eg, hallucination, delusion, avolition, depression, and mania) should be used to char-acterize patients, not categorical distinctions.

Third, there is neither a dichotomy nor a continuum. Psychotic and affective symptoms can occur in the same patient and in various constellations. Diagnoses are then built upon psychopathology and outcome [23] or on mechanism and treatment response [33].

Within these three nosologies of psychosis, there are several possible defi nitions of schizoaffective disorder:

1. Distinct diagnostic entity (the DSM-IV-TR concept) 2. Variant of schizophrenia or mood disorder 3. Heterogeneous group (some are patients with

schizo-phrenia, some are patients with a mood disorder) 4. Form of concurrent schizophrenia and mood disorder 5. On a continuum between schizophrenia and

mood disorder.

Options for the DSM-V

Considering the current status of the schizoaffective dis-order diagnosis and the major nosological positions, there are at least fi ve options for the DSM-V, each increasingly more radical (Table 2).

Making no changes is not reasonable because the evi-dence reviewed here overwhelmingly favors a change. At a minimum, criterion C must be revised simply because of poor reliability and questionable feasibility. Reliability could be increased by including a quantitative threshold (eg, 30%), but the signifi cant challenge of collecting data for such an assessment would remain. In addition, crite-rion B should be reviewed, as it excludes the concurrent subtype of schizoaffective disorder (which is included in the ICD defi nition of schizoaffective disorder).

As a next step, the diagnosis of schizoaffective dis-order could be removed, leaving schizophrenia, bipolar

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disorder, and major depression in place. Affective psycho-sis could then be described with specifi er criteria (using categories or ordinal rating scales) that would be added to these three diagnoses. This would create three mixed categories (schizophrenia + affective symptoms, bipolar disorder + psychotic symptoms, and major depression + psychotic symptoms) and would in part resemble the fi rst two editions of the DSM, which defi ned schizoaffective disorder as a subtype of schizophrenia. Removing schizoaf-fective disorder without adding specifi ers would not be an improvement because it would ignore the substantial clini-cal overlap between psychotic and mood disorders.

Only a radical change of the current nosology would result in the removal of the diagnosis of schizophrenia (or all diagnostic categories). Such a change would make schizoaffective disorder obsolete. A dimensional diag-nostic system would then be required to capture affective psychosis with multiple dimensions.

Conclusions

The fi fth edition of the DSM provides the opportunity to improve the reliability and clinical utility of the schizoaf-fective disorder diagnosis. Based on the available evidence, we need to revise the current criteria, which have been unchanged since 1987. However, current scientifi c data are not yet suffi cient to defi nitively decide the nosology of affective psychosis.

Acknowledgment

Dr. Heckers is a member of the DSM-V Work Group on Psychotic Disorders. The opinions expressed in this arti-cle do not necessarily refl ect the consensus of the DSM-V Work Group or Task Force.

Disclosure

No potential confl ict of interest relevant to this article was reported.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as:

• Of importance •• Of major importance

1. Kasanin J: The acute schizoaffective psychoses. Am J Psychiatry 1933, 90:97–126.

2. Marneros A: The schizoaffective phenomenon: the state of the art. Acta Psychiatr Scand Suppl 2003, 418:29–33. 3. American Psychiatric Association: Diagnostic and Statistical

Manual of Mental Disorders, edn 1. Washington, DC: American Psychiatric Association; 1952.

4. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, edn 2. Washington, DC: American Psychiatric Association; 1968.

5. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, edn 3. Washington, DC: American Psychiatric Association; 1980.

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This article reviews the theoretical advantages of a dimensional assessment of psychiatric patients over the current categorical assessment in the DSM-IV-TR. It proposes adding categorical diagnoses in the DSM-V.

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Table 2. Options for the diagnosis of schizoaffective disorder in the DSM-V

1. No change

2. Revise the diagnostic criteria

Specify an explicit threshold for criterion C

Include concurrent subtype of schizoaffective disorder (ie, remove criterion B)

3. Continue with schizophrenia, bipolar disorder, and major depression but remove schizoaffective disorder Add specifi er criteria to the diagnostic criteria of schizophrenia, bipolar disorder, and major depression

Categorical specifi ers Dimensional specifi ers Add no specifi er criteria

4. Discontinue psychotic disorder categories and defi ne 1 psychosis spectrum

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14.• Salvatore P, Baldessarini RJ, Tohen M, et al.: McLean-Har-vard International First-Episode Project: two-year stability of DSM-IV diagnoses in 500 fi rst-episode psychotic disorder patients. J Clin Psychiatry 2009, 70:458–466.

The authors of this study observed fi rst-episode patients over a 2-year period and documented a high conversion rate of schizo-phrenia to schizoaffective disorder, as mood symptoms were not prominent during the initial evaluation but evolved during the study period.

15. Vollmer-Larsen A, Jacobsen TB, Hemmingsen R, Parnas J: Schizoaffective disorder—the reliability of its clinical diagnostic use. Acta Psychiatr Scand 2006, 113:402–407. 16. Abrams DJ, Rojas DC, Arciniegas DB: Is schizoaffective

disorder a distinct categorical diagnosis? A critical review of the literature. Neuropsychiatr Dis Treat 2008, 4:1089–1109. 17.•• Cheniaux E, Landeira-Fernandez J, Lessa Telles L, et al.:

Does schizoaffective disorder really exist? A systematic review of the studies that compared schizoaffective disorder with schizophrenia or mood disorders. J Affect Disord 2008, 106:209–217.

This was a comprehensive review of the evidence for and against the diagnosis of schizoaffective disorder as an independent class between schizophrenia and mood disorders.

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19.• Potash JB: Carving chaos: genetics and the classifi cation of mood and psychotic syndromes. Harv Rev Psychiatry 2006, 14:47–63.

This was a thoughtful analysis of the nosology of affective psychosis combined with a review of the genetic epidemiology and molecular genetics.

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25. Hamshere ML, Bennett P, Williams N, et al.: Genomewide linkage scan in schizoaffective disorder: signifi cant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13. Arch Gen Psychiatry 2005, 62:1081–1088. 26. Murray RM, Sham P, Van Os J, et al.: A

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