It is generally accepted that the first building block of modern psychiatric nosology was Kraepelin’s distinction between those disorders we now know as mood disorders and the illness (or illnesses) we now know as schizophrenia. Nevertheless, beginning with Bleuler (1911/1950), the observation was repeatedly made over the years that a substantial proportion of patients diagnosed with schizophrenia manifest some sort of “depressive-like” symptoms at certain points during their clinical course. These two propositions were difficult to reconcile because the Kraepelinian dichotomy maintained a powerful influence in psychiatry and empirical observations and understanding of the depressive state in patients with schizophrenia were slow to accumulate.

The seeming non sequitur of “depressive” symptoms in schizophrenia, as a consequence of Kraepelin’s original observations, generated a tendency either to ignore or to psychologize depressive states in schizophrenia in the early and middle years of the 20th century. In some psychodynamic writings, the question of depression in schizophrenia was written off entirely on the basis of a thesis that schizophrenia patients, by definition, lacked the proper ego structures to develop depression. Elsewhere in the literature, psychodynamic formulations were used to explain states of depression in patients with schizophrenia. Meyer-Gross wrote about depression as being a reaction of despair to the psychotic process and a denial of the future (see McGlashan and Carpenter 1976b).

Other central psychodynamic themes included loss (Miller and Sonnenberg 1973; Roth 1970; Semrad 1966) and the notion that a state of depression was a necessary stage in the progression out of the more pathological narcissistic regressed 31 state that was represented by florid psychosis (Semrad 1966). Semrad (1966) also understood the depressed state to be influenced by the pain and/or despair of an “empty ego.” Both he and Eissler (1951), however, saw depression in schizophrenia as a moment of therapeutic opportunity, when insight and mastery might overcome more primitive defensive psychotic ego states as they receded.

In this light, depression in the course of schizophrenia was seen as a significant positive prognostic sign. Clearly, though, in all these writings, depression tended to be seen not as a diathesis from which the patient was suffering, but rather as a reaction, in one form or another, to the primary illness of schizophrenia and/or its consequences. Little considered was the possibility that a natural diathesis for depression was complicating the course of schizophrenia in any substantial proportion of patients.

In more recent years, however, depression in schizophrenia became the subject of a more data-based approach to research. The frequency and intensity of depression have been documented in patients with schizophrenia (Bowers and Astrachan 1967; McGlashan and Carpenter 1976a; Siris 1991, 2000), as the definitions of both schizophrenia and depression have become more operationalized. In the latter part of the century, with the emergence of psychopharmacology as the central treatment modality for schizophrenia, the prognostic implications of depression appeared to change.

Investigators began to observe that the outcomes were less favorable, rather than more favorable, for those schizophrenia patients who manifest depressive symptoms (Falloon et al. 1978). Such patients were noted, then, to be at higher risk for relapse or rehospitalization (Birchwood et al. 1993; Johnson 1988; Mandel et al. 1982; Roy et al. 1983) or even suicide (Caldwell and Gottesman 1990; Drake and Cotton 1986; Roy et al. 1983).

Indeed, it has become recognized, over time, that approximately 10% of schizophrenia patients end their lives in suicide (Caldwell and Gottesman 1990; Miles 1977). Depressive states appear to figure importantly in this, as it has been noted that suicidal ideation is associated with depression in schizophrenia (Barnes et al. 1989) and that many suicides (Drake and Cotton 1986; Heilä et al. 1997; Roy 1982; Stephens et al. 1999) or suicide attempts (Prasad and Kumar 1988; Roy 1986) among persons with schizophrenia involve individuals who have had recent or past histories of depressive symptoms, especially psychological symptoms such as hopelessness (Drake and Cotton 1986). In one study, in fact, more than 80% of the explained variance in suicidal behavior among outpatient schizophrenia patients was accounted for by depression (Bartels et al. 1992).

Over time, a variety of names have been attached to the state of depression occurring in the course of schizophrenia. One of the recurring appellations in the literature is the term postpsychotic depression, which, despite the controversy that surrounds it and the confusion it easily engenders with regard to the possibilities of causality, is used in ICD-10 (World Health Organization 1988) and, more recently, in Appendix B of DSM-IV (American Psychiatric Association 1994) to describe this disorder.

Much of the confusion about this name stems from the misunderstanding that it implies a depression necessarily occurring immediately after resolution of the psychotic state. This is not the case. Rather, the only implication is that the depressed condition follows the psychosis, but without any specification of the interval-which could be brief, intermediate, or lengthy-as earlier had been clear in the diagnostic category “depression superimposed on residual schizophrenia” included in the Research Diagnostic Criteria (RDC; Spitzer et al. 1978).

But no matter what name is used to describe it, a depression-like syndrome can play a disastrous role in the long-term course of illness in at least some patients with schizophrenia. The syndrome can be associated with substantial reductions in social and vocational functioning and devastating personal suffering for patients and their families.

Patients may lose energy, self-esteem, and self-confidence; their ability to concentrate may be impaired; they can lose interest and enjoyment in activities; and sleep, appetite, and motor activities can become dysregulated. Blue mood, pessimism, doubt, guilt, and nihilistic notions may come to dominate the patient’s mental life, and it is possible that these themes, and this affect, can become intertwined with the symptoms of the psychosis itself.

Although a variety of hypotheses have been advanced, the etiology and mechanisms of the depressive state in the course of schizophrenia have not been definitively established. Indeed, it is likely that there are a variety of conditions that can mimic a course-related depression in schizophrenia.

These range from biological to psychological to social, and from concepts that are an intrinsic component of the schizophrenia diathesis itself to those that are attributable to the environment or extraneous happenstance. An appropriate consideration of the syndrome of depression in the course of schizophrenia, and the approach to its treatment, therefore begin with a consideration of its differential diagnosis.

Samuel G. Siris, M.D.

References

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• Bartels ..... full References ... »