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.
Medical/Organic Factors
A large number of medical/organic factors are possible as causes of depression in patients with schizophrenia (Bartels and Drake 1988). Obviously, any medical/organic factor that can lead to a depressive syndrome in an individual who does not have schizophrenia can also lead to a depressive state in a person with schizophrenia. Such possibilities include a number of common medical conditions (anemia, cancer, neurological disorders, infectious diseases, and metabolic or endocrine disorders), various medications used in the treatment of medical problems (antihypertensive medications such as beta-blockers, sedative-hypnotics, sulfonamides, and indomethacin), and discontinuation of other prescribed medications (most typically corticosteroids and psychostimulants).
Substances of abuse, such as alcohol, cannabis, cocaine, and narcotics, can contribute to phenocopies of depression on the basis of acute use, chronic use, or discontinuation. Importantly, the discontinuation of two "legal" substances very commonly used by schizophrenia patients--nicotine and caffeine--can lead to withdrawal states that can mimic depression (Lavin et al. 1996). In particular, "smoke-free" and "decaf" policies on many inpatient units can lead to diagnostic confusion unless the possibility of withdrawal symptoms is considered in the differential diagnosis of "depressive" states.
Negative Symptoms of Schizophrenia
Conceptually, the presentation of negative symptoms in patients with schizophrenia overlaps with the syndrome of depression in a number of domains (Andreasen and Olsen 1982; Bermanzohn and Siris 1992; Carpenter et al. 1985; Crow 1980; Siris et al. 1988a). Overlapping symptoms include poor energy, diminished interest, lack of pleasure, lowered drive state, reduced motor activity, impaired concentration, and general sense of helplessness. Other symptoms, however, may be helpful in making the distinction (Barnes et al. 1989; Kuck et al. 1992; Lindenmayer et al. 1991; Norman and Malla 1991). ....
More than two dozen studies have been published examining the rates of occurrence of depression in the course of schizophrenia (Koreen et al. 1993; Sands and Harrow 1999; Siris 1991, 1995; Tapp et al. 1994). They have varied considerably in terms of a number of methodological considerations: the definition employed for schizophrenia, the definition used for depression, the interval surveyed, the methodology of the survey, and the patients' treatment status at the time of the observation. The most notable conclusion that can be drawn from these studies is that, no matter what definitions and conditions prevail, at least some meaningful rate of phenotypic depression is observed in the course of schizophrenia.
Among these studies, the rates of depression varied from a low of 7% in a cross-sectional assessment of patients with DSM-III-defined schizophrenia who were chronically hospitalized and in whom an effort was made to distinguish depression from negative symptoms (Hirsch et al. 1989), to a high of 75% for at least one positive assessment of depression by either one of two criteria among patients with "first break" RDC-defined schizophrenia who were evaluated on a weekly to monthly basis for up to 5 years (Koreen et al. 1993). The modal rate for all these studies was 25%, a fair benchmark that has endured through the course of a number of reviews (Johnson 1981b; Mandel et al. 1982; McGlashan and Carpenter 1976b; Siris 1991, 1995; Winokur 1972).
Since depression is observed more frequently in females among people without schizophrenia (Kessler et al. 1993), and since the expression of schizophrenia in general is different in women than it is in men in a number of ways (Goldstein and Link 1988), it would be interesting to know if sex differences are observed with regard to the presentation of depression in patients with schizophrenia (Goldstein and Tsuang 1990; Seeman 1997). Indeed, such differences, if found, would have theoretical nosological implications ...
Treatment Strategies
An appropriate treatment approach to depression begins with a consideration of the differential diagnostic possibilities outlined earlier in this chapter. Obviously, since there are no available biological tests (except for the medical/organic conditions), or even psychological tests, that are known to be informative in drawing these diagnostic distinctions, these diagnoses must be made on a purely clinical basis.
Figure 21 depicts an integrative schema that conceptualizes the interplay of extrinsic and intrinsic factors with the schizophrenia diathesis. The basis for this formulation is the familiar stress-diathesis model of schizophrenia (Nuechterlein and Dawson 1984; Zubin and Spring 1977), supported by more recent understanding of the neuropsychological underpinnings of the pathophysiology of schizophrenia (Weinberger 1987).
In Figure 21, the vertical axis represents vulnerability to psychotic symptoms of the schizophrenic type and the horizontal axis depicts the proportion of the general population. At the far left, a tiny fraction of the population manifests a very high vulnerability to psychosis, with an everdecreasing loading for such risk moving to the right along the curve.
Only a fraction of 1% of the population express a vulnerability so great that a schizophrenic psychosis will emerge under virtually any level of life stress, no matter how minor ...
Figure 21. Model of vulnerability, stress, and schizophrenic diathesis.
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