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 (Goldstein et al. 1990; Seeman 1996b).

Unfortunately, in most studies sex has not been specifically examined with reference to depression in schizophrenia, especially in any way that attempts to account for the various elements of the differential diagnosis outlined earlier. Addington et al. (1996), in the strongest attempt to rule out negative symptoms and extrapyramidal side effects in a prospective assessment of depression with the Calgary Depression Scale for Schizophrenia, found similar rates of depression for both sexes. Several other studies also failed to find significant differences between the sexes in terms of depression rates in patients with schizophrenia (Haas et al. 1990; Hafner et al. 1994; Shtasel et al. 1992).

On the other hand, three careful chart reviews have suggested such differences: McGlashan and Bardenstein (1990) examined Chestnut Lodge patients according to a dichotomous variable (depressed vs. not depressed) and found that women with schizophrenia were more likely to be depressed than men with schizophrenia; Goldstein et al. (1990), also using a dichotomous variable, found more dysphoria (not exactly the same as “depression”) in females with schizophrenia (54%) than in males with schizophrenia (45%) in the Iowa-500 and Iowa non-500 data; and Goldstein and Link (1988) found female schizophrenia inpatients to have more depressed mood than male schizophrenia inpatients.

In this last study, the investigators also found a relationship between depressed mood and psychosis in women with schizophrenia but not in men with schizophrenia. Other data suggest that negative symptoms may be more depression-like in women with schizophrenia than they are in men with schizophrenia (Lewine 1985).

Additionally, with regard to sex differences, it is relevant to note that women’s psychopathology ratings worsen in general during that phase of the menstrual cycle when estrogen levels are low (Hallonquist et al. 1993; Riecher-Rossler et al. 1994; Seeman 1996a, 1997), and that this is likely to be true for depression ratings. However, depressed mood may not always be exacerbated by low estrogen levels (Hafner et al. 1994), and this effect is certainly not specific to schizophrenia.

Results from large-scale, controlled prospective studies of focusing on the symptom of depression in female schizophrenia patients over the course of the menstrual cycle have not been published. Thus, overall, although it is likely that there might be some differences in the rates or expression of depression in women and men with schizophrenia, this phenomenology has not yet been fully clarified with prospective observations.

Samuel G. Siris, M.D.

References

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• Bartels ..... full References ... »