Research reportPredictors of recurrence in affective disorder — analyses accounting for individual heterogeneity☆
Introduction
Episodes in unipolar (recurrent depressive disorder) and bipolar affective disorders may develop in the interplay between biological, psychological and social factors. Psychosocial stress and major life events may precipitate affective episodes in susceptible individuals. Some evidence suggests that the individual vulnerability increases with the number of affective episodes as more psychosocial stressors have been found to be involved in the first episode than in subsequent episodes of major affective disorder (review by Goodwin and Jamison, 1990, pp. 142–146; Post, 1992). However, this relation between the prevalence of precipitating events and the course of episodes has not been found in all studies of unipolar disorder (Perris, 1984, Bidzinska, 1984) or bipolar disorder (Bidzinska, 1984, Ellicott et al., 1990, Hammen and Gitlin, 1997). Furthermore, it has been objected that, in the primary retrospective studies of precipitating events, patients are more likely to search for stressors prior to the onset of the illness, whereas once the illness is accepted less attention is paid to stressors (Goodwin and Jamison, 1990, p. 143; Johnson and Roberts, 1995).
Studies with prospective rigorous assessment of stressors are few and include a short follow-up period only (up to 3 years, Ellicott et al., 1990, Pardoen et al., 1996, Paykel et al., 1996, Monroe et al., 1996, Hammen and Gitlin, 1997). Thus, no study encompasses appropriately long follow-up time to compare the presence of prospectively assessed life events before early episodes and before later episodes, as pointed out by Hammen and Gitlin (1997).
In this regard, register data offer some remarkable advantages. They often include a large number of patients followed for a long period of time and recall bias is completely avoided since data are ‘hard facts’ collected routinely and independently of researchers.
We have previously used data from the the nationwide Danish Psychiatric Central Register to identify predictors of recurrence at successive episodes in affective disorder (Kessing et al., 1998, Kessing, 1998). In these studies, the risk of recurrence was expressed as the risk of readmission after successive discharges in affective disorder. Initially in the course of unipolar and bipolar illness, sociodemographic variables such as sex, age (partly) and marital status were found to predict recurrence whereas these variables had no effect later in the course of the illnesses. Patients who had never been married had greater risk of recurrence after the first and the second episode but not after subsequent episodes, and divorced/separated patients had greater risk of recurrence after the first episode but not after subsequent episodes.
It is, however, a major statistical problem in every study of the effect of psychosocial stressors during the course of affective illness that it is difficult to assess whether the difference in effect between early and late episodes is statistically significant. Analyses at successive episodes are not independent of each other as patients with many episodes will be a subgroup of patients with few episodes, and hence patients with many episodes and great liability to recurrence will tend to dominate the analyses.
However, it is possible to account for this individual liability to recurrence with the use of either frailty models (Andersen et al., 1993) or generalised linear mixed models (Breslow and Clayton, 1993; see also Kessing et al., 1999). The present study used models of the latter type to reanalyse the effect of age, gender and marital status on the risk of recurrence during the course of illness with the use of data from the Danish Psychiatric Case Register.
Section snippets
The register
In Denmark, all psychiatric admissions have been registered in a nationwide register (Dupont, 1983; Munk-Jørgensen and Mortensen, 1997) with the same diagnostic system, the International Classification of Diseases, 8th Revision (National Board of Health, Denmark, 1971) from 1 April 1969 to 31 December 1993. For various reasons, and to achieve better diagnostic reliability over time, it was decided not to change to ICD, 9th revision in 1978. Since there are no private psychiatric hospitals or
Results
From 1971 to 1993, 17 447 patients got a diagnosis of depression (code 296.09 and 296.29) and 2903 patients got a diagnosis of mania or circular episode (code 296.19 and 296.39) at first admission. The entire sample was, however, not included in analyses due to limitations in computer memory. Thus, a random sample of 7047 patients (4558 women and 2489 men) among the 20 350 patients was selected using the random number generator in sas, version 6.12.
Table 1 presents the effect of predictors for
Discussion
To our knowledge this study and the studies previously reported (Kessing et al., 1998, Kessing, 1998) are the first studies to present within-patient analyses in which the effect of sociodemographic variables and life events for the individual is studied at early episodes and at later episodes. Long-term prospective studies of the impact of psychosocial stressors on the course of affective illness may be difficult to perform in a valid way since they may be hampered by selective drop-out.
Acknowledgements
This work was supported by The Foundation for Psychiatric Research (Denmark).
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This study was conducted in cooperation with the Department of Psychiatric Demography, University of Aarhus, Psychiatric Hospital, Risskov, Denmark.