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EDITORIAL COMMENT |
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0603
Jonas and Mussolino (1) make a compelling case that preexisting depressive symptoms are an important risk factor for a significantly increased incidence of stroke. Their report is based on a secondary analysis of data from the National Health and Nutrition Examination Survey I (NHANES-I) Epidemiological Follow-up Study. The analysis strategy they selected seems appropriate, the data are solid and consistent, and the conclusions are conservative and supported by the data. It is remarkable that a high level of depressive symptoms was a greater risk factor for stroke (relative risk = 1.73) than 13 other risk factors; only gender (male) was slightly stronger (relative risk = 1.74). Even the relative risk of stroke with an intermediate level of depressive symptoms exceeded that of five other risk factors for stroke (ie, race, >12 years of education, high systolic blood pressure, high serum cholesterol level, and a low to moderate level of physical activity). In short, this study is of interest and is likely to be important for public health.
While reading the article, I was struck by the remarkable degree of agreement between the NHANES-I data reported by Jonas and Mussolino (1) and data from other recent studies, including our own, of patients with unipolar major depressive disorder (MDD). I highlight some of these areas of agreement to emphasize how corroborating data from diverse research strategies and different samples of depressed people is mutually validating and results in a better understanding of this very common and serious mental disorder and its negative sequelae.
In 1996, the World Health Organization (WHO), in its landmark study with the World Bank, reported that unipolar MDD was the fourth leading cause of disability worldwide among noncommunicable diseases, as measured by disability-adjusted life-years (2). Unipolar MDD was also projected to be the second leading cause of disability in 2020, when it would account for approximately 11% of the world’s total disease burden. Many public health experts were amazed that unipolar MDD was associated with such high levels of disability worldwide. But it was not surprising to mood disorder experts because it had been established that unipolar MDD is among the most prevalent illnesses in the healthcare spectrum (3); is primarily a chronic, often life-long illness (4–7); and is associated with significant and pervasive psychosocial impairment affecting most of the essential everyday functions (eg, work and key interpersonal relationships) (8, 9). However, Jonas and Mussolino (1) and others have now documented another important dimension of disability associated with unipolar depression that was not accounted for in the WHO or other previous investigations of disability. It seems that in addition to having a direct impact on psychosocial function, depressive symptoms are also a risk factor for other common and serious medical illnesses, such as hypertension (10), heart disease (11), and stroke. Furthermore, it has been shown that depression is an important complicating comorbid condition that can significantly increase morbidity and mortality when it occurs with medical illnesses like myocardial infarction (12).
The Depression Scale of the General Well-Being Schedule was used in the Jonas and Mussolino (1) study. This scale contains only four depressive symptom items plus an analog scale anchored by "depressive" or "cheerful" at each end. From these data, categorical DSM-IV depressive disorder diagnoses cannot be derived. As a result, the authors grouped depressive symptoms along a dimensional continuum of symptom severity into categories of high, intermediate, and low. Some may question the validity of a low or intermediate depressive symptoms grouping, but recent evidence indicates that minor and subthreshold depressive symptoms are very common (8, 13), are associated with significant psychosocial impairment (9, 14), and have the characteristics of a clinically relevant depressive condition (15). In addition, we reported, in a weekly analysis of depressive symptom severity in a large cohort of patients with unipolar MDD, that during the long-term course of illness (
12 years), patients with unipolar MDD spent three times as many weeks with minor and subthreshold symptoms (43% of weeks) as with MDD-level symptoms (15%) (7). It seems that unipolar depression is expressed symptomatically along a dimensional continuum of depressive symptom severity in which depressive subtypes (eg, MDD or minor depression) are not discrete disorders but are phases of illness activity and intensity that change and fluctuate frequently in the same patient during the long-term course of illness (7). Thus, the validity of the dimensional symptom grouping used by Jonas and Mussolino in their analyses is supported by both other studies of depression and the risk gradient for stroke that they identified.
In a detailed study of psychosocial disability during the long-term course of unipolar MDD, we observed a similar progressive linear gradient of psychosocial impairment that was significantly associated with each increment in depressive symptom severity, ranging from subthreshold to minor to major depressive levels. Global psychosocial function was "very good" or "good" when patients were asymptomatic, "fair" during weeks of subthreshold depression, approached "poor" with minor depressive symptoms, and was "poor" to "very poor" when symptoms were at the MDD level. The bar graph illustrating our psychosocial impairment data (14) is very similar to Jonas and Mussolino’s Figure 1, which compares the gradient of relative risk associated with high, intermediate, and low depressive symptoms.
The most intriguing implication of the Jonas and Mussolino study is the possibility that stroke risk can be reduced by effective treatment of depressive symptoms. Given that we are now able to manage most cases of depression effectively, the prospect of being able to not only manage the adverse effects of depression but also reduce the incidence of stroke is indeed very promising. In this regard, we showed that patients whose recovery from episodes of MDD was incomplete and characterized by ongoing residual subthreshold symptoms of depression relapsed five times faster to new episodes than patients who recovered fully and were symptom free (16). We contend that true recovery of MDD episodes is not achieved when symptoms merely fall below syndromal criteria for the episode but only when all depressive symptoms abate. We predict that if treatment of depression does reduce the risk of stroke, that treatment to full asymptomatic status will be associated with the most significant decrease in stroke risk.
In summary, unipolar depression is a very common and pernicious illness. Depressive symptoms during the long-term course of illness are expressed as a fluctuating dimensional continuum of illness activity and symptom severity. Each level of depressive symptom severity is associated with both a gradient of psychosocial impairment and, as shown by Jonas and Mussolino (1), a risk gradient for serious medical illnesses like stroke. Effective treatment of depressive symptoms may reduce the risk of stroke, but this intriguing suggestion awaits prospective and controlled investigation.
REFERENCES
This article has been cited by other articles:
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  J. E. Dimsdale Comorbidity Studies: A Core Area for Psychosomatic Research Psychosom Med, March 1, 2001; 63(2): 201 - 202. [Full Text] [PDF]
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