Although prior studies have demonstrated the association of many putative risk indicators with depression outcome, our study is the first, to our knowledge, to identify optimal risk indicators for incident major depressive episodes in a cohort of older primary care patients well-characterized as to current minor or subsyndromal depression. Moreover, we used a wider range of operationalized measures of psychopathology, medical conditions, and psychosocial factors than prior investigators (8
). We found that a combination of risks, including minor or subsyndromal depression, impaired functional status, and history of major or minor depression, did identify a group at very high risk for incident depression. The number needed to treat was 5, a figure low enough to make an effective preventive intervention potentially cost effective. It is, perhaps, not surprising that our results point to the importance of “indicated” prevention strategies (32
) (i.e., targeting persons already somewhat symptomatic and with a history of depression, but these data demonstrate the usefulness of focusing on these specific factors together with functional impairment compared with other putative risks).
Also of note is the presence of functional disability, rather than medical illness burden, in the final risk indicator models. Medical burden long has been associated with depression in later life, and specific medical illnesses may be of particular etiological or prognostic significance (e.g., the role of small vessel cerebrovascular disease [33
]) in selected subgroups. However, growing evidence suggests that the effects of medical illnesses may more broadly, perhaps mediated through functional disability, play the greatest roles in the heterogeneous populations found in primary care settings (34
). Although none of the other psychosocial measures appeared in the final risk models, perceived family criticism had predictive characteristics comparable with that of functional disability (). We opted to make the next-level risk model conditional on functional disability rather than family criticism because functional disability is commonly addressed in primary care and other clinical settings, while family criticism is rarely assessed formally. Future work should continue to examine the potential role of family and other psychosocial factors in predicting incident depression, in part to identify mechanisms of depression onset that might inform innovative approaches to preventive psychosocial interventions.
Several study limitations must be acknowledged. Our findings may not generalize to other populations, including groups with greater representation of non-Caucasian seniors, although it is not clear how our findings might differ in other settings. Further, there was no evidence of systematic bias in our recruitment methods, and the inclusion of race as a covariate supports the validity of the results based on any “missing at random” data. Our study cohort may reflect biases introduced during the recruitment and retention phases, although the inclusion rates compare favorably with other studies using such labor-intensive assessment methodologies. The absolute number of incident depression cases was relatively modest, limiting power to detect predictors. However, this makes the present findings more striking. Our analyses assumed that risk indicators exerted the same effects on outcome across the entire cohort (i.e., we did not examine particular subgroups). Last, the numbers needed to treat were based on the assumption of a fully effective preventive intervention. Although useful to guide the optimal targeting of interventions, our findings underestimate the number needed to treat values for any interventions likely to be available for the foreseeable future. It also must be noted that elimination of a risk marker may not necessarily improve outcomes (i.e., the marker may be a proxy for the actual pathogenic factors, hence our use of the terms risk indicator or marker as distinguished from true risk factors). However, our identification of risks that suggest an “indicated” prevention strategy (e.g., current minor or subsyndromal depression) increases the likelihood that reduction of a risk will improve outcomes.
Preventive interventions research might focus fruitfully on at-risk subject groups identified by the predictors identified in the present study. However, it remains unclear what interventions are most likely to be efficacious. Additionally, to achieve effectiveness in actual practice, a preventive intervention must be acceptable to persons who largely do not identify themselves as being depressed. Antidepressant medications might be considered, but psychosocial treatments may be somewhat more effective than medications for treating milder forms of depression, such as subsyndromal depression (35
). One approach might be to adapt evidence-based psychotherapy for depression (e.g., interpersonal psychotherapy or problem solving therapy) to the context of persons suffering from subsyndromal depression rather than full-fledged major depression. Alternatively, or in tandem with depression-specific therapy, an intervention that focuses on coping with functional disability or that involves increasing physical activity or exercise (36
) may be more acceptable to these patients and may hold promise of preventive efficacy.
Pending the development and empirical validation of preventive interventions, the present study may inform current clinical practice by fostering early detection and intervention critical to improving patient outcomes for depression. The risk markers identified are clinical domains routinely assessed, at least informally, in primary care evaluations, although quantification and chart documentation of these risks in practice remain quite variable. As practices move toward adopting chronic disease management approaches based on electronic medical records, it will be straightforward to identify and “flag” patients at risk for incident depression. Such patients could be followed closely over time using cost-effective methods, such as telephone-based depression symptom scales (37
). Treatment outcomes for patients who go on to develop diagnosable depressive disorders may be maximized by the use of evidence-based depression care management paradigms, administered within primary care practices (38
) or via telephone (40
). Future research must refine the recommendations for such screening and demonstrate its cost effectiveness as well as determine the effectiveness of preventive interventions. Further, the methodologies of the present analyses should be applied to more narrowly defined populations for whom depression poses particularly grave risks, such as those with specific chronic medical conditions (e.g., heart failure, stroke), with similar goals of identifying those at greatest risk for developing depression and elucidating potential targets for intervention.