The current study results extend our understanding regarding the long-term consequences associated with a lifetime history that includes both MDD and anxiety. As compared with women with a history of either MDD or anxiety, women with a comorbid history were more likely to report a lifetime history that included recurrent MDD, multiple lifetime anxiety disorders (such as panic disorder) and greater treatment-seeking, as well as elevations in current anxiety and depressive symptoms. This latter finding held after controlling for current diagnostic status, suggesting that elevated symptom profiles include chronic or residual symptoms that persist beyond acute disorder episodes. Contrary to our hypotheses, women with a comorbid history did not report an earlier age of disorder onset. This null finding may, however, result from faulty participant recall, given the lengthy (often 20 year) interval since first disorder onset.
The current findings build upon yet extend the literature in this area, which has predominantly focused on treatment-seeking clinical samples, or samples explicitly selected to meet current diagnostic criteria.7, 12
While important, such studies raise questions regarding the potential for distress-related reporting bias. In contrast, the current study reports on a community based sample of midlife women, most of whom (83%) did not meet any
current depressive or anxiety diagnosis. Thus, these findings expand the extant literature, highlighting the broad and enduring consequences
that a comorbid lifetime history has on women's social functioning, stress sensitivity, and residual symptom profiles.
A comorbid history of MDD and anxiety, and the residual symptoms that follow, may leave women vulnerable to future MDD recurrence via a number of mechanisms. First, a lifetime history of anxiety and recurrent MDD may, over time, undermine women's social function and ability to garner social support in times of life stress. Indeed, our data indicate that women with a comorbid history reported the lowest levels of social support. We would note that while the comorbid group differed by only 2 points from, for example, women with a history of anxiety alone (see ), this group difference on the 16-point MOS Social Support scale fell in the moderate-to-large effect size range (Cohen's d=.63), and warrants further elaboration with more detailed and sensitive measures of lifetime social function and perceived social support.
Second, a comorbid history of MDD and anxiety may influence the likelihood of encountering negative life events, as well as the emotional distress experienced in the face of such events. Research indicates that women with MDD generate or create stressful life situations,[34–36]
and that this stress-generating effect can be observed well beyond the acute MDD episode.
Similarly, we observed that women with a history of MDD report more past-year life events, and that women with a comorbid history of both MDD and anxiety experience these events as particularly distressing.
Clinically, enhanced interventions are needed to reduce lifetime symptom burden and improve long-term functional outcomes for women with this high-risk profile. Importantly, these data suggest that interventions should aggressively target residual inter-episode depressive and anxiety symptoms, while concomitantly seeking to improve social function and support, enhance emotion regulation, and bolster effective problem-solving in the face of life stress,
In line with previous findings,[7, 38]
our exploratory analyses suggest an etiologic role of childhood abuse or neglect in the development of lifetime MDD and anxiety comorbidity. Exposure to childhood trauma or abuse may undermine the development of secure attachment styles in adulthood, and may have lasting effects on limbic brain systems that govern autonomic nervous system outflow associated with physiologic patterns of stress reactivity. For example, we have found that depressed women with a lifetime trauma history display decrements in parasympathetic (vagal) function in response to acute laboratory stressors,
and that depressed women who report childhood emotional abuse display greater mood and blood pressure reactivity in response to interpersonal stressors.
Additional research is needed to clarify the nature of observed relationships between childhood abuse and patterns of social dysfunction and stress reactivity among women with a history of MDD and anxiety.
Several limitations should be considered in interpreting our findings. First, SCID data collected as part of the SWAN-MHS did not include diagnoses of PTSD or lifetime GAD, which may have resulted in diagnostic misclassification. However, because some argue that MDD-GAD comorbidity represents boundary problems rather than true syndromal co-occurrence,41–42
the impact of excluding these diagnoses is uncertain. Second, the current study did not include assessment of personality pathology, which may play a role in the patterns of psychiatric, social and stress-related dysfunction observed in the current report. Third, the current study could not evaluate temporal patterns of lifetime comorbidity, and the sample size did not allow for analyses separated by individual anxiety disorder diagnoses. Finally, the SWAN study was limited to females; thus, the extent to which the observed findings would hold for males is unknown.
Strengths of the current study include the evaluation of a large, ethnically diverse, community-based sample of mid-life women. In addition, the rich SWAN study data base and careful MHS psychiatric assessments enabled us to characterize many of the clinical, psychological, social, and stress-related concomitants associated with a lifetime history of depression and anxiety.