Insomnia, whether assessed via polysomnographic markers or via self-report, was found to be a risk factor for depression symptoms at follow-up among participants who had been free of depression 4 years earlier in our population-based, observational study. Our study was unique in that we assessed both polysomnographic markers and self-reported symptoms of insomnia. Insomnia markers reflecting decreased sleep continuity and its symptoms, including number of symptoms and difficulty initiating sleep, predicted the occurrence of depression after adjustment for possible confounders. To our knowledge, significant graded associations between insomnia (increasing number of symptoms, difficulty initiating and maintaining sleep) and depression have not been previously reported. Our findings regarding self-reported insomnia's positive relation to depression are broadly consistent with results from most prospective epidemiologic studies conducted in various US and European populations (3
), with a few exceptions (10
) possibly due to the use of differing methods (e.g., insomnia definition or duration (12
), sample characteristics, follow-up periods).
An important limitation of our study is that only 26 (4.7%) participants developed depression (defined as Zung score ≥50), since we emphasized specificity in our incident depression classification. Because the small number of outcome events (defined dichotomously) may have led to biased multivariable regression estimates and confidence intervals, we examined mean (continuous) depression values at follow-up to help address this limitation. Analyses based on mean scores were largely consistent with significant dichotomous results (based on the clinical cutpoint) and showed similar patterns. Fully adjusted multivariable regression results also resembled minimally adjusted or nonadjusted results. Nevertheless, larger study samples yielding a greater number of incident depression events may be warranted for confirmation of our findings.
The associations we found were not likely to have been due to subsyndromal depression in insomnia (scores near Zung's depression cutpoint). Average depression scores did not differ at baseline according to higher levels of, versus lower or absent, polysomnographic markers and were far from the depression cutpoint. For number of symptoms, depression scores were merely 2 points higher for 3 or 4 symptoms versus no symptoms, and far (12 points) from the 50 threshold. Moreover, average Zung scores less than 50 at baseline were similar for participants developing and not developing depression.
Although the definition of insomnia sometimes includes daytime consequences or impairment/interference (21
), our definition did not, which limited the potential for built-in associations. To avoid overestimating insomnia's association with depression, we used a modified depression scale excluding 2 sleep-related items, a method rarely used (10
). Estimates, though slightly attenuated, remained significant. Because antidepressants may be used for conditions beyond depression (43
), we reanalyzed the data after excluding users of antidepressant medication (irrespective of depression symptoms) from follow-up; patterns and trends remained unchanged (), even after adjustment. Relative risks were 2.8 (P
= 0.05) for difficulty falling asleep, 4.8 (P
< 0.001) for waking after sleep onset ≥79 minutes, and 2.9 (P
= 0.02) for sleep latency ≥14 minutes.
When standard polysomnographic cutpoints considered clinically significant were analyzed, sleep efficiency <80% and sleep latency >30 minutes remained significantly associated with depression (Zung score ≥50); total sleep time <360 minutes and waking after sleep onset ≥30 minutes did not. The graded relation of total sleep time quartiles with depression was perhaps diluted by the binary cutpoint; waking after sleep onset was significant only at upper quartile values.
Several polysomnographic cutpoints used were more conservative than those typically utilized to define poor sleep (total sleep time <360–390 minutes, sleep efficiency <85%) (44
). Our lowest quartiles of total sleep time (<334 minutes) and sleep efficiency (<78%) were similar to objective insomniacs’ mean values in clinical settings (329 minutes and 75%, respectively) (45
), suggesting that clinically relevant “objective” markers were assessed. Analyses further suggested that polysomnographic markers corresponded to self-reported difficulty in initiating and maintaining sleep.
Among our study's limitations, we were unable to examine whether depression was season-related (seasonal affective disorder) or to differentiate between first-onset and recurrent depression, since information on past depression was not available. Nevertheless, findings that insomnia predicts depression symptoms in persons without depression at baseline may be relevant for preventive purposes, irrespective of whether depression at follow-up is first-onset or recurrent. Furthermore, an interaction between insomnia and age was not observed, increasing the likelihood that a reasonably high proportion of newly developed (vs. recurrent) depression was identified at follow-up. Self-reported depression symptoms may also be more labile. Depression is dynamic and is characterized by symptomatic fluidity (16
), suggesting that our inability to differentiate between first-onset depression and recurrent depression may be less pertinent.
Both early and middle insomnia—difficulty in initiating and maintaining sleep, respectively—predicted depression symptoms. Similarly, Perlis et al. (13
) found that chronic middle insomnia predicted depression. In contrast to our study, they found persistent delayed (early morning awakening) insomnia symptoms to be somewhat related to depression and persistent early insomnia to be unrelated (13
). A clinical study by Fava et al. (46
) suggested that delayed and initial insomnia are prodromal depression symptoms. Our findings that early and middle insomnia were most related to depression are thus partially consistent with prior studies; differences may relate to these studies’ examining chronic insomnia or clinical populations.
The follow-up participation rate in the overall cohort has been 80%, on average. Proportions of insomnia and depression did not vary according to number of follow-up visits completed, suggesting an absence of selection bias. Despite the use of polysomnography, variability (night-to-night) and instrumentation errors were possible. However, the measurement error was probably nondifferential, thus likely underestimating our positive findings. A first-night effect (47
) resulting in regression dilution bias is possible given 1 night of polysomnography. However, the fact that significant associations were found may highlight the strength of our findings.
The Zung scale has limitations; it is based on self-reporting and does not correspond directly to the criteria of the Diagnostic and Statistical Manual of Mental Disorders
, Fourth Edition (48
). Nevertheless, its strengths include a high correlation with clinical evaluation (38
) and wide usage in research. Other potential limitations include confounding due to unmeasured factors like pain (24
), though we adjusted for back pain. The external validity of our findings should be limited to the incidence of both first-onset and recurrent depression. Moreover, the findings may not be generalizable beyond a middle-aged population with similar characteristics or to persons assessed as depressed by a clinician.
Our study's strengths include the collection of longitudinal data from a large population-based sample, longer follow-up, high-quality polysomnographic and self-report assessments, consistent findings across insomnia measures, and consideration of multiple confounding factors. Because our baseline sample comprised mainly working persons and because we excluded depressed participants and adjusted for common comorbid conditions, baseline insomnia was probably unrelated to medical or psychiatric conditions. Significant results persisted after removal of participants with anxiety, suggesting that the association observed was not merely due to anxiety.
Despite its high prevalence, insomnia remains largely undiagnosed among patients seen in primary-care settings, due to factors ranging from inadequate training of primary care providers to concerns and misperceptions about sleep medications, lack of familiarity with behavioral techniques, and inadequate amounts of time spent with patients (50
). Our findings suggest that insomnia may increase the risk of subsequent depression symptoms. If confirmed by future studies, our results suggest that recognition and treatment of insomnia by health-care providers may be critical for preventing or mitigating the occurrence of depression. Prevention of depression, even mild or subthreshold depression, has wide-ranging implications given its high (including invisible) costs (51
), such as increased health-service utilization, its chronic recurrent nature, and undertreatment (16