The timing of depression: an epidemiological perspective




Hans-Ulrich WITTCHEN, PhD
Stefan UHMANN, Dipl Psych
Institute of Clinical Psychology
and Psychotherapy
Dresden, GERMANY

The timing of depression:
an epidemiological perspective

by H. U. Wi t tchen
and S. Uhmann,Germany

A number of the characteristics of depression are known to vary over time. A full and comprehensive epidemiological characterization of the temporal characteristics of depression is, however, lacking. In this paper, we discuss the methodological challenges and provide a selective review of recent epidemiological evidence covering the following issues: (i) prevalence of major depression by age and gender; (ii) patterns of incidence by age of onset and birth cohort; and (iii) number and duration of major depressive episodes. We also discuss vulnerability and risk factors influencing the temporal characteristics of depression, and comment on cohort trend findings that suggest that there has been an increase in the rate of depression over time. One can conclude that despite the relatively stable pathoplastic structure of depression, there is epidemiological evidence of considerable variability in the onset, episode frequency, and duration of depression over the lifespan. An early onset in youth is associated with a greater frequency of depressive episodes of mostly shorter duration compared with depression with an older age of onset. Depression in old age is associated with considerably greater persistence, as indicated by high proportions of long episodes (>51 weeks) and chronicity. We also confirm the existence of substantial birth cohort effects, and a shift of first onset of depression to a younger age. Overall, this suggests that the rates of major depressive disorders are increasing.

Medicographia. 2010;32:115-125 (see French abstract on page 125)

Several salient characteristics of depression vary over time. This is reflected, for example, in the typically episodic nature of major depression and the relevance of biological rhythms in its etiology (manifest, for example, as sleep pattern disturbance), but also in our heavy reliance on the characteristic duration and persistence of depressive symptoms in the differential diagnosis and when separating clinical depression from normal mood variations. The importance of temporal issues is also evident when considering the incidence patterns of depression over the lifespan of males and females, and the associated variation in terms of number and length of episodes and risk factors. Despite numerous epidemiological studies, our current understanding about the timing of depression remains fragmented and incomplete.

Figure 1
Figure 1. Point (1-month), 12-month, and lifetime estimates for
major depressive disorder in community surveys of the European
Union. Based on data from reference 14.

*Lifetime risk is an estimation of the total risk for major depressive disorder up
to the age of 75 years, assuming that subjects younger than 75 years will have
the same prospective risk as subjects who are currently old.

Several critical issues can be held responsible for this deficit: (i) few studies have ever attempted a comprehensive epidemiological characterization of depression across the lifespan, including number and duration of episodes; (ii) temporal aspects are mostly studied in isolation, and interactions with developmental risk factors are rarely addressed; (iii) methodological factors, such as reliance on retrospective cross-sectional studies, sampling, age group composition and power, differences in diagnostic assessment tools used, and other factors (somatic factors, secular trends, etc) make the aggregation of findings difficult; (iv) the determination of age of onset and number and duration of episodes depends on retrospective accounts from patients, which are subject to recall bias, current mood state, other comorbid conditions, as well as birth cohort effects1-6; (v) the interpretation of depression findings is further complicated by the possibility that secular trends might exist7-10: that is, younger birth cohorts might have a substantially higher risk of experiencing depressive episodes and suffering from depression at an earlier age than older birth cohorts. This could be relevant, because an early onset of depressive disorders has been shown to be a risk factor for more frequent and longer episodes11; and (vi) there is no general agreed strategy on how to define the onset and offset of episodes.12 From a broader dimensional view, critical questions arise, such as: should onset be defined as the point in time at which all diagnostic criteria for a particular depressive disorder are met, or should subthreshold expressions that might precede or follow the episode—when dealing with duration—also be taken into account? And if yes, how much symptomatology would be regarded as sufficient? Because of the substantially greater difficulties with such broader concepts, this article will concentrate mainly on major depression and major depressive episodes (MDE), for which firmer evidence is available.

Against these mostly methodological caveats, we will provide a selective review of recent epidemiological evidence covering the following issues: (i) lifetime and current estimates for major depression by age group and gender; (ii) patterns of incidence by age of onset and birth cohort; and (iii) characteristics of duration and course. Furthermore, we will discuss vulnerability and risk factors influencing the temporal characteristics, and comment on cohort trend findings.

Lifetime and current estimates of major depression

_ How frequently does depression occur over the lifespan?
An abundance of epidemiological research13-15 over the past decades throughout the world10,16 has provided evidence that depressive disorders and major depression are much more frequent than was thought in the early 1980s and before. Believed to be relatively rare disorders with cross-sectional rates of 1%-2% and lifetime rates of 4%-5% in the pre-Diagnostic and Statistical Manual of Mental Disorders (DSM)-III studies, increasing and substantial evidence from most studies in the 1990s suggested that major depression and MDE are in fact much more frequent, especially when considering rates of 12-month and lifetime depression. Figure 1 clarifies the different time period references for these rates, ranging from point prevalence (1 month) to lifetime risk.14

In a previous review,10 Wittchen et al reported a median point prevalence of major depressive disorder from studies up to the early 1990s of 3.1 (1.5-4.9), a median rate of 6.5% (2.6%- 9.8%) for 6-month and 1-year prevalence, and 16.1% (4.4%- 18%) for lifetime rates in the community. These data also suggest that we can estimate that up to a high age, the “true” rate of major depression is likely to be above 21%. The differences between fairly low point and high lifetime rates also underline that major depression is an episodic disorder. It is noteworthy that these estimates are conservative, because subthreshold (prodromal or residual) and successfully-treated depressive patients are not considered! This review also explained the higher estimates in more recent studies, which use increasingly more sophisticated depression assessment methodologies that probe more intensively for the presence particularly of past episodes and the existence of cohort effects. Cohort effects suggest that depression rates have been increasing over the last decades due to increasingly higher rates in more recent birth cohorts compared with older cohorts.

Figure 2
Figure 2. Lifetime (A) and 12-month (B) prevalence estimates for major depressive episode by age group and gender, according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition/Composite International Diagnostic Interview. Based on data from reference 5.

_ Depression rates and age of onset
Concentrating on MDE in adults (18-65+ years of age), the most recent US National Comorbidity Survey-Replication (NCS-R)5 found—by and large consistent with the most recent studies in the European Union14—that the lifetime prevalence of MDE is 22.9% in females and 15.1% in males (Figure 2A).

Rates are highest in the age group 35-49 (females 26.7%, males 18.6%), and are dramatically lower among subjects aged 65+ (females 13.0%, males 5.3%). Interestingly, the youngest age group reveals onlymarginally lower lifetime rates compared with the older groups. 12-month prevalence rates (Figure 2B) are about half the rates for lifetime, revealing similar patterns for age and gender. These findings are counterintuitive at first sight: first, there are high rates even among the youngest age group and there is only a small difference with regard to the age group 35-49, typically assumed to be the high-risk phase and the age group mostly frequently seen in inpatient and outpatient settings. Second, the considerably lower lifetime rates in the elderly appear to be inconsistent with the perception that rates of depression in the elderly should be higher, and not lower, because of their considerably longer time period at risk formajor depressive disorder, and because of other factors (see later).

_ High prevalence and incidence risk in childhood and adolescence?
Carefully conducted prospective longitudinal studies17-21 all come to the same conclusion: major depressive disorder and MDE, although rare in children (age <10 years) of both sexes, are already quite prevalent in adolescence, a time period during which the gender difference becomes apparent. Figure 3 displays this gender differentiation using data from birth to the mid 30s from the prospective-multiwave Early Developmental Stages of Psychopathology (EDSP) study. The curves reveal a higher estimated cumulative incidence (35.6%) for first onset in females at age 33 years than for males (23.1%). Most cases with MDE emerged between the ages of 12 and 25 years, with a significant gender difference apparent at around age 14 years. Both males and females showed continued new onsets of MDE after the age of 25 years, suggesting continued, though attenuated, incidence rates over the lifespan. The consistent evidence of high depression rates in adolescence and young adulthood, along with similar or even stronger evidence for substantial impairment, disability, and treatment rates associated with young age depression,5,21,22 leaves little doubt that the high community estimates in the young describe clinically meaningful depression.

Figure 3
Figure 3. Age of onset hazard ratios for major
depressive episode (MDE) in males and females.

After reference 21: Beesdo K, Höfler M, Leibenluft E,
Lieb R, Bauer M, Pfennig A. Bipolar Disord. 2009;11:
637-649. Copyright © 2009, John Wiley & Sons.

Figure 4
Figure 4.
Resilience
model for
depression
over the
human
lifespan.

After reference
26: Fiske A,
Wetherell JL,
Gatz M. Annu
Rev Clin Psychol.
2009;5:
363-389.
Copyright ©
2009, Annual
Reviews.

_ Low rates in the elderly?
The substantially lower rates for the elderly are puzzling and have prompted the search for reasons for this finding. Initially, research suggested that the diagnostic instruments were not valid and were inappropriate for older adults,2 with authors suggesting a series of modifications in order to account for different response styles in the elderly. However, these adaptations did not result in substantial increases in subsequent estimations. Kessler et al5 also excluded the possibility that recall failure accounts for the difference, by showing that the estimate ratio for subjects aged 65+ is lower for both 30-day and 12-month estimates (31%-32%) than for lifetime prevalence. This gradient suggests that recall error is not responsible for the lower prevalence among the elderly. Recall error, as suggested by Simon and vonKorff,23 would produce an opposite pattern. Related observations are that: the ratio of 12- month prevalence to lifetime prevalence is consistently lower among respondents aged 65+ (22%-28%) than in younger respondents (37%-57%), depression in the elderly is more frequently “clinically mild” (21.8% vs 8.2% in 18-34 year olds, 6.8% in 35-49 year olds, and 10.3% in 50-64 year olds), and is associated with a significantly lower degree of severe role impairment and a lower number of days out of social role because of depression. Consistent with some previous research,24,25 these findings suggest that community rates of major depressive disorder and MDE in the elderly, as defined by DSM-IV criteria, are indeed considerably lower than in the younger age cohorts.

Several explanations have been suggested for this finding, such as: (i) the existence of cohort effects; (ii) a different phenomenological presentation of depression in the elderly requiring possibly a modified set of criteria; (iii) disproportionably high (as compared with younger age groups) exclusion rates of severely ill older subjects suffering from somatic and neurological and neurodegenerative diseases; and (iv) increased resilience of older people that protects them against severe depression (Figure 4).

_ Phenomenology
Depression in old age differs both in subtle and obvious ways from depression earlier in the lifespan. Presentation, etiology, risk, and protective factors all reflect aspects of the older adult’s position in the lifespan. Further, there is some consensus that late-onset depression in old age has distinctly different risk factors (eg, increased rates of vascular, including cerebrovascular, disorders)27 and presentation (eg, decreased rates of cognitive-affective symptoms of depression and increased sleep disturbance)28 than earlier-onset depression. In this context, a number of old age depression variants have been suggested: for example, “vascular depression executive dysfunction syndrome,”29 “depression without sadness” or “depletion syndrome,”30,31 Parkinson’s Disease Depression,32 or Alzheimer’s Disease Depression.33 Yet none of these concepts has received wider acceptance. Furthermore, there is little evidence from psychometric explorations that the structure of depression in the elderly is overall significantly different from that seen in younger age groups.34

_ Exclusion of severely comorbid patients
Undoubtedly, rates of major depression among older subjects are substantially higher in particular high-risk subsets of the population, such as those requiring intensive medical attention, including inpatient and residential treatment. For example, epidemiological studies in Parkinson’s disease patients report amean prevalence of at least 17%35 and up to 25.2%.36 Similarly elevated rates have been reported for Alzheimer’s dementia patients,37 patients with stroke and coronary heart disease,38,39 and residents of long-term care facilities (14%- 42%).34,40,41 Thus, one might speculate that the lower rates in the elderly could be due to the exclusion of such high-risk populations in epidemiological “door to door” surveys. However, given the prevalence of these conditions, it is unlikely that this factor alone can account for the difference. Furthermore, the recent World Mental Health Survey found no indication that the increased burden of pain and somatic diseases in the elderly is associated with corresponding increases in depression status.16 The majority of older people in this analysis had chronic physical or pain conditions without comorbid mental disorders and depression in particular. Yet it remains unclear as to how these findings match the well-established finding that pain and chronic somatic conditions can be risk factors for depression, and the significant relationship between increased rates of depression and somatic syndromes—in particular, increasing rates as a function of number of multimorbid somatic diseases.42,43

_ Increased resilience
Since most older adults experience disability, pain, and bereavement and have agerelated changes in immune, neurological, and other biological systems, there has been some research into resilience factors that might explain why the elderly less frequently report experiencing depression. As summarized by Fiske et al26 and Hendrie et al,44 three groups of explanations have been suggested as representing depression buffers (Figure 4): (i) the perceived importance of resources like socioeconomic status, remaining cognitive function, and health; (ii) life experiences that have taught older adults psychological strategies and ways to use social support and manage the stress; and (iii) the role of meaningful engagement, whether in social activities, volunteer work, or religion.

To conclude, none of the current explanations fully accounts for the observed low depression rates in older adults. The preponderance of current evidence indicates that at least major depressive disorder is less common in old age, while clinically significant subthreshold depression, which can also be consequential and is treatable,45 might be quite common.

Number of episodes and duration

With very few exceptions,5,46-49 most studiesmerely report rates of MDE by age group, but do not specify frequency and duration. Thus, even the proportion of single versus recurrent episodes, or chronic versus episodic depression, remains frequently unreported.

Figure 5
Figure 5. Birth (current age) cohort effect for estimates of major depressive episode
in the general population. Based on data from reference 50.

Kessler et al5 report a mean age of onset of 26.2 years for a first episode of MDE, with the lowest age of onset for 18-34 year olds (mean 17.8 years) and substantially higher ages for subsequent age groups (35-49 age group, 25.5 years; 50-64 age group, 33.1 years; 65+ age group, 43.0 years). Among cases with recurrent depression, the mean number of MDE was 18.6 overall, with the lowest number among the young (18-44 years, 15.4 episodes) and the highest for the elderly (30.2 episodes). Spijker et al48 reported a median duration of MDE of 3 months in the community. A total of 50% of the participants recovered within 3 months, 63% within 6 months, and 76% within 12 months, and nearly 20% were not recovered at 24 months. Determinants of persistence of the episode were severity of depression and comorbid dysthymia; recurrent depression typically had a shorter episode duration. This is by and large in agreement with a more fine-graded analysis50 based on a total of 736 DSM-IIIR MDE cases from the general population. Considerable birth cohort effects regarding the total cumulative MDE risk and age of onset were found (Figure 5), suggesting that the number of episodes and their duration might be different by birth cohort. Overall in this analysis, 53% reported only one episode, while 17.4% had 2-3 episodes, and 29.6% had 4 or more episodes (Figure 6A, see page 120).

The proportion of cases with one single episode of MDE declined fairly consistently from 67.9% in those with less than 10 years at risk, to 46.2% among cases with 40-50 years at risk. Conversely, the proportion of those with 2-3 episodes increased from 9.5% to 19%, and for those with 4+ episodes from 22.7% to 34.7%. This finding is in agreement with a similar analysis recently reported for patient populations by Coryell et al.51 What is remarkable though, is that the oldest group with the longest period at risk for depression also revealed a higher proportion of single episodes, suggesting a substantial number of new-onset cases in old age.

In terms of episode duration, overall, 39.6%had short episodes (2-5 weeks) and 17% had an intermediate length of 6-20 weeks (Figure 6B). The majority of cases of MDE reported an episode duration of more than 21 weeks, and chronic depres- sion (more than 51+ weeks) is strikingly frequent (32%). The proportion of long episodes (21+ weeks) increased steadily by time at risk, being lowest in those with exposure time of less than 10 years (33.5%) and highest among the elderly (exposure time 50+ years; 66.7%). Rates of episodes lasting 51+ weeks increased accordingly from 27% (<10 years) to 59% (50+ years). Figure 6
Figure 6. Number of depressive episodes (A) and episode duration in weeks (B) among community cases with lifetime major depressive episode (MDE) by years at risk.

These findings suggest that in contrast to recent interpretations of clinical samples,51 there is a pathoplastic effect of age or birth cohort on the temporal expression of depression over the lifespan, with more frequent episodes of shorter duration in the young, and the elderly being characterized mainly by long episodes and chronic depression.

Factors influencing the timing of depression

_ Sociodemographic factors
Gender is the best-supported risk marker for depression.43,52,53 The approximately twofold higher risk of women suffering from depressive disorders than men is consistent over cultures and most age groups (see Figure 2).5,49,54,55 The 2:1 ratio develops not before puberty and cannot be observed among children before the age of 10 years.56 Attempts to explain this gender difference by psychosocial, sociodemographic,57 or biological factors have, however, been inconclusive.58 Recent attempts to shed light on this gender difference focus on the interaction of genetic and biological factors on the one side, and environmental and psychosocial factors on the other (see below).53,54

Consistently, studies have found associations between higher lifetime and 12-month prevalence and one or more markers of less privileged social position, such as being unemployed or disabled, living in—or near—poverty, and having a low income. Homemakers were found to have elevated rates of 12- month, but not consistently lifetime, MDE. Being unmarried was also consistently found to be related to depressive disorders,13,55 the risk for those having lost their partner through divorce, separation, or death of the partner sometimes being found to be even higher.13 The effects of marital breakdown or death of the partner appear to be stronger for men; ie, the increase in risk for a depressive disorder is more pronounced among men. This sometimes results in comparable rates of depressive disorders above 20% among men and women who are divorced, separated, or widowed.57 No consistent associations are generally reported for different geographical areas when other confounding factors are taken into account.59

_ Family genetic factors
There is consistent evidence from family studies that parental depression substantially increases the risk of the offspring also developing depressive episodes.60-63 Such studies have also included examinations of the familial aggregation of recurrence risk60,64-66 and duration of key symptoms.61,67 Meta-analyses of family, twin, and adoption studies reveal that the risk of recurrence of major depression is the measure with strongest empirical support for familial aggregation, while evidence for duration is less convincing.63 However, it should be noted that there is little diagnostic specificity. That is, familial anxiety, substance use disorder, or other mental disorders have often been found to be as important as depression or other mood disorders in predicting depression.13

A particularly informative community study in this respect was carried out by Lieb et al,68 who prospectively studied the longitudinal risk of depressive episodes in 3021 offspring over the first three decades of life by parental mental disorder status, assessed by independent diagnostic interviews. Offspring of depressed mothers (odds ratio, 2.9) and depressed fathers (odds ratio, 3.0) were at substantially increased risk of also developing depression up to age 28. The effects were more pronounced when both parents had suffered a lifetime episode of depression and were also elevated in comorbid anxiety disorders. Particularly noteworthy was the finding that parental depression shifts the age of onset of depression in childhood significantly forward. Furthermore, affected offspring had an increased risk of recurrent episodes (among those with nonaffected parents the mean number of recurrent episodes was 2.7, among those with affected parents it was 5.2; odds ratio, 1.8), and persistent depression (9 weeks versus 30 weeks; odds ratio, 4.5).69

_ Childhood and developmental adversities, life events and disasters
Retrospective assessment in cross-sectional studies has shown that childhood adversities, including traumatic events, are significant predictors of an increased prevalence of depression and earlier age of onset. Intercorrelations between different types of childhood adversities make it difficult to pinpoint any particularly important type of adversity.13 More recent prospective longitudinal studies have also highlighted the particular caution that is warranted if using only retrospective designs.70 By comparison with childhood adversities, more specificity has been found in the effects of stressful life events and their relationship to depression.43 Stressors involving loss are more strongly related to depression, while stressors involving threat and danger are more strongly associated with anxiety, and stressors involving both a combination of danger and loss are related to comorbid presentations and higher levels of persistence.52,71,72 There are also important associations with lack of social support73 as well as familial and genetic elements.63 The effects of life events in women seem to be slightlymore pronounced than inmen across all ages,74,75 suggesting one potential reason for the gender difference in prevalence. The relationship between life events and first onset76 and remission77,78 appears to be stronger than for successive recurrent episodes, which seem to be less dependent on external triggers.79 These findings, however, might be dependent on the type of life event or stress assessed; chronic stress seems to be more relevant for the first episode, and acute stress and an interaction of chronic and acute stress80 might foster recurrent episodes.81 The complex interplay with neurobiological factors in this respect has been recently highlighted by Caspi et al,82 Moffit et al,83 and Zimmermann,84 revealing that adverse events are particularly pathogenic in individuals with genetic or familial genetic susceptibility.

Adverse events and chronic life difficulties have also been suggested as an explanation for sociodemographic associations between depression and socially disadvantaged groups, who might have fewer resources to cope with stressful situations. Recently, Kessler et al presented an impressive example of the effect of life events on the risk for mental disorders, and the temporal pattern,85 in a representative sample of prehurricane residents involved in Hurricane Katrina. Contrary to results from other disaster studies in which psychiatric morbidity has typically declined with time, substantial increases in post traumatic stress disorder (14.9% to 20.9%) as well as depressive disorders (10.9% to 14%) over a 2-year observation time were found. Unresolved hurricanerelated stresses accounted for large proportions of the intertemporal increases in depression (89.2%).

_ Effects of cormorbid conditions
_ Mental disorders
The effect of all anxiety disorders86,87 on the onset and course of depression has been well established through cross-sectional88- 94 and prospective longitudinal investigations,86,95-97 as well as through clinical studies.98,99 Studies in adolescents and young adults are particularly informative, because this is the high-risk incidence phase for anxiety disorders. Such studies95,100 have demonstrated the substantially and consistently increased risk of subsequent depression, as well as a moremalignant course and character of secondary depression.

With some variation according to type of anxiety disorder, up to 50% of all subjects (Figure 7A, page 122) with a primary anxiety disorder have been shown to develop depression, constituting a threefold increased risk of depression. Furthermore, a considerable shift forward in the age of onset of the first episode of depression has been found (see Figure 7B), so that depression occurs earlier. These findings suggest etiologic links between these two types of disorders. Similar, though less consistent, data have also been found for other mental disorders (eg, somatoform disorders,101 substance use disorders102).

_ Somatic comorbidity
Community studies103 show a close relationship between major depression and physical illness. Evidence for the possibly bidirectional influence of somatic and mental disorders has been provided for such diverse conditions as acute coronary syndromes and depression,104 as well as “disorders of the female reproductive cycle”105-109 for example. Among adults, particularly strong associations were found between chronic disorders and increased risk for MDE, particularly if the disorders involved pain and suffering or major long-lasting restrictions or disability ormultimorbidity.42 Chronic diseases and poor general health were particularly predictive of new depressive episodes over a period of 1 year.110 It should be noted though that the relationship is apparently quite complex, since there is no consistent linear relationship between the degree of somatic morbidity and the risk of depression, nor a consistent relationship with aging,5 suggesting that there are also interactions with environmental and biological factors at play.111 Because of the complexity of multimorbid presentations, there is still insufficient knowledge and data to identify causal relationships and risk factors.112

Figure 7
Figure 7.
A. The risk from
primary pure
anxiety disorders
for development
of a secondary
depressive
episode over a
period of 10
years, by type of
anxiety disorder.
B. The risk of a
major depressive
episode (MDE)
according to age
of onset of MDE,
in those with and
without a primary
anxiety disorder.
GAD,

generalized
anxiety disorder.

Age cohort effects: are depression rates increasing?

Given the topic “the timing of depression,” it is almost inevitable that finally one should address the controversial question of whether depression rates are increasing. Examination of the epidemiological evidence leaves little doubt: almost invariably across studies, using a range of different methods, higher overall rates of depression have been documented over time as well as successively younger birth cohorts. Particularly increasing rates in the young have been found, which are associated with a shift forward to younger ages in each successively younger age group. Furthermore, despite proportionally lower rates for the elderly, there is also evidence from recent studies that rates of depression in the elderly are higher compared with those of the 1980s. Thus, why question this trend? At the core of this continued controversy is the question of whether this constitutes a “true” increase, that is, have people in communities around the world “really” become more frequently depressed than 2-3 decades ago? This is almost a philosophical question, because we deal with a theoretical construct measured with imperfect assessment instruments, in studies that are necessarily imperfect as well. Because our understanding of depression, the defining criteria, and our assessment instruments have changed, as has probably the awareness and perception of depression in society, it seems impossible to give a definite answer. Admittedly the meaning of the increasing rates and the cohort effects remain not well understood, and there are other valid concerns that range from methodological concerns regarding the reliability and validity of diagnostic criteria and assessment tools used in the studies, to design and statistical issues inherent in time trend analyses, to speculations about the artifactual nature of such findings, for example with regard to the role of recall failure, response biases, and willingness to report depressive symptoms. However, most of these issues have directly or indirectly been addressed,5,25,113 revealing that none of these factors alone or in combination is able to explain the increase and the cohort effects.

Furthermore, the demonstration of increasing rates is consistent with a broad range of external indicators, such as increased rates of depression in mental health care and primary care institutions, substantially higher rates of children and adolescents receiving treatment, increased rates of suicide attempts, and substantially increasing disability burden due to depression.14 Assuming that such cohort effects and increases exist, there are tremendous implications for the future. For example, the higher rates and the shift to an earlier age of onset in younger birth cohorts can be expected to be associated with an increasing risk for recurrent episodes and increasingly longer and chronic episodes over the lifespan. In addition, given the continued increase in life expectancy in most countries, one can anticipate a continued high—and even increasing—global societal burden, and a substantial challenge for the mental health field. _

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Keywords: depression; age of onset; disease course; risk factor; development; prevalence; rate