Vincent van Gogh, a few months before his death, painted a picture of an older man who was sitting on a simple chair in a bare room and was leaning forward while balling his hands over his eyes. The picture graphically depicts depression in later life and what is frequently thought to be the origins. First, as this man is elderly and perhaps infirm, he would appear to have every reason to be depressed. His posture graphically depicts the psychological pain he is experiencing. The room is empty of all, except the most essential furniture, and, therefore, his earthly possessions are quite limited. He would appear to exemplify the bio-psychosocial model of depression. Yet, van Gogh titled this picture At Eternity’s Gate. The artist was known to be most interested in spiritual factors, even though he never fit comfortably into the established religions of his day.1
This painting provides a graphic example of the transdisciplinary origins of late-life depression, including the biological, psychological, social, and spiritual origins.2 It neglects, however, to portray an equally important perspective about depression in the elderly. Namely, older people may bring strengths to the challenges of aging, as well as vulnerabilities. Late-life depression presents a paradox to clinicians and epidemiologists. On the one hand, virtually every risk for depression across the life cycle is magnified in the elderly. Yet the frequency of late-life depression in Western community settings has consistently been estimated to be lower than at earlier ages. In this article, I review examples of increased risk for late-life depression, as well as potential factors that may mitigate against the onset of persistence of these depressive episodes, that is, protective factors. This review includes representative studies but in no way attempts to be comprehensive. I consider risk and protective factors as those that are biological, psychological, social, and religious/spiritual. Only through such a transdisciplinary approach can the clinician best understand and assist the older patient through the emotional suffering of depression.
There is considerable evidence that late-life depression, as depression across the lifecycle, is driven, in part, by genetic predisposition. Twin studies have consistently revealed the genetic factors that explain between 20% and 30% of the variance in mood in the elderly.3 Even so, no single gene has been identified as specifically causing depression in the later years. Also, it is unlikely that a specific gene will be identified in the future. The genetic origins of depression are necessarily complex. Nevertheless, there are findings that may have clinical utility in treating depressed elders.
For example, a study from Duke University Medical Center has built upon the recognition that dysregulation of central serotonin neurotransmission is an important contributor to major depression.4 In this study of 87 depressed older adults and 219 controls, a single nucleotide polymorphism (SNP) in the rate-limiting enzyme of neuronal serotonin synthesis, human tryptophan hydroxylase-2 (hTPH2), has been identified. Among the depressed patients, more than 10% carried the mutant allele, whereas only three subjects carried the allele among the controls. In addition, the dysfunctional SNP was not found among 60 bipolar disorder patients. Of significance, seven of the subjects with the mutant allele exhibited lack of responsiveness to a selective serotonin reuptake inhibitor (SSRI), whereas the other two patients responded only to a higher dose of an SSRI. This finding suggests that, in a minority of elderly patients, a genetic screen may provide information that can inform clinicians as to whether an older adult will respond to an antidepressant medication. Of course, these findings must be replicated and tested in clinical trials, yet such data provide a window into how knowledge of the human genome can eventually inform clinical practice.
Of all of the potential biological risks for depression in later life, the association of depression with vascular lesions in the subcortical areas of the brain are by far the most consistent and compelling.5,6 In fact, criteria for “vascular depression” have been suggested to describe this subset of the depressive disorders in late life. Compared with major depression without vascular changes, vascular depression is more frequent in the oldest old, has a later age of onset, and tends to be nonpsychotic. Family history is less frequent, and prominent symptoms include anhedonia and executive function impairment. Functional disability is a common correlate of vascular depression.
Of special importance in vascular depression is the finding of impairment in executive function.7 Executive dysfunction is defined by disturbances in planning, sequencing, organizing, and extracting information. In contrast to memory impairment, executive dysfunction is associated with relapse and recurrence of depression in late life. It may result from a disruption of the cortico-striatal-pallido-thalamo-cortical pathway (the function of which is modulated by the raphe nuclei, the locus ceruleus, and the ventral tegmentum). These pathways are thought to be disrupted by the vascular lesions and the resultant degenerative processes.
Age-related changes in neurotransmitter systems do not appear to place the older adult at relative greater risk for depression than people in middle age.8 Virtually all markers of noradrenergic and serotonin activity tend to diminish with aging, such as alpha-2-binding and 5-HT2a receptor binding (but the rate of decrease in binding slows dramatically after midlife). Therefore, the changes in neurotransmission and dysregulation of receptor sites associated with depression are equally important in late life as they are in midlife, but there is no reason to believe older persons are uniquely vulnerable to depression in terms of neurotransmission.
Among the most important biological factors contributing to late-life depression are comorbid medical illnesses.9 Perhaps the most frequently studied has been cardiovascular disease, in which a clear and frequently replicated association has been identified.10,11 Not only does cardiovascular disease increase the risk of depression, but comorbid depression and cardiovascular disease increase the mortality of individuals with cardiovascular disease. Chronic pain, such as pain from cancer, is also associated with late-life depression.12 For many years, investigators and clinicians have recognized that depression is often associated with Alzheimer’s disease13 and stroke,14 especially left-sided stroke. Finally, late-life depression is associated with a number of physical symptoms, such as urinary incontinence and shortness of breath.15
An interesting and important area for further exploration is the mechanism by which physical illnesses may contribute to the onset of late-life depression. For example, the stress of these physical illnesses may be sufficient to explain the onset of depressive symptoms. Others, however, suggest that a direct relationship between factors, such as cardiovascular functioning and depression, can be identified.16 An equally interesting and important finding has been the association of stress, with a downturn in mood and changes within the brain, which, in turn, may increase the propensity of older adults to experience depression. For example, stress leads to a downturn in mood and elevated cortisol levels.17 Elevated cortisol, over years, may inhibit neurogenesis and lead to hippocampal volume loss, which, in turn, leads to cognitive symptoms of depression.18,19
By far, the most frequent psychological factor discussed in the literature, as related to depression across the life cycle, is cognitive distortions.20 Cognitive distortions can predispose the older adult to depression when the elder has unrealistic expectations, overgeneralizes adverse events, overreacts to events, and personalizes events. For example, an older man who is living alone may, upon learning that his daughter will not visit as she had planned on a Saturday afternoon, overgeneralize by thinking that she no longer cares for him. In reality, the daughter simply was forced to cancel a scheduled visit because she was caring for the needs of a teenage son. In one case-control study, patients with major depression in late life perceived greater negative effect of life offense compared with patients with dysthymic disorder and healthy controls.21
Yet the psychological vulnerability to cognitive distortions in late life and other psychological vulnerabilities may be mitigated by protective factors. One such factor, difficult to quantify yet recognized intuitively, is wisdom. In other words, older persons are thought to accumulate wisdom through the lifecycle and, therefore, are thought to be better prepared to manage stressful events when they occur.
Wisdom is said to be the final stage of personality development. Individuals who are thought to be wise score high on Eric Erikson’s measures of ego integrity.22,23 These include the ability to problem find (to search for the unanswerable instead of constantly seeking answers). For example, an older woman who has been certain about her political convictions throughout adulthood may ask, “How can I be so certain that the platform of my political party is actually the best for our country at this time?” The wise also are thought to have an ability to integrate multiple accounts to a single dialectic whole. For example, an old man may recapitulate the consequences of a past event as follows: “I did not attain that job years ago. At the time I thought not being hired was about the worst thing that could happen to me. Now, I realize that I was fortunate not to be hired. I found a better position some years later, a position that would not have been available if I had taken that other job.”
Additional characteristics of wisdom include dealing with uncertainty and the lack of perfect knowledge. For example, the older adult may say, “I just don’t know how the Bible and evolution can be reconciled, and I probably never will.” Yet another characteristic of wisdom is transcendence of personal interest. For example, the older person may look beyond herself in considering how her financial resources can best be distributed. She may determine that she can live more frugally so that she can support a cause of importance to her at her local church.
Finally, a characteristic of wisdom is mastering one’s finitude. Death tends to be more a psychological crisis in midlife, often when a close friend or relative of nearly the same age dies of a natural cause, than in later life.
Stressful life events can lead to depression regardless of age. In a meta-analysis of 25 studies of the relationship between negative life events and depression in late life, it was found that the total number of life offense and the total number of daily hassles were strongly associated with depressive symptoms, whereas sudden unexpected events were not related to depression.24 In other studies, chronic strain has been found to be associated with depression and over adults. For example, the prevalence of depressive symptoms and caregivers of people with dementia is as high as 43% to 47%.25,26 In yet another study, older Mexican-Americans who experienced financial strain were much more likely to be depressed than those who did not.15 From these and other studies, it appears that daily hassles and chronic strain are more likely to lead to depression in the elderly than a specific major event. However, we cannot underestimate the potential negative consequences of a severe event, such as the loss of a spouse or the sudden onset of a severe medical illness.
Most older adults believe that they have enough contact with family and friends, despite the general assumption that older persons are lonely. In general, social support is perceived to be more than adequate among older persons, even in clinical samples. Yet when the social network is depleted suddenly, the loss of a network member (such as a spouse or child) or through a change in the quality of the relationship (such as a dispute with a family member), impaired social support may be a most important contributors to late-life depression. The most robust relationship between impaired support and late-life depression symptoms have been found with perceived support.27 For example, in a community survey in Hong Kong, impaired social support in depressive symptoms were associated with satisfaction, with the social network being a most important factor.28
Two more recent approaches to exploring the effect on late-life depression of social factors are neighborhood effects and social network analysis. In neighborhood effects, structural and functional characteristics of neighborhoods, such as poverty racial/ethnic composition, the prevalence of crime, and the availability of institutional resources are explored in relationship to a health outcome, such as late-life depression (see Figure). In this analysis, individual characteristics, such as socioeconomic status and race, are controlled. The results have been mixed, with one study suggesting that problematic neighborhood effects have an independent association with late-life depression,29 and one not showing a relationship.30
Figure. A Model of the Interaction Between Neighborhood Effects and Individual Effects.
In social network analysis, characteristics of the social erections of an individual beyond simply qualitative assessments of the adequacy of these relationships are used to explore health outcome, such as depression. In a study of a community sample of older adults, five network types, based on marital status, number of children, contacts with children, religious service attendance, contact with friends and family, and meeting attendance, were determined.31 These included nonfamily/restricted networks (little contact with family or friends); nonfriend but average family contact networks; family networks (high family contact with average friend contact and also associated with religious service attendance); diverse networks (high scores in all categories); and friend networks (high friend contact with average interaction with family members). Depressive symptoms were higher for individuals in the non-friends network and lowest for individuals in the diverse network. This suggests that lower family contacts, yet good contacts with friends, are less detrimental than lower friend contacts along with adequate family contacts.
A paradox emerges from these data, which has intrigued investigators studying depression in the elderly.32 In most community surveys, the prevalence of major depression and dysthymia in cross-sectional studies of community samples is lower in late life compared with earlier stages of the lifecycle. If older persons are at greater risk biologically to developing depression (such as the increased risks that can carry to medical illness and vascular depression), why are these prevalence estimates in the community lower? One explanation is that older persons may experience significant protection from late-life depression because of psychological factors, such as wisdom and social factors, such as supportive social networks.
Of all the psychiatric disorders, the depressive disorders have been most closely correlated with ordinary spiritual experience. We often recognized in our patients that the struggle with depression reaches to the very core of the spiritual experience in many faith traditions. For example, in the Bible, Job states, “May the day of my birth perish, and the night it was said, ‘a boy is born’ ... Why is light given to those in misery, and life to the bitter of soul, to those who long for death that does not come ... ?’ (Job 3:3–21).
Eric Erikson proposed that the developmental task of old-age is the achievement of integrity in the light of the challenges faced when aging.23,33 Failure to do so leads to despair. Religion is critical for the lifelong quest to grasp the “cosmic order” as one’s one and only life approaches it completion. Erikson expanded this proposition through his exploration of the life of Martin Luther. He believed extraordinary individuals, such as Luther, may encounter lifelong and intense challenges with religious/spiritual integration. Because they are unsatisfied with the traditional answers to the most difficult questions of life’s meaning, they are burdened by a melancholy world view. Their personal struggles can lead to major revolutions in a society’s orientation to religion. In fact, biographers have noted that Luther did experience multiple episodes of melancholy.34
When we review the empirical evidence, however, some interesting patterns emerge. First, there is some (but minimal) evidence that the expression of depression may vary by religious background. One study compared depression in middle-aged and older adults in French Canada and Hungary. The study was done before the fall of Communism and, at that time, Hungary was much more secular than Canada, with Canada being greatly influenced by Catholic traditions. Investigators found that the French-Canadians were more likely be agitated and to link their depression with self-blame based on religious beliefs.35
For many years, it’s been believed that religious affiliation may be related to depression, yet the empirical data is mixed. For example, in a study from the Bronx, being Jewish was found to be a risk factor for the prevalence and incidence of depression among older adults.36 In contrast, in another study, Jews were found to have a lower risk of developing depression than Catholics in a 3-year follow-up of the elderly.37 Religious affiliation may not, however, be the factor leading to depression. For example, in a community study from North Carolina, investigators found that Pentecostals were three times more likely to experience major depression than non-Pentecostals.38 In this cross-sectional study, the discrepancy may be because of the aggressive evangelistic outreach of Pentecostals to people in lower socioeconomic classes and other groups at high risk for depression, and the optimistic message of the Pentecostals may, in fact, try to help the depressed.
By far, the most consistent, positive association between religion/spirituality and depression involves the assessment of religious activity, most often attendance at religious services. In a study from the Bronx, the rate of depression in older subjects who attended religious services regularly were significantly lower than for subjects who attended services infrequently or not at all, even controlling for physical health, social support, sex, and race.36 Religious salience has proven less consistent as a predictor of lower rates of depression. In one study, those with a low score in religious salience, specifically older adults living in the community who indicated that a strong religious faith was “not important” in their lives, were found to be three times more likely to become depressed than those who indicated that faith was “very important.”39
Upon review of potential biological factors, which contribute to late-life depression, overall biological vulnerability is perhaps the greatest for vascular lesions in the brain, chronic stress leading to changes structural brain changes over time, especially in the hippocampus, and medical illnesses. When considering psychological factors, we must recognize that some factors may at times increase risk and other factors may protect against the risk of late-life depression. For example, cognitive distortions clearly increased the risk and persistence of depression in the elderly. In contrast, the accumulation of wisdom over many years may be an important protective factor against late life depression. Social factors also may increase vulnerability for and protect older adults against depression. For example, stressful events certainly increase the risk of depression in the elderly, yet the availability of supportive social network (the norm in later life) is protective. When exploring social factors in the future, new approaches to ascertaining the nature of the social network as it relates to late-life depression should include neighborhood effects meant to be individual effects and more in-depth assessment of social networks. Of the religious/spiritual factors, only religious participation appears to be a consistent protective factor against late-life depression in empirical studies. Given the resilience of older adults and their strengths, we must always remember, “Where there is depression, there is hope.”
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