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Psychobiological factors of resilience and depression in late life

Kelsey T. Laird, Beatrix Krause, Cynthia Funes and 1 more

Translational Psychiatry · 2019 · Review · CC BY

doi:10.1038/s41398-019-0424-7

Abstract

In contrast to traditional perspectives of resilience as a stable, trait-like characteristic, resilience is now recognized as a multidimentional, dynamic capacity influenced by life-long interactions between internal and environmental resources. We review psychosocial and neurobiological factors associated with resilience to late-life depression (LLD). Recent research has identified both psychosocial characteristics associated with elevated LLD risk (e.g., insecure attachment, neuroticism) and psychosocial processes that may be useful intervention targets (e.g., self-efficacy, sense of purpose, coping behaviors, social support). Psychobiological factors include a variety of endocrine, genetic, inflammatory, metabolic, neural, and cardiovascular processes that bidirectionally interact to affect risk for LLD onset and course of illness. Several resilience-enhancing intervention modalities show promise for the prevention and treatment of LLD, including cognitive/psychological or mind–body (positive psychology; psychotherapy; heart rate variability biofeedback; meditation), movement-based (aerobic exercise; yoga; tai chi), and biological approaches (pharmacotherapy, electroconvulsive therapy). Additional research is needed to further elucidate psychosocial and biological factors that affect risk and course of LLD. In addition, research to identify psychobiological factors predicting differential treatment response to various interventions will be essential to the development of more individualized and effective approaches to the prevention and treatment of LLD.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 22, 2026. Paragraph numbers are ours, so an answer can point at one.

Depression vs. resilience in late life

Late-life depression (LLD) is a common and debilitating condition, with less frequent remission and more frequent recurrence following first-line antidepressant treatment compared to depression experienced earlier in life–. Factors contributing to LLD are multifaceted, including biological (e.g., genetic), psychological (e.g., personality), and social influences (e.g., social support). With the world population rapidly aging, it is increasingly important to identify factors that increase resilience to the development and maintenance of LLD.

Psychological resilience has been broadly defined as “the capacity to maintain, or regain, psychological well-being in the face of challenge”. Resilience is a complex construct that can be conceptualized as an attribute (a trait) that is possessed to varying degrees by different individuals, a dynamic process (a state) with bidirectional relations to developmental and environmental factors, and as an outcome in the face of stress and adversity. Depending on the theoretical perspective, population, and risk factor in question, resilient outcomes may be operationalized as either the presence of a positive outcome (e.g., life satisfaction) or the absence of a negative one (e.g., lack of psychopathology). We conceptualize psychological resilience as a multidimensional, dynamic capacity influenced by the interaction of internal factors (e.g., cognitive capacity, personality, physical health) and external resources (e.g., social status, financial stability). In the context of major depressive disorder (MDD), psychological resilience refers to the net effects of a variety of psychosocial and biological variables that decrease risk of onset or relapse, decrease illness severity, or increase probability or speed of recovery. The current review describes resilience and vulnerability factors related to LLD. We summarize psychosocial resilience factors that are universal across age groups as well as those unique to aging. We also present results of research investigating the neurobiological, genetic, and immunological biomarkers of resilience.

Psychological resilience factors

Multiple psychological resilience factors reduce an individual’s risk for depression across the lifespan. Enduring individual characteristics such as temperament, attachment style, and personality each prospectively predict risk for depression. In addition, multiple psychological processes are proposed to mediate this effect, including beliefs and coping behavior. Psychosocial and biological correlates of LLD are presented in Table 1. A proposed model of how biopsychosocial factors influence risk for LLD and illness course is presented in Fig. 1.

Temperament

Temperament is a basic inherited style, the structure of which has been inferred largely from genetic studies. Meta-analytic data indicate that within the temperament dimensions, harm avoidance (i.e., “behavioral inhibition”) is associated with greater MDD risk and decreased treatment responsivity. Research on individuals with age-related illness suggests that harm avoidance is similarly predictive of MDD in late life,. In contrast, meta-analytic data indicate that positive emotionality (e.g., positive affect, extraversion, and behavioral activation) decreases risk for depression. Related longitudinal research suggests that the capacity to experience positive emotions such as gratitude, interest, and love is one mechanism by which resilient individuals are buffered against risk for depression following trauma.

Attachment

Because early life attachment is thought to shape subsequent relationships, attachment theory– offers an important framework for understanding the etiology and development of depression across the lifespan. Insecure attachment is a risk factor for depression onset, illness severity, and relapse. Research suggests that increased emotional awareness and coping self-efficacy, may be two mechanisms by which secure attachment decreases stress reactivity. Longitudinal studies as well as studies of children raised in orphanages indicate that disorganized attachment during infancy predicts greater amygdala volume—a hypothesized biomarker of difficulty with emotion regulation. Although attachment style remains moderately stable throughout life, stressful life events have potential to decrease secure attachment, while high relationship satisfaction and emotional openness may increase secure attachment. Research indicates that insecure attachment continues to increase risk for depression in late life,.

Personality

Multiple personality factors increase risk for MDD. A recent meta-analysis controlling for baseline depressive symptoms found that low extraversion, high neuroticism, and low conscientiousness predicted depressive symptoms 5 years later. Research on stroke survivors, individuals with Parkinson’s Disease, and nonclinical older adult samples has found similar associations, suggesting that these effects are also observed in late life. Another personality characteristic associated with resilience is grit, defined as “perseverance and passion for long-term goals” in the face of setbacks. A recent study of 337 adults with LLD found that grit was associated with decreased severity of depression, apathy, and anxiety.

Beliefs and coping behavior

Cognitive behavioral theory posits that an individual’s beliefs about themselves, others, and the environment influence coping behavior and subsequent psychosocial adjustment,. For example, two recent meta-analyses found that low self-esteem (i.e., a negative evaluation of one’s self-worth) prospectively increased risk for depression,. Similarly, an individual’s self-efficacy for coping with a given stressor impacts the coping strategy they select and how long they persist in their efforts. Coping can be broadly divided into two domains: active (efforts to directly “solve” the source of stress) and accommodative (efforts to accept or adapt to the source of stress). Research indicates that the ability to flexibly apply active vs. accommodative strategies—i.e., using active approaches for controllable stressors and accommodative approaches for uncontrollable stressors—results in more favorable mental health outcomes–. A recent study of 337 adults with LLD found that both active coping self-efficacy and accommodative coping self-efficacy were associated with decreased depressive symptoms, apathy, and anxiety. In addition, greater baseline accommodative coping self-efficacy predicted antidepressant treatment responsivity. In general, individuals with high self-efficacy for managing stress through adaptive approaches such as physical exercise, social support, and self-care are more likely to engage in these strategies and less likely to develop prolonged symptoms of depression. In contrast, low coping self-efficacy is associated with passive coping, avoidance, lower treatment adherence,, substance use, and other maladaptive coping strategies that may serve to increase risk or course of depression.

An internal locus of control (i.e., “mastery”) is the general belief in one’s ability to influence outcomes. Because this belief increases self-efficacy for coping with a range of stressors, mastery can be conceptualized as another resilience factor. Similarly, evidence suggests that a “growth mindset”—the belief that one’s abilities can be enhanced through effort—increases resilience by increasing grit. Finally, a strong sense of meaning/purpose in life increases resilience to depression across the lifespan. A study of 1475 older Australian adults found that higher sense of purpose was associated with less disability, higher neurocognitive performance, and decreased depressive symptoms, and predicted increased survival in late life. By contrast, depressed older adults with symptoms of apathy generally have poorer clinical outcomes, quality of life (QOL),, treatment response,, cognitive impairment, and disability, possibly resulting from decreased engagement in social- and health-related behaviors. Other studies have investigated the effect of meaning/purpose on risk for depression among those at high risk due to exposure to acute or chronic stress. A longitudinal study of bereaved adults showed that two construals of meaning—making sense of the loss and finding benefit in the experience—both independently predicted decreased depressive symptoms. Other studies conducted with cancer survivors and individuals with terminal illness also report associations between meaning and decreased depressive symptoms. The results of one study suggest that increases in perceived meaning and benefit finding may be one way by which cognitive behavioral therapy helps prevent depression among cancer patients.

A final category of beliefs that increases risk for poor outcomes in depression is mental illness stigma. A recent meta-analysis found strong associations between internalized mental illness stigma and poorer psychological resources (hope, self-esteem, empowerment), lower treatment adherence, and greater mental illness symptom severity. In a study of adults with LLD, higher baseline depression-related stigma predicted worse treatment response, after controlling for baseline depression severity,. However, results of a longitudinal study of adults with LLD suggest that mastery may moderate this effect. In that sample, anticipated stigma only predicted increased depressive symptoms among those with low mastery. Mastery may counteract the negative impact of anticipated stigma on mental health by increasing older adults’ confidence in their ability to cope with stressors such as interpersonal rejection.

Religion and spirituality

Religion and spirituality have been shown to prospectively reduce risk for depression. Whether such effects are attributable to religious beliefs, behavior, or social support remains a matter of debate. One investigation of this question involved a study of over 1000 adult Detroit residents. In that study, religious attendance (e.g., church, temple, synagogue) was associated with greater psychological well-being and less emotional distress; frequency of prayer was associated with lower well-being and more distress; and belief in eternal life was associated with greater well-being but unrelated to distress. Religious attendance was associated with lower distress even after controlling for sociodemographic variables (e.g., age, sex, education), stressors (e.g., health problems, financial problems), social resources (family contact, support, and negative interaction), and psychological resources (self-esteem and personal mastery). By contrast, a study of almost 3000 older Taiwanese adults found that religious attendance no longer predicted decreased depressive symptoms after controlling for health behaviors, social networks, and supports. Consistent with the results of the Detroit study, religious beliefs and depressive symptoms were unrelated. Finally, a study of almost 8000 US older adults found that frequent attendance of religious services predicted decreased depression onset and frequent private prayer predicted increased depression remission 2 years later. Results of these studies indicate that religious coping behaviors may be more strongly protective against depression than religious beliefs.

Psychological factors specific to late life

The types of stressors encountered by older adults are qualitatively different than those faced by younger age groups. Late-life stressors include voluntary or forced retirement, chronic illness, cognitive decline, caregiving, financial stress, loss of independence, and bereavement. If these types of stressors are less controllable than those encountered by younger age groups, this could make accommodative coping especially essential in geriatric populations. Indeed, older adults appear to engage in more accommodative coping and less instrumental action coping compared to younger adults. Wrosch and colleagues propose a developmental theory in which age-adapted selection of coping strategies relates to optimal well-being. Consistent with this theory, active coping (i.e., “persistence”) was significantly associated with well-being in young adulthood and midlife, but not late life. Among older adults, accommodative coping was more strongly associated with psychological well-being than was persistence. Another study of LLD found that accommodative coping self-efficacy was uniquely predictive of subsequent remission.

Attitudes and stereotypes

One category of beliefs especially relevant to resilience in late life includes attitudes about aging itself. Studies in which negative stereotypes about aging are experimentally activated have found that both implicit/subconscious and explicit/conscious stereotypes negatively impact performance in older people attempting physical and cognitive tasks,. Other studies employing a cross-cultural approach have found larger age differences in cognitive performance in cultures with more negative stereotypes,.

Social role and identity changes

Traditional perspectives have assumed that major life changes inherently stressful. However, research suggests that role transitions such as retirement exert a wide range of possible mental health effects–, including increasing well-being when the change represents an escape from a chronically stressful role situation. A large Canadian survey found that retiring from a low-stress job increased depressive symptoms compared to not retiring, whereas retiring from a high-stress job resulted in an effect twice as large in the opposite direction.

Several studies have found that a greater number of “absences” in major social role-identities (marital, parental, and employment) is associated with poor late-life psychological adjustment–. Cumulating evidence indicates that formal volunteering may buffer against this effect by increasing social engagement, life satisfaction, self-worth, personal growth, and sense of purpose/meaning,–. For example, a US study of almost 400 older adults found that a greater number of major role-identity absences was associated with more negative affect, less positive affect, and less purpose in life. Formal volunteering was associated with positive affect, and volunteering positively moderated the relationship between role-identity absences and purpose in life. Other studies have found that older adults typically experience greater increases in life satisfaction with volunteering compared to younger adults and that adoption of a volunteer role may offset the negative impact of spousal bereavement on subsequent depressive symptoms.

Social resilience factors

Systematic reviews suggest that both perceived social support and objective social network size protect against depression in the general population as well as in older adults specifically. Research investigating the mechanisms by which social networks enhance psychological resilience indicates that both emotional support and tangible (“instrumental”) support are important contributors. Research has also begun to distinguish between the effects of objective vs. perceived social isolation (i.e., loneliness). One study of over 1300 older Irish adults concluded that these constructs were distinct and that each independently predicted depressive symptoms. An even larger US study of 20,000 adults found that loneliness was correlated with a host of other risk factors—less physical exercise, lower sleep quality, lower social engagement, and poorer physical health. Each of these factors likely interact to predict susceptibility to MDD. A cross-cultural review of additional social resilience factors identified being married or cohabiting, male, and having a higher family income each as associated with reduced risk of depression in the US and Japan. However, a 3-year longitudinal study of American adults aged 50–67 found that loneliness uniquely predicted depressive symptoms after controlling for demographic and psychosocial covariates such as marital status, perceived stress, and social support.

Social factors specific to late life

Adults tend to maintain fewer peripheral social partners as they age. It is hypothesized that an increasing awareness of time as limited influences older adults to prefer smaller and more emotionally satisfying social networks. Despite changes in social network structure over time, the average degree of loneliness appears fairly constant from middle- to late-life. In a sample of over 1600 older adults participating in the Health and Retirement Study, 43% reported feeling lonely. Similarly to findings with younger and middle-ages adults, loneliness increases risk for depression in late life. For example, a study of elderly Finish adults found that loneliness predicted long-term trajectories of depression. Additional social factors known to increase risk for LLD include bereavement, sleep disturbance, disability, prior depression, and female gender. A meta-analysis of gender differences in LLD suggests that some of these effects are attenuated once sex differences in prevalence of widowhood, health, and socioeconomic status are accounted for. Depression is also more common in older adults living in institutions compared to those living at home,.

Cognitive factors affecting resilience in LLD

LLD is associated with risk of cognitive decline,, mild cognitive impairment (MCI),, and dementia,,. One possible explanation for this association is that LLD and cognitive decline are manifestations of the same underlying neuropathology. Indeed, both LLD and dementia are associated with reduced brain volume, increased hippocampal atrophy, increased white matter microstructural changes, and altered structural and functional connectivity. Research suggests that chronic stress-associated stimulation of the hypothalamic pituitary adrenal (HPA) axis and associated over-secretion of the stress hormone cortisol contribute to neurodegeneration, that may increase risk for both LLD and cognitive decline. In addition, depressive symptoms may contribute to cognitive decline. Evidence supporting this hypothesis comes from a longitudinal study of 1764 older adults without cognitive impairment at baseline. In that study, depressive symptoms predicted cognitive decline independent of the neuropathologic hallmarks of dementia. Other research indicates that psychological resilience may be neuroprotective. A recent study found significant associations between self-reported resilience and language performance among 288 adults with LLD. In addition, the resilience factor grit was associated with greater structural integrity of the genu of the corpus callosum and cingulum, pathways implicated in cognitive and emotion regulation (N = 70).

The term cognitive reserve has been used to explain differences in susceptibility to cognitive decline resulting from brain aging, pathology, or insult. Individual differences in cognitive reserve are determined by such factors as early-life general cognitive ability/intelligence, education level, occupation complexity, physical exercise, social engagement, and ongoing cognitive engagement. These environmental and social factors are believed to enhance neural networks that promote neuroplasticity. Cognitive reserve may also serve as a psychological resilience factor. A recent systematic review representing data from over 37,000 older adults found that cognitive reserve decreased the association between cognitive impairment and depressed mood. Of course, factors associated with cognitive reserve such as education are also associated with engagement in health-promoting behaviors that may further protect the individual against both depression and cognitive decline.

Other research has attempted to identify cognitive factors that predict treatment response in LLD. One recent study found that impairment in response inhibition (a fundamental executive function) predicted poor antidepressant response in LLD. Other studies have similarly found that baseline impairments in episodic working memory, processing speed, executive function, as well as severity of baseline white matter hyperintensities (WMH) predict decreased LLD improvement with antidepressant treatment.

The stress response and LLD

Recent research has begun to investigate the biological mechanisms by which chronic stress increases risk for depression–. In a psychobiological framework, resilience can be defined as the adaptive maintenance of homeostasis in the face of stress or adversity. Building psychobiological resilience begins with prenatal and early-life development. Experimental studies in animals as well as observational studies in humans, point to an inverted U-shape between early life challenges and adult stress reactivity, with moderate challenges in early life predicting optimal mental health in adulthood. Animal studies indicate that this so-called “early-life stress inoculation” decreases subsequent cortisol secretion and increases subsequent exploration of novel situations, cognitive control, and ventromedial prefrontal cortical volumes. It is hypothesized that prefrontal myelination and cortical expansion induced by successful early-life coping lead to enduring adaptive cognitive and emotional changes. By contrast, high levels of early-life adversity adversely impact attachment, personality, core beliefs, and coping tendencies, ultimately leading to enduring changes in endocrine, autonomic, and immunological processes, and increasing vulnerability to depression,. Genetic factors also contribute. One study found that a functional polymorphism in the promoter region of the serotonin transporter (5-HTT) gene moderated the influence of both childhood stress and later stressful life events on risk for depression.

One prominent hypothesis for how chronic stress increases risk for depression is through sustained activation and ultimate dysregulation of the HPA axis. Of the stress hormones, cortisol has received the most research attention due to its widespread regulatory influence. Research suggests that although uncontrollable stress initially amplifies cortisol secretion, sustained elevated levels of cortisol eventually suppress output of corticotropin-releasing hormone (CRH) and adrenocorticotropin hormone, resulting in below-normal cortisol levels in chronically stressed populations. This ultimate blunting of HPA axis responsivity is proposed to underlie the withdrawal and disengagement behaviors that often accompany chronic uncontrollable stress–. Disrupted HPA axis activity as evidenced by failure to suppress cortisol in the dexamethasone test predicts increased suicide risk in both MDD and LLD, and recent research indicates that low mineralocorticoid receptor availability also increases risk for depression.

In addition to altering cortisol secretion, sustained activation of the HPA axis results in deficient monoamine transmission, disruption of neurotrophic processes (e.g., the neuroprotective brain-derived neurotrophic factor (BDNF)), oxidative stress, widespread inflammatory processes, and neurodegeneration,. Dysfunction in serotonergic and dopaminergic transmission contribute to the common mood and cognitive symptoms observed in depression,. Once in motion, this stress-related biological cascade can be exacerbated by environmental factors (e.g., social isolation) or maladaptive coping behaviors (sedentary lifestyle, substance abuse).

Neuropeptides

Multiple neuropeptides are known to modulate emotional processing. Neuropeptide Y (NPY) has been proposed as an endogenous mediator of resilience to stress-related psychiatric illness, including depression. NPY plays a key role in the maintenance of homeostasis and has been implicated in diverse motivational, perceptual, and affective processes including circadian rhythm, anxiety, appetite, alcohol consumption, and pain perception. NPY receptors are densely expressed in brain regions relevant to mood disorders including the cortex, hippocampus, and amygdala. Low NPY levels have been reported in MDD compared to healthy controls, and genetic variation associated with low NPY expression increases risk for MDD,. Results of one study suggest that this effect may be mediated by increased neuronal response to affective stimuli in the medial prefrontal and anterior cingulate cortices among individuals with low-expression NPY genotypes.

Endocrine changes in aging and depression

One potential vulnerability for depression specific to older adults is age-associated decline in reproductive hormones. Perimenopause increases risk for both recurrent and new-onset depression. Loss of normal estradiol (the primary circulating estrogen) cycling is proposed to account for this increased vulnerability via effects on neurotransmitter and mood regulatory systems. Estrogen receptor polymorphisms have been associated with heightened depression risk in older women,, and maintenance of normal estrogen levels is important for several brain regions vulnerable to age-related changes (e.g., the prefrontal cortex (PFC) and hippocampus),,. Similarly, age-related reduction in dehydroepiandrosterone (DHEA) has been linked to depression, cognitive decline, reduced immune function, and decreased physical health,. Individuals with LLD demonstrate lower DHEA levels compared to non-depressed older adults, and DHEA levels increase with remission.

Cardiovascular markers

There is strong evidence for a bi-directional association between depression and cardiovascular disease. Prospective studies indicate that individuals with depression are at nearly twice the risk of developing cardiovascular disease and have nearly a three times higher mortality rate following a cardiac event,. Conversely, cardiovascular disease prospectively predicts depression,. Although unhealthy behaviors (e.g., unhealthy diet, lack of physical activity) undoubtedly contribute to this effect, lifestyle factors do not fully explain the relation between heart health and depression.

Autonomic nervous system (ANS) dysregulation is one biological mechanism that may explain the link between cardiovascular risk and depression. Heart rate variability (HRV) is a surrogate index of resting cardiac vagal outflow that represents the ability of the ANS to adapt to a changing psychological, social and physical environment. Higher HRV is thought to reflect greater self-regulatory capacity (i.e., regulation of behavioral, cognitive, and emotional processes), and meta-analytic data suggest that this effect is larger for older compared to younger adults. Recent research suggests that high HRV may serve as a biomarker of resilience to the development of stress-related disorders including depression,. However, age-related differences have been reported in the frequency of the HRV most predictive of depression. Whereas low high-frequency (HF)-HRV (reflecting parasympathetic activity) is associated with depression among children, adolescents, and young adults, only low low-frequency (LF)-HRV (reflecting both sympathetic and parasympathetic activity) appears associated with depression among older adults. Decreased parasympathetic activity with age appears to result in decreased HRV in the general (primarily non-depressed) older adult population,, which may partially account for this finding.

Inflammation in aging and depression

Cumulating evidence indicates immune and metabolic dysregulation among individuals with depression. Immunometabolic dysregulation is associated with more severe and chronic depressive symptoms– as well as decreased response to antidepressant treatment–, and may explain the increased prevalence of cardiovascular disease and diabetes in MDD. While studies of younger adults typically show upregulation of metabolic processes in depression, studies of LLD report both upregulation and downregulation of these processes–. Both younger and older adults with depression show increased levels of inflammatory cytokines, secreted proteins that interact with virtually every depression-relevant neurophysiological domain (e.g., neurotransmitter metabolism, neuroendocrine function, and neural plasticity). Additional evidence for the role of inflammation in depression comes from studies indicating that (1) pro-inflammatory factors precede depressive symptom onset, (2) antidepressant treatments reduce pro-inflammatory factors, and (3) anti-cytokine therapy decreases depressive symptoms in placebo-controlled trials. Experimental data indicate that acute psychosocial stress (e.g., public speaking, mental arithmetic) stimulates inflammatory signaling molecules, and these responses are exaggerated in patients with depression. Both childhood maltreatment and chronic stress in adulthood– are associated with increased inflammation. Thus, inflammation may be one pathway by which these psychosocial factors increase risk for depression.

Genetic factors in aging and depression

At least three genes have been associated with increased risk for LLD: the methionine (Met) allele of the neurotrophic factor BDNF, APOE-e4 (involved in myelin repair and Aβ metabolism), and SLC6A4 (the short allele of the serotonin transporter 5-HTTLPR). BDNF is a protein that stimulates neurogenesis and is important for long-term memory. The Met variation of the BDNF gene is associated with decreased BDNF secretion, poorer memory performance, and increased risk for a range of neuropsychiatric disorders. Interestingly, a meta-analysis found that the Met allele predicted MDD among men but not women. Another meta-analysis found that the Met allele significantly moderated the effect of stressful life events on MDD risk, suggesting that Met carriers are more genetically sensitive to adverse life experiences. A recent longitudinal study conducted with over 1000 older adults found that epigenetic regulation of the BDNF gene was associated with depression. Another study of individuals with LLD found that the Met allele predicted poorer response to paroxetine, and that this effect was moderated by the cyclic AMP responsive element binding protein 1 (CREB1).

Neuroimaging biomarkers of aging and depression

Emerging research evidence suggests that MDD is associated with reduced structural and functional plasticity,. Brain structures important for learning and applying adaptive coping strategies (e.g., the hippocampus and PFC) show atrophy in MDD–, possibly resulting from depression-related hypercortisolemia,. Similar abnormalities (i.e., decreased limbic structure volumes and reduced PFC activity) have been found in LLD,–. However, research suggests that at least with regard to decreased hippocampal volumes, these effects may be more pronounced for individuals with earlier depression onset. Narayan and colleagues propose that prior depressive episodes, aging, stress, hypercortisolemia, and reduced BDNF levels cause focal atrophy and may decrease the threshold for mood disorders in late life.

Neuroimaging biomarkers of emotion regulation, coping, and grit

Substantial neuroimaging research has investigated the neural networks implicated in emotion regulation and coping with stress. Despite the neural structures hypothesized to underlie emotion regulation being vulnerable to age-related decline, behavioral evidence suggests that older adults have better emotion regulation capacity compared to younger adults. Functional magnetic neuroimaging (fMRI) studies have documented increased activation of the PFC and amygdala, in older vs. younger adults during tasks requiring emotion regulation tasks, possibly reflecting compensation for less efficient cognitive processing.

Other studies have attempted to identify the neural correlates of adaptive coping with stress. For example, a study of 102 heathy adults found that the functional connectivity of regions associated with the default mode and anterior salience networks was associated with propensity to adopt various coping strategies (e.g., problem-focused, avoidant, social support seeking). Others have investigated individual differences in brain structure that relate to personality characteristics associated with resilience to depression. As reported above, grit has been associated with greater structural integrity of the genu of the corpus callosum and cingulum in LLD—pathways implicated in cognitive and emotion regulation,. Finally, several studies have documented neuroimaging correlates of self-reported resilience. Among healthy adults, self-reported resilience was correlated with decreased electroencephalogram (EEG) responsivity to adverse images. In LLD, correlates included low amygdala blood perfusion at rest and greater functional connectivity between the amygdala and the ventral default mode network.

Structural brain changes and cerebrovascular disease in aging and depression

WMH are another related biological mechanism that may explain the link between cardio- and cerebrovascular disease and depression in late life. LLD is consistently associated with greater WMH severity,, and individuals with late onset exhibit greater WMH severity,– and greater cognitive impairment– compared to those with first onset earlier in life. Depressed older adults who present with WMH are said to have “vascular depression”, a subtype of depression characterized by cognitive deficits, psychomotor retardation, lack of insight, and disability disproportional to depression severity. Such vascular abnormalities are linked to greater depressive symptom severity and poorer treatment response,. WMH are also strongly and independently associated with symptoms of apathy–.

Psychobiological factors associated with early- vs. late-onset LLD

Several studies have investigated the clinical correlates of early- vs. late-onset LLD. One study investigated illness severity and symptoms, cognitive function, antecedent life events, physical health, genetic factors, and vascular health as a function of age of onset in 57 adults with LLD. They found that early onset was associated with increased symptoms of anxiety and greater heritability. Several studies of LLD have found that early-onset recurrent illness predicts slower treatment responses and greater relapse compared to late onset. This may be due to a greater number of depressive episodes, which is associated with the depletion of neural, interpersonal, and psychosocial resources,. These results are seemingly in contrast to the results of studies identifying characteristics associated with late onset (i.e., increased subcortical hyperintensities, decreased cognitive performance), which have also been associated with inadequate treatment response,.

Resilience-enhancing interventions

Resilience-enhancing interventions can be implemented either preventatively to reduce susceptibility to MDD or as a treatment following MDD onset. Prevention strategies promote well-being even in the absence of current psychopathology, and can be applied both to healthy individuals or to those at high risk (i.e., those with chronic stress, trauma, or history of prior depressive episodes). The field of positive psychology defines well-being as not the absence of a mental disorder, but rather the presence of well-being, and advocates for the widespread application of such techniques regardless of the presence or absence of psychopathology.

Positive psychology interventions

Positive psychology interventions (PPIs) are “treatment methods or intentional activities that aim to cultivate positive feelings, behaviors, or cognitions”(p. 468). PPIs typically target hedonic well-being (e.g., positive affect, life satisfaction, happiness), eudaimonic well-being (e.g., self-acceptance, positive relations, autonomy, purpose in life),, or both, and are typically amenable to self-administration. Such approaches vary widely in intensity, ranging from a several minute-long daily gratitude journal to more in-depth journal exercises, meditations, and intentional social behaviors. Research suggests that PPIs not only increase well-being, but also improve the individual’s capacity to “bounce back” from adversity. A recent meta-analysis of PPIs including data from over four thousand adults indicated a highly significant, moderate effect of PPIs on both well-being (r = 0.29) and depressive symptoms (r = 0.31). PPIs included expressing gratitude,, reflecting upon one’s ideal future self–, identifying one’s strengths, practicing mindfulness, and practicing compassion/ acts of kindness–. Interventions delivered individually were most effective, followed by those administered in a group, then by self-administered PPIs. The efficacy of PPIs increased linearly with participant age, and depressed individuals benefitted more than non-depressed individuals. Another PPI shown to improve mood in individuals at risk for depression due to trauma exposure is “benefit finding”, or the intentional identification of positive ways in which their lives have changed as a result of a traumatic event,. Bower and colleagues propose an integrative conceptual model in which benefit finding promotes the development of interpersonal resources (e.g., adaptive coping strategies including cognitive re-appraisal; increased self-efficacy for coping with stress; more salient sense of one’s values/purpose) and intrapersonal resources (e.g., enhancement of social relationships) that facilitate more adaptive responses to future stressors. More broadly, PPIs that increase one’s feeling of connection to others (e.g., expressive gratitude, practicing compassion may not only directly improve mood but also exert beneficial neuroendocrine, cardiovascular, and immune systems changes. PPIs aimed at enhancing meaning/purpose (e.g., reflecting upon one’s ideal future self; identifying strengths) are also thought to improve markers of immune functioning. In addition, it is possible that the positive psychological changes elicited through PPIs have their own mechanistic pathways distinct from those associated with distress—e.g., parasympathetic nervous system activity, growth factors, and other neuroendocrine factors such as oxytocin. Although PPIs are not recommended as a stand-alone treatment for moderate-to-severe MDD, research suggests that PPIs may be useful for the prevention or adjunct treatment of depression.

Meditation

Meditation refers to a category of mind–body techniques most commonly involving the directed focus of attention. One form of Buddhist meditation techniques that has been adapted to a variety of secular settings in the West is mindfulness—intentional, non-judgmental, present-focused awareness. A recent meta-analysis indicated that mindfulness-based interventions are significantly more effective than psychoeducation, supportive psychotherapy, relaxation training, and guided imagery for improving a range of mental and physical health symptoms, with the largest effects demonstrated for mental health symptoms including depression. A recent review of randomized controlled trials (RCTs) of mindfulness-based interventions for older adults concluded that Mindfulness-Based Stress Reduction (MBSR) is effective for improving symptoms of depression, anxiety, positive affect, insomnia, chronic pain, memory, and executive functioning in late life. Other research conducted with adults with MDD has found that MBSR is effective for preventing relapse in those with a history of three or more depressive episodes. A recent systematic review evaluating the biopsychological mechanisms by which mindfulness practice affects clinical outcomes concluded that decreases in cognitive reactivity, emotional reactivity, rumination, and worry may mediate the effect of mindfulness interventions on mental health. Mindfulness practice appears to alter both brain structure and function, most notably in areas related to attentional control, self-awareness, and emotion regulation–. In addition, mindfulness interventions may protect against age-related decreases in gray matter volume, attention performance, and cellular aging.

Other forms of yogic-style meditation include those involving repetition of sounds (mantras) or hand positions (mudras). A recent study found that Kirtan Kriya (which combines mantras and mudras) was more effective for improving mental health and cognitive functioning in dementia caregivers compared to passive listening to relaxing music. Further, Kirtan Kriya reversed the pattern of increased pro-inflammatory cytokine and decreased innate antiviral response gene transcription observed in chronically stressed individuals. Results of this study indicate inflammatory and antiviral transcription pathways as one mechanism by which meditation may increase resilience in older adults. Another randomized study of mantra meditation for elderly women with hypertension found that chanting significantly reduced depression, anxiety, stress, blood pressure, and cognitive impairment. Studies investigating the neurohemodynamic correlates of mantra meditation suggest that deactivation of the limbic system may account for observed decreases in physiological arousal and improvements in well-being.

Psychotherapy

Meta-analytic data suggest that psychotherapy is similarly effective as pharmacological approaches in the treatment of LLD,, with a number needed to treat of 3 (ref. 288). A meta-analysis of RCTs comparing psychotherapy for LLD to various control conditions found the largest effects for cognitive behavior therapy (CBT; g = 0.45), problem-solving therapy (g = 0.46), and life review therapy (g = 0.59). A more recent review focused on mindfulness-based CBT found such interventions to be similarly effective for improving late-life depressive symptoms (g = 0.55). Results of another meta-analysis suggest that music therapy significantly augments the efficacy of standard treatments for LLD. Because alterations of the HPA axis and the ANS appear to be involved in the development and maintenance of depression, it is conceivable that these dysregulations may interact with psychotherapeutic treatment to influence outcomes. A meta-analysis that attempted to investigate the effect of psychotherapy on HPA and ANS regulation in adults with mixed mental health disorders concluded that this effect could not be estimated due to the large degree of heterogeneity of methodologies across studies.

Movement-based interventions

Physical exercise is effective for the treatment of MDD, with effect sizes similar to those observed with pharmacological and psychological therapies. A recent systematic review confirmed that physical activity interventions are also effective in LLD. In addition to the documented effects on mood, physical activity is associated with improved balance, greater strength, and decreased disability. One mechanism by which exercise interventions affect both physical and mental health may be via reduction in inflammatory cytokine responses resulting from hemodynamic hormonal changes during physical activity. Movement-based interventions that also incorporate mindfulness are referred to as mind–body therapies (MBTs). A recent review of the efficacy of such interventions for late-life mood and cognitive disorders concluded that MBTs such as yoga and tai chi may outperform conventional physical exercise with regard to effects on mood, QOL, and cognitive functioning. A review of the neural mechanisms of movement-based vs. stationary meditation found that these two approaches affect multiple common brain regions including those involved in attention, memory, awareness, and emotional processing. Yoga appears to reduce HPA axis activity in younger healthy adults, as well as in sedentary community-dwelling older adults without depression. It is possible that restoration of HPA axis dysregulation may be one mechanism by which MBTs improve mood in older adults with depressive symptoms,–.

Pharmacotherapy

Second-generation antidepressant medications, including selective serotonin reuptake inhibitors (SSRIs), bupropion, mirtazapine, venlafaxine, and duloxetine are the most commonly prescribed pharmacological treatments for LLD. A recent meta-analysis of second-generation antidepressants vs. placebo for treatment of LLD found that response rates were modest (44% for antidepressant vs. 35% for placebo). Response rates were higher for 10–12-week trials (55%) compared to 6–8-week trials (38%). However, results of another meta-analysis comparing placebo-controlled vs. comparator trials in LLD suggest that these effects may underestimate those in clinical settings, when patient expectations of improvement may be higher. Discontinuation rates due to adverse events associated with second-generation antidepressant medication range from 8–27%, compared to 1–11% for placebo. The precise neurophysiological mechanisms of antidepressant medications remain unknown. However, meta-analytic data indicate normalization of neural responses to positive and negative stimuli in limbic regions as well as increased self-regulatory potential via changes in the dorsolateral PFC.

Electroconvulsive therapy

Electroconvulsive therapy (ECT) is widely used for the management of severe and refractory MDD. As the most effective biological treatment for major depression, ECT is associated with remission rates of 51% (ref. ) and standardized effect sizes of 0.91 compared to sham ECT. Reviews indicate that ECT is especially effective in older adult patients, with remission rates reaching 73–90% (refs. –). In addition, psychotic and melancholic features predict greater response. Use of ECT for LLD is safe, well-tolerated, and effective for improving cognition and psychomotor symptoms. Maintenance ECT, with treatments spaced over weekly to monthly intervals, is often used for relapse prevention. Recommendations for optimal administration of ECT for LLD can be found elsewhere. The results of one study investigating the neurological effects of ECT suggest that increases in frontal white matter fractional anisotropy (FA) (typically reduced in LLD compared to age-matched controls) may account for ECT’s antidepressant effect. Another study found gray matter volume increases in the right caudate nucleus with ECT treatment for LLD, a change which correlated with improved psychomotor function.

HRV biofeedback

Small uncontrolled studies have shown some promise for HRV biofeedback in the treatment of MDD,, and one RCT found that HRV biofeedback significantly improved depressive symptoms in first-time cardiac surgery patients compared to usual care. It is thought that strengthened homeostasis or effects on the vagal afferent pathway to frontal cortical areas may account for this effect. However, no RCTs to date have examined the efficacy of HRV biofeedback in LLD.

Directions for future research and public policy

During this critical time of accelerated global aging, understanding factors that promote resilience vs. risk for the development of LLD and related comorbidities is more important than ever. Continued research in this area is essential for informing practice and public policy to promote successful aging, reduce disability, and mitigate rising healthcare costs. One fruitful area for future research is the investigation of individual characteristics that moderate risk factors for LLD. For example, research suggests that risk factors for depression may vary according to generation, gender, and cultural origin. Variables such as self-esteem and self-efficacy are highly culturally and contextually dependent, such that the efficacy of interventions targeting these processes will likely vary across cultures. Indeed, PPIs as a whole appear more effective among members of individualist cultures, perhaps because the rationale for such approaches resonates more strongly with individuals from cultures endorsing the pursuit of individual happiness. It is possible that individuals from collectivist cultures may derive greater benefit from prosocial and other-focused PPIs (e.g., performing acts of kindness, writing a letter of gratitude), compared to self-focused PPIs (e.g., reflecting on personal strengths).

Similarly, continued investigation of the biological factors that increase or mitigate risk for depression is of paramount importance. Results of a recent meta-analysis suggest that depressed individuals with higher baseline cortisol levels are less responsive to psychological therapy. Because elevated cortisol has been linked to concentration and memory difficulties, the authors propose that difficulty engaging in learning processes may reduce the efficacy of psychotherapy in this subset of MDD patients. Additional research is needed to identify other biomarkers of depression “subtypes” as well as determine as well as the interventions most effective for each. Continued work in this area is essential for the development of more effective approaches to the treatment of LLD.

Resilience-enhancing interventions can be applied not only at the individual level, but also at the level of the family, organization, or community. A recent systematic review of family-oriented interventions found that dyadic interventions such as ecosystems therapy, psychoeducation, family counseling, behavioral therapy, and CBT are feasible and effective for the treatment of LLD. In addition, the results of two pilot studies suggest that mindfulness training delivered jointly to older adult patients and their caregivers is effective for reducing depressive symptoms–.

Other research has identified potentially useful directions for organizations that wish to promote resilience in their older adult volunteers. A recent study of almost 400 older adult volunteers identified adequate training, ongoing support, and greater volunteer choice as predictors of larger volunteer mental health benefits. This effect was mediated by the volunteer’s belief that their work had meaningfully contributed to the well-being of others.

Factors influencing risk for LLD can also be identified at the community and public policy levels. Because loneliness affects nearly half of the Americans and independently predicts severity and course of LLD, loneliness is a promising target for intervention. Of note, a recent review of seven RCTs found that social robot interventions may be effective for helping to alleviate depressive symptoms in older adults when used during group activities. Programs to promote greater integration of older adults into their communities (e.g., by facilitating the sharing of meals, joint physical activity, support groups, or interactive volunteer work) are recommended. Of course, factors such as a balanced diet, physical activity, and sufficient sleep are also of paramount importance. As such, public policies that provide food stamps and low-cost healthy food options, safe opportunities for physical exercise, preventative medical care, and financial assistance to those older adults in need will reduce the economic, social, and individual QOL burden of LLD.

Conclusion

With the global population rapidly aging and depression as the leading cause of disability worldwide, identification of factors that increase resilience to LLD is of paramount public health importance. Risk for LLD begins as early as embryonic development and is determined by complex interactions between biological and psychological factors. Research has elucidated both trait-like psychological factors that identify those at greatest risk and psychosocial processes that may be fruitful targets for intervention. Psychobiological factors include endocrine, genetic, inflammatory, neural, and cardiovascular processes that bidirectionally interact to affect LLD risk. Intervention research suggests that MBTs (including yoga,,, MBSR, tai chi,, qigong, and meditation,) have potential for improving HPA axis regulation and depressive symptoms in older adults with depression,– as well as in non-depressed older adults–,–.

Additional research into the biophysiological mechanisms by which psychosocial processes affect risk for LLD will identify novel targets for intervention. In addition, continued research testing the efficacy of interventions designed to enhance resilience to LLD is critically important. Further work in this area has potential to greatly increase QOL, reduce morbidity, and decrease healthcare costs for aging adults.

References 336

  1. 1.

    Alexopoulos GS, Young RC, Abrams RC, Meyers B, Shamoian CA. Chronicity and relapse in geriatric depression. Biol. Psychiatry. 1989;26:551-564.

    Not in our library10.1016/0006-3223(89)90080-2

  2. 2.

    Reynolds, C. F. 3rd et al. Maintenance treatment of major depression in old age. N. Engl. J. Med. 354, 1130–1138 (2006).

    Not in our library10.1056/nejmoa052619

  3. 3.

    Nelson JC, Delucchi K, Schneider LS. Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence. Am. J. Geriatr. Psychiatry. 2008;16:558-567.

    Not in our library10.1097/01.jgp.0000308883.64832.ed

  4. 4.

    Nelson JC, Delucchi KL, Schneider LS. Moderators of outcome in late-life depression: a patient-level meta-analysis. Am. J. Psychiatry. 2013;170:651-659.

    Not in our library10.1176/appi.ajp.2012.12070927

  5. 5.

    Rutherford BR, Roose SP. A model of placebo response in antidepressant clinical trials. Am. J. Psychiatry. 2013;170:723-733.

    Not in our library10.1176/appi.ajp.2012.12040474

  6. 6.

    Sackeim HA, Roose SP, Burt T. Optimal length of antidepressant trials in late-life depression. J. Clin. Psychopharmacol. 2005;25:S34-S37.

    Not in our library10.1097/01.jcp.0000170683.25802.12

  7. 7.

    Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J. Clin. Psychiatry. 2001;62:869-877.

    Not in our library10.4088/jcp.v62n1106

  8. 8.

    Ryff CD, Friedman EM, Morozink JA, Tsenkova V. Psychological resilience in adulthood and later life: implications for health. Annu. Rev. Gerontol. Geriatr. 2012;32:73-92.

    Not in our library10.1891/0198-8794.32.73

  9. 9.

    Smith GC, Hayslip B. Resilience in adulthood and later life: what does it mean and where are we heading? Annu. Rev. Gerontol. Geriatr. 2012;32:3.

    Not in our library10.1891/0198-8794.32.3

  10. 10.

    Vanderbilt-Adriance E, Shaw DS. Conceptualizing and re-evaluating resilience across levels of risk, time, and domains of competence. Clin. Child Fam. Psychol. Rev. 2008;11:30.

    Not in our library10.1007/s10567-008-0031-2

  11. 11.

    Windle G. What is resilience? A review and concept analysis. Rev. Clin. Gerontol. 2011;21:152-169.

    Not in our library10.1017/s0959259810000420

  12. 12.

    Lavretsky, Irwin MR. Resilience and aging. Aging Health. 2007;3:309-323.

    Not in our library10.2217/1745509x.3.3.309

  13. 13.

    Kampman O, Poutanen O. Can onset and recovery in depression be predicted by temperament? A systematic review and meta-analysis. J. Affect. Disord. 2011;135:20-27.

    Not in our library10.1016/j.jad.2010.12.021

  14. 14.

    Afanasiev S, Aharon-Peretz J, Granot M. Personality type as a predictor for depressive symptoms and reduction in quality of life among stroke survivals. Am. J. Geriatr. Psychiatry. 2013;21:832-839.

    Not in our library10.1016/j.jagp.2013.04.012

  15. 15.

    Buchman AS, et al. Harm avoidance is associated with progression of parkinsonism in community-dwelling older adults: a prospective cohort study. BMC Geriatr. 2014;14:54.

    Not in our library10.1186/1471-2318-14-54

  16. 16.

    Khazanov GK, Ruscio AM. Is low positive emotionality a specific risk factor for depression? A meta-analysis of longitudinal studies. Psychol. Bull. 2016;142:991.

    Not in our library10.1037/bul0000059

  17. 17.

    Fredrickson BL, Tugade MM, Waugh CE, Larkin GR. What good are positive emotions in crisis? A prospective study of resilience and emotions following the terrorist attacks on the United States on September 11th, 2001. J. Pers. Soc. Psychol. 2003;84:365.

    Not in our library10.1037/0022-3514.84.2.365

  18. 18.

    Bowlby J. Attachment and Loss: Attachment. 1969.

    Not in our library

  19. 19.

    Bowlby J. Attachment and Loss: Separation. 1973.

    Not in our library

  20. 20.

    Bowlby J. Attachment and Loss: Loss, Sadness, and Depression. 1980.

    Not in our library

  21. 21.

    Dagan O, Facompré CR, Bernard K. Adult attachment representations and depressive symptoms: a meta-analysis. J. Affect. Disord. 2018;236:274-290.

    Not in our library10.1016/j.jad.2018.04.091

  22. 22.

    Kidd T, et al. Attachment anxiety predicts depression and anxiety symptoms following coronary artery bypass graft surgery. Br. J. Health Psychol. 2016;21:796-811.

    Not in our library10.1111/bjhp.12191

  23. 23.

    Conradi HJ, Kamphuis JH, de Jonge P. Adult attachment predicts the seven-year course of recurrent depression in primary care. J. Affect Disord. 2018;225:160-166.

    Not in our library10.1016/j.jad.2017.08.009

  24. 24.

    Monti JD, Rudolph KD. Emotional awareness as a pathway linking adult attachment to subsequent depression. J. Couns. Psychol. 2014;61:374.

    Not in our library10.1037/cou0000016

  25. 25.

    Laird KT, Preacher KJ, Walker LS. Attachment and adjustment in adolescents and young adults with a history of pediatric functional abdominal pain. Clin. J. Pain. 2015;31:152.

    Not in our library10.1097/ajp.0000000000000090

  26. 26.

    Porter LS, Davis D, Keefe FJ. Attachment and pain: recent findings and future directions. Pain. 2007;128:195-198.

    Not in our library10.1016/j.pain.2007.02.001

  27. 27.

    Lyons-Ruth K, Pechtel P, Yoon SA, Anderson CM, Teicher MH. Disorganized attachment in infancy predicts greater amygdala volume in adulthood. Behav. Brain Res. 2016;308:83-93.

    Not in our library10.1016/j.bbr.2016.03.050

  28. 28.

    Tottenham N, et al. Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Dev. Sci. 2010;13:46-61.

    Not in our library10.1111/j.1467-7687.2009.00852.x

  29. 29.

    McConnell M, Moss E. Attachment across the life span: factors that contribute to stability and change. Aust. J. Educ. Dev. Psychol. 2011;11:60-77.

    Not in our library

  30. 30.

    Pietrzak RH, Cook JM. Psychological resilience in older US veterans: results from the national health and resilience in veterans study. Depress. Anxiety. 2013;30:432-443.

    Not in our library10.1002/da.22083

  31. 31.

    Paradiso S, Naridze R, Holm‐Brown E. Lifetime romantic attachment style and social adaptation in late‐onset depression. Int. J. Geriatr. Psychiatry. 2012;27:1008-1016.

    Not in our library10.1002/gps.2814

  32. 32.

    Hakulinen C, et al. Personality and depressive symptoms: Individual participant meta‐analysis of 10 cohort studies. Depress. Anxiety. 2015;32:461-470.

    Not in our library10.1002/da.22376

  33. 33.

    Damholdt MF, Callesen MB, Møller A. Personality characteristics of depressed and non-depressed patients with Parkinson’s disease. J. Neuropsychiatry Clin. Neurosci. 2014;26:329-334.

    Not in our library10.1176/appi.neuropsych.13040085

  34. 34.

    Henriques-Calado J, et al. Predicting relatedness and self-definition depressive experiences in aging women based on personality traits: a preliminary study. Bull. Menninger Clin. 2013;77:269-288.

    Not in our library10.1521/bumc.2013.77.3.269

  35. 35.

    Duckworth AL, Peterson C, Matthews MD, Kelly DR. Grit: perseverance and passion for long-term goals. J. Pers. Soc. Psychol. 2007;92:1087.

    Not in our library10.1037/0022-3514.92.6.1087

  36. 36.

    Laird KT, et al. Clinical correlates of resilience factors in geriatric depression. Int. Psychogeriatr. 2018;2018:1-10.

    Not in our library10.1017/s1041610217002873

  37. 37.

    McGinn LK. Cognitive behavioral therapy of depression: theory, treatment, and empirical status. Am. J. Psychother. 2000;54:257-262.

    Not in our library10.1176/appi.psychotherapy.2000.54.2.257

  38. 38.

    Abramowitz JS. The practice of exposure therapy: relevance of cognitive-behavioral theory and extinction theory. Behav. Ther. 2013;44:548-558.

    Not in our library10.1016/j.beth.2013.03.003

  39. 39.

    Sowislo JF, Orth U. Does low self-esteem predict depression and anxiety? A meta-analysis of longitudinal studies. Psychol. Bull. 2013;139:213.

    Not in our library10.1037/a0028931

  40. 40.

    Orth U, Robins RW, Meier LL, Conger RD. Refining the vulnerability model of low self-esteem and depression: Disentangling the effects of genuine self-esteem and narcissism. J. Pers. Soc. Psychol. 2016;110:133.

    Not in our library10.1037/pspp0000038

  41. 41.

    Lazarus RS, Folkman S. Stress, Appraisal, and Coping. 1984.

    Not in our library

  42. 42.

    Thomsen T, Greve W. Accommodative coping in early adolescence: an investigation of possible developmental components. J. Adolesc. 2013;36:971-981.

    Not in our library10.1016/j.adolescence.2013.08.003

  43. 43.

    Forsythe CJ, Compas BE. Interaction of cognitive appraisals of stressful events and coping: testing the goodness of fit hypothesis. Cogn. Ther. Res. 1987;11:473-485.

    Not in our library10.1007/bf01175357

  44. 44.

    Zakowski SG, Hall MH, Klein LC, Baum A. Appraised control, coping, and stress in a community sample: a test of the goodness-of-fit hypothesis. Ann. Behav. Med. 2001;23:158-165.

    Not in our library10.1207/s15324796abm2303_3

  45. 45.

    Cheng C, Lau HPB, Chan MPS. Coping flexibility and psychological adjustment to stressful life changes: A meta-analytic review. Psychological bulletin. 2014;140:1582-1607.

    Not in our library10.1037/a0037913

  46. 46.

    Seltzer MM, Greenberg JS, Floyd FJ, Hong J. Accommodative coping and well-being of midlife parents of children with mental health problems or developmental disabilities. Am. J. Orthopsychiatry. 2004;74:187.

    Not in our library10.1037/0002-9432.74.2.187

  47. 47.

    Boerner K. Adaptation to disability among middle-aged and older adults: the role of assimilative and accommodative coping. J. Gerontol. B Psychol. Sci. Soc. Sci. 2004;59:P35-P42.

    Not in our library10.1093/geronb/59.1.p35

  48. 48.

    Isaacowitz DM, Seligman MEP. Cognitive style predictors of affect change in older adults. Int. J. Aging Human. Dev. 2002;54:233-253.

    Not in our library10.2190/j6e5-np5k-2uc4-2f8b

  49. 49.

    Wrosch C, Dunne E, Scheier MF, Schulz R. Self-regulation of common age-related challenges: benefits for older adults’ psychological and physical health. J. Behav. Med. 2006;29:299-306.

    Not in our library10.1007/s10865-006-9051-x

  50. 50.

    Laird KT, Lavretsky H, St Cyr N, Siddarth P. Resilience predicts remission in antidepressant treatment of geriatric depression. Int. J. Geriatr. Psychiatry. 2018;33:1596-1603.

    Not in our library10.1002/gps.4953

  51. 51.

    Walker LS, Smith CA, Garber J, Claar RL. Testing a model of pain appraisal and coping in children with chronic abdominal pain. Health Psychol. 2005;24:364-374.

    Not in our library10.1037/0278-6133.24.4.364

  52. 52.

    Anderson JR, et al. A dyadic multiple mediation model of patient and spouse stressors predicting patient dietary and exercise adherence via depression symptoms and diabetes self-efficacy. J. Behav. Med. 2016;39:1020-1032.

    Not in our library10.1007/s10865-016-9796-9

  53. 53.

    Clarke J, et al. Effects of mental health self-efficacy on outcomes of a mobile phone and web intervention for mild-to-moderate depression, anxiety and stress: secondary analysis of a randomised controlled trial. BMC Psychiatry. 2014;14:272.

    Not in our library10.1186/s12888-014-0272-1

  54. 54.

    Newcomb MD, Harlow LL. Life events and substance use among adolescents: mediating effects of perceived loss of control and meaninglessness in life. J. Pers. Soc. Psychol. 1986;51:564.

    Not in our library10.1037/0022-3514.51.3.564

  55. 55.

    Rippetoe PA, Rogers RW. Effects of components of protection-motivation theory on adaptive and maladaptive coping with a health threat. J. Pers. Soc. Psychol. 1987;52:596.

    Not in our library10.1037/0022-3514.52.3.596

  56. 56.

    Wang Q, Bowling NA, Eschleman KJ. A meta-analytic examination of work and general locus of control. J. Appl. Psychol. 2010;95:761.

    Not in our library10.1037/a0017707

  57. 57.

    Rotter JB. Generalized expectancies for internal versus external control of reinforcement. Psychol. Monogr. 1966;80:1.

    Not in our library10.1037/h0092976

  58. 58.

    Wang S, et al. Neuroanatomical correlates of grit: growth mindset mediates the association between gray matter structure and trait grit in late adolescence. Hum. Brain Mapp. 2018;39:1688-1699.

    Not in our library10.1002/hbm.23944

  59. 59.

    Windsor TD, Curtis RG, Luszcz MA. Sense of purpose as a psychological resource for aging well. Dev. Psychol. 2015;51:975.

    Not in our library10.1037/dev0000023

  60. 60.

    Yuen GS, et al. Apathy in late-life depression: common, persistent, and disabling. Am. J. Geriatr. Psychiatry. 2015;23:488-494.

    Not in our library10.1016/j.jagp.2014.06.005

  61. 61.

    Groeneweg-Koolhoven I, de Waal MWM, van der Weele GM, Gussekloo J, van der Mast RC. Quality of life in community-dwelling older persons with apathy. Am. J. Geriatr. Psychiatry. 2014;22:186-194.

    Not in our library10.1016/j.jagp.2012.10.024

  62. 62.

    Tierney SM, Woods SP, Weinborn M, Bucks RS. Real-world implications of apathy among older adults: Independent associations with activities of daily living and quality of life. J. Clin. Exp. Neuropsychol. 2018;40:895-903.

    Not in our library10.1080/13803395.2018.1444736

  63. 63.

    Yuen GS, et al. Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response. J. Affect. Disord. 2014;166:179-186.

    Not in our library10.1016/j.jad.2014.05.008

  64. 64.

    Lavretsky H, et al. Citalopram, methylphenidate, or their combination in geriatric depression: a randomized, double-blind, placebo-controlled trial. Am. J. Psychiatry. 2015;172:561-569.

    Not in our library10.1176/appi.ajp.2014.14070889

  65. 65.

    Davis CG, Nolen-Hoeksema S, Larson J. Making sense of loss and benefiting from the experience: two construals of meaning. J. Pers. Soc. Psychol. 1998;75:561.

    Not in our library10.1037/0022-3514.75.2.561

  66. 66.

    Simonelli LE, Fowler J, Maxwell GL, Andersen BL. Physical sequelae and depressive symptoms in gynecologic cancer survivors: meaning in life as a mediator. Ann. Behav. Med. 2008;35:275-284.

    Not in our library10.1007/s12160-008-9029-8

  67. 67.

    Nelson CJ, Rosenfeld B, Breitbart W, Galietta M. Spirituality, religion, and depression in the terminally ill. Psychosomatics. 2002;43:213-220.

    Not in our library10.1176/appi.psy.43.3.213

  68. 68.

    Antoni MH, et al. Cognitive-behavioral stress management intervention decreases the prevalence of depression and enhances benefit finding among women under treatment for early-stage breast cancer. Health Psychol. 2001;20:20.

    Not in our library10.1037/0278-6133.20.1.20

  69. 69.

    Drapalski AL, et al. A model of internalized stigma and its effects on people with mental illness. Psychiatr. Serv. 2014;64:264-269.

    Not in our library10.1176/appi.ps.001322012

  70. 70.

    Livingston JD, Boyd JE. Correlates and consequences of internalized stigma for people living with mental illness: a systematic review and meta-analysis. Soc. Sci. Med. 2010;71:2150-2161.

    Not in our library10.1016/j.socscimed.2010.09.030

  71. 71.

    Lysaker PH, Davis LW, Warman DM, Strasburger A, Beattie N. Stigma, social function and symptoms in schizophrenia and schizoaffective disorder: associations across 6 months. Psychiatry Res. 2007;149:89-95.

    Not in our library10.1016/j.psychres.2006.03.007

  72. 72.

    Raeifar E, Halkett A, Lohman MC, Sirey JA. The relation between mastery, anticipated stigma and depression among older adults in a primary care setting. J. Nerv. Ment. Dis. 2017;205:801-804.

    Not in our library10.1097/nmd.0000000000000686

  73. 73.

    Miller L, et al. Religiosity and major depression in adults at high risk: a ten-year prospective study. Am. J. Psychiatry. 2012;169:89-94.

    Not in our library10.1176/appi.ajp.2011.10121823

  74. 74.

    Ellison CG, Boardman JD, Williams DR, Jackson JS. Religious involvement, stress, and mental health: findings from the 1995 Detroit Area Study. Soc. Forces. 2001;80:215-249.

    Not in our library10.1353/sof.2001.0063

  75. 75.

    Yeager DM, et al. Religious involvement and health outcomes among older persons in Taiwan. Soc. Sci. Med. 2006;63:2228-2241.

    Not in our library10.1016/j.socscimed.2006.05.007

  76. 76.

    Aldwin CM, Sutton KJ, Chiara G, Spiro A. Age differences in stress, coping, and appraisal: findings from the Normative Aging Study. J. Gerontol. B Psychol. Sci. Soc. Sci. 1996;51:P179-P188.

    Not in our library10.1093/geronb/51b.4.p179

  77. 77.

    Brandtstädter J, Renner G. Tenacious goal pursuit and flexible goal adjustment: explication and age-related analysis of assimilative and accommodative strategies of coping. Psychol. Aging. 1990;5:58.

    Not in our library10.1037/0882-7974.5.1.58

  78. 78.

    Horton S, Baker J, Pearce GW, Deakin JM. On the malleability of performance: Implications for seniors. J. Appl. Gerontol. 2008;27:446-465.

    Not in our library10.1177/0733464808315291

  79. 79.

    Meisner BA. A meta-analysis of positive and negative age stereotype priming effects on behavior among older adults. J. Gerontol. B Psychol. Sci. Soc. Sci. 2011;67:13-17.

    Not in our library10.1093/geronb/gbr062

  80. 80.

    Levy B, Langer E. Aging free from negative stereotypes: successful memory in China among the American deaf. J. Pers. Soc. Psychol. 1994;66:989.

    Not in our library10.1037/0022-3514.66.6.989

  81. 81.

    Yoon C, Hasher L, Feinberg F, Rahhal TA, Winocur G. Cross-cultural differences in memory: the role of culture-based stereotypes about aging. Psychol. Aging. 2000;15:694.

    Not in our library10.1037/0882-7974.15.4.694

  82. 82.

    Thoits PA. Conceptual, methodological, and theoretical problems in studying social support as a buffer against life stress. J. Health Soc. Behav. 1982;52:145-159.

    Not in our library10.1177/0022146510395592

  83. 83.

    Midanik LT, Soghikian K, Ransom LJ, Tekawa IS. The effect of retirement on mental health and health behaviors: the Kaiser Permanente Retirement Study. J. Gerontol. B Psychol. Sci. Soc. Sci. 1995;50:S59-S61.

    Not in our library10.1093/geronb/50b.1.s59

  84. 84.

    Reitzes DC, Mutran EJ, Fernandez ME. Does retirement hurt weil-being? Factors influencing self-esteem and depression among retires and workers. Gerontologist. 1996;36:649-656.

    Not in our library10.1093/geront/36.5.649

  85. 85.

    Lee J, Smith JP. Work, retirement, and depression. J. Popul. Ageing. 2009;2:57-71.

    Not in our library10.1007/s12062-010-9018-0

  86. 86.

    Coleman, L. M., Antonucci, T. C. & Adelmann, P. K. Role involvement, gender, and well-being. In F. J. Crosby (Ed.), Spouse, parent, worker: On gender and multiple roles (pp. 138–153). New Haven, CT, US: Yale University Press (1987).

    Not in our library

  87. 87.

    Greenfield EA, Marks NF. Formal volunteering as a protective factor for older adults' psychological well-being. J. Gerontol. B Psychol. Sci. Soc. Sci. 2004;59:S258-S264.

    Not in our library10.1093/geronb/59.5.s258

  88. 88.

    Coleman, L. M., Antonucci, T. C. & Adelmann P. K. Role involvement, gender, and well-being (1987).

    Not in our library

  89. 89.

    Hong J, Seltzer MM. The psychological consequences of multiple roles: the nonnormative case. J. Health Soc. Behav. 1995;36:386-398.

    Not in our library10.2307/2137327

  90. 90.

    Morrow-Howell N, Kinnevy S, Mann M. The perceived benefits of participating in volunteer and educational activities. J. Gerontol. Soc. Work. 1999;3:65-80.

    Not in our library10.1300/j083v32n02_06

  91. 91.

    Van Willigen M. Differential benefits of volunteering across the life course. J. Gerontol. B Psychol. Sci. Soc. Sci. 2000;55:S308-S318.

    Not in our library10.1093/geronb/55.5.s308

  92. 92.

    Hendricks J, Cutler SJ. Volunteerism and socioemotional selectivity in later life. J. Gerontol. B Psychol. Sci. Soc. Sci. 2004;59:S251-S257.

    Not in our library10.1093/geronb/59.5.s251

  93. 93.

    Li Y, Ferraro KF. Volunteering and depression in later life: social benefit or selection processes? J. Health Soc. Behav. 2005;46:68-84.

    Not in our library10.1177/002214650504600106

  94. 94.

    Li Y. Recovering from spousal bereavement in later life: does volunteer participation play a role? J. Gerontol. B Psychol. Sci. Soc. Sci. 2007;62:S257-S266.

    Not in our library10.1093/geronb/62.4.s257

  95. 95.

    Santini ZI, Koyanagi A, Tyrovolas S, Mason C, Haro JM. The association between social relationships and depression: a systematic review. J. Affect. Disord. 2015;175:53-65.

    Not in our library10.1016/j.jad.2014.12.049

  96. 96.

    Schwarzbach M, Luppa M, Forstmeier S, König HH, Riedel‐Heller SG. Social relations and depression in late life—a systematic review. Int. J. Geriatr. Psychiatry. 2014;29:1-21.

    Not in our library10.1002/gps.3971

  97. 97.

    Hakulinen C, et al. Social isolation and loneliness as risk factors for myocardial infarction, stroke and mortality: UK Biobank cohort study of 479 054 men and women. Heart. 2018;104:1536-1542.

    Not in our library10.1136/heartjnl-2017-312663

  98. 98.

    Golden J, et al. Loneliness, social support networks, mood and wellbeing in community‐dwelling elderly. Int. J. Geriatr. Psychiatry. 2009;24:694-700.

    Not in our library10.1002/gps.2181

  99. 99.

    Cigna. Cigna U.S. Loneliness Index https://www.multivu.com/players/English/8294451-cigna-us-loneliness-survey/docs/IndexReport_1524069371598-173525450.pdf (2018). Accessed 25 August 2018.

    Not in our library

  100. 100.

    Inaba A, et al. Depression in the United States and Japan: gender, marital status, and SES patterns. Soc. Sci. Med. 2005;61:2280-2292.

    Not in our library10.1016/j.socscimed.2005.07.014

  101. 101.

    Cacioppo JT, Hughes ME, Waite LJ, Hawkley LC, Thisted RA. Loneliness as a specific risk factor for depressive symptoms: cross-sectional and longitudinal analyses. Psychol. Aging. 2006;21:140.

    Not in our library10.1037/0882-7974.21.1.140

  102. 102.

    Fung HH, Carstensen LL, Lang FR. Age-related patterns in social networks among European Americans and African Americans: implications for socioemotional selectivity across the life span. Int. J. Aging Human. Dev. 2001;52:185-206.

    Not in our library10.2190/1abl-9be5-m0x2-lr9v

  103. 103.

    Carstensen LL. Evidence for a life-span theory of socioemotional selectivity. Curr. Dir. Psychol. Sci. 1995;4:151-156.

    Not in our library10.1111/1467-8721.ep11512261

  104. 104.

    Böger A, Huxhold O. Age-related changes in emotional qualities of the social network from middle adulthood into old age: how do they relate to the experience of loneliness? Psychol. Aging. 2018;33:482-496.

    Not in our library10.1037/pag0000222

  105. 105.

    Perissinotto CM, Cenzer IS, Covinsky KE. Loneliness in older persons: a predictor of functional decline and death. Arch. Intern. Med. 2012;172:1078-1084.

    Not in our library10.1001/archinternmed.2012.1993

  106. 106.

    Heikkinen RL, Kauppinen M. Depressive symptoms in late life: a 10-year follow-up. Arch. Gerontol. Geriatr. 2004;38:239-250.

    Not in our library10.1016/j.archger.2003.10.004

  107. 107.

    Cole MG, Dendukuri N. Risk factors for depression among elderly community subjects: a systematic review and meta-analysis. Am. J. Psychiatry. 2003;160:1147-1156.

    Not in our library10.1176/appi.ajp.160.6.1147

  108. 108.

    Pinquart M, Sörensen S. Gender differences in self-concept and psychological well-being in old age: a meta-analysis. J. Gerontol. B Psychol. Sci. Soc. Sci. 2001;56:P195-P213.

    Not in our library10.1093/geronb/56.4.p195

  109. 109.

    McDougall FA, Matthews FE, Kvaal K, Dewey ME, Brayne C. Prevalence and symptomatology of depression in older people living in institutions in England and Wales. Age Ageing. 2007;36:562-568.

    Not in our library10.1093/ageing/afm111

  110. 110.

    Margrett J, et al. Depression among centenarians and the oldest old: contributions of cognition and personality. Gerontology. 2010;56:93-99.

    Not in our library10.1159/000272018

  111. 111.

    Wilson RS, et al. Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology. 2002;59:364-370.

    Not in our library10.1212/wnl.59.3.364

  112. 112.

    Köhler S, et al. Depressive symptoms and cognitive decline in community‐dwelling older adults. J. Am. Geriatr. Soc. 2010;58:873-879.

    Not in our library10.1111/j.1532-5415.2010.02807.x

  113. 113.

    Barnes DE, Alexopoulos GS, Lopez OL, Williamson JD, Yaffe K. Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study. Arch. Gen. Psychiatry. 2006;63:273-279.

    Not in our library10.1001/archpsyc.63.3.273

  114. 114.

    Geda YE, et al. Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. Arch. Neurol. 2006;63:435-440.

    Not in our library10.1001/archneur.63.3.435

  115. 115.

    Saczynski JS, et al. Depressive symptoms and risk of dementia The Framingham Heart Study. Neurology. 2010;75:35-41.

    Not in our library10.1212/wnl.0b013e3181e62138

  116. 116.

    Barnes DE, et al. Midlife vs late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia. Arch. Gen. Psychiatry. 2012;69:493-498.

    Not in our library10.1001/archgenpsychiatry.2011.1481

  117. 117.

    Ballmaier M, et al. Hippocampal morphology and distinguishing late-onset from early-onset elderly depression. Am. J. Psychiatry. 2008;165:229-237.

    Not in our library10.1176/appi.ajp.2007.07030506

  118. 118.

    Elbejjani M, et al. Depression, depressive symptoms, and rate of hippocampal atrophy in a longitudinal cohort of older men and women. Psychol. Med. 2015;45:1931-1944.

    Not in our library10.1017/s0033291714003055

  119. 119.
  120. 120.

    Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin. Neurosci. 2006;8:383.

    Not in our library10.31887/dcns.2006.8.4/ssmith

  121. 121.

    Salvat-Pujol N, et al. Hypothalamic-pituitary-adrenal axis activity and cognition in major depression: the role of remission status. Psychoneuroendocrinology. 2017;76:38-48.

    Not in our library10.1016/j.psyneuen.2016.11.007

  122. 122.

    Wilson RS, et al. Clinical-pathologic study of depressive symptoms and cognitive decline in old age. Neurology. 2014;83:702-709.

    Not in our library10.1212/wnl.0000000000000715

  123. 123.

    Laird KT, Lavretsky H, Wu P, Krause B, Siddarth P. Neurocognitive correlates of resilience in late-life depression. Am. J. Geriatr. Psychiatry. 2018;27:12-17.

    Not in our library10.1016/j.jagp.2018.08.009

  124. 124.

    Vlasova RM, et al. Resilience and white matter integrity in geriatric depression. Am. J. Geriatr. Psychiatry. 2018;26:874-883.

    Not in our library10.1016/j.jagp.2018.04.004

  125. 125.

    Stern, Y. et al. Whitepaper: defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement. 1–7 (2018).

    Not in our library10.1016/j.jalz.2018.07.219

  126. 126.

    Stern Y. Cognitive reserve. Neuropsychologia. 2009;47:2015-2028.

    Not in our library10.1016/j.neuropsychologia.2009.03.004

  127. 127.

    Opdebeeck C, Quinn C, Nelis SM, Clare L. Does cognitive reserve moderate the association between mood and cognition? A systematic review. Rev. Clin. Gerontol. 2015;25:181-193.

    Not in our library10.1017/s0959259815000155

  128. 128.

    Lachman ME, Agrigoroaei S. Promoting functional health in midlife and old age: long-term protective effects of control beliefs, social support, and physical exercise. PLoS ONE. 2010;5:e13297.

    Not in our library10.1371/journal.pone.0013297

  129. 129.

    Sneed JR, et al. Response inhibition predicts poor antidepressant treatment response in very old depressed patients. Am. J. Geriatr. Psychiatry. 2007;15:553-563.

    Not in our library10.1097/jgp.0b013e3180302513

  130. 130.

    Sheline YI, et al. Support for the vascular depression hypothesis in late-life depression: results of a 2-site, prospective, antidepressant treatment trial. Arch. Gen. Psychiatry. 2010;67:277-285.

    Not in our library10.1001/archgenpsychiatry.2009.204

  131. 131.

    Hammen C. Stress and depression. Annu. Rev. Clin. Psychol. 2005;1:293-319.

    Not in our library10.1146/annurev.clinpsy.1.102803.143938

  132. 132.

    Conway CC, Raposa EB, Hammen C, Brennan PA. Transdiagnostic pathways from early social stress to psychopathology: a 20‐year prospective study. J. Child Psychol. Psychiatry. 2018;59:855-862.

    Not in our library10.1111/jcpp.12862

  133. 133.

    Charney DS. Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am. J. Psychiatry. 2004;161:195-216.

    Not in our library10.1176/appi.ajp.161.2.195

  134. 134.

    McEwen BS. Sex, stress and the hippocampus: allostasis, allostatic load and the aging process. Neurobiol. Aging. 2002;23:921-939.

    Not in our library10.1016/s0197-4580(02)00027-1

  135. 135.

    Lee RS, Sawa A. Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal axis. Neuroendocrinology. 2014;100:278-287.

    Not in our library10.1159/000369585

  136. 136.

    Pfau ML, Russo SJ. Peripheral and central mechanisms of stress resilience. Neurobiol. Stress. 2015;1:66-79.

    Not in our library10.1016/j.ynstr.2014.09.004

  137. 137.

    Seery MD, Leo RJ, Lupien SP, Kondrak CL, Almonte JL. An upside to adversity? Moderate cumulative lifetime adversity is associated with resilient responses in the face of controlled stressors. Psychol. Sci. 2013;24:1181-1189.

    Not in our library10.1177/0956797612469210

  138. 138.

    Lyons DM, Parker KJ, Katz M, Schatzberg AF. Developmental cascades linking stress inoculation, arousal regulation, and resilience. Front. Behav. Neurosci. 2009;3:32.

    Not in our library10.3389/neuro.08.032.2009

  139. 139.

    Pakulak E, Stevens C, Neville H. Neuro-, cardio-, and immunoplasticity: effects of early adversity. Annu. Rev. Psychol. 2018;69:131-156.

    Not in our library10.1146/annurev-psych-010416-044115

  140. 140.

    Booth T, et al. Association of allostatic load with brain structure and cognitive ability in later life. Neurobiol. Aging. 2015;36:1390-1399.

    Not in our library10.1016/j.neurobiolaging.2014.12.020

  141. 141.

    Caspi A, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301:386-389.

    Not in our library10.1126/science.1083968

  142. 142.

    Chopra K, Kumar B, Kuhad A. Pathobiological targets of depression. Expert Opin. Ther. Targets. 2011;15:379-400.

    Not in our library10.1517/14728222.2011.553603

  143. 143.

    Miller GE, Chen E, Zhou ES. If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychol. Bull. 2007;133:25.

    Not in our library10.1037/0033-2909.133.1.25

  144. 144.

    Heim C, Ehlert U, Hellhammer DH. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology. 2000;25:1-35.

    Not in our library10.1016/s0306-4530(99)00035-9

  145. 145.

    Gold PW, Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol. Psychiatry. 2002;7:254.

    Not in our library10.1038/sj.mp.4001032

  146. 146.

    Mason JW, et al. Psychogenic lowering of urinary cortisol levels linked to increased emotional numbing and a shame-depressive syndrome in combat-related posttraumatic stress disorder. Psychosom. Med. 2001;63:387-401.

    Not in our library10.1097/00006842-200105000-00008

  147. 147.

    Mann JJ, et al. Can biological tests assist prediction of suicide in mood disorders? Int. J. Neuropsychopharmacol. 2006;9:465-474.

    Not in our library10.1017/s1461145705005687

  148. 148.

    Jokinen J, Nordstrom P. HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients. Psychoneuroendocrinology. 2008;33:1387-1393.

    Not in our library10.1016/j.psyneuen.2008.07.012

  149. 149.

    ter Heegde F, De Rijk RH, Vinkers CH. The brain mineralocorticoid receptor and stress resilience. Psychoneuroendocrinology. 2015;52:92-110.

    Not in our library10.1016/j.psyneuen.2014.10.022

  150. 150.

    Leonard BE. Inflammation and depression: a causal or coincidental link to the pathophysiology? Acta Neuropsychiatr. 2018;30:1-16.

    Not in our library10.1017/neu.2016.69

  151. 151.
  152. 152.

    Tatemoto, K. Neuropeptide Y: history and overview. In Neuropeptide Y and related peptides (pp. 1–21). Springer, Berlin, Heidelberg (2004).

    Not in our library

  153. 153.

    Heilig M, et al. Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. J. Psychiatr. Res. 2004;38:113-121.

    Not in our library10.1016/s0022-3956(03)00101-8

  154. 154.

    Mickey BJ, et al. Emotion processing, major depression, and functional genetic variation of neuropeptide Y. Arch. Gen. Psychiatry. 2011;68:158-166.

    Not in our library10.1001/archgenpsychiatry.2010.197

  155. 155.

    Newhouse P, Albert K. Estrogen, stress, and depression: a neurocognitive model. JAMA Psychiatry. 2015;72:727-729.

    Not in our library10.1001/jamapsychiatry.2015.0487

  156. 156.

    Ryan J, Carriere I, Scali J, Ritchie K, Ancelin ML. Lifetime hormonal factors may predict late-life depression in women. Int. Psychogeriatr. 2008;20:1203-1218.

    Not in our library10.1017/s1041610208007412

  157. 157.

    Ryan J, et al. Oestrogen receptor polymorphisms and late-life depression. Br. J. Psychiatry. 2011;199:126-131.

    Not in our library10.1192/bjp.bp.111.091751

  158. 158.

    Peters R. Ageing and the brain. Postgrad. Med. J. 2006;82:84-88.

    Not in our library10.1136/pgmj.2005.036665

  159. 159.

    Hara Y, Waters EM, McEwen BS, Morrison JH. Estrogen effects on cognitive and synaptic health over the lifecourse. Physiol. Rev. 2015;95:785-807.

    Not in our library10.1152/physrev.00036.2014

  160. 160.

    McEwen BS, Morrison JH. The brain on stress: vulnerability and plasticity of the prefrontal cortex over the life course. Neuron. 2013;79:16-29.

    Not in our library10.1016/j.neuron.2013.06.028

  161. 161.

    Rutkowski K, Sowa P, Rutkowska-Talipska J, Kuryliszyn-Moskal A, Rutkowski R. Dehydroepiandrosterone (DHEA): hypes and hopes. Drugs. 2014;74:1195-1207.

    Not in our library10.1007/s40265-014-0259-8

  162. 162.

    Samaras N, Samaras D, Frangos E, Forster A, Philippe J. A review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: is treatment beneficial? Rejuvenation Res. 2013;16:285-294.

    Not in our library10.1089/rej.2013.1425

  163. 163.

    Fabian TJ, et al. Endogenous concentrations of DHEA and DHEA-S decrease with remission of depression in older adults. Biol. Psychiatry. 2001;50:767-774.

    Not in our library10.1016/s0006-3223(01)01198-2

  164. 164.

    Carney RM, Freedland KE, Sheline YI, Weiss ES. Depression and coronary heart disease: a review for cardiologists. Clin. Cardiol. 1997;20:196-200.

    Not in our library10.1002/clc.4960200304

  165. 165.

    Nicholson A, Kuper H, Hemingway H. Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur. Heart J. 2006;27:2763-2774.

    Not in our library10.1093/eurheartj/ehl338

  166. 166.

    Hare DL, Toukhsati SR, Johansson P, Jaarsma T. Depression and cardiovascular disease: a clinical review. Eur. Heart J. 2013;35:1365-1372.

    Not in our library10.1093/eurheartj/eht462

  167. 167.

    Valkanova V, Ebmeier KP. Vascular risk factors and depression in later life: a systematic review and meta-analysis. Biol. Psychiatry. 2013;73:406-413.

    Not in our library10.1016/j.biopsych.2012.10.028

  168. 168.

    Brown L, et al. Heart rate variability alterations in late life depression: a meta-analysis. J. Affect. Disord. 2018;235:456-466.

    Not in our library10.1016/j.jad.2018.04.071

  169. 169.

    Carney RM, Freedland KE. Depression and coronary heart disease. Nat. Rev. Cardiol. 2017;14:145.

    Not in our library10.1038/nrcardio.2016.181

  170. 170.

    Appelhans BM, Luecken LJ. Heart rate variability as an index of regulated emotional responding. Rev. Gen. Psychol. 2006;10:229.

    Not in our library10.1037/1089-2680.10.3.229

  171. 171.

    Holzman JB, Bridgett DJ. Heart rate variability indices as bio-markers of top-down self-regulatory mechanisms: a meta-analytic review. Neurosci. Biobehav. Rev. 2017;74:233-255.

    Not in our library10.1016/j.neubiorev.2016.12.032

  172. 172.
  173. 173.

    Koenig J, Kemp AH, Beauchaine TP, Thayer JF, Kaess M. Depression and resting state heart rate variability in children and adolescents—a systematic review and meta-analysis. Clin. Psychol. Rev. 2016;46:136-150.

    Not in our library10.1016/j.cpr.2016.04.013

  174. 174.
  175. 175.

    Kemp AH, et al. Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis. Biol. Psychiatry. 2010;67:1067-1074.

    Not in our library10.1016/j.biopsych.2009.12.012

  176. 176.

    Yoo HJ, et al. Brain structural concomitants of resting state heart rate variability in the young and old: evidence from two independent samples. Brain Struct. Funct. 2018;223:727-737.

    Not in our library10.1007/s00429-017-1519-7

  177. 177.

    Umetani K, Singer DH, McCraty R, Atkinson M. Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades. J. Am. Coll. Cardiol. 1998;31:593-601.

    Not in our library10.1016/s0735-1097(97)00554-8

  178. 178.

    Vogelzangs N, Comijs HC, Oude Voshaar RC, Stek ML, Penninx BW. Late-life depression symptom profiles are differentially associated with immunometabolic functioning. Brain Behav. Immun. 2014;41:109-115.

    Not in our library10.1016/j.bbi.2014.05.004

  179. 179.

    Duivis HE, et al. Depressive symptoms, health behaviors, and subsequent inflammation in patients with coronary heart disease: prospective findings from the heart and soul study. Am. J. Psychiatry. 2011;168:913-920.

    Not in our library10.1176/appi.ajp.2011.10081163

  180. 180.

    Kahl KG, et al. Prevalence of the metabolic syndrome in unipolar major depression. Eur. Arch. Psychiatry Clin. Neurosci. 2012;262:313-320.

    Not in our library10.1007/s00406-011-0277-4

  181. 181.

    Viinamäki H, et al. Association of depressive symptoms and metabolic syndrome in men. Acta Psychiatr. Scand. 2009;120:23-29.

    Not in our library10.1111/j.1600-0447.2008.01333.x

  182. 182.

    Eller T, Vasar V, Shlik J, Maron E. Pro-inflammatory cytokines and treatment response to escitaloprsam in major depressive disorder. Prog. NeuroPsychopharmacol. Biol. Psychiatry. 2008;32:445-450.

    Not in our library10.1016/j.pnpbp.2007.09.015

  183. 183.

    Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology. 2000;22:370-379.

    Not in our library10.1016/s0893-133x(99)00134-7

  184. 184.

    Kloiber S, et al. Overweight and obesity affect treatment response in major depression. Biol. Psychiatry. 2007;62:321-326.

    Not in our library10.1016/j.biopsych.2006.10.001

  185. 185.
  186. 186.

    Siennicki-Lantz A, André-Petersson L, Elmståhl S. Decreasing blood pressure over time is the strongest predictor of depressive symptoms in octogenarian men. Am. J. Geriatr. Psychiatry. 2013;21:863-871.

    Not in our library10.1016/j.jagp.2012.11.007

  187. 187.

    Giltay EJ, et al. Serum cholesterol, apolipoprotein E genotype and depressive symptoms in elderly European men: the FINE study. J. Affect. Disord. 2009;115:471-477.

    Not in our library10.1016/j.jad.2008.10.004

  188. 188.

    Kuo SY, Lin KM, Chen CY, Chuang YL, Chen WJ. Depression trajectories and obesity among the elderly in Taiwan. Psychol. Med. 2011;41:1665-1676.

    Not in our library10.1017/s0033291710002473

  189. 189.

    Marijnissen RM, Naudé PJW, Comijs HC, Schoevers RA, Voshaar RCO. Waist circumference and neutrophil gelatinase-associated lipocalin in late-life depression. Brain Behav. Immun. 2014;37:231-239.

    Not in our library10.1016/j.bbi.2013.12.021

  190. 190.

    Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol. Psychiatry. 2009;65:732-741.

    Not in our library10.1016/j.biopsych.2008.11.029

  191. 191.

    Martinez-Cengotitabengoa M, et al. Peripheral inflammatory parameters in late-life depression: a systematic review. Int. J. Mol. Sci. 2016;17:8-15.

    Not in our library10.3390/ijms17122022

  192. 192.

    Wiedlocha M, et al. Effect of antidepressant treatment on peripheral inflammation markers - a meta-analysis. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2018;80(Pt C):217-226.

    Not in our library10.1016/j.pnpbp.2017.04.026

  193. 193.
  194. 194.

    Bierhaus A, et al. A mechanism converting psychosocial stress into mononuclear cell activation. Proc. Natl Acad. Sci. USA. 2003;100:1920-1925.

    Not in our library10.1073/pnas.0438019100

  195. 195.

    Danese A, Pariante CM, Caspi A, Taylor A, Poulton R. Childhood maltreatment predicts adult inflammation in a life-course study. Proc. Natl Acad. Sci. USA. 2007;104:1319-1324.

    Not in our library10.1073/pnas.0610362104

  196. 196.

    McDade TW, Hawkley LC, Cacioppo JT. Psychosocial and behavioral predictors of inflammation in middle-aged and older adults: the Chicago health, aging, and social relations study. Psychosom. Med. 2006;68:376-381.

    Not in our library10.1097/01.psy.0000221371.43607.64

  197. 197.

    Kiecolt-Glaser JK, et al. Hostile marital interactions, proinflammatory cytokine production, and wound healing. Arch. Gen. Psychiatry. 2005;62:1377-1384.

    Not in our library10.1001/archpsyc.62.12.1377

  198. 198.

    Miller GE, et al. A functional genomic fingerprint of chronic stress in humans: blunted glucocorticoid and increased NF-κB signaling. Biol. Psychiatry. 2008;64:266-272.

    Not in our library10.1016/j.biopsych.2008.03.017

  199. 199.

    Pei Y, et al. The brain-derived neurotrophic-factor (BDNF) val66met polymorphism is associated with geriatric depression: a meta-analysis. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2012;159b:560-566.

    Not in our library10.1002/ajmg.b.32062

  200. 200.

    Tsang RS, Mather KA, Sachdev PS, Reppermund S. Systematic review and meta-analysis of genetic studies of late-life depression. Neurosci. Biobehav. Rev. 2017;75:129-139.

    Not in our library10.1016/j.neubiorev.2017.01.028

  201. 201.

    Egan MF, et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112:257-269.

    Not in our library10.1016/s0092-8674(03)00035-7

  202. 202.

    Hariri AR, et al. Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J. Neurosci. 2003;23:6690-6694.

    Not in our library10.1523/jneurosci.23-17-06690.2003

  203. 203.

    Gratacòs M, et al. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol. Psychiatry. 2007;61:911-922.

    Not in our library10.1016/j.biopsych.2006.08.025

  204. 204.

    Verhagen M, et al. Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity. Mol. Psychiatry. 2010;15:260.

    Not in our library10.1038/mp.2008.109

  205. 205.
  206. 206.

    Januar V, Ancelin ML, Ritchie K, Saffery R, Ryan J. BDNF promoter methylation and genetic variation in late-life depression. Transl. Psychiatry. 2015;5:e619.

    Not in our library10.1038/tp.2015.114

  207. 207.

    Murphy GM, et al. BDNF and CREB1 genetic variants interact to affect antidepressant treatment outcomes in geriatric depression. Pharmacogenet. Genomics. 2013;23:301-313.

    Not in our library10.1097/fpc.0b013e328360b175

  208. 208.

    Garcia R. Stress, synaptic plasticity, and psychopathology. Rev. Neurosci. 2002;13:195-208.

    Not in our library10.1515/revneuro.2002.13.3.195

  209. 209.

    Duman RS, Malberg J, Nakagawa S, D’Sa C. Neuronal plasticity and survival in mood disorders. Biol. Psychiatry. 2000;48:732-739.

    Not in our library10.1016/s0006-3223(00)00935-5

  210. 210.

    Öngür D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc. Natl Acad. Sci. USA. 1998;95:13290-13295.

    Not in our library10.1073/pnas.95.22.13290

  211. 211.

    Rosoklija G, et al. Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings. Arch. Gen. Psychiatry. 2000;57:349-356.

    Not in our library10.1001/archpsyc.57.4.349

  212. 212.

    Cotter D, et al. Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cereb. Cortex. 2002;12:386-394.

    Not in our library10.1093/cercor/12.4.386

  213. 213.

    Miguel-Hidalgo JJ, Rajkowska G. Morphological brain changes in depression. CNS Drugs. 2002;16:361-372.

    Not in our library10.2165/00023210-200216060-00001

  214. 214.

    Rajkowska G. Cell pathology in mood disorders. Semin. Clin. Neuropsychiatry. 2002;7:281-292.

    Not in our library10.1053/scnp.2002.35228

  215. 215.

    Geerlings MI, Gerritsen L. Late-life depression, hippocampal volumes, and hypothalamic-pituitary-adrenal axis regulation: a systematic review and meta-analysis. Biol. Psychiatry. 2017;82:339-350.

    Not in our library10.1016/j.biopsych.2016.12.032

  216. 216.

    Dwivedi Y. Involvement of brain-derived neurotrophic factor in late-life depression. Am. J. Geriatr. Psychiatry. 2013;21:433-449.

    Not in our library10.1016/j.jagp.2012.10.026

  217. 217.

    Aizenstein HJ, et al. Altered functioning of the executive control circuit in late-life depression: episodic and persistent phenomena. Am. J. Geriatr. Psychiatry. 2009;17:30-42.

    Not in our library10.1097/jgp.0b013e31817b60af

  218. 218.

    Crocco EA, Castro K, Loewenstein DA. How late-life depression affects cognition: neural mechanisms. Curr. Psychiatry Rep. 2010;12:34-38.

    Not in our library10.1007/s11920-009-0081-2

  219. 219.

    Khundakar AA, Thomas AJ. Morphometric changes in early-and late-life major depressive disorder: evidence from postmortem studies. Int. Psychogeriatr. 2009;21:844-854.

    Not in our library10.1017/s104161020999007x

  220. 220.

    Janssen J, et al. Hippocampal volume and subcortical white matter lesions in late-life depression: comparison of early-and late-onset depression. J. Neurol. Neurosurg. Psychiatry. 2007;78:638-640.

    Not in our library10.1136/jnnp.2006.098087

  221. 221.

    Narayan M, Bremner JD, Kumar A. Neuroanatomic substrates of late-life mental disorders. J. Geriatr. Psychiatry Neurol. 1999;12:95-106.

    Not in our library10.1177/089198879901200303

  222. 222.

    Ebner NC, Fischer H. Emotion and aging: evidence from brain and behavior. Front. Psychol. 2014;5:996.

    Not in our library10.3389/fpsyg.2014.00996

  223. 223.

    Urry HL, Gross JJ. Emotion regulation in older age. Curr. Dir. Psychol. Sci. 2010;19:352-357.

    Not in our library10.1177/0963721410388395

  224. 224.

    Allard ES, Kensinger EA. Age-related differences in neural recruitment during the use of cognitive reappraisal and selective attention as emotion regulation strategies. Front. Psychol. 2014;5:296.

    Not in our library10.3389/fpsyg.2014.00296

  225. 225.
  226. 226.

    Santarnecchi E, et al. Brain functional connectivity correlates of coping styles. Cogn. Affect. Behav. Neurosci. 2018;18:495-508.

    Not in our library10.3758/s13415-018-0583-7

  227. 227.

    Chen D, et al. Negative association between resilience and event-related potentials evoked by negative emotion. Sci. Rep. 2018;8:7149.

    Not in our library10.1038/s41598-018-25555-w

  228. 228.

    Leaver AM, et al. Resilience and amygdala function in older healthy and depressed adults. J. Affect. Disord. 2018;237:27-34.

    Not in our library10.1016/j.jad.2018.04.109

  229. 229.

    Coffey CE, Figiel GS, Djang WT, Saunders WB, Weiner RD. White matter hyperintensity on magnetic resonance imaging: clinical and neuroanatomic correlates in the depressed elderly. J. Neuropsychiatry Clin. Neurosci. 1989;1:135-144.

    Not in our library10.1176/jnp.1.2.135

  230. 230.

    Dolan RJ, Poynton AM, Bridges PK, Trimble MR. Altered magnetic resonance white-matter T 1 values in patients with affective disorder. Br. J. Psychiatry. 1990;157:107-110.

    Not in our library10.1192/bjp.157.1.107

  231. 231.

    Lavretsky H, Lesser IM, Wohl M, Miller BL. Relationship of age, age at onset, and sex to depression in older adults. Am. J. Geriatr. Psychiatry. 1998;6:248-256.

    Not in our library10.1097/00019442-199808000-00007

  232. 232.

    Herrmann LL, LeMasurier M, Ebmeie KP. White matter hyperintensities in late life depression: a systematic review. J. Neurol. Neurosurg. Psychiatry. 2007;79:619-624.

    Not in our library10.1136/jnnp.2007.124651

  233. 233.

    de Groot JC, et al. Cerebral white matter lesions and depressive symptoms in elderly adults. Arch. Gen. Psychiatry. 2000;57:1071-1076.

    Not in our library10.1001/archpsyc.57.11.1071

  234. 234.

    Salloway S, et al. MRI and neuropsychological differences in early-and late-life-onset geriatric depression. Neurology. 1996;46:1567-1574.

    Not in our library10.1212/wnl.46.6.1567

  235. 235.

    Dillon C, et al. Late-versus early-onset geriatric depression in a memory research center. Neuropsychiatr. Dis. Treat. 2009;5:517.

    Not in our library10.2147/ndt.s7320

  236. 236.

    Rapp MA, et al. Neuropsychological differences between late-onset and recurrent geriatric major depression. Am. J. Psychiatry. 2005;162:691-698.

    Not in our library10.1176/appi.ajp.162.4.691

  237. 237.

    Krishnan KR, Hays JC, Blazer DG. MRI-defined vascular depression. Am. J. Psychiatry. 1997;154:497-501.

    Not in our library10.1176/ajp.154.4.497

  238. 238.

    Alexopoulos GS, Meyers BS, Young RC, Kakuma T. Clinically defined vascular depression. Am. J. Psychiatry. 1997;154:562.

    Not in our library10.1176/ajp.154.4.562

  239. 239.

    Taylor WD, Aizenstein HJ, Alexopoulos GS. The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol. Psychiatry. 2013;18:963-974.

    Not in our library10.1038/mp.2013.20

  240. 240.

    Taylor WD, Steffens DC, Krishnan KR. Psychiatric disease in the twenty-first century: The case for subcortical ischemic depression. Biol. Psychiatry. 2006;60:1299-1303.

    Not in our library10.1016/j.biopsych.2006.05.028

  241. 241.

    Kamat R, et al. Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection. J. Clin. Exp. Neuropsychol. 2014;36:854-866.

    Not in our library10.1080/13803395.2014.950636

  242. 242.

    Alves GS, et al. Clinical characteristics in subcortical ischemic white matter disease. Arq. Neuropsiquiatr. 2009;67(2A):173-178.

    Not in our library10.1590/s0004-282x2009000200001

  243. 243.

    Grool AM, et al. Structural MRI correlates of apathy symptoms in older persons without dementia AGES-Reykjavik Study. Neurology. 2014;82:1628-1635.

    Not in our library10.1212/wnl.0000000000000378

  244. 244.

    Bruce DG, et al. Apathy in older patients with type 2 diabetes. Am. J. Geriatr. Psychiatry. 2015;23:615-621.

    Not in our library10.1016/j.jagp.2014.09.010

  245. 245.

    Ligthart SA, et al. Association of vascular factors with apathy in community-dwelling elderly individuals. Arch. Gen. Psychiatry. 2012;69:636-642.

    Not in our library10.1001/archgenpsychiatry.2011.1858

  246. 246.

    Baldwin RC, Tomenson B. Depression in later life: a comparison of symptoms and risk factors in early and late onset cases. Br. J. Psychiatry. 1995;167:649-652.

    Not in our library10.1192/bjp.167.5.649

  247. 247.

    Driscoll HC, et al. Late‐onset major depression: clinical and treatment‐response variability. Int. J. Geriatr. Psychiatry. 2005;20:661-667.

    Not in our library10.1002/gps.1334

  248. 248.

    Whyte EM, et al. Geriatric depression treatment in nonresponders to selective serotonin reuptake inhibitors. J. Clin. Psychiatry. 2004;65:1634-1641.

    Not in our library10.4088/jcp.v65n1208

  249. 249.

    Karp JF, et al. Time to remission in late‐life depression: analysis of effects of demographic, treatment, and life‐events measures. Depression. 1993;1:250-256.

    Not in our library10.1002/depr.3050010503

  250. 250.

    Reynolds CFr, et al. Effects of age at onset of first lifetime episode of recurrent major depression on treatment response and illness course in elderly patients. Am. J. Psychiatry. 1998;155:795-799.

    Not in our library10.1176/ajp.155.11.1621

  251. 251.

    Seligman, M. E. & Csikszentmihalyi, M. Positive Psychology: An Introduction (Vol. 55, p. 5–14), American Psychological Association (2000).

    Not in our library10.1037//0003-066x.55.1.5

  252. 252.

    Sin NL, Lyubomirsky S. Enhancing well‐being and alleviating depressive symptoms with positive psychology interventions: a practice‐friendly meta‐analysis. J. Clin. Psychol. 2009;65:467-487.

    Not in our library10.1002/jclp.20593

  253. 253.

    Diener E. Subjective well-being. Psychol. Bull. 1984;95:542.

    Not in our library10.1037/0033-2909.95.3.542

  254. 254.

    Ryan RM, Deci EL. On happiness and human potentials: a review of research on hedonic and eudaimonic well-being. Annu. Rev. Psychol. 2001;52:141-166.

    Not in our library10.1146/annurev.psych.52.1.141

  255. 255.

    Ryff CD. Happiness is everything, or is it? Explorations on the meaning of psychological well-being. J. Pers. Soc. Psychol. 1989;57:1069.

    Not in our library10.1037/0022-3514.57.6.1069

  256. 256.

    Seligman MEP, Steen TA, Park N, Peterson C. Positive psychology progress: empirical validation of interventions. Am. Psychol. 2005;60:410.

    Not in our library10.1037/0003-066x.60.5.410

  257. 257.

    Sheldon KM, Lyubomirsky S. How to increase and sustain positive emotion: the effects of expressing gratitude and visualizing best possible selves. J. Posit. Psychol. 2006;1:73-82.

    Not in our library10.1080/17439760500510676

  258. 258.

    Peters ML, Flink IK, Boersma K, Linton SJ. Manipulating optimism: can imagining a best possible self be used to increase positive future expectancies? J. Posit. Psychol. 2010;5:204-211.

    Not in our library10.1080/17439761003790963

  259. 259.

    Peters ML, Meevissen YMC, Hanssen MM. Specificity of the Best Possible Self intervention for increasing optimism: comparison with a gratitude intervention. Ter. Psicol. 2013;31:93-100.

    Not in our library10.4067/s0718-48082013000100009

  260. 260.

    Meevissen YMC, Peters ML, Alberts HJEM. Become more optimistic by imagining a best possible self: effects of a two week intervention. J. Behav. Ther. Exp. Psychiatry. 2011;42:371-378.

    Not in our library10.1016/j.jbtep.2011.02.012

  261. 261.

    Zautra AJ, et al. Comparison of cognitive behavioral and mindfulness meditation interventions on adaptation to rheumatoid arthritis for patients with and without history of recurrent depression. J. Consult. Clin. Psychol. 2008;76:408.

    Not in our library10.1037/0022-006x.76.3.408

  262. 262.

    Lyubomirsky S, Sheldon KM, Schkade D. Pursuing happiness: the architecture of sustainable change. Rev. Gen. Psychol. 2005;9:111.

    Not in our library10.1037/1089-2680.9.2.111

  263. 263.

    Anik, L., Aknin, L. B., Norton, M. I. & Dunn, E. W. Feeling Good About Giving: the Benefits (And Costs) of Self-interested Charitable Behavior. Harvard Business School Marketing Unit Working Paper (2009).

    Not in our library

  264. 264.

    Lyubomirsky, S., Tkach, C. & Sheldon K. M. Pursuing sustained happiness through random acts of kindness and counting one’s blessings: tests of two six-week interventions. Unpublished raw data (2004).

    Not in our library

  265. 265.

    Buchanan KE, Bardi A. Acts of kindness and acts of novelty affect life satisfaction. J. Soc. Psychol. 2010;150:235-237.

    Not in our library10.1080/00224540903365554

  266. 266.

    Helgeson VS, Reynolds KA, Tomich PL. A meta-analytic review of benefit finding and growth. J. Consult. Clin. Psychol. 2006;74:797.

    Not in our library10.1037/0022-006x.74.5.797

  267. 267.

    Algoe, S. B. & Stanton, A. L. Is benefit finding good for individuals with chronic disease? In C. L. Park, S. C. Lechner, M. H. Antoni, & A. L. Stanton (Eds.), Medical illness and positive life change: Can crisis lead to personal transformation? (pp. 173–193). Washington, DC, US: American Psychological Association (2009).

    Not in our library

  268. 268.

    Bower JE, Moskowitz JT, Epel E. Is benefit finding good for your health? Pathways linking positive life changes after stress and physical health outcomes. Curr. Dir. Psychol. Sci. 2009;18:337-341.

    Not in our library10.1111/j.1467-8721.2009.01663.x

  269. 269.

    Uchino BN, Cacioppo JT, Kiecolt-Glaser JK. The relationship between social support and physiological processes: a review with emphasis on underlying mechanisms and implications for health. Psychol. Bull. 1996;119:488.

    Not in our library10.1037/0033-2909.119.3.488

  270. 270.

    Bower JE, Kemeny ME, Taylor SE, Fahey JL. Finding positive meaning and its association with natural killer cell cytotoxicity among participants in a bereavement-related disclosure intervention. Ann. Behav. Med. 2003;25:146-155.

    Not in our library10.1207/s15324796abm2502_11

  271. 271.

    Bower JE, Segerstrom SC. Stress management, finding benefit, and immune function: positive mechanisms for intervention effects on physiology. J. Psychosom. Res. 2004;56:9-11.

    Not in our library10.1016/s0022-3999(03)00120-x

  272. 272.

    Kabat-Zinn J. Mindfulness‐based interventions in context: past, present, and future. Clin. Psychol. Sci. Pract. 2003;10:144-156.

    Not in our library10.1093/clipsy.bpg016

  273. 273.

    Khoury B, et al. Mindfulness-based therapy: a comprehensive meta-analysis. Clin. Psychol. Rev. 2013;33:763-771.

    Not in our library10.1016/j.cpr.2013.05.005

  274. 274.

    Hazlett-Stevens, H., Singer, J. & Chong, A. Mindfulness-based stress reduction and mindfulness-based cognitive therapy with older adults: a qualitative review of randomized controlled outcome research. Clin. Gerontol. 1–12 (2018).

    Not in our library10.1080/07317115.2018.1518282

  275. 275.

    Piet J, Hougaard E. The effect of mindfulness-based cognitive therapy for prevention of relapse in recurrent major depressive disorder: a systematic review and meta-analysis. Clin. Psychol. Rev. 2011;31:1032-1040.

    Not in our library10.1016/j.cpr.2011.05.002

  276. 276.

    Gu J, Strauss C, Bond R, Cavanagh K. How do mindfulness-based cognitive therapy and mindfulness-based stress reduction improve mental health and wellbeing? A systematic review and meta-analysis of mediation studies. Clin. Psychol. Rev. 2015;37:1-12.

    Not in our library10.1016/j.cpr.2015.01.006

  277. 277.

    Luders E. Exploring age‐related brain degeneration in meditation practitioners. Ann. N. Y. Acad. Sci. 2014;1307:82-88.

    Not in our library10.1111/nyas.12217

  278. 278.

    Boccia M, Piccardi L, Guariglia P. The meditative mind: a comprehensive meta-analysis of MRI studies. BioMed Res. Int. 2015;2015:1-11.

    Not in our library10.1155/2015/419808

  279. 279.

    Tang YY, Hölzel BK, Posner MI. The neuroscience of mindfulness meditation. Nat. Rev. Neurosci. 2015;16:213.

    Not in our library10.1038/nrn3916

  280. 280.

    Chiesa A, Serretti A. A systematic review of neurobiological and clinical features of mindfulness meditations. Psychol. Med. 2010;40:1239-1252.

    Not in our library10.1017/s0033291709991747

  281. 281.

    Kurth F, Cherbuin N, Luders E. Aging mindfully to minimize cognitive decline. J. Cogn. Enhanc. 2017;1:108-114.

    Not in our library10.1007/s41465-017-0027-2

  282. 282.

    Epel E, Daubenmier J, Moskowitz JT, Folkman S, Blackburn E. Can meditation slow rate of cellular aging? cognitive stress, mindfulness, and telomeres. Ann. N. Y. Acad. Sci. 2009;1172:34-53.

    Not in our library10.1111/j.1749-6632.2009.04414.x

  283. 283.

    Lavretsky H, et al. A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: effects on mental health, cognition, and telomerase activity. Int. J. Geriatr. Psychiatry. 2013;28:57-65.

    Not in our library10.1002/gps.3790

  284. 284.

    Black DS, et al. Yogic meditation reverses NF-kappaB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial. Psychoneuroendocrinology. 2013;38:348-355.

    Not in our library10.1016/j.psyneuen.2012.06.011

  285. 285.

    Amin A, et al. Beneficial effects of OM chanting on depression, anxiety, stress and cognition in elderly women with hypertension. Indian J. Clin. Anat. Physiol. 2016;3:253-255.

    Not in our library10.5958/2394-2126.2016.00056.6

  286. 286.
  287. 287.

    Cuijpers P, Karyotaki E, Pot AM, Park M, Reynolds Iii CF. Managing depression in older age: psychological interventions. Maturitas. 2014;79:160-169.

    Not in our library10.1016/j.maturitas.2014.05.027

  288. 288.

    Pinquart M, Duberstein PR, Lyness JM. Treatments for later-life depressive conditions: a meta-analytic comparison of pharmacotherapy and psychotherapy. Am. J. Psychiatry. 2006;163:1493-1501.

    Not in our library10.1176/ajp.2006.163.9.1493

  289. 289.

    Kishita N, Takei Y, Stewart I. A meta‐analysis of third wave mindfulness‐based cognitive behavioral therapies for older people. Int. J. Geriatr. Psychiatry. 2017;32:1352-1361.

    Not in our library10.1002/gps.4621

  290. 290.

    Zhao K, Bai ZG, Bo A, Chi I. A systematic review and meta‐analysis of music therapy for the older adults with depression. Int. J. Geriatr. Psychiatry. 2016;31:1188-1198.

    Not in our library10.1002/gps.4494

  291. 291.

    Laufer S, Engel S, Knaevelsrud C, Schumacher S. Cortisol and alpha-amylase assessment in psychotherapeutic intervention studies: a systematic review. Neurosci. Biobehav. Rev. 2018;95:235-262.

    Not in our library10.1016/j.neubiorev.2018.09.023

  292. 292.

    Wegner M, et al. Effects of exercise on anxiety and depression disorders: review of meta-analyses and neurobiological mechanisms. CNS Neurol. Disord. Drug Targets. 2014;13:1002-1014.

    Not in our library10.2174/1871527313666140612102841

  293. 293.

    Blake H, Mo P, Malik S, Thomas S. How effective are physical activity interventions for alleviating depressive symptoms in older people? A systematic review. Clin. Rehabil. 2009;23:873-887.

    Not in our library10.1177/0269215509337449

  294. 294.

    Hoffman-Goetz L, Pedersen BK. Exercise and the immune system: a model of the stress response? Immunol. Today. 1994;15:382-387.

    Not in our library10.1016/0167-5699(94)90177-5

  295. 295.

    Laird KT, Paholpak P, Roman M, Rahi B, Lavretsky H. Mind-body therapies for late-life mental and cognitive health. Curr. Psychiatry Rep. 2018;20:2.

    Not in our library10.1007/s11920-018-0864-4

  296. 296.

    Acevedo BP, Pospos S, Lavretsky H. The neural mechanisms of meditative practices: novel approaches for healthy aging. Curr. Behav. Neurosci. Rep. 2016;3:328-339.

    Not in our library10.1007/s40473-016-0098-x

  297. 297.

    Pascoe MC, Bauer IE. A systematic review of randomised control trials on the effects of yoga on stress measures and mood. J. Psychiatr. Res. 2015;68:270-282.

    Not in our library10.1016/j.jpsychires.2015.07.013

  298. 298.

    Pascoe MC, Thompson DR, Ski CF. Yoga, mindfulness-based stress reduction and stress-related physiological measures: a meta-analysis. Psychoneuroendocrinology. 2017;86:152-168.

    Not in our library10.1016/j.psyneuen.2017.08.008

  299. 299.

    Gothe NP, Keswani RK, McAuley E. Yoga practice improves executive function by attenuating stress levels. Biol. Psychol. 2016;121(Pt A):109-116.

    Not in our library10.1016/j.biopsycho.2016.10.010

  300. 300.

    Prakhinkit S, Suppapitiporn S, Tanaka H, Suksom D. Effects of Buddhism walking meditation on depression, functional fitness, and endothelium-dependent vasodilation in depressed elderly. J. Altern. Complement. Med. 2014;20:411-416.

    Not in our library10.1089/acm.2013.0205

  301. 301.

    Shahidi M, et al. Laughter yoga versus group exercise program in elderly depressed women: a randomized controlled trial. Int. J. Geriatr. Psychiatry. 2011;26:322-327.

    Not in our library10.1002/gps.2545

  302. 302.

    Tsang HW, et al. Psycho-physical and neurophysiological effects of qigong on depressed elders with chronic illness. Aging Ment. Health. 2013;17:336-348.

    Not in our library10.1080/13607863.2012.732035

  303. 303.

    Sneed JR, et al. Design makes a difference: a meta-analysis of antidepressant response rates in placebo-controlled versus comparator trials in late-life depression. Am. J. Geriatr. Psychiatry. 2008;16:65-73.

    Not in our library10.1097/jgp.0b013e3181256b1d

  304. 304.

    Ma Y. Neuropsychological mechanism underlying antidepressant effect: a systematic meta-analysis. Mol. Psychiatry. 2015;20:311.

    Not in our library10.1038/mp.2014.24

  305. 305.

    Davidson JR. Major depressive disorder treatment guidelines in America and Europe. J. Clin. Psychiatry. 2010;71:e04.

    Not in our library10.4088/jcp.9058se1c.04gry

  306. 306.

    Dierckx B, Heijnen WT, van den Broek WW, Birkenhäger TK. Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a meta‐analysis. Bipolar Disord. 2012;14:146-150.

    Not in our library10.1111/j.1399-5618.2012.00997.x

  307. 307.

    Carney S, et al. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet. 2003;361:799-808.

    Not in our library10.1016/s0140-6736(03)12705-5

  308. 308.

    O'Connor MK, et al. The influence of age on the response of major depression to electroconvulsive therapy: a CORE Report. Am. J. Geriatr. Psychiatry. 2001;9:382-390.

    Not in our library10.1097/00019442-200111000-00006

  309. 309.

    Hickie I, Mason C, Parker G, Brodaty H. Prediction of ECT response: validation of a refined sign-based (CORE) system for defining melancholia. Br. J. Psychiatry. 1996;169:68-74.

    Not in our library10.1192/bjp.169.1.68

  310. 310.

    Tew JD, et al. Acute efficacy of ECT in the treatment of major depression in the old-old. Am. J. Psychiatry. 1999;156:1865-1870.

    Not in our library10.1176/ajp.156.12.1865

  311. 311.

    Van der Wurff FB, Stek ML, Hoogendijk WJG, Beekman ATF. The efficacy and safety of ECT in depressed older adults: a literature review. Int. J. Geriatr. Psychiatry. 2003;18:894-904.

    Not in our library10.1002/gps.944

  312. 312.

    Flint AJ, Gagnon N. Effective use of electroconvulsive therapy in late-life depression. Can. J. Psychiatry. 2002;47:734-741.

    Not in our library10.1177/070674370204700804

  313. 313.

    Bouckaert F, et al. Grey matter volume increase following electroconvulsive therapy in patients with late life depression: a longitudinal MRI study. J. Psychiatry Neurosci. 2016;41:105.

    Not in our library10.1503/jpn.140322

  314. 314.

    Sackeim HA. Electroconvulsive therapy in late-life depression. Clin. Geriatr. Psychopharmacol. 2004;4:385-422.

    Not in our library

  315. 315.

    Nobuhara K, et al. Effects of electroconvulsive therapy on frontal white matter in late-life depression: a diffusion tensor imaging study. Neuropsychobiology. 2004;50:48-53.

    Not in our library10.1159/000077941

  316. 316.

    Karavidas MK, et al. Preliminary results of an open label study of heart rate variability biofeedback for the treatment of major depression. Appl. Psychophysiol. Biofeedback. 2007;32:19-30.

    Not in our library10.1007/s10484-006-9029-z

  317. 317.

    Siepmann M, Aykac V, Unterdörfer J, Petrowski K, Mueck-Weymann M. A pilot study on the effects of heart rate variability biofeedback in patients with depression and in healthy subjects. Appl. Psychophysiol. Biofeedback. 2008;33:195-201.

    Not in our library10.1007/s10484-008-9064-z

  318. 318.

    Patron E, et al. Biofeedback assisted control of respiratory sinus arrhythmia as a biobehavioral intervention for depressive symptoms in patients after cardiac surgery: a preliminary study. Appl. Psychophysiol. Biofeedback. 2013;38:1-9.

    Not in our library10.1007/s10484-012-9202-5

  319. 319.
  320. 320.

    Lyubomirsky S, Dickerhoof R, Boehm JK, Sheldon KM. Becoming happier takes both a will and a proper way: an experimental longitudinal intervention to boost well-being. Emotion. 2011;11:391.

    Not in our library10.1037/a0022575

  321. 321.

    Fischer S, Strawbridge R, Vives AH, Cleare AJ. Cortisol as a predictor of psychological therapy response in depressive disorders: systematic review and meta-analysis. Br. J. Psychiatry. 2017;210:105-109.

    Not in our library10.1192/bjp.bp.115.180653

  322. 322.

    Schlosser N, Wolf OT, Wingenfeld K. Cognitive correlates of hypothalamic–pituitary–adrenal axis in major depression. Expert Rev. Endocrinol. Metab. 2011;6:109-126.

    Not in our library10.1586/eem.10.79

  323. 323.

    Stahl ST, et al. Systematic review of dyadic and family‐oriented interventions for late‐life depression. Int. J. Geriatr. Psychiatry. 2016;31:963-973.

    Not in our library10.1002/gps.4434

  324. 324.

    Paller KA, et al. Benefits of mindfulness training for patients with progressive cognitive decline and their caregivers. Am. J. Alzheimer's Dis. Other Demen. 2015;30:257-267.

    Not in our library10.1177/1533317514545377

  325. 325.

    Birnie K, Garland SN, Carlson LE. Psychological benefits for cancer patients and their partners participating in mindfulness‐based stress reduction (MBSR). Psychooncology. 2010;19:1004-1009.

    Not in our library10.1002/pon.1651

  326. 326.

    Berk L, Warmenhoven F, van Os J, van Boxtel M. Mindfulness training for people with dementia and their caregivers: rationale, current research, and future directions. Front. Psychol. 2018;9:982.

    Not in our library10.3389/fpsyg.2018.00982

  327. 327.

    Tang F, Choi E, Morrow-Howell N. Organizational support and volunteering benefits for older adults. Gerontologist. 2010;50:603-612.

    Not in our library10.1093/geront/gnq020

  328. 328.

    Holvast F, et al. Loneliness is associated with poor prognosis in late-life depression: Longitudinal analysis of the Netherlands study of depression in older persons. J. Affect. Disord. 2015;185:1-7.

    Not in our library10.1016/j.jad.2015.06.036

  329. 329.

    Chen SC, Jones C, Moyle W. Social robots for depression in older adults: a systematic review. J. Nurs. Scholarsh. 2018;50:612.

    Not in our library10.1111/jnu.12377

  330. 330.

    Bonura KB, Tenenbaum G. Effects of yoga on psychological health in older adults. J. Phys. Act. Health. 2014;11:1334-1341.

    Not in our library10.1123/jpah.2012-0365

  331. 331.

    Eyre HA, et al. A randomized controlled trial of Kundalini yoga in mild cognitive impairment. Int. Psychogeriatr. 2017;29:557-567.

    Not in our library10.1017/s1041610216002155

  332. 332.

    Zhang JX, et al. Mindfulness-based stress reduction for chronic insomnia in adults older than 75 years: a randomized, controlled, single-blind clinical trial. Explore (NY). 2015;11:180-185.

    Not in our library10.1016/j.explore.2015.02.005

  333. 333.

    Dechamps A, et al. Effects of exercise programs to prevent decline in health-related quality of life in highly deconditioned institutionalized elderly persons: a randomized controlled trial. Arch. Intern. Med. 2010;170:162-169.

    Not in our library10.1001/archinternmed.2009.489

  334. 334.

    Lam LCW, et al. A 1-year randomized controlled trial comparing mind body exercise (Tai Chi) with stretching and toning exercise on cognitive function in older Chinese adults at risk of cognitive decline. J. Am. Med. Dir. Assoc. 2012;13:568.e15-568.e20.

    Not in our library10.1016/j.jamda.2012.03.008

  335. 335.
  336. 336.

    Waelde LC, Meyer H, Thompson JM, Thompson L, Gallagher-Thompson D. Randomized controlled trial of inner resources meditation for family dementia caregivers. J. Clin. Psychol. 2017;73:1629-1641.

    Not in our library10.1002/jclp.22470

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