Psychobiological factors of resilience and depression in late life

Translational Psychiatry - Tập 9 Số 1
Kelsey T. Laird1, Beatrix Krause1, Cynthia Funes1, Helen Lavretsky1
1Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA

Tóm tắt

AbstractIn 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.

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Tài liệu tham khảo

Alexopoulos, G. S., Young, R. C., Abrams, R. C., Meyers, B. & Shamoian, C. A. Chronicity and relapse in geriatric depression. Biol. Psychiatry 26, 551–564 (1989).

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

Nelson, J. C., Delucchi, K. & Schneider, L. S. Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence. Am. J. Geriatr. Psychiatry 16, 558–567 (2008).

Nelson, J. C., Delucchi, K. L. & Schneider, L. S. Moderators of outcome in late-life depression: a patient-level meta-analysis. Am. J. Psychiatry 170, 651–659 (2013).

Rutherford, B. R. & Roose, S. P. A model of placebo response in antidepressant clinical trials. Am. J. Psychiatry 170, 723–733 (2013).

Sackeim, H. A., Roose, S. P. & Burt, T. Optimal length of antidepressant trials in late-life depression. J. Clin. Psychopharmacol. 25, S34–S37 (2005).

Entsuah, A. R., Huang, H. & Thase, M. E. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J. Clin. Psychiatry 62, 869–877 (2001).

Ryff, C. D., Friedman, E. M., Morozink, J. A. & Tsenkova, V. Psychological resilience in adulthood and later life: implications for health. Annu. Rev. Gerontol. Geriatr. 32, 73–92 (2012).

Smith, G. C. & Hayslip, B. Jr Resilience in adulthood and later life: what does it mean and where are we heading? Annu. Rev. Gerontol. Geriatr. 32, 3 (2012).

Vanderbilt-Adriance, E. & Shaw, D. S. Conceptualizing and re-evaluating resilience across levels of risk, time, and domains of competence. Clin. Child Fam. Psychol. Rev. 11, 30 (2008).

Windle, G. What is resilience? A review and concept analysis. Rev. Clin. Gerontol. 21, 152–169 (2011).

Lavretsky. & Irwin, M. R. Resilience and aging. Aging Health 3, 309–323 (2007).

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

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 21, 832–839 (2013).

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

Khazanov, G. K. & Ruscio, A. M. Is low positive emotionality a specific risk factor for depression? A meta-analysis of longitudinal studies. Psychol. Bull. 142, 991 (2016).

Fredrickson, B. L., Tugade, M. M., Waugh, C. E. & Larkin, G. R. 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. 84, 365 (2003).

Bowlby, J. Attachment and Loss: Attachment. (Basic Books, New York, NY, 1969).

Bowlby, J. Attachment and Loss: Separation. (Basic Books, New York, NY, 1973).

Bowlby, J. Attachment and Loss: Loss, Sadness, and Depression. (Basic Books, New York, NY, 1980).

Dagan, O., Facompré, C. R. & Bernard, K. Adult attachment representations and depressive symptoms: a meta-analysis. J. Affect. Disord. 236, 274–290 (2018).

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

Conradi, H. J., Kamphuis, J. H. & de Jonge, P. Adult attachment predicts the seven-year course of recurrent depression in primary care. J. Affect Disord. 225, 160–166 (2018).

Monti, J. D. & Rudolph, K. D. Emotional awareness as a pathway linking adult attachment to subsequent depression. J. Couns. Psychol. 61, 374 (2014).

Laird, K. T., Preacher, K. J. & Walker, L. S. Attachment and adjustment in adolescents and young adults with a history of pediatric functional abdominal pain. Clin. J. Pain 31, 152 (2015).

Porter, L. S., Davis, D. & Keefe, F. J. Attachment and pain: recent findings and future directions. Pain 128, 195–198 (2007).

Lyons-Ruth, K., Pechtel, P., Yoon, S. A., Anderson, C. M. & Teicher, M. H. Disorganized attachment in infancy predicts greater amygdala volume in adulthood. Behav. Brain Res. 308, 83–93 (2016).

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

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

Pietrzak, R. H. & Cook, J. M. Psychological resilience in older US veterans: results from the national health and resilience in veterans study. Depress. Anxiety 30, 432–443 (2013).

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

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

Damholdt, M. F., Callesen, M. B. & Møller, A. Personality characteristics of depressed and non-depressed patients with Parkinson’s disease. J. Neuropsychiatry Clin. Neurosci. 26, 329–334 (2014).

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. 77, 269–288 (2013).

Duckworth, A. L., Peterson, C., Matthews, M. D. & Kelly, D. R. Grit: perseverance and passion for long-term goals. J. Pers. Soc. Psychol. 92, 1087 (2007).

Laird, K. T. et al. Clinical correlates of resilience factors in geriatric depression. Int. Psychogeriatr. 2018, 1–10 (2018).

McGinn, L. K. Cognitive behavioral therapy of depression: theory, treatment, and empirical status. Am. J. Psychother. 54, 257–262 (2000).

Abramowitz, J. S. The practice of exposure therapy: relevance of cognitive-behavioral theory and extinction theory. Behav. Ther. 44, 548–558 (2013).

Sowislo, J. F. & Orth, U. Does low self-esteem predict depression and anxiety? A meta-analysis of longitudinal studies. Psychol. Bull. 139, 213 (2013).

Orth, U., Robins, R. W., Meier, L. L. & Conger, R. D. Refining the vulnerability model of low self-esteem and depression: Disentangling the effects of genuine self-esteem and narcissism. J. Pers. Soc. Psychol. 110, 133 (2016).

Lazarus, R. S. & Folkman, S. Stress, Appraisal, and Coping. (Springer Publishing Company, New York, 1984).

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

Forsythe, C. J. & Compas, B. E. Interaction of cognitive appraisals of stressful events and coping: testing the goodness of fit hypothesis. Cogn. Ther. Res. 11, 473–485 (1987).

Zakowski, S. G., Hall, M. H., Klein, L. C. & Baum, A. Appraised control, coping, and stress in a community sample: a test of the goodness-of-fit hypothesis. Ann. Behav. Med. 23, 158–165 (2001).

Cheng, C., Lau, H. P. B. & Chan, M. P. S. Coping flexibility and psychological adjustment to stressful life changes: A meta-analytic review. Psychological bulletin 140, 1582–1607 (2014).

Seltzer, M. M., Greenberg, J. S., Floyd, F. J. & Hong, J. Accommodative coping and well-being of midlife parents of children with mental health problems or developmental disabilities. Am. J. Orthopsychiatry 74, 187 (2004).

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. 59, P35–P42 (2004).

Isaacowitz, D. M. & Seligman, M. E. P. Cognitive style predictors of affect change in older adults. Int. J. Aging Human. Dev. 54, 233–253 (2002).

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

Laird, K. T., Lavretsky, H., St Cyr, N. & Siddarth, P. Resilience predicts remission in antidepressant treatment of geriatric depression. Int. J. Geriatr. Psychiatry 33, 1596–1603 (2018).

Walker, L. S., Smith, C. A., Garber, J. & Claar, R. L. Testing a model of pain appraisal and coping in children with chronic abdominal pain. Health Psychol. 24, 364–374 (2005).

Anderson, J. R. 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. 39, 1020–1032 (2016).

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 14, 272 (2014).

Newcomb, M. D. & Harlow, L. L. Life events and substance use among adolescents: mediating effects of perceived loss of control and meaninglessness in life. J. Pers. Soc. Psychol. 51, 564 (1986).

Rippetoe, P. A. & Rogers, R. W. Effects of components of protection-motivation theory on adaptive and maladaptive coping with a health threat. J. Pers. Soc. Psychol. 52, 596 (1987).

Wang, Q., Bowling, N. A. & Eschleman, K. J. A meta-analytic examination of work and general locus of control. J. Appl. Psychol. 95, 761 (2010).

Rotter, J. B. Generalized expectancies for internal versus external control of reinforcement. Psychol. Monogr. 80, 1 (1966).

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. 39, 1688–1699 (2018).

Windsor, T. D., Curtis, R. G. & Luszcz, M. A. Sense of purpose as a psychological resource for aging well. Dev. Psychol. 51, 975 (2015).

Yuen, G. S. et al. Apathy in late-life depression: common, persistent, and disabling. Am. J. Geriatr. Psychiatry 23, 488–494 (2015).

Groeneweg-Koolhoven, I., de Waal, M. W. M., van der Weele, G. M., Gussekloo, J. & van der Mast, R. C. Quality of life in community-dwelling older persons with apathy. Am. J. Geriatr. Psychiatry 22, 186–194 (2014).

Tierney, S. M., Woods, S. P., Weinborn, M. & Bucks, R. S. Real-world implications of apathy among older adults: Independent associations with activities of daily living and quality of life. J. Clin. Exp. Neuropsychol 40, 895–903 (2018).

Yuen, G. S. et al. Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response. J. Affect. Disord. 166, 179–186 (2014).

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

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

Simonelli, L. E., Fowler, J., Maxwell, G. L. & Andersen, B. L. Physical sequelae and depressive symptoms in gynecologic cancer survivors: meaning in life as a mediator. Ann. Behav. Med. 35, 275–284 (2008).

Nelson, C. J., Rosenfeld, B., Breitbart, W. & Galietta, M. Spirituality, religion, and depression in the terminally ill. Psychosomatics 43, 213–220 (2002).

Antoni, M. H. 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. 20, 20 (2001).

Drapalski, A. L. et al. A model of internalized stigma and its effects on people with mental illness. Psychiatr. Serv. 64, 264–269 (2014).

Livingston, J. D. & Boyd, J. E. Correlates and consequences of internalized stigma for people living with mental illness: a systematic review and meta-analysis. Soc. Sci. Med. 71, 2150–2161 (2010).

Lysaker, P. H., Davis, L. W., Warman, D. M., Strasburger, A. & Beattie, N. Stigma, social function and symptoms in schizophrenia and schizoaffective disorder: associations across 6 months. Psychiatry Res. 149, 89–95 (2007).

Raeifar, E., Halkett, A., Lohman, M. C. & Sirey, J. A. The relation between mastery, anticipated stigma and depression among older adults in a primary care setting. J. Nerv. Ment. Dis. 205, 801–804 (2017).

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

Ellison, C. G., Boardman, J. D., Williams, D. R. & Jackson, J. S. Religious involvement, stress, and mental health: findings from the 1995 Detroit Area Study. Soc. Forces 80, 215–249 (2001).

Yeager, D. M. et al. Religious involvement and health outcomes among older persons in Taiwan. Soc. Sci. Med. 63, 2228–2241 (2006).

Aldwin, C. M., Sutton, K. J., Chiara, G. & Spiro, A. Age differences in stress, coping, and appraisal: findings from the Normative Aging Study. J. Gerontol. B Psychol. Sci. Soc. Sci. 51, P179–P188 (1996).

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 5, 58 (1990).

Horton, S., Baker, J., Pearce, G. W. & Deakin, J. M. On the malleability of performance: Implications for seniors. J. Appl. Gerontol. 27, 446–465 (2008).

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

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

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

Thoits, P. A. Conceptual, methodological, and theoretical problems in studying social support as a buffer against life stress. J. Health Soc. Behav. 52, 145–159 (1982).

Midanik, L. T., Soghikian, K., Ransom, L. J. & Tekawa, I. S. The effect of retirement on mental health and health behaviors: the Kaiser Permanente Retirement Study. J. Gerontol. B Psychol. Sci. Soc. Sci. 50, S59–S61 (1995).

Reitzes, D. C., Mutran, E. J. & Fernandez, M. E. Does retirement hurt weil-being? Factors influencing self-esteem and depression among retires and workers. Gerontologist 36, 649–656 (1996).

Lee, J. & Smith, J. P. Work, retirement, and depression. J. Popul. Ageing 2, 57–71 (2009).

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).

Greenfield, E. A. & Marks, N. F. Formal volunteering as a protective factor for older adults' psychological well-being. J. Gerontol. B Psychol. Sci. Soc. Sci. 59, S258–S264 (2004).

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

Hong, J. & Seltzer, M. M. The psychological consequences of multiple roles: the nonnormative case. J. Health Soc. Behav. 36, 386–398 (1995).

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

Van Willigen, M. Differential benefits of volunteering across the life course. J. Gerontol. B Psychol. Sci. Soc. Sci. 55, S308–S318 (2000).

Hendricks, J. & Cutler, S. J. Volunteerism and socioemotional selectivity in later life. J. Gerontol. B Psychol. Sci. Soc. Sci. 59, S251–S257 (2004).

Li, Y. & Ferraro, K. F. Volunteering and depression in later life: social benefit or selection processes? J. Health Soc. Behav. 46, 68–84 (2005).

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

Santini, Z. I., Koyanagi, A., Tyrovolas, S., Mason, C. & Haro, J. M. The association between social relationships and depression: a systematic review. J. Affect. Disord. 175, 53–65 (2015).

Schwarzbach, M., Luppa, M., Forstmeier, S., König, H. H. & Riedel‐Heller, S. G. Social relations and depression in late life—a systematic review. Int. J. Geriatr. Psychiatry 29, 1–21 (2014).

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 104, 1536–1542 (2018).

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

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.

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

Cacioppo, J. T., Hughes, M. E., Waite, L. J., Hawkley, L. C. & Thisted, R. A. Loneliness as a specific risk factor for depressive symptoms: cross-sectional and longitudinal analyses. Psychol. Aging 21, 140 (2006).

Fung, H. H., Carstensen, L. L. & Lang, F. R. 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. 52, 185–206 (2001).

Carstensen, L. L. Evidence for a life-span theory of socioemotional selectivity. Curr. Dir. Psychol. Sci. 4, 151–156 (1995).

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 33, 482–496 (2018).

Perissinotto, C. M., Cenzer, I. S. & Covinsky, K. E. Loneliness in older persons: a predictor of functional decline and death. Arch. Intern. Med. 172, 1078–1084 (2012).

Heikkinen, R.-L. & Kauppinen, M. Depressive symptoms in late life: a 10-year follow-up. Arch. Gerontol. Geriatr. 38, 239–250 (2004).

Cole, M. G. & Dendukuri, N. Risk factors for depression among elderly community subjects: a systematic review and meta-analysis. Am. J. Psychiatry 160, 1147–1156 (2003).

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. 56, P195–P213 (2001).

McDougall, F. A., Matthews, F. E., Kvaal, K., Dewey, M. E. & Brayne, C. Prevalence and symptomatology of depression in older people living in institutions in England and Wales. Age Ageing 36, 562–568 (2007).

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

Wilson, R. S. et al. Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology 59, 364–370 (2002).

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

Barnes, D. E., Alexopoulos, G. S., Lopez, O. L., Williamson, J. D. & Yaffe, K. Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study. Arch. Gen. Psychiatry 63, 273–279 (2006).

Geda, Y. E. et al. Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. Arch. Neurol. 63, 435–440 (2006).

Saczynski, J. S. et al. Depressive symptoms and risk of dementia The Framingham Heart Study. Neurology 75, 35–41 (2010).

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

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

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

Hollocks, M. J. et al. Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes. Brain 138, 3803–3815 (2015).

Smith, S. M. & Vale, W. W. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin. Neurosci. 8, 383 (2006).

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

Wilson, R. S. et al. Clinical-pathologic study of depressive symptoms and cognitive decline in old age. Neurology 83, 702–709 (2014).

Laird, K. T., Lavretsky, H., Wu, P., Krause, B. & Siddarth, P. Neurocognitive correlates of resilience in late-life depression. Am. J. Geriatr. Psychiatry 27, 12–17 (2018).

Vlasova, R. M. et al. Resilience and white matter integrity in geriatric depression. Am. J. Geriatr. Psychiatry 26, 874–883 (2018).

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

Stern, Y. Cognitive reserve. Neuropsychologia 47, 2015–2028 (2009).

Opdebeeck, C., Quinn, C., Nelis, S. M. & Clare, L. Does cognitive reserve moderate the association between mood and cognition? A systematic review. Rev. Clin. Gerontol. 25, 181–193 (2015).

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

Sneed, J. R. et al. Response inhibition predicts poor antidepressant treatment response in very old depressed patients. Am. J. Geriatr. Psychiatry 15, 553–563 (2007).

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

Hammen, C. Stress and depression. Annu. Rev. Clin. Psychol. 1, 293–319 (2005).

Conway, C. C., Raposa, E. B., Hammen, C. & Brennan, P. A. Transdiagnostic pathways from early social stress to psychopathology: a 20‐year prospective study. J. Child Psychol. Psychiatry 59, 855–862 (2018).

Charney, D. S. Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am. J. Psychiatry 161, 195–216 (2004).

McEwen, B. S. Sex, stress and the hippocampus: allostasis, allostatic load and the aging process. Neurobiol. Aging 23, 921–939 (2002).

Lee, R. S. & Sawa, A. Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal axis. Neuroendocrinology 100, 278–287 (2014).

Pfau, M. L. & Russo, S. J. Peripheral and central mechanisms of stress resilience. Neurobiol. Stress 1, 66–79 (2015).

Seery, M. D., Leo, R. J., Lupien, S. P., Kondrak, C. L. & Almonte, J. L. An upside to adversity? Moderate cumulative lifetime adversity is associated with resilient responses in the face of controlled stressors. Psychol. Sci. 24, 1181–1189 (2013).

Lyons, D. M., Parker, K. J., Katz, M. & Schatzberg, A. F. Developmental cascades linking stress inoculation, arousal regulation, and resilience. Front. Behav. Neurosci. 3, 32 (2009).

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

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

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

Chopra, K., Kumar, B. & Kuhad, A. Pathobiological targets of depression. Expert Opin. Ther. Targets 15, 379–400 (2011).

Miller, G. E., Chen, E. & Zhou, E. S. If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychol. Bull. 133, 25 (2007).

Heim, C., Ehlert, U. & Hellhammer, D. H. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 25, 1–35 (2000).

Gold, P. W. & Chrousos, G. P. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol. Psychiatry 7, 254 (2002).

Mason, J. W. 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. 63, 387–401 (2001).

Mann, J. J. et al. Can biological tests assist prediction of suicide in mood disorders? Int. J. Neuropsychopharmacol. 9, 465–474 (2006).

Jokinen, J. & Nordstrom, P. HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients. Psychoneuroendocrinology 33, 1387–1393 (2008).

ter Heegde, F., De Rijk, R. H. & Vinkers, C. H. The brain mineralocorticoid receptor and stress resilience. Psychoneuroendocrinology 52, 92–110 (2015).

Leonard, B. E. Inflammation and depression: a causal or coincidental link to the pathophysiology? Acta Neuropsychiatr. 30, 1–16 (2018).

Enman, N. M., Sabban, E. L., McGonigle, P. & Van Bockstaele, E. J. Targeting the neuropeptide Y system in stress-related psychiatric disorders. Neurobiol. Stress 1, 33–43 (2015).

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

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. 38, 113–121 (2004).

Mickey, B. J. et al. Emotion processing, major depression, and functional genetic variation of neuropeptide Y. Arch. Gen. Psychiatry 68, 158–166 (2011).

Newhouse, P. & Albert, K. Estrogen, stress, and depression: a neurocognitive model. JAMA Psychiatry 72, 727–729 (2015).

Ryan, J., Carriere, I., Scali, J., Ritchie, K. & Ancelin, M. L. Lifetime hormonal factors may predict late-life depression in women. Int. Psychogeriatr. 20, 1203–1218 (2008).

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

Peters, R. Ageing and the brain. Postgrad. Med. J. 82, 84–88 (2006).

Hara, Y., Waters, E. M., McEwen, B. S. & Morrison, J. H. Estrogen effects on cognitive and synaptic health over the lifecourse. Physiol. Rev. 95, 785–807 (2015).

McEwen, B. S. & Morrison, J. H. The brain on stress: vulnerability and plasticity of the prefrontal cortex over the life course. Neuron 79, 16–29 (2013).

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

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. 16, 285–294 (2013).

Fabian, T. J. et al. Endogenous concentrations of DHEA and DHEA-S decrease with remission of depression in older adults. Biol. Psychiatry 50, 767–774 (2001).

Carney, R. M., Freedland, K. E., Sheline, Y. I. & Weiss, E. S. Depression and coronary heart disease: a review for cardiologists. Clin. Cardiol. 20, 196–200 (1997).

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. 27, 2763–2774 (2006).

Hare, D. L., Toukhsati, S. R., Johansson, P. & Jaarsma, T. Depression and cardiovascular disease: a clinical review. Eur. Heart J. 35, 1365–1372 (2013).

Valkanova, V. & Ebmeier, K. P. Vascular risk factors and depression in later life: a systematic review and meta-analysis. Biol. Psychiatry 73, 406–413 (2013).

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

Carney, R. M. & Freedland, K. E. Depression and coronary heart disease. Nat. Rev. Cardiol. 14, 145 (2017).

Appelhans, B. M. & Luecken, L. J. Heart rate variability as an index of regulated emotional responding. Rev. Gen. Psychol. 10, 229 (2006).

Holzman, J. B. & Bridgett, D. J. Heart rate variability indices as bio-markers of top-down self-regulatory mechanisms: a meta-analytic review. Neurosci. Biobehav. Rev. 74, 233–255 (2017).

Carnevali, L., Koenig, J., Sgoifo, A. & Ottaviani, C. Autonomic and brain morphological predictors of stress resilience. Front. Neurosci. 12, 228 (2018).

Koenig, J., Kemp, A. H., Beauchaine, T. P., Thayer, J. F. & Kaess, M. Depression and resting state heart rate variability in children and adolescents—a systematic review and meta-analysis. Clin. Psychol. Rev. 46, 136–150 (2016).

Shaffer, F., McCraty, R. & Zerr, C. L. A healthy heart is not a metronome: an integrative review of the heart's anatomy and heart rate variability. Front. Psychol. 5, 1040 (2014).

Kemp, A. H. et al. Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis. Biol. Psychiatry 67, 1067–1074 (2010).

Yoo, H. J. et al. Brain structural concomitants of resting state heart rate variability in the young and old: evidence from two independent samples. Brain Struct. Funct. 223, 727–737 (2018).

Umetani, K., Singer, D. H., 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. 31, 593–601 (1998).

Vogelzangs, N., Comijs, H. C., Oude Voshaar, R. C., Stek, M. L. & Penninx, B. W. Late-life depression symptom profiles are differentially associated with immunometabolic functioning. Brain Behav. Immun. 41, 109–115 (2014).

Duivis, H. E. 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 168, 913–920 (2011).

Kahl, K. G. et al. Prevalence of the metabolic syndrome in unipolar major depression. Eur. Arch. Psychiatry Clin. Neurosci. 262, 313–320 (2012).

Viinamäki, H. et al. Association of depressive symptoms and metabolic syndrome in men. Acta Psychiatr. Scand. 120, 23–29 (2009).

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

Lanquillon, S., Krieg, J. C., Bening-Abu-Shach, U. & Vedder, H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22, 370–379 (2000).

Kloiber, S. et al. Overweight and obesity affect treatment response in major depression. Biol. Psychiatry 62, 321–326 (2007).

Penninx, B. W., Milaneschi, Y., Lamers, F. & Vogelzangs, N.Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile. BMC Med. 11, 129 (2013).

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 21, 863–871 (2013).

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

Kuo, S. Y., Lin, K. M., Chen, C. Y., Chuang, Y. L. & Chen, W. J. Depression trajectories and obesity among the elderly in Taiwan. Psychol. Med. 41, 1665–1676 (2011).

Marijnissen, R. M., Naudé, P. J. W., Comijs, H. C., Schoevers, R. A. & Voshaar, R. C. O. Waist circumference and neutrophil gelatinase-associated lipocalin in late-life depression. Brain Behav. Immun. 37, 231–239 (2014).

Miller, A. H., Maletic, V. & Raison, C. L. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol. Psychiatry 65, 732–741 (2009).

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

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

Kappelmann, N., Lewis, G., Dantzer, R., Jones, P. B. & Khandaker, G. M. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol. Psychiatry 23, 335–343 (2018).

Bierhaus, A. et al. A mechanism converting psychosocial stress into mononuclear cell activation. Proc. Natl Acad. Sci. USA 100, 1920–1925 (2003).

Danese, A., Pariante, C. M., Caspi, A., Taylor, A. & Poulton, R. Childhood maltreatment predicts adult inflammation in a life-course study. Proc. Natl Acad. Sci. USA 104, 1319–1324 (2007).

McDade, T. W., Hawkley, L. C. & Cacioppo, J. T. Psychosocial and behavioral predictors of inflammation in middle-aged and older adults: the Chicago health, aging, and social relations study. Psychosom. Med. 68, 376–381 (2006).

Kiecolt-Glaser, J. K. et al. Hostile marital interactions, proinflammatory cytokine production, and wound healing. Arch. Gen. Psychiatry 62, 1377–1384 (2005).

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

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. 159b, 560–566 (2012).

Tsang, R. S., Mather, K. A., Sachdev, P. S. & Reppermund, S. Systematic review and meta-analysis of genetic studies of late-life depression. Neurosci. Biobehav. Rev. 75, 129–139 (2017).

Egan, M. F. et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257–269 (2003).

Hariri, A. R. et al. Brain-derived neurotrophic factor val66met polymorphism affects human memory-related hippocampal activity and predicts memory performance. J. Neurosci. 23, 6690–6694 (2003).

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 61, 911–922 (2007).

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

Hosang, G. M., Shiles, C., Tansey, K. E., McGuffin, P. & Uher, R. Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis. BMC Med. 12, 7 (2014).

Januar, V., Ancelin, M. L., Ritchie, K., Saffery, R. & Ryan, J. BDNF promoter methylation and genetic variation in late-life depression. Transl. Psychiatry 5, e619 (2015).

Murphy, G. M. et al. BDNF and CREB1 genetic variants interact to affect antidepressant treatment outcomes in geriatric depression. Pharmacogenet. Genomics 23, 301–313 (2013).

Garcia, R. Stress, synaptic plasticity, and psychopathology. Rev. Neurosci. 13, 195–208 (2002).

Duman, R. S., Malberg, J., Nakagawa, S. & D’Sa, C. Neuronal plasticity and survival in mood disorders. Biol. Psychiatry 48, 732–739 (2000).

Öngür, D., Drevets, W. C. & Price, J. L. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc. Natl Acad. Sci. USA 95, 13290–13295 (1998).

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

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 12, 386–394 (2002).

Miguel-Hidalgo, J. J. & Rajkowska, G. Morphological brain changes in depression. CNS Drugs 16, 361–372 (2002).

Rajkowska, G. Cell pathology in mood disorders. Semin. Clin. Neuropsychiatry 7, 281–292 (2002).

Geerlings, M. I. & Gerritsen, L. Late-life depression, hippocampal volumes, and hypothalamic-pituitary-adrenal axis regulation: a systematic review and meta-analysis. Biol. Psychiatry 82, 339–350 (2017).

Dwivedi, Y. Involvement of brain-derived neurotrophic factor in late-life depression. Am. J. Geriatr. Psychiatry 21, 433–449 (2013).

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

Crocco, E. A., Castro, K. & Loewenstein, D. A. How late-life depression affects cognition: neural mechanisms. Curr. Psychiatry Rep. 12, 34–38 (2010).

Khundakar, A. A. & Thomas, A. J. Morphometric changes in early-and late-life major depressive disorder: evidence from postmortem studies. Int. Psychogeriatr. 21, 844–854 (2009).

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 78, 638–640 (2007).

Narayan, M., Bremner, J. D. & Kumar, A. Neuroanatomic substrates of late-life mental disorders. J. Geriatr. Psychiatry Neurol. 12, 95–106 (1999).

Ebner, N. C. & Fischer, H. Emotion and aging: evidence from brain and behavior. Front. Psychol. 5, 996 (2014).

Urry, H. L. & Gross, J. J. Emotion regulation in older age. Curr. Dir. Psychol. Sci. 19, 352–357 (2010).

Allard, E. S. & Kensinger, E. A. Age-related differences in neural recruitment during the use of cognitive reappraisal and selective attention as emotion regulation strategies. Front. Psychol. 5, 296 (2014).

Dolcos, S., Katsumi, Y. & Dixon, R. A. The role of arousal in the spontaneous regulation of emotions in healthy aging: a fMRI investigation. Front. Psychol. 5, 681 (2014).

Santarnecchi, E. et al. Brain functional connectivity correlates of coping styles. Cogn. Affect. Behav. Neurosci. 18, 495–508 (2018).

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

Leaver, A. M. et al. Resilience and amygdala function in older healthy and depressed adults. J. Affect. Disord. 237, 27–34 (2018).

Coffey, C. E., Figiel, G. S., Djang, W. T., Saunders, W. B. & Weiner, R. D. White matter hyperintensity on magnetic resonance imaging: clinical and neuroanatomic correlates in the depressed elderly. J. Neuropsychiatry Clin. Neurosci 1, 135–144 (1989).

Dolan, R. J., Poynton, A. M., Bridges, P. K. & Trimble, M. R. Altered magnetic resonance white-matter T 1 values in patients with affective disorder. Br. J. Psychiatry 157, 107–110 (1990).

Lavretsky, H., Lesser, I. M., Wohl, M. & Miller, B. L. Relationship of age, age at onset, and sex to depression in older adults. Am. J. Geriatr. Psychiatry 6, 248–256 (1998).

Herrmann, L. L., LeMasurier, M. & Ebmeie, K. P. White matter hyperintensities in late life depression: a systematic review. J. Neurol. Neurosurg. Psychiatry 79, 619–624 (2007).

de Groot, J. C. et al. Cerebral white matter lesions and depressive symptoms in elderly adults. Arch. Gen. Psychiatry 57, 1071–1076 (2000).

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

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

Rapp, M. A. et al. Neuropsychological differences between late-onset and recurrent geriatric major depression. Am. J. Psychiatry 162, 691–698 (2005).

Krishnan, K. R., Hays, J. C. & Blazer, D. G. MRI-defined vascular depression. Am. J. Psychiatry 154, 497–501 (1997).

Alexopoulos, G. S., Meyers, B. S., Young, R. C. & Kakuma, T. Clinically defined vascular depression. Am. J. Psychiatry 154, 562 (1997).

Taylor, W. D., Aizenstein, H. J. & Alexopoulos, G. S. The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol. Psychiatry 18, 963–974 (2013).

Taylor, W. D., Steffens, D. C. & Krishnan, K. R. Psychiatric disease in the twenty-first century: The case for subcortical ischemic depression. Biol. Psychiatry 60, 1299–1303 (2006).

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. 36, 854–866 (2014).

Alves, G. S. et al. Clinical characteristics in subcortical ischemic white matter disease. Arq. Neuropsiquiatr. 67(2A), 173–178 (2009).

Grool, A. M. et al. Structural MRI correlates of apathy symptoms in older persons without dementia AGES-Reykjavik Study. Neurology 82, 1628–1635 (2014).

Bruce, D. G. et al. Apathy in older patients with type 2 diabetes. Am. J. Geriatr. Psychiatry 23, 615–621 (2015).

Ligthart, S. A. et al. Association of vascular factors with apathy in community-dwelling elderly individuals. Arch. Gen. Psychiatry 69, 636–642 (2012).

Baldwin, R. C. & Tomenson, B. Depression in later life: a comparison of symptoms and risk factors in early and late onset cases. Br. J. Psychiatry 167, 649–652 (1995).

Driscoll, H. C. et al. Late‐onset major depression: clinical and treatment‐response variability. Int. J. Geriatr. Psychiatry 20, 661–667 (2005).

Whyte, E. M. et al. Geriatric depression treatment in nonresponders to selective serotonin reuptake inhibitors. J. Clin. Psychiatry 65, 1634–1641 (2004).

Karp, J. F. et al. Time to remission in late‐life depression: analysis of effects of demographic, treatment, and life‐events measures. Depression 1, 250–256 (1993).

Reynolds, C. Fr 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 155, 795–799 (1998).

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

Sin, N. L. & Lyubomirsky, S. Enhancing well‐being and alleviating depressive symptoms with positive psychology interventions: a practice‐friendly meta‐analysis. J. Clin. Psychol. 65, 467–487 (2009).

Diener, E. Subjective well-being. Psychol. Bull. 95, 542 (1984).

Ryan, R. M. & Deci, E. L. On happiness and human potentials: a review of research on hedonic and eudaimonic well-being. Annu. Rev. Psychol. 52, 141–166 (2001).

Ryff, C. D. Happiness is everything, or is it? Explorations on the meaning of psychological well-being. J. Pers. Soc. Psychol. 57, 1069 (1989).

Seligman, M. E. P., Steen, T. A., Park, N. & Peterson, C. Positive psychology progress: empirical validation of interventions. Am. Psychol. 60, 410 (2005).

Sheldon, K. M. & Lyubomirsky, S. How to increase and sustain positive emotion: the effects of expressing gratitude and visualizing best possible selves. J. Posit. Psychol. 1, 73–82 (2006).

Peters, M. L., Flink, I. K., Boersma, K. & Linton, S. J. Manipulating optimism: can imagining a best possible self be used to increase positive future expectancies? J. Posit. Psychol. 5, 204–211 (2010).

Peters, M. L., Meevissen, Y. M. C. & Hanssen, M. M. Specificity of the Best Possible Self intervention for increasing optimism: comparison with a gratitude intervention. Ter. Psicol. 31, 93–100 (2013).

Meevissen, Y. M. C., Peters, M. L. & Alberts, H. J. E. M. Become more optimistic by imagining a best possible self: effects of a two week intervention. J. Behav. Ther. Exp. Psychiatry 42, 371–378 (2011).

Zautra, A. J. 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. 76, 408 (2008).

Lyubomirsky, S., Sheldon, K. M. & Schkade, D. Pursuing happiness: the architecture of sustainable change. Rev. Gen. Psychol. 9, 111 (2005).

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).

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).

Buchanan, K. E. & Bardi, A. Acts of kindness and acts of novelty affect life satisfaction. J. Soc. Psychol. 150, 235–237 (2010).

Helgeson, V. S., Reynolds, K. A. & Tomich, P. L. A meta-analytic review of benefit finding and growth. J. Consult. Clin. Psychol. 74, 797 (2006).

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).

Bower, J. E., Moskowitz, J. T. & Epel, E. Is benefit finding good for your health? Pathways linking positive life changes after stress and physical health outcomes. Curr. Dir. Psychol. Sci. 18, 337–341 (2009).

Uchino, B. N., Cacioppo, J. T. & Kiecolt-Glaser, J. K. The relationship between social support and physiological processes: a review with emphasis on underlying mechanisms and implications for health. Psychol. Bull. 119, 488 (1996).

Bower, J. E., Kemeny, M. E., Taylor, S. E. & Fahey, J. L. Finding positive meaning and its association with natural killer cell cytotoxicity among participants in a bereavement-related disclosure intervention. Ann. Behav. Med. 25, 146–155 (2003).

Bower, J. E. & Segerstrom, S. C. Stress management, finding benefit, and immune function: positive mechanisms for intervention effects on physiology. J. Psychosom. Res. 56, 9–11 (2004).

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

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

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).

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. 31, 1032–1040 (2011).

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. 37, 1–12 (2015).

Luders, E. Exploring age‐related brain degeneration in meditation practitioners. Ann. N. Y. Acad. Sci. 1307, 82–88 (2014).

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

Tang, Y.-Y., Hölzel, B. K. & Posner, M. I. The neuroscience of mindfulness meditation. Nat. Rev. Neurosci. 16, 213 (2015).

Chiesa, A. & Serretti, A. A systematic review of neurobiological and clinical features of mindfulness meditations. Psychol. Med. 40, 1239–1252 (2010).

Kurth, F., Cherbuin, N. & Luders, E. Aging mindfully to minimize cognitive decline. J. Cogn. Enhanc. 1, 108–114 (2017).

Epel, E., Daubenmier, J., Moskowitz, J. T., Folkman, S. & Blackburn, E. Can meditation slow rate of cellular aging? cognitive stress, mindfulness, and telomeres. Ann. N. Y. Acad. Sci. 1172, 34–53 (2009).

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 28, 57–65 (2013).

Black, D. S. et al. Yogic meditation reverses NF-kappaB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial. Psychoneuroendocrinology 38, 348–355 (2013).

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. 3, 253–255 (2016).

Kalyani, B. G. et al. Neurohemodynamic correlates of ‘OM’chanting: a pilot functional magnetic resonance imaging study. Int. J. Yoga 4, 3 (2011).

Cuijpers, P., Karyotaki, E., Pot, A. M., Park, M. & Reynolds Iii, C. F. Managing depression in older age: psychological interventions. Maturitas 79, 160–169 (2014).

Pinquart, M., Duberstein, P. R. & Lyness, J. M. Treatments for later-life depressive conditions: a meta-analytic comparison of pharmacotherapy and psychotherapy. Am. J. Psychiatry 163, 1493–1501 (2006).

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

Zhao, K., Bai, Z. G., Bo, A. & Chi, I. A systematic review and meta‐analysis of music therapy for the older adults with depression. Int. J. Geriatr. Psychiatry 31, 1188–1198 (2016).

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

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

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. 23, 873–887 (2009).

Hoffman-Goetz, L. & Pedersen, B. K. Exercise and the immune system: a model of the stress response? Immunol. Today 15, 382–387 (1994).

Laird, K. T., Paholpak, P., Roman, M., Rahi, B. & Lavretsky, H. Mind-body therapies for late-life mental and cognitive health. Curr. Psychiatry Rep. 20, 2 (2018).

Acevedo, B. P., Pospos, S. & Lavretsky, H. The neural mechanisms of meditative practices: novel approaches for healthy aging. Curr. Behav. Neurosci. Rep. 3, 328–339 (2016).

Pascoe, M. C. & Bauer, I. E. A systematic review of randomised control trials on the effects of yoga on stress measures and mood. J. Psychiatr. Res. 68, 270–282 (2015).

Pascoe, M. C., Thompson, D. R. & Ski, C. F. Yoga, mindfulness-based stress reduction and stress-related physiological measures: a meta-analysis. Psychoneuroendocrinology 86, 152–168 (2017).

Gothe, N. P., Keswani, R. K. & McAuley, E. Yoga practice improves executive function by attenuating stress levels. Biol. Psychol. 121(Pt A), 109–116 (2016).

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. 20, 411–416 (2014).

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

Tsang, H. W. et al. Psycho-physical and neurophysiological effects of qigong on depressed elders with chronic illness. Aging Ment. Health 17, 336–348 (2013).

Sneed, J. R. 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 16, 65–73 (2008).

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

Davidson, J. R. Major depressive disorder treatment guidelines in America and Europe. J. Clin. Psychiatry 71, e04 (2010).

Dierckx, B., Heijnen, W. T., van den Broek, W. W. & Birkenhäger, T. K. Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a meta‐analysis. Bipolar Disord. 14, 146–150 (2012).

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

O'Connor, M. K. et al. The influence of age on the response of major depression to electroconvulsive therapy: a CORE Report. Am. J. Geriatr. Psychiatry 9, 382–390 (2001).

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 169, 68–74 (1996).

Tew, J. D. Jr et al. Acute efficacy of ECT in the treatment of major depression in the old-old. Am. J. Psychiatry 156, 1865–1870 (1999).

Van der Wurff, F. B., Stek, M. L., Hoogendijk, W. J. G. & Beekman, A. T. F. The efficacy and safety of ECT in depressed older adults: a literature review. Int. J. Geriatr. Psychiatry 18, 894–904 (2003).

Flint, A. J. & Gagnon, N. Effective use of electroconvulsive therapy in late-life depression. Can. J. Psychiatry 47, 734–741 (2002).

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

Sackeim, H. A. Electroconvulsive therapy in late-life depression. Clin. Geriatr. Psychopharmacol. 4, 385–422 (2004).

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

Karavidas, M. K. et al. Preliminary results of an open label study of heart rate variability biofeedback for the treatment of major depression. Appl. Psychophysiol. Biofeedback 32, 19–30 (2007).

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 33, 195–201 (2008).

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 38, 1–9 (2013).

Lehrer, P. M. & Gevirtz, R. Heart rate variability biofeedback: how and why does it work? Front. Psychol. 5, 756 (2014).

Lyubomirsky, S., Dickerhoof, R., Boehm, J. K. & Sheldon, K. M. Becoming happier takes both a will and a proper way: an experimental longitudinal intervention to boost well-being. Emotion 11, 391 (2011).

Fischer, S., Strawbridge, R., Vives, A. H. & Cleare, A. J. Cortisol as a predictor of psychological therapy response in depressive disorders: systematic review and meta-analysis. Br. J. Psychiatry 210, 105–109 (2017).

Schlosser, N., Wolf, O. T. & Wingenfeld, K. Cognitive correlates of hypothalamic–pituitary–adrenal axis in major depression. Expert Rev. Endocrinol. Metab. 6, 109–126 (2011).

Stahl, S. T. et al. Systematic review of dyadic and family‐oriented interventions for late‐life depression. Int. J. Geriatr. Psychiatry 31, 963–973 (2016).

Paller, K. A. et al. Benefits of mindfulness training for patients with progressive cognitive decline and their caregivers. Am. J. Alzheimer's Dis. Other Demen. 30, 257–267 (2015).

Birnie, K., Garland, S. N. & Carlson, L. E. Psychological benefits for cancer patients and their partners participating in mindfulness‐based stress reduction (MBSR). Psychooncology 19, 1004–1009 (2010).

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. 9, 982 (2018).

Tang, F., Choi, E. & Morrow-Howell, N. Organizational support and volunteering benefits for older adults. Gerontologist 50, 603–612 (2010).

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. 185, 1–7 (2015).

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

Bonura, K. B. & Tenenbaum, G. Effects of yoga on psychological health in older adults. J. Phys. Act. Health 11, 1334–1341 (2014).

Eyre, H. A. et al. A randomized controlled trial of Kundalini yoga in mild cognitive impairment. Int. Psychogeriatr. 29, 557–567 (2017).

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

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. 170, 162–169 (2010).

Lam, L. C. W. 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. 13, 568.e15–568.e20 (2012).

Vasudev, A. et al. A training programme involving automatic self-transcending meditation in late-life depression: preliminary analysis of an ongoing randomised controlled trial. BJPsych. Open 2, 195–198 (2016).

Waelde, L. C., Meyer, H., Thompson, J. M., Thompson, L. & Gallagher-Thompson, D. Randomized controlled trial of inner resources meditation for family dementia caregivers. J. Clin. Psychol. 73, 1629–1641 (2017).