Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Moderators of treatment response in late-life depression

Neuropsychopharmacology (2026)Cite this article

Subjects

Abstract

As late-life depression is associated with a high degree of treatment resistance, understanding predictors of outcome may inform management. In this review, we examine a spectrum of factors that may moderate treatment response. These include clinical moderators related to depression presentation and history, social moderators, psychosocial stressors, personality, and cognitive factors. As there has been substantial research on biological predictors of response, we also include a review of neuroimaging moderators, including markers of accelerated brain aging, as well as other peripheral or central biomarkers of response.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Summary of reported brain regions that are associated with changes in depression severity post treatment of antidepressants.

Similar content being viewed by others

References

  1. Subramanian S, Oughli HA, Gebara MA, Palanca BJA, Lenze EJ. Treatment-resistant late-life depression: a review of clinical features, neuropsychology, neurobiology, and treatment. Psychiatr Clin N Am. 2023;46:371–89.

    Article  Google Scholar 

  2. Steffens DC. Depression and dementia risk: research findings that are shovel-ready for clinicians. Am J Geriatr Psychiatry. 2021;29:927–9.

    Article  PubMed  Google Scholar 

  3. Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry. 2013;202:329–35.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Culang ME, Sneed JR, Keilp JG, Rutherford BR, Pelton GH, Devanand DP, et al. Change in cognitive functioning following acute antidepressant treatment in late-life depression. Am J Geriatr Psychiatry. 2009;17:881–8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Schatzberg A, Roose S. A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. Am J Geriatr Psychiatry. 2006;14:361–70.

    Article  PubMed  Google Scholar 

  6. Newhouse PA, Krishnan KR, Doraiswamy PM, Richter EM, Batzar ED, Clary CM. A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients. J Clin Psychiatry. 2000;61:559–68.

    Article  CAS  PubMed  Google Scholar 

  7. Ji M, Sun Y, Zhou J, Li X, Wei H, Wang Z. Comparative effectiveness and acceptability of psychotherapies for late-life depression: a systematic review and network meta-analysis. J Affect Disord. 2023;323:409–16.

    Article  PubMed  Google Scholar 

  8. Buchalter ELF, Oughli HA, Lenze EJ, Dixon D, Miller JP, Blumberger DM, et al. Predicting remission in late-life major depression: a clinical algorithm based upon past treatment history. J Clin Psychiatry. 2019;80:18m12483

  9. Nomikos GG, Tomori D, Zhong W, Affinito J, Palo W. Efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients aged 55 years or older. CNS Spectr. 2017;22:348–62.

    Article  PubMed  Google Scholar 

  10. Lenze EJ, Mulsant BH, Blumberger DM, Karp JF, Newcomer JW, Anderson SJ, et al. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386:2404–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Berlim MT, Turecki G. What is the meaning of treatment resistant/refractory major depression (TRD)? A systematic review of current randomized trials. Eur Neuropsychopharmacol. 2007;17:696–707.

    Article  CAS  PubMed  Google Scholar 

  12. Gaynes BN, Lux L, Gartlehner G, Asher G, Forman-Hoffman V, Green J, et al. Defining treatment-resistant depression. Depress Anxiety. 2020;37:134–45.

    Article  PubMed  Google Scholar 

  13. Lenze EJ, Mulsant BH, Roose SP, Lavretsky H, Reynolds CF 3rd, Blumberger DM, et al. Antidepressant augmentation versus switch in treatment-resistant geriatric depression. N Engl J Med. 2023;388:1067–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sackeim HA, Roose SP, Burt T. Optimal length of antidepressant trials in late-life depression. J Clin Psychopharmacol. 2005;25:S34–537.

    Article  PubMed  Google Scholar 

  15. Rush AJ, Kraemer HC, Sackeim HA, Fava M, Trivedi MH, Frank E, et al. Report by the ACNP Task Force on response and remission in major depressive disorder. Neuropsychopharmacology. 2006;31:1841–53.

    Article  PubMed  Google Scholar 

  16. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:55–61.

    Article  Google Scholar 

  17. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–9.

    Article  CAS  PubMed  Google Scholar 

  18. Hawley CJ, Gale TM, Sivakumaran T. Defining remission by cut off score on the MADRS: selecting the optimal value. J Affect Disord. 2002;72:177–84.

    Article  CAS  PubMed  Google Scholar 

  19. Taylor WD, McQuoid DR, Steffens DC, Krishnan KR. Is there a definition of remission in late-life depression that predicts later relapse? Neuropsychopharmacology. 2004;29:2272–7.

    Article  PubMed  Google Scholar 

  20. Greenland S, Rothman KJ. Concepts of interaction. In: Rothman KJ, Greenland S, editors. Modern epidemiology. New York: Lippincott-Raven; 1998. p. 329–42.

  21. Dunlop BW, Kelley ME, Aponte-Rivera V, Mletzko-Crowe T, Kinkead B, Ritchie JC, et al. Effects of patient preferences on outcomes in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) Study. Am J Psychiatry. 2017;174:546–56.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tunvirachaisakul C, Gould RL, Coulson MC, Ward EV, Reynolds G, Gathercole RL, et al. Predictors of treatment outcome in depression in later life: a systematic review and meta-analysis. J Affect Disord. 2018;227:164–82.

    Article  PubMed  Google Scholar 

  23. Bosworth HB, McQuoid DR, George LK, Steffens DC. Time-to-remission from geriatric depression: psychosocial and clinical factors. Am J Geriatr Psychiatry. 2002;10:551–9.

    Article  PubMed  Google Scholar 

  24. Deng Y, McQuoid DR, Potter GG, Steffens DC, Albert K, Riddle M, et al. Predictors of recurrence in remitted late-life depression. Depress Anxiety. 2018;35:658–67.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Steffens DC, Fahed M, Manning KJ, Wang L. The neurobiology of apathy in depression and neurocognitive impairment in older adults: a review of epidemiological, clinical, neuropsychological and biological research. Transl Psychiatry. 2022;12:525.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Nelson JC, Delucchi KL, Schneider LS. Moderators of outcome in late-life depression: a patient-level meta-analysis. Am J Psychiatry. 2013;170:651–9.

    Article  PubMed  Google Scholar 

  27. Nelson JC, Delucchi K, Schneider LS. Anxiety does not predict response to antidepressant treatment in late life depression: results of a meta-analysis. Int J Geriatr Psychiatry. 2009;24:539–44.

    Article  PubMed  Google Scholar 

  28. Saade YM, Nicol G, Lenze EJ, Miller JP, Yingling M, Wetherell JL, et al. Comorbid anxiety in late-life depression: Relationship with remission and suicidal ideation on venlafaxine treatment. Depress Anxiety. 2019;36:1125–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yuen GS, Gunning FM, Woods E, Klimstra SA, Hoptman MJ, Alexopoulos GS. Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response. J Affect Disord. 2014;166:179–86.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Yuen GS, Bhutani S, Lucas BJ, Gunning FM, AbdelMalak B, Seirup JK, et al. Apathy in late-life depression: common, persistent, and disabling. Am J Geriatr Psychiatry. 2015;23:488–94.

    Article  PubMed  Google Scholar 

  31. Lampe IK, Heeren TJ. Is apathy in late-life depressive illness related to age-at-onset, cognitive function or vascular risk? Int Psychogeriatr. 2004;16:481–6.

    Article  PubMed  Google Scholar 

  32. Groeneweg-Koolhoven I, Ploeg M, Comijs HC, Wjh Penninx B, van der Mast RC, Schoevers RA, et al. Apathy in early and late-life depression. J Affect Disord. 2017;223:76–81.

    Article  PubMed  Google Scholar 

  33. Sudol K, Conway C, Szymkowicz SM, Elson D, Kang H, Taylor WD. Cognitive, disability, and treatment outcome implications of symptom-based phenotyping in late-life depression. Am J Geriatr Psychiatry. 2023;31:919–31.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Oslin DW, Datto CJ, Kallan MJ, Katz IR, Edell WS, TenHave T. Association between medical comorbidity and treatment outcomes in late-life depression. J Am Geriatr Soc. 2002;50:823–8.

    Article  PubMed  Google Scholar 

  35. Borza T, Engedal K, Bergh S, Benth JS. Selbaek G. The course of depression in late life as measured by the Montgomery and Asberg Depression Rating Scale in an observational study of hospitalized patients. BMC Psychiatry. 2015;15:191.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Karp JF, Scott J, Houck P, Reynolds CF 3rd, Kupfer DJ, Frank E. Pain predicts longer time to remission during treatment of recurrent depression. J Clin Psychiatry. 2005;66:591–7.

    Article  PubMed  Google Scholar 

  37. Brown PJ, Roose SP, O’Boyle KR, Ciarleglio A, Maas B, Igwe KC, et al. Frailty and its correlates in adults with late life depression. Am J Geriatr Psychiatry. 2020;28:145–54.

    Article  PubMed  Google Scholar 

  38. Vaughan L, Corbin AL, Goveas JS. Depression and frailty in later life: a systematic review. Clin Interv Aging. 2015;10:1947–58.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Collard RM, Comijs HC, Naarding P, Penninx BW, Milaneschi Y, Ferrucci L, et al. Frailty as a predictor of the incidence and course of depressed mood. J Am Med Dir Assoc. 2015;16:509–14.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Oude Voshaar RC, Dimitriadis M, vandenBrink RHS, Aprahamian I, Borges MK, Marijnissen RM, et al. A 6-year prospective clinical cohort study on the bidirectional association between frailty and depressive disorder. Int J Geriatr Psychiatry. 2021;36:1699–707.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Alexopoulos GS. Mechanisms and treatment of late-life depression. Transl Psychiatry. 2019;9:188.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Blazer DG. Depression and social support in late life: a clear but not obvious relationship. Aging Ment Health. 2005;9:497–9.

    Article  CAS  PubMed  Google Scholar 

  43. Ghesquiere AR, Park M, Bogner HR, Greenberg RL, Bruce ML. The effect of recent bereavement on outcomes in a primary care depression intervention study. Am J Geriatr Psychiatry. 2014;22:1555–64.

    Article  PubMed  Google Scholar 

  44. Oxman TE, Hull JG. Social support and treatment response in older depressed primary care patients. J Gerontol B Psychol Sci Soc Sci. 2001;56:35–45.

    Article  Google Scholar 

  45. Manning KJ, Chan G, Steffens DC, Pierce CW, Potter GG. The interaction of personality and social support on prospective suicidal ideation in men and women with late-life depression. Am J Geriatr Psychiatry. 2021;29:66–77.

    Article  PubMed  Google Scholar 

  46. Davies M, Adshead F. Closing the gap in a generation: health equity through action on the social determinants of health. An international conference based on the work of the Commission on Social Determinants of Health, 6-7 November 2008, London. Glob Health Promot. 2009;95–6:108–9. 7–8.

    Article  Google Scholar 

  47. AreĂ¡n P, Miranda J. The treatment of depression in elderly primary care patients: a naturalistic study. J Clin Geropsychol. 1996;2:153–60.

    Google Scholar 

  48. Arean PA, Gum A, McCulloch CE, Bostrom A, Gallagher-Thompson D, Thompson L. Treatment of depression in low-income older adults. Psychol Aging. 2005;20:601–9.

    Article  PubMed  Google Scholar 

  49. Ishtiak-Ahmed K, Rohde C, Kohler-Forsberg O, Christensen KS, Gasse C. Depression treatment trajectories and associated social determinants: a three-year follow-Up dtudy in 66,540 older adults undergoing first-time depression treatment in Denmark. Int J Geriatr Psychiatry. 2024;39:e70006.

    Article  PubMed  Google Scholar 

  50. Gerlach LB, Kavanagh J, Watkins D, Chiang C, Kim HM, Kales HC. With a little help from my friends?: racial and gender differences in the role of social support in later-life depression medication adherence. Int Psychogeriatr. 2017;29:1485–93.

    Article  PubMed  Google Scholar 

  51. Patrick RE, Dickinson RA, Gentry MT, Kim JU, Oberlin LE, Park S, et al. Treatment resistant late-life depression: A narrative review of psychosocial risk factors, non-pharmacological interventions, and the role of clinical phenotyping. J Affect Disord. 2024;356:145–54.

    Article  PubMed  Google Scholar 

  52. Comijs HC, van Exel E, van der Mast RC, Paauw A, Oude Voshaar R, Stek ML. Childhood abuse in late-life depression. J Affect Disord. 2013;147:241–6.

    Article  PubMed  Google Scholar 

  53. Naismith SL, Norrie LM, Mowszowski L, Hickie IB. The neurobiology of depression in later-life: clinical, neuropsychological, neuroimaging and pathophysiological features. Prog Neurobiol. 2012;98:99–143.

    Article  PubMed  Google Scholar 

  54. Steffens DC, Manning KJ, Wu R, Grady JJ, Fortinsky RH, Tennen HA. Methodology and preliminary results from the neurobiology of late-life depression study. Int Psychogeriatr. 2015;27:1987–97.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Karp JF, Frank E, Anderson B, George CJ, Reynolds CF, Mazumdar S. Time to remission in late-life depression: analysis of effects of demographic, treatment, and life-events measures. Depression. 1993;1:250–6.

    Article  Google Scholar 

  56. Dimitriadis M, van den Brink RHS, Comijs HC, Oude Voshaar RC. Prognostic effect of serum BDNF levels in late-life depression: moderated by childhood trauma and SSRI usage? Psychoneuroendocrinology. 2019;103:276–83.

    Article  CAS  PubMed  Google Scholar 

  57. Marquett RM, Thompson LW, Reiser RP, Holland JM, O’Hara RM, Kesler SR, et al. Psychosocial predictors of treatment response to cognitive-behavior therapy for late-life depression: an exploratory study. Aging Ment Health. 2013;17:830–8.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Muller J, Elsaesser M, Muller W, Hellmich M, Hammen M, Zehender N, et al. Differential psychological treatment effects in patients with late-life depression and a history of childhood maltreatment. Am J Geriatr Psychiatry. 2024;32:1325–36.

    Article  PubMed  Google Scholar 

  59. Zannas AS, McQuoid DR, Steffens DC, Chrousos GP, Taylor WD. Stressful life events, perceived stress, and 12-month course of geriatric depression: direct effects and moderation by the 5-HTTLPR and COMT Val158Met polymorphisms. Stress. 2012;15:425–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Steffens DC, Wu R, Grady JJ, Manning KJ. Presence of neuroticism and antidepressant remission rates in late-life depression: results from the Neurobiology of Late-Life Depression (NBOLD) study. Int Psychogeriatr. 2018;30:1069–74.

    Article  PubMed  Google Scholar 

  61. Costa PT, McCrae RR. Revised NEO personality inventory (NEO-PI-R) and NEO five-factor inventory (NEO-FFI) professional manual. Odessa, FL: Psychological Assessment Resources; 1992.

  62. Steffens DC, McQuoid DR, Smoski MJ, Potter GG. Clinical outcomes of older depressed patients with and without comorbid neuroticism. Int Psychogeriatr. 2013;25:1985–90.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Jeuring HW, Stek ML, Huisman M, Oude Voshaar RC, Naarding P, Collard RM, et al. A six-year prospective study of the prognosis and predictors in patients With late-life depression. Am J Geriatr Psychiatry. 2018;26:985–97.

    Article  PubMed  Google Scholar 

  64. Manning KJ, Chan G, Steffens DC. Neuroticism traits selectively impact long term illness course and cognitive decline in late-life depression. Am J Geriatr Psychiatry. 2017;25:220–9.

    Article  PubMed  Google Scholar 

  65. Jang Y, Clay OJ, Roth DL, Haley WE, Mittelman MS. Neuroticism and longitudinal change in caregiver depression: impact of a spouse-caregiver intervention program. Gerontologist. 2004;44:311–7.

    Article  PubMed  Google Scholar 

  66. Naito M, Kato M, Koshikawa Y, Bandou H, Sakai S, Takekita Y, et al. Personality as a basis for antidepressant selection for patients with depression: a two-point outcome study at 4 and 8 weeks. J Affect Disord. 2022;314:27–33.

    Article  PubMed  Google Scholar 

  67. Bock C, Bukh JD, Vinberg M, Gether U, Kessing LV. The influence of comorbid personality disorder and neuroticism on treatment outcome in first episode depression. Psychopathology. 2010;43:197–204.

    Article  PubMed  Google Scholar 

  68. Kim SY, Stewart R, Bae KY, Kim SW, Shin IS, Hong YJ, et al. Influences of the Big Five personality traits on the treatment response and longitudinal course of depression in patients with acute coronary syndrome: a randomised controlled trial. J Affect Disord. 2016;203:38–45.

    Article  PubMed  Google Scholar 

  69. Zuidersma M, de Vries YA, Bogers ICHM, Rhebergen D, Oude Voshaar RC. Six-year course over time and predictors of suicidal ideation in depressed older patients. J Affect Disord. 2025;370:90–9.

    Article  PubMed  Google Scholar 

  70. Bhalla RK, Butters MA, Becker JT, Houck PR, Snitz BE, Lopez OL, et al. Patterns of mild cognitive impairment after treatment of depression in the elderly. Am J Geriatr Psychiatry. 2009;17:308–16.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Pimontel MA, Rindskopf D, Rutherford BR, Brown PJ, Roose SP, Sneed J. A meta-analysis of executive dysfunction and antidepressant treatment response in late-life depression. Am J Geriatr Psychiatry. 2016;24:31–41.

    Article  PubMed  Google Scholar 

  72. Kalayam B, Alexopoulos GS. Prefrontal dysfunction and treatment response in geriatric depression. Arch Gen Psychiatry. 1999;56:713–8.

    Article  CAS  PubMed  Google Scholar 

  73. Alexopoulos GS, Kiosses DN, Heo M, Murphy CF, Shanmugham B, Gunning-Dixon F. Executive dysfunction and the course of geriatric depression. Biol Psychiatry. 2005;58:204–10.

    Article  PubMed  Google Scholar 

  74. Alexopoulos GS, Kiosses DN, Murphy C, Heo M. Executive dysfunction, heart disease burden, and remission of geriatric depression. Neuropsychopharmacology. 2004;29:2278–84.

    Article  PubMed  Google Scholar 

  75. Potter GG, Kittinger JD, Wagner HR, Steffens DC, Krishnan KR. Prefrontal neuropsychological predictors of treatment remission in late-life depression. Neuropsychopharmacology. 2004;29:2266–71.

    Article  PubMed  Google Scholar 

  76. Beaudreau SA, Rideaux T, O’Hara R, Arean P. Does cognition predict treatment response and remission in psychotherapy for late-life depression? Am J Geriatr Psychiatry. 2015;23:215–9.

    Article  PubMed  Google Scholar 

  77. Ainsworth NJ, Oughli H, Lavretsky H, Blumberger DM, Brown PJ, Butters MA, et al. The cognitive profile of older adults with treatment-resistant depression: an analysis of the OPTIMUM randomized controlled trial. Am J Geriatr Psychiatry. 2025;33:361–71.

    Article  PubMed  Google Scholar 

  78. Morimoto SS, Gunning FM, Kanellopoulos D, Murphy CF, Klimstra SA, Kelly RE Jr., et al. Semantic organizational strategy predicts verbal memory and remission rate of geriatric depression. Int J Geriatr Psychiatry. 2012;27:506–12.

    Article  PubMed  Google Scholar 

  79. Morimoto SS, Gunning FM, Murphy CF, Kanellopoulos D, Kelly RE, Alexopoulos GS. Executive function and short-term remission of geriatric depression: the role of semantic strategy. Am J Geriatr Psychiatry. 2011;19:115–22.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Sneed JR, Roose SP, Keilp JG, Krishnan KR, Alexopoulos GS, Sackeim HA. Response inhibition predicts poor antidepressant treatment response in very old depressed patients. Am J Geriatr Psychiatry. 2007;15:553–63.

    Article  PubMed  Google Scholar 

  81. Alexopoulos GS, Manning K, Kanellopoulos D, McGovern A, Seirup JK, Banerjee S, et al. Cognitive control, reward-related decision making and outcomes of late-life depression treated with an antidepressant. Psychol Med. 2015;45:3111–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Manning KJ, Alexopoulos GS, Banerjee S, Morimoto SS, Seirup JK, Klimstra SA, et al. Executive functioning complaints and escitalopram treatment response in late-life depression. Am J Geriatr Psychiatry. 2015;23:440–5.

    Article  PubMed  Google Scholar 

  83. Taylor WD, Ajilore O, Karim HT, Butters MA, Krafty R, Boyd BD, et al. Assessing depression recurrence, cognitive burden, and neurobiological homeostasis in late life: Design and rationale of the REMBRANDT Study. J Mood Anxiety Disord. 2024;55:100038.

  84. Story TJ, Potter GG, Attix DK, Welsh-Bohmer KA, Steffens DC. Neurocognitive correlates of response to treatment in late-life depression. Am J Geriatr Psychiatry. 2008;16:752–9. PMC2722450.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Aizenstein HJ, Khalaf A, Walker SE, Andreescu C. Magnetic resonance imaging predictors of treatment response in late-life depression. J Geriatr Psychiatry Neurol. 2014;27:24–32.

    Article  PubMed  Google Scholar 

  86. Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M. Vascular depression’ hypothesis. Arch Gen Psychiatry. 1997;54:915–22.

    Article  CAS  PubMed  Google Scholar 

  87. Gerlach AR, Karim HT, Pecina M, Ajilore O, Taylor WD, Butters MA, et al. MRI predictors of pharmacotherapy response in major depressive disorder. NeuroImage Clin. 2022;36:103157.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Hsieh MH, McQuoid DR, Levy RM, Payne ME, MacFall JR, Steffens DC. Hippocampal volume and antidepressant response in geriatric depression. Int J Geriatr Psychiatry. 2002;17:519–25.

    Article  PubMed  Google Scholar 

  89. Sheline YI, Disabato BM, Hranilovich J, Morris C, D’Angelo G, Pieper C, et al. Treatment course with antidepressant therapy in late-life depression. Am J Psychiatry. 2012;169:1185–93.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Taylor WD, McQuoid DR, Payne ME, Zannas AS, MacFall JR, Steffens DC. Hippocampus atrophy and the longitudinal course of late-life depression. Am J Geriatr Psychiatry. 2014;22:1504–12.

    Article  PubMed  Google Scholar 

  91. Ahmed R, Ryan C, Christman S, Elson D, Bermudez C, Landman BA, et al. Structural MRI-based measures of accelerated brain aging do not moderate the acute antidepressant response in late-life depression. Am J Geriatr Psychiatry. 2022;30:1015–25.

    Article  PubMed  Google Scholar 

  92. Khalaf A, Edelman K, Tudorascu D, Andreescu C, Reynolds CF, Aizenstein H. White matter hyperintensity accumulation during treatment of late-life depression. Neuropsychopharmacology. 2015;40:3027–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. MacQueen GM, Yucel K, Taylor VH, Macdonald K, Joffe R. Posterior hippocampal volumes are associated with remission rates in patients with major depressive disorder. Biol Psychiatry. 2008;64:880–3.

    Article  PubMed  Google Scholar 

  94. Gunning FM, Cheng J, Murphy CF, Kanellopoulos D, Acuna J, Hoptman MJ, et al. Anterior cingulate cortical volumes and treatment remission of geriatric depression. Int J Geriatr Psychiatry. 2009;24:829–36.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Motter JN, Lee S, Sneed JR, Doraiswamy PM, Pelton GH, Petrella JR, et al. Cortical thickness predicts remission of depression with antidepressants in patients with late-life depression and cognitive impairment. J Affect Disord. 2021;295:438–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Voineskos A, Zhukovsky P, Butters M, Lavretsky H, Brown P, Shimony J, et al. Brain-cognition relationships and treatment outcome in treatment-resistant late-life depression. Res Sq. 2025 3:rs.3.rs-6340032.

  97. Hickie I, Scott E, Mitchell P, Wilhelm K, Austin MP, Bennett B. Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression. Biol Psychiatry. 1995;37:151–60.

    Article  CAS  PubMed  Google Scholar 

  98. Janssen J, Hulshoff Pol HE, Schnack HG, Kok RM, Lampe IK, de Leeuw FE, et al. Cerebral volume measurements and subcortical white matter lesions and short-term treatment response in late life depression. Int J Geriatr Psychiatry. 2007;22:468–74.

    Article  PubMed  Google Scholar 

  99. Bella R, Pennisi G, Cantone M, Palermo F, Pennisi M, Lanza G, et al. Clinical presentation and outcome of geriatric depression in subcortical ischemic vascular disease. Gerontology. 2010;56:298–302.

    Article  CAS  PubMed  Google Scholar 

  100. Gunning-Dixon FM, Walton M, Cheng J, Acuna J, Klimstra S, Zimmerman ME, et al. MRI signal hyperintensities and treatment remission of geriatric depression. J Affect Disord. 2010;126:395–401.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Sneed JR, Culang-Reinlieb ME, Brickman AM, Gunning-Dixon FM, Johnert L, Garcon E, et al. MRI signal hyperintensities and failure to remit following antidepressant treatment. J Affect Disord. 2011;135:315–20.

    Article  CAS  PubMed  Google Scholar 

  102. Salloway S, Correia S, Boyle P, Malloy P, Schneider L, Lavretsky H, et al. MRI subcortical hyperintensities in old and very old depressed outpatients: the important role of age in late-life depression. J Neurol Sci. 2002;203-204:227–33.

    Article  PubMed  Google Scholar 

  103. Alexopoulos GS, Kiosses DN, Choi SJ, Murphy CF, Lim KO. Frontal white matter microstructure and treatment response of late-life depression: a preliminary study. Am J Psychiatry. 2002;159:1929–32.

    Article  PubMed  Google Scholar 

  104. Alexopoulos GS, Murphy CF, Gunning-Dixon FM, Latoussakis V, Kanellopoulos D, Klimstra S, et al. Microstructural white matter abnormalities and remission of geriatric depression. Am J Psychiatry. 2008;165:238–44.

    Article  PubMed  Google Scholar 

  105. Taylor WD, Kuchibhatla M, Payne ME, Macfall JR, Sheline YI, Krishnan KR, et al. Frontal white matter anisotropy and antidepressant remission in late-life depression. PLoS ONE. 2008;3. e3267.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Taylor WD, Macfall JR, Boyd B, Payne ME, Sheline YI, Krishnan RR, et al. One-year change in anterior cingulate cortex white matter microstructure: relationship with late-life depression outcomes. Am J Geriatr Psychiatry. 2011;19:43–52.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Allman JM, Hakeem A, Erwin JM, Nimchinsky E, Hof P. The anterior cingulate cortex. The evolution of an interface between emotion and cognition. Ann N Y Acad Sci. 2001;935:107–17.

    Article  CAS  PubMed  Google Scholar 

  108. Pizzagalli DA. Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology. 2011;36:183–206.

    Article  PubMed  Google Scholar 

  109. Emam H, Steffens DC, Pearlson GD, Wang L. Increased ventromedial prefrontal cortex activity and connectivity predict poor sertraline treatment outcome in late-life depression. Int J Geriatr Psychiatry. 2019;34:730–7.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Andreescu C, Tudorascu DL, Butters MA, Tamburo E, Patel M, Price J, et al. Resting state functional connectivity and treatment response in late-life depression. Psychiatry Res. 2013;214:313–21.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Wu M, Andreescu C, Butters MA, Tamburo R, Reynolds CF 3rd, Aizenstein H. Default-mode network connectivity and white matter burden in late-life depression. Psychiatry Res. 2011;194:39–46.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Karim HT, Andreescu C, Tudorascu D, Smagula SF, Butters MA, Karp JF, et al. Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters. Mol Psychiatry. 2017;22:450–7.

    Article  CAS  PubMed  Google Scholar 

  113. Thompson DG, Kesler SR, Sudheimer K, Mehta KM, Thompson LW, Marquett RM, et al. FMRI activation during executive function predicts response to cognitive behavioral therapy in older, depressed adults. Am J Geriatr Psychiatry. 2015;23:13–22.

    Article  PubMed  Google Scholar 

  114. Solomonov N, Victoria LW, Mir Z, Phan D, Hoptman MJ, Arean P, et al. Brain activation associated with response to psychotherapies for late-life depression: a task-based fMRI study. Am J Geriatr Psychiatry. 2025;33:611–23.

    Article  PubMed  Google Scholar 

  115. Aizenstein HJ, Butters MA, Wu M, Mazurkewicz LM, Stenger VA, Gianaros PJ, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Khalaf A, Karim H, Berkout OV, Andreescu C, Tudorascu D, Reynolds CF, et al. Altered functional magnetic resonance imaging markers of affective processing during treatment of late-life depression. Am J Geriatr Psychiatry. 2016;24:791–801.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Laifenfeld D, Albeldas C, Solal TC, McIntyre RS, Stahl S. Toward precision psychiatry: innovations and prospects in treating depression. Prim Care Companion CNS Disord. 2025;27:25nr03970.

  118. McGrath CL, Kelley ME, Holtzheimer PE, Dunlop BW, Craighead WE, Franco AR, et al. Toward a neuroimaging treatment selection biomarker for major depressive disorder. JAMA Psychiatry. 2013;70:821–9.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Dunlop BW, Rajendra JK, Craighead WE, Kelley ME, McGrath CL, Choi KS, et al. Functional connectivity of the subcallosal cingulate cortex and differential outcomes to treatment with cognitive-behavioral therapy or antidepressant medication for major depressive disorder. Am J Psychiatry. 2017;174:533–45.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, et al. Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry. 2004;61:34–41.

    Article  PubMed  Google Scholar 

  121. Solomonov N, Victoria LW, Dunlop K, Respino M, Hoptman MJ, Zilcha-Mano S, et al. Resting state functional connectivity and outcomes of psychotherapies for late-life depression. Am J Geriatr Psychiatry. 2020;28:859–68.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Zhang M, Mo J, Zhang H, Tang Y, Guo K, OuYang X, et al. Efficacy and tolerability of repetitive transcranial magnetic stimulation for late-life depression: a systematic review and meta-analysis. J Affect Disord. 2023;323:219–31.

    Article  PubMed  Google Scholar 

  123. Jorge RE, Moser DJ, Acion L, Robinson RG. Treatment of vascular depression using repetitive transcranial magnetic stimulation. Arch Gen Psychiatry. 2008;65:268–76.

    Article  PubMed  Google Scholar 

  124. Karim HT, Gerlach A, Butters MA, Krafty R, Boyd BD, Banihashemi L, et al. Brain age Is not a significant predictor of relapse risk in late-life depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2025;10:103–10.

    PubMed  Google Scholar 

  125. Taylor WD, Boyd BD, Elson D, Andrews P, Albert K, Vega J, et al. Preliminary evidence that cortical amyloid burden predicts poor response to antidepressant medication treatment in cognitively intact individuals with late-life depression. Am J Geriatr Psychiatry. 2021;29:448–57.

    Article  PubMed  Google Scholar 

  126. Cohen SE, Zantvoord JB, Wezenberg BN, Bockting CLH, van Wingen GA. Magnetic resonance imaging for individual prediction of treatment response in major depressive disorder: a systematic review and meta-analysis. Transl Psychiatry. 2021;11:168.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Patel MJ, Andreescu C, Price JC, Edelman KL, Reynolds CF, Aizenstein HJ. Machine learning approaches for integrating clinical and imaging features in late-life depression classification and response prediction. Int J Geriatr Psychiatry. 2015;30:1056–67.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Poirot MG, Ruhe HG, Mutsaerts HMM, Maximov I, Groote IR, Bjornerud A, et al. Treatment response prediction in major depressive disorder using multimodal MRI and clinical data: Secondary analysis of a randomized clinical trial. Am J Psychiatry. 2024;181:223–33.

    Article  PubMed  Google Scholar 

  129. Sajjadian M, Uher R, Ho K, Hassel S, Milev R, Frey BN, et al. Prediction of depression treatment outcome from multimodal data: a CAN-BIND-1 report. Psychol Med. 2023;53:5374–84.

    Article  PubMed  Google Scholar 

  130. Marshe VS, Maciukiewicz M, Rej S, Tiwari AK, Sibille E, Blumberger DM, et al. Norepinephrine transporter gene variants and remission from depression with venlafaxine treatment in older adults. Am J Psychiatry. 2017;174:468–75.

    Article  PubMed  Google Scholar 

  131. Pollock BG, Ferrell RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA, et al. Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology. 2000;23:587–90.

    Article  CAS  PubMed  Google Scholar 

  132. Taylor WD, McQuoid DR, Ashley-Koch A, Macfall JR, Bridgers J, Krishnan RR, et al. BDNF Val66Met genotype and 6-month remission rates in late-life depression. Pharmacogenom J. 2011;11:146–54.

  133. Alexopoulos GS, Glatt CE, Hoptman MJ, Kanellopoulos D, Murphy CF, Kelly RE, et al. BDNF val66met polymorphism, white matter abnormalities and remission of geriatric depression. J Affect Disord. 2010;125:262–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Marshe VS, Islam F, Maciukiewicz M, Bousman C, Eyre HA, Lavretsky H, et al. Pharmacogenetic implications for antidepressant pPharmacotherapy in late-life depression: a systematic review of the literature for response, pharmacokinetics and adverse drug reactions. Am J Geriatr Psychiatry. 2020;28:609–29.

    Article  PubMed  Google Scholar 

  135. Marshe VS, Maciukiewicz M, Hauschild AC, Islam F, Qin L, Tiwari AK, et al. Genome-wide analysis suggests the importance of vascular processes and neuroinflammation in late-life antidepressant response. Transl Psychiatry. 2021;11:127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Forester BP, Parikh SV, Weisenbach S, Ajilore O, Vahia I, Rothschild AJ, et al. Combinatorial pharmacogenomic testing improves outcomes for older adults with depression. Am J Geriatr Psychiatry. 2020;28:933–45.

    Article  PubMed  Google Scholar 

  137. van der Schans J, Hak E, Postma M, Breuning L, Brouwers J, Ditters K, et al. Effects of pharmacogenetic screening for CYP2D6 among elderly starting therapy with nortriptyline or venlafaxine: a pragmatic randomized controlled trial (CYSCE Trial). J Clin Psychopharmacol. 2019;39:583–90.

    Article  PubMed  Google Scholar 

  138. Marshe VS, Islam F, Maciukiewicz M, Fiori LM, Yerko V, Yang J, et al. Validation study of microRNAs previously associated with antidepressant response in older adults treated for late-life depression with venlafaxine. Prog Neuropsychopharmacol Biol Psychiatry. 2020;100:109867.

    Article  CAS  PubMed  Google Scholar 

  139. Zheng K, Hu F, Zhou Y, Zhang J, Zheng J, Lai C, et al. miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer’s disease. Nat Commun. 2021;12:1903.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Grzenda A, Siddarth P, Laird KT, Yeargin J, Lavretsky H. Transcriptomic signatures of treatment response to the combination of escitalopram and memantine or placebo in late-life depression. Mol Psychiatry. 2021;26:5171–9.

    Article  CAS  PubMed  Google Scholar 

  141. Martocchia A, Curto M, Scaccianoce S, Comite F, Xenos D, Nasca C, et al. Effects of escitalopram on serum BDNF levels in elderly patients with depression: a preliminary report. Aging Clin Exp Res. 2014;26:461–4.

    Article  PubMed  Google Scholar 

  142. Kruse JL, Congdon E, Olmstead R, Njau S, Breen EC, Narr KL, et al. Inflammation and improvement of depression following electroconvulsive therapy in treatment-resistant depression. J Clin Psychiatry. 2018;79:17m11597.

  143. Ryan KM, McLoughlin DM. Peripheral blood inflammatory markers in depression: Response to electroconvulsive therapy and relationship with cognitive performance. Psychiatry Res. 2022;315:114725.

    Article  CAS  PubMed  Google Scholar 

  144. Carlier A, Berkhof JG, Rozing M, Bouckaert F, Sienaert P, Eikelenboom P, et al. Inflammation and remission in older patients with depression treated with electroconvulsive therapy; findings from the MODECT study (☆). J Affect Disord. 2019;256:509–16.

    Article  PubMed  Google Scholar 

  145. Kosanovic Rajacic B, Sagud M, Begic D, Nikolac Perkovic M, Kozmar A, Rogic D, et al. Increased interleukin-6 levels in responders with treatment-resistant depression after bright light therapy. Biomolecules. 2025;15:295.

  146. Gasparini A, Callegari C, Lucca G, Bellini A, Caselli I, Ielmini M. Inflammatory biomarker and response to antidepressant in major depressive disorder: a systematic review and meta-analysis. Psychopharmacol Bull. 2022;52:36–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Sampson E, Mills NT, Hori H, Cearns M, Schwarte K, Hohoff C, et al. Long-term characterisation of the relationship between change in depression severity and change in inflammatory markers following inflammation-stratified treatment with vortioxetine augmented with celecoxib or placebo. Brain Behav Immun. 2025;123:43–56.

    Article  CAS  PubMed  Google Scholar 

  148. Diniz BS, Seitz-Holland J, Sehgal R, Kasamoto J, Higgins-Chen AT, Lenze E. Geroscience-centric perspective for geriatric psychiatry: integrating aging biology with geriatric mental health research. Am J Geriatr Psychiatry. 2024;32:1–16.

    Article  PubMed  Google Scholar 

  149. Seitz-Holland J, Mulsant BH, Reynolds CF, Blumberger DM, Karp JF, Butters MA, et al. Major depression, physical health and molecular senescence markers abnormalities. Nat Ment Health. 2023;1:200–9.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Diniz BS, Vieira EM, Mendes-Silva AP, Bowie CR, Butters MA, Fischer CE, et al. Mild cognitive impairment and major depressive disorder are associated with molecular senescence abnormalities in older adults. Alzheimers Dement. 2021;7:e12129.

    Google Scholar 

  151. Diniz BS, Reynolds CF, Sibille E, Lin CW, Tseng G, Lotrich F, et al. Enhanced molecular aging in late-life depression: the senescent-associated secretory phenotype. Am J Geriatr Psychiatry. 2017;25:64–72.

    Article  PubMed  Google Scholar 

  152. Diniz BS, Mulsant BH, Reynolds CF, Blumberger D, Karp JF, Butters MA, et al. Association of molecular senescence markers in late-life depression with clinical characteristics and treatment outcome. JAMA Netw Open. 2022;5:e2219678.

    Article  PubMed  PubMed Central  Google Scholar 

  153. Alexopoulos GS, Hoptman MJ, Kanellopoulos D, Murphy CF, Lim KO, Gunning FM. Functional connectivity in the cognitive control network and the default mode network in late-life depression. J Affect Disord. 2012;139:56–65.

    Article  PubMed  PubMed Central  Google Scholar 

  154. Steffens DC, Wang L, Pearlson GD. Functional connectivity predictors of acute depression treatment outcome. Int Psychogeriatr. 2019;31:1831–5.

    Article  PubMed  PubMed Central  Google Scholar 

  155. Oberlin LE, Victoria LW, Ilieva I, Dunlop K, Hoptman MJ, Avari J, et al. Comparison of functional and structural neural network features in older adults with depression with vs without apathy and association with response to escitalopram: secondary analysis of a nonrandomized clinical trial. JAMA Netw Open. 2022;5:e2224142.

    Article  PubMed  PubMed Central  Google Scholar 

  156. Ahmed R, Boyd BD, Elson D, Albert K, Begnoche P, Kang H, et al. Influences of resting-state intrinsic functional brain connectivity on the antidepressant treatment response in late-life depression. Psychol Med. 2023;53:6261–70.

    Article  PubMed  Google Scholar 

  157. Ribeiz SR, Duran F, Oliveira MC, Bezerra D, Castro CC, Steffens DC, et al. Structural brain changes as biomarkers and outcome predictors in patients with late-life depression: a cross-sectional and prospective study. PLoS ONE. 2013;8:e80049.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Bouckaert F, De Winter FL, Emsell L, Dols A, Rhebergen D, Wampers M, et al. Grey matter volume increase following electroconvulsive therapy in patients with late life depression: a longitudinal MRI study. J Psychiatry Neurosci. 2016;41:105–14.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Marano CM, Workman CI, Lyman CH, Munro CA, Kraut MA, Smith GS. Structural imaging in late-life depression: association with mood and cognitive responses to antidepressant treatment. Am J Geriatr Psychiatry. 2015;23:4–12.

    Article  PubMed  Google Scholar 

  160. Bouckaert F, Emsell L, Vansteelandt K, De Winter FL, Van den Stock J, Obbels J, et al. Electroconvulsive therapy response in late-life depression unaffected by age-related brain changes. J Affect Disord. 2019;251:114–20.

    Article  PubMed  Google Scholar 

  161. Victoria LW, Alexopoulos GS, Ilieva I, Stein AT, Hoptman MJ, Chowdhury N, et al. White matter abnormalities predict residual negative self-referential thinking following treatment of late-life depression with escitalopram: A preliminary study. J Affect Disord. 2019;243:62–9.

    Article  CAS  PubMed  Google Scholar 

  162. He X, Pueraro E, Kim Y, Garcia CM, Maas B, Choi J, et al. Association of white matter integrity with executive function and antidepressant treatment outcome in patients with late-life depression. Am J Geriatr Psychiatry. 2021;29:1188–98.

    Article  PubMed  PubMed Central  Google Scholar 

  163. Narushima K, McCormick LM, Yamada T, Thatcher RW, Robinson RG. Subgenual cingulate theta activity predicts treatment response of repetitive transcranial magnetic stimulation in participants with vascular depression. J Neuropsychiatry Clin Neurosci. 2010;22:75–84.

    Article  PubMed  PubMed Central  Google Scholar 

  164. Ha J, Fang Y, Kittur C, Cron GO, Song OK, Park JY, et al. Effect of combined transcranial direct current stimulation and cognitive training on brain microstructure and network homogeneity in late-life depression: a pilot study. J Affect Disord Rep. 2025;21:100973.

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Center on Aging (BSD), University of Connecticut School of Medicine, Farmington, CT, USA

    David C. Steffens, Breno S. Diniz, Neha Jain, Jessica Kluewer-D’Amico, Kevin J. Manning & Lihong Wang

Authors
  1. David C. Steffens
    View author publications

    Search author on:PubMed Google Scholar

  2. Breno S. Diniz
    View author publications

    Search author on:PubMed Google Scholar

  3. Neha Jain
    View author publications

    Search author on:PubMed Google Scholar

  4. Jessica Kluewer-D’Amico
    View author publications

    Search author on:PubMed Google Scholar

  5. Kevin J. Manning
    View author publications

    Search author on:PubMed Google Scholar

  6. Lihong Wang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Steffens was responsible for the final draft of the manuscript. Diniz, Jain, Kluewer-D’Amico, Manning, and Wang each contributed to the writing of a section based on their expertise.

Corresponding author

Correspondence to David C. Steffens.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Steffens, D.C., Diniz, B.S., Jain, N. et al. Moderators of treatment response in late-life depression. Neuropsychopharmacol. (2026). https://doi.org/10.1038/s41386-026-02337-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41386-026-02337-x

Search

Advanced search

Quick links