Heterogeneity in the prognosis of major depression: From the common cold to a highly debilitating and recurrent illness
Open accessAbstract
Two different and seemingly competing views on the diagnosis of major depressive disorder (MDD) exist. The first is that the diagnosis conflates adaptive sadness reactions with pathological states of depressed mood and that MDD is overdiagnosed and overtreated. The second is that MDD is an underdiagnosed and undertreated disorder, and one that is best characterised by a severe, chronic, recurrent or treatment-resistant course. Existing research suggests that both views are valid and merit being integrated. Anywhere from 30 to 50% of individuals will meet criteria for MDD at some point in their life. About half of these episodes are of brief duration and unlikely to recur. However, a remaining half is either chronic or recurrent. Data on the outpatient diagnosis of depression support the view that depression is simultaneously underdiagnosed and undertreated as well as overdiagnosed and overtreated. About one-third of the patients who meet criteria for MDD and receive placebos experience clinically significant and long-lasting improvement. Many other patients, however, are unresponsive to one or multiple active treatments. Thus, the diagnosis of MDD likely applies to individuals who are experiencing either normal periods of sadness or single-episode afflictions that are mild, unlikely to recur, and are placebo responsive, as well as to individuals with more severe clinical profiles. More research is needed that can help ascertain what contextual or biopsychological variables help distinguish between individuals who may be experiencing adaptive states of negative affect and those who experience severe, chronic, recurrent or treatment-resistant depressions.
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The diagnosis of major depressive disorder is likely causally heterogeneous.
“Further, the diagnosis of major depressive disorder (MDD) is likely causally heterogeneous.”
From Risk factors for relapse and recurrence of depression in adults and how they operate: A four-phase systematic review and meta-synthesis (2018) · cites this paper as Lorenzo-Luaces, 2015
The Abstract says the MDD diagnosis encompasses both potentially adaptive sadness and severe, recurrent depression. Future recommendations call for research into contextual and biopsychological differences between these presentations. That is consistent with possible causal heterogeneity, but the paper does not establish that the diagnosed conditions have different causes. (LLM, conf=0.78)
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1 retracted
Hollon, S. D., DeRubeis, R. J., Fawcett, J., Amsterdam, J. D., Shelton, R. C., Zajecka, J., Young, P. R., & Gallop, R. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1054 · Cited by 179 · see citing works
RetractedMurray, C. J. L., Vos, T., Lozano, R., Naghavi, M., Flaxman, A. D., Michaud, C., Ezzati, M., Shibuya, K., Salomon, J. A., Abdalla, S., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61689-4 · Cited by 8,888 · see citing works
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., Rush, A. J., Walters, E. E., & Wang, P. S. (2003) · JAMA · doi:10.1001/jama.289.23.3095 · Cited by 7,988 · see citing works
Helplessness: On Depression, Development, and Death
Seligman, M. E. P. (1975) · CERN Document Server (European Organization for Nuclear Research) · Cited by 6,181 · see citing works
Genetic Epidemiology of Major Depression: Review and Meta-Analysis
Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.10.1552 · Cited by 3,431 · see citing works
Kirsch, I., Deacon, B. J., Huedo-Medina, T. B., Scoboria, A., Moore, T. J., & Johnson, B. T. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050045 · Cited by 2,442 · see citing works
Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis
Fournier, J. C., DeRubeis, R. J., Hollon, S. D., Dimidjian, S., Amsterdam, J. D., Shelton, R. C., & Fawcett, J. (2010) · JAMA · doi:10.1001/jama.2009.1943 · Cited by 2,009 · see citing works
Clinical diagnosis of depression in primary care: a meta-analysis
Mitchell, A. J., Vaze, A., & Rao, S. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60879-5 · Cited by 1,251 · see citing works
Placebo Response in Studies of Major Depression: Variable, Substantial, and Growing
Walsh, B. T., Seidman, S. N., Sysko, R., & Gould, M. (2002) · JAMA · doi:10.1001/jama.287.14.1840 · Cited by 1,109 · see citing works
Exercise Treatment for Major Depression: Maintenance of Therapeutic Benefit at 10 Months
Babyak, M., Blumenthal, J. A., Herman, S., Khatri, P., Doraiswamy, M., Moore, K., Edward Craighead, W., Baldewicz, T. T., & Ranga Krishnan, K. (2000) · Psychosomatic Medicine · doi:10.1097/00006842-200009000-00006 · Cited by 1,063 · see citing works
Horwitz, A. V., & Wakefield, J. C. (2007) · doi:10.1093/oso/9780195313048.001.0001 · Cited by 1,019 · see citing works
Moffitt, T. E., Caspi, A., Taylor, A., Kokaua, J., Milne, B. J., Polanczyk, G., & Poulton, R. (2010) · Psychological Medicine · doi:10.1017/s0033291709991036 · Cited by 938 · see citing works
Recurrence after recovery from major depressive disorder during 15 years of observational follow-up
Mueller, T. I., Leon, A. C., Keller, M. B., Solomon, D. A., Endicott, J., Coryell, W., Warshaw, M., & Maser, J. D. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.7.1000 · Cited by 897 · see citing works
Cuijpers, P., Donker, T., van Straten, A., Li, J., & Andersson, G. (2010) · Psychological Medicine · doi:10.1017/s0033291710000772 · Cited by 832 · see citing works
The Loss of Sadness: How Psychiatry Transformed Normal Sorrow into Depressive Disorder
(2009) · PsycEXTRA Dataset · doi:10.1037/e671332011-001 · Cited by 752 · see citing works
Population-based study of first onset and chronicity in major depressive disorder
Eaton, W. W., Shao, H., Nestadt, G., Lee, B. H., Bienvenu, O. J., & Zandi, P. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.5.513 · Cited by 612 · see citing works
Cuijpers, P., Karyotaki, E., Weitz, E., Andersson, G., Hollon, S. D., & van Straten, A. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.02.026 · Cited by 586 · see citing works
The bright side of being blue: depression as an adaptation for analyzing complex problems.
Andrews, P. W., & Thomson, J. A. (2009) · Psychological Review · doi:10.1037/a0016242 · Cited by 549 · see citing works
Limitations of Diagnostic Criteria and Assessment Instruments for Mental Disorders
Regier, D. A., Kaelber, C. T., Rae, D. S., Farmer, M. E., Knaüper, B., Kessler, R. C., & NORQUIST, G. S. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.2.109 · Cited by 549 · see citing works
Spijker, J., De Graaf, R., Bijl, R. V., Beekman, A. T. F., Ormel, J., & Nolen, W. A. (2002) · British Journal of Psychiatry · doi:10.1192/bjp.181.3.208 · Cited by 514 · see citing works
Eaton, W. W. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830230023003 · Cited by 489 · see citing works
Lakeman, R. (2013) · Psychosis · doi:10.1080/17522439.2013.830642 · Cited by 473 · see citing works
Judd, L. L., Paulus, M. J., Schettler, P. J., Akiskal, H. S., Endicott, J., Leon, A. C., Maser, J. D., Mueller, T., Solomon, D. A., & Keller, M. B. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.9.1501 · Cited by 458 · see citing works
Khan, A., Leventhal, R. M., Khan, S. R., & Brown, W. A. (2002) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200202000-00007 · Cited by 456 · see citing works
(2014) · Choice Reviews Online · doi:10.5860/choice.51-3280 · Cited by 449 · see citing works
Rohde, P., Lewinsohn, P. M., Klein, D. N., Seeley, J. R., & Gau, J. M. (2012) · Clinical Psychological Science · doi:10.1177/2167702612457599 · Cited by 416 · see citing works
Meta-analysis of the placebo response in antidepressant trials.
Rief, W., Nestoriuc, Y., Weiss, S., Welzel, E., Barsky, A. J., & Hofmann, S. G. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.01.029 · Cited by 346 · see citing works
Eaton, W. W., Neufeld, K., Chen, L.-S., & Cai, G. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.3.217 · Cited by 339 · see citing works
Life events, first depression onset and the serotonin transporter gene
Wilhelm, K. A., Mitchell, P. B., Niven, H., Finch, A. W., Wedgwood, L., Scimone, A., Blair, I. P., Parker, G. B., & Schofield, P. R. (2006) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.105.009522 · Cited by 309 · see citing works
Depression's Vicious Scree: Self-Propagating and Erosive Processes in Depression Chronicity
Joiner, T. E. (2000) · Clinical Psychology Science and Practice · doi:10.1093/clipsy.7.2.203 · Cited by 284 · see citing works
Extending the Bereavement Exclusion for Major Depression to Other Losses
Wakefield, J. C., Schmitz, M. F., First, M. B., & Horwitz, A. V. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.4.433 · Cited by 263 · see citing works
Proportion Of Antidepressants Prescribed Without A Psychiatric Diagnosis Is Growing
Mojtabai, R., & Olfson, M. (2011) · Health Affairs · doi:10.1377/hlthaff.2010.1024 · Cited by 252 · see citing works
Recurrence in major depression: A conceptual analysis
Monroe, S. M., & Harkness, K. L. (2011) · Psychological Review · doi:10.1037/a0025190 · Cited by 225 · see citing works
Barbui, C., Cipriani, A., Patel, V., Ayuso‐Mateos, J. L., & van Ommeren, M. (2011) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.109.076448 · Cited by 216 · see citing works
Accuracy of Reports of Lifetime Mental and Physical Disorders
Takayanagi, Y., Spira, A. P., Roth, K. B., Gallo, J. J., Eaton, W. W., & Mojtabai, R. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.3579 · Cited by 211 · see citing works
Driessen, E., Cuijpers, P., Hollon, S. D., & Dekker, J. J. M. (2010) · Journal of Consulting and Clinical Psychology · doi:10.1037/a0020570 · Cited by 208 · see citing works
A Registry-Based Twin Study of Depression in Men
Lyons, M. J., Eisen, S. A., Goldberg, J. H., True, W., Lin, N., Meyer, J. M., Toomey, R., Faraone, S. V., Merla-Ramos, M., & Tsuang, M. T. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.5.468 · Cited by 188 · see citing works
Mojtabai, R., & Olfson, M. (2008) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v69n0704 · Cited by 185 · see citing works
Brunoni, A. R., Lopes, M., Kaptchuk, T. J., & Fregni, F. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004824 · Cited by 173 · see citing works
Steinert, C., Hofmann, M., Kruse, J., & Leichsenring, F. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.10.017 · Cited by 148 · see citing works
The Loss of Sadness: How Psychiatry Transformed Normal Sorrow Into Depressive Disorder
Seritan, A. L. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07081263 · Cited by 146 · see citing works
The Book of Woe: The DSM and the Unmaking of Psychiatry
Greenberg, G. (2013) · Medical Entomology and Zoology · Cited by 133 · see citing works
Wakefield, J. C., & Schmitz, M. F. (2013) · World Psychiatry · doi:10.1002/wps.20015 · Cited by 133 · see citing works
The Book of Woe: The DSM and the Unmaking of Psychiatry
Bard, J. S. (2013) · Journal of Legal Medicine · doi:10.1080/01947648.2013.831304 · Cited by 131 · see citing works
Structural and functional models of depression: from sub‐types to substrates
Malhi, G. S., Parker, G. B., & Greenwood, J. (2005) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2004.00475.x · Cited by 112 · see citing works
Is depression overdiagnosed? Yes
Parker, G. B. (2007) · BMJ · doi:10.1136/bmj.39268.475799.ad · Cited by 105 · see citing works
The long-term course of depressive disorders in the Lundby Study
MATTISSON, C., BOGREN, M., HORSTMANN, V., MUNK-JÖRGENSEN, P., & NETTELBLADT, P. (2007) · Psychological Medicine · doi:10.1017/s0033291707000074 · Cited by 95 · see citing works
Defining melancholia: the primacy of psychomotor disturbance
Parker, G. B. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2007.00959.x · Cited by 87 · see citing works
Angst, J., Paksarian, D., Cui, L., Merikangas, K. R., Hengartner, M. P., Ajdacic‐Gross, V., & Wulf Rössler, A. (2015) · Epidemiology and Psychiatric Sciences · doi:10.1017/s204579601500027x · Cited by 86 · see citing works
Wakefield, J. C., & Schmitz, M. F. (2013) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12184 · Cited by 82 · see citing works
Salmon, P., Humphris, G. M., Ring, A., Davies, J. C., & Dowrick, C. F. (2006) · Psychosomatic Medicine · doi:10.1097/01.psy.0000227690.95757.64 · Cited by 79 · see citing works
A systematic review of long-term studies of drug treated and non-drug treated depression
Hughes, S., & Cohen, D. (2009) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.01.027 · Cited by 71 · see citing works
The persistence of the placebo response in antidepressant clinical trials
Khan, A., Redding, N., & Brown, W. A. (2007) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2007.10.004 · Cited by 68 · see citing works
Shorter, E. (2013) · Oxford University Press eBooks · doi:10.1093/oso/9780199948086.001.0001 · Cited by 64 · see citing works
Antidepressant Use in the Absence of Common Mental Disorders in the General Population
Pagura, J., Katz, L. Y., Mojtabai, R., Druss, B. G., Cox, B. J., & Sareen, J. (2011) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.09m05776blu · Cited by 57 · see citing works
Initial 6-month follow-up of patients with major depressive disorder
Shapiro, R. W., & Keller, M. B. (1981) · Journal of Affective Disorders · doi:10.1016/0165-0327(81)90023-9 · Cited by 56 · see citing works
Predictors of the Longitudinal Course of Major Depression in a Canadian Population Sample
Patten, S. B., Wang, J., Williams, J. V. A., Lavorato, D. H., Khaled, S. M., & Bulloch, A. G. (2010) · The Canadian Journal of Psychiatry · doi:10.1177/070674371005501006 · Cited by 55 · see citing works
Is depression a chronic mental illness?
Monroe, S. M., & Harkness, K. L. (2012) · Psychological Medicine · doi:10.1017/s0033291711002066 · Cited by 52 · see citing works
How everyone became depressed: the rise and fall of the nervous breakdown
(2013) · Choice Reviews Online · doi:10.5860/choice.51-1530 · Cited by 51 · see citing works
Antidepressant Use and Lifetime History of Mental Disorders in a Community Sample
Takayanagi, Y., Spira, A. P., Bienvenu, O. J., Hock, R. S., Carras, M. C., Eaton, W. W., & Mojtabai, R. (2014) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13m08824 · Cited by 40 · see citing works
Is depression overdiagnosed? No
Hickie, I. B. (2007) · BMJ · doi:10.1136/bmj.39268.497350.ad · Cited by 31 · see citing works
Parker, G. B., Fletcher, K., & Hadži-Pavlović, D. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2010.11.021 · Cited by 24 · see citing works
How Should Mood Disorders be Modelled?
Parker, G. B. (2008) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/00048670802345458 · Cited by 24 · see citing works
Reasons for preferring a primary care physician for care if depressed.
Wun, Y. T., Lam, T. P., Goldberg, D. P., Lam, K. F., Li, K. T. D., & Yip, K. C. (2011) · PubMed · Cited by 22 · see citing works
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Research works printed but not linked: 1
- [13]13. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, Fawcett J (2010). Antidepressant drug effects and depression severity. The Journal of the American Medical Association 303, 47-53.
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Buckman, J. E. J., Underwood, A., Clarke, K., Saunders, R., Hollon, S. D., Fearon, P., & Pilling, S. (2018) · Clinical Psychology Review · doi:10.1016/j.cpr.2018.07.005 · Cited by 398 · see citing works
“…to those who experience prolonged periods of sadness as a reaction to a life event in one-off episodes that frequently remit spontaneously, and to those with chronic, sometimes decades-long episodes that are unresponsive to multiple treatments (Baldessarini et al., 2017; Lorenzo-Luaces, 2015).”
BackgroundUnder-diagnosis of mood disorders in Canada
Pelletier, L., O'Donnell, S., Dykxhoorn, J., McRae, L., & Patten, S. B. (2017) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796016000329 · Cited by 57 · see citing works
Lorenzo-Luaces, L., Johns, E., & Keefe, J. R. (2018) · Journal of Medical Internet Research · doi:10.2196/10113 · Cited by 36 · see citing works
Self-citation
- Authors
- Lorenzo-Luaces, L.
- ORCID
- Lorenzo-Luaces, L.
- Venue
- Epidemiology and Psychiatric Sciences
- Publisher
- Cambridge University Press (CUP)
- Published
- 2015-06-17
- Volume
- 24
- Issue
- 6
- Pages
- 466-472
- ISSN
- 2045-7960 (ISSN-L)
- 2045-7979
- PMC
- PMC8367371
- OpenAlex
- W1701884225
- Cited by
- 55
- References
- 64
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 2
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epidemiology and Psychiatric Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, depression heterogeneity, prognosis, overdiagnosis, underdiagnosis, placebo response, treatment-resistant depression, chronic depression, recurrent depression, epidemiology of depression, diagnostic validity
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