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Subthreshold depression as a risk indicator for major depressive disorder: a systematic review of prospective studies
Open accessAbstract
Objective: In order to examine whether the incidence of major depressive disorder (MDD) is increased in subjects with subthreshold depression, or sD (clinically relevant depressive symptoms, without meeting criteria for a full‐blown MDD), we conducted a review of prospective studies examining the incidence of MDD in subjects with sD. Method: A systematic literature search was conducted. For all studies, the relative risk of developing MDD was calculated, based on person‐years. Results: Twenty studies (23 comparisons) were found, based on community samples, general medical patients and high‐risk subjects. Most comparisons showed that subjects with sD had a consistently larger chance of developing MDD. The studies differed considerably in the definition of sD, the recency (occurrence of the last sD) and the in‐/exclusion of lifetime MDD. Conclusion: The incidence of MDD in subjects with sD is larger than in subjects without sD. Otherwise, the concept of sD is too broad to be used. In future studies, some consensus should be reached regarding the definition of sD.
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“Prospective epidemiologic studies report much higher lifetime prevalence of major depression in the range of 30-40%. 141”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [141]
In the citing paper
“Most estimates of lifetime prevalence of depression are based on retrospective reports and need to be interpreted with caution as they are likely to underestimate true lifetime prevalence. 141”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [141]
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“It is highly related to a subject’s mental state and the risk of developing depression [19,20].”
From Mobile Sensing and Support for People With Depression: A Pilot Trial in the Wild (2016) · cites this paper as [20]
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“StD can be defined as a severity cut point on a self-administered depression measure, which may vary in the duration and requirements of core symptoms, but typically requires the absence of MDD (Kroenke, 2017).”
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Should antidepressants be used in minor depression?
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Suicidal Ideators without Major Depression—Whom are We Not Reaching?
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“The onset of MD occurs more frequently at younger ages(4,5) and may be preceded by subthreshold symptoms, including suicidal ideation.(6,7) Suicide rates begin to climb in adolescence, and although men outnumber women by 3 to 4 times by adulthood,(8) individuals who present for care related to suicidality may not diff…”
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“PSE class 3 (some depressive symptoms) was also included in our study, because this so-called subthreshold depression can be regarded as a risk indicator for major depressive disorder (37).”
BackgroundCorrection for "'Caseness' for Depression and Anxiety in a Depressed Outpatient Population
Demyttenaere, K., Verhaeghen, A., Dantchev, N., Grassi, L. G., Montejo, A. L., David, P., Quail, D., Reed, C. C., Tylee, A. T., & Bauer, M. (2010) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.08m00748blu · Cited by 23
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BackgroundPeople with diabetes need a lower cut-off than others for depression screening with PHQ-9
Cichoń, E., Kiejna, A., Kokoszka, A., Gondek, T. M., Radzio, R., Jastrzębski, A., Andrzejewska, B. E., Alosaimi, F. D., Lloyd, C. E., & Sartorius, N. (2020) · PLOS ONE · doi:10.1371/journal.pone.0240209 · Cited by 22
“This issue is critical as there is a need for improved recognition and treatment of depressive symptoms in order to prevent severe depression among patients and reduce treatment-related costs [57].”
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“In addition, it has been reported that StD in 8–12% of patients progresses to MDD [3, 4].”
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“A subclinical level of depressive symptoms, also called Subthreshold Depression (SD), is a precursor condition toMDD in adults [19,20] and in adolescents [21–23].”
BackgroundFactor structure of the Emotions as a Child Scale in late adolescence and emerging adulthood.
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“Late adolescent depression also predicts mental health problems in young adulthood and later in the life span (Cuijpers & Smit, 2004; Rao, Hammen, & Daley, 1999), making emotion socialization an important construct to study at this time.”
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“Although minor depressive disorder is thought to be a risk factor for developing major depressive disorder [7–9], the personality traits of minor depressive disorder have not been made clear.”
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“Previous studies pointed out that persistent depressive symptoms below the threshold for a diagnosis of major depression could cause chronic illness and have a high risk of progression to more serious disorders (Cuijpers and Smit, 2004; Cuijpers et al., 2007).”
BackgroundSymptomatic and functional recovery in depression in later life
Collard, R. M., Wassink‐Vossen, S., Schene, A. H., Naarding, P., Verhaak, P. F. M., Voshaar, R. C. O., & Comijs, H. C. (2018) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-018-1540-z · Cited by 21
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“The risk of developing MDD is substantially increased, along with risk of co-morbid disorder development and related functional impairments (Cuijpers and Smit, 2004).”
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“Close family members of patients with chronic depression are therefore more likely to develop subthreshold depression, which is a strong risk factor for MDD [6].”
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“This finding is vital since subthreshold depression (also known as subclinical depression) is clinically relevant and was found to be highly prevalent (Cuijpers and Smit, 2004).”
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Self-citationLeisure-time physical activity and metabolic syndrome plus depressive symptoms in the FIN-D2D survey
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“Persons with DS are at high risk of major depression (Cuijpers and Smit, 2004), which today has become one of the most important public health issues in Finland.”
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“FKBP5, a competitive inhibitor of GCs in GR binding, exerts a negative effect on the HPA axis regulation.”
BackgroundResultAre antidepressants useful in the treatment of minor depression
Hegerl, U., Schönknecht, P., & Mergl, R. (2011) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e32834dc15d · Cited by 19
“an episode of major depression within 1–3 years [15].”
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“…psychological conditions, associated with specific impairments in psychological well-being, could represent a key risk factor either for the exacerbation of an overt psychiatric disorder (Cuijpers & Smit, 2004) or a negative clinical course of the cardiac illness, as demonstrated by our findings.”
ResultActivity patterns related to depression symptoms in stressed dementia caregivers
Smagula, S. F., Hasler, B. P., Schulz, R., Graves, J., Reynolds, C. F., Aizenstein, H. J., Buysse, D. J., Krafty, R. T., & Hall, M. H. (2019) · International Psychogeriatrics · doi:10.1017/s1041610219001601 · Cited by 19
“Major depressive episodes often do not “come out of the blue;” instead, the presence of some depressive symptoms predicts the development of more symptoms (Joling et al., 2012) and major depressive disorder (Cuijpers and Smit, 2004).”
BackgroundYeung, M. K.-C., Lee, T., & Chan, A. S.-Y. (2021) · Psychophysiology · doi:10.1111/psyp.13802 · Cited by 18
Freund, J., Titzler, I., Thielecke, J., Braun, L., Baumeister, H., Berking, M., & Ebert, D. D. (2020) · BMC Psychiatry · doi:10.1186/s12888-020-02800-z · Cited by 21
“The different IMIs are addressing risk factors for the incidence of depression including subclinical depressive symptoms [66], insomnia [67], stress [68], anxiety [69], chronic pain [70], harmful alcohol use [71, 72] and subclinical depressive symptoms in the context of diabetes [73].”
BackgroundNexø, M. A., Borg, V., Sejbæk, C. S., Carneiro, I. G., Hjarsbech, P. U., & Rugulies, R. (2015) · BMC Public Health · doi:10.1186/s12889-015-1973-1 · Cited by 23
“In accordance with other recent studies, our study indicated that the presence of even mild depressive symptoms had significant work related consequences [30, 32, 44], including decisions to retire early by EVR [32].”
ResultImproving Health-Related Quality of Life in Older African American and Non-Latino White Patients
Jimenez, D. E., Begley, A. E., Bartels, S. J., Alegria, M. M., Thomas, S. B., Quinn, S. C., & Reynolds, C. F. (2014) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2014.08.001 · Cited by 18
“Older adults who are already symptomatic are at increased risk for developing major depression.(25) Therefore, only mildly symptomatic individuals were recruited in order to maximize the efficiency of the depression prevention trial.”
BackgroundRoberts, W., Verplaetse, T. L., Moore, K. E., Oberleitner, L., Picciotto, M. R., & McKee, S. A. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117699618 · Cited by 18
“However, subclinical depressive symptoms are highly prevalent and a recognized risk factor for later onset of clinical depression (Cuijpers and Smit, 2004).”
BackgroundChristl, J., Grumbach, P., Jockwitz, C., Wege, N., Caspers, S., & Meisenzahl, E. M. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.12.099 · Cited by 22
Schnyder, U. (2022) · Psychotherapy and Psychosomatics · doi:10.1159/000527462 · Cited by 19
Song, Y., Xiao, Z., Zhang, L., & Shi, W. (2023) · Behavioral Sciences · doi:10.3390/bs13060448 · Cited by 17
“Since trait depression is a precursor stage of clinical depression [7], the effect of depression on subjective well-being can be extended to the effect of trait depression on subjective well-being.”
BackgroundEl‐Ammari, A., Malki, H. E., Moutawakkil, S. G., Hilaly, J. E., Houari, F. E., Gnaoui, S. E., Ragala, M. E. A., Rhazi, K. E., & Zarrouq, B. (2023) · BMC Psychiatry · doi:10.1186/s12888-023-05245-2 · Cited by 17
Kong, F., Yu, L., Hou, Y., Zhu, L., Zhou, J., Huang, L., Lv, Y., Wang, L., Zhang, L., Yang, Y., et al. (2024) · Journal of Medical Internet Research · doi:10.2196/40187 · Cited by 17
Interpersonal Psychotherapy: Evaluation, Support, Triage
Weissman, M. M., & Verdeli, H. (2012) · Clinical Psychology & Psychotherapy · doi:10.1002/cpp.1775 · Cited by 16
On the transience or stability of subthreshold psychopathology
Schreuder, M. J., Wigman, J. T. W., Groen, R. N., Wichers, M., & Hartman, C. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-02711-3 · Cited by 18
Pawlak, M., Schmidtler, H., & Kopala‐Sibley, D. C. (2024) · Development and Psychopathology · doi:10.1017/s0954579424000130 · Cited by 21
Booij, S. H., Bos, E. H., de Jonge, P., & Oldehinkel, A. J. (2014) · Psychophysiology · doi:10.1111/psyp.12329 · Cited by 16
Sohn, J. H., Ahn, S. H., Seong, S. J., Ryu, J. M., & Cho, M. J. (2013) · Journal of Korean Medical Science · doi:10.3346/jkms.2013.28.2.280 · Cited by 16
“Several previous studies have focused on subthreshold depression (13-16), but few have reported on the situation in Korea.”
BackgroundJiang, T. X., Ge, H., Sun, J. P., Li, R., Han, R., & Liu, J. (2017) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph14040402 · Cited by 16
“Furthermore, psychological distress is recognized as a strong predictor of the onset of a major depressive episode [12].”
BackgroundMei, G., Li, Y., Chen, S., Cen, M., & Bao, M. (2020) · Psychiatry Research · doi:10.1016/j.psychres.2020.113499 · Cited by 14
“…of Major Depressive Disorder (MDD) (for a review, Rodríguez et al., 2012), have received much attention in recent years, because StD is more prevalent than MDD, has a high risk of developing into MDD and negatively affect quality of life (for reviews, Cuijpers and Smit, 2010; Lee et al., 2018).”
Caruso, R., Rossi, A., Barraco, A., Quail, D., Grassi, L. G., & Italian FINDER study group (2010) · Annals of General Psychiatry · doi:10.1186/1744-859x-9-33 · Cited by 15
Wijnen, B. F. M., Lokman, S., Leone, S. S., Evers, S., & Smit, F. (2018) · Journal of Medical Internet Research · doi:10.2196/10455 · Cited by 15
“In addition, slightly more than 1 million people (1,006,700) had subclinical depression (ie, people with the core symptoms of depression otherwise not fulfilling the diagnostic criteria of major depression) [3].”
BackgroundSelf-citationGonzález, F. L. V., Otero, P., María, L., Blanco, V., & Ángela, T. (2010) · Clínica y Salud · doi:10.5093/cl2010v21n1a6 · Cited by 15
Alonso, S., Marsman, J.-B. C., Kringelbach, M. L., Deco, G., & Horst, G. J. T. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102299 · Cited by 15
“Another study by Figueroa et al. (2019) demonstrated that remitted patients with recurrent MDD had more difficulties to engage in a state involving the cognitive control system.”
InfluentialOrbitofrontal cortex grey matter volume is related to children’s depressive symptoms
Vandermeer, M. R. J., Liu, P., Ali, O. M., Daoust, A. R., Joanisse, M. F., Barch, D. M., & Hayden, E. P. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102395 · Cited by 16
“Given the known homotypic continuity of early depressive symptoms with later depressive disorder (Cuijpers and Smit, 2004; Klein et al., 2013; Shankman et al., 2009), these findings highlight structural brain markers of youth”
BackgroundPublic Health Perspectives on Depressive Disorders
Cohen, N. L. (2017) · Johns Hopkins University Press eBooks · doi:10.1353/book.52762 · Cited by 15
Orbitofrontal and Cingulate Thickness Asymmetry Associated with Depressive Symptom Dimensions
Dotson, V. M., Taiwo, Z., Minto, L. R., Bogoian, H. R., & Gradone, A. M. (2021) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-021-00923-8 · Cited by 14
“Our study is unique in its focus on a community sample with primarily subthreshold depressive symptoms, which could be a prodrome tomore significant clinical depression in some individuals (Cuijpers & Smit, 2004; Tuithof et al., 2018).”
BackgroundMata, J., & Gotlib, I. H. (2010) · International Journal of Eating Disorders · doi:10.1002/eat.20850 · Cited by 14
Li, Y., Wang, R., & Zhang, T. (2022) · Nonlinear Dynamics · doi:10.1007/s11071-021-07079-7 · Cited by 14
“Some researchers believe that it may be a prodromal period of depression, and that it may exist in the state of the intermission or incomplete recovery of MDD [34–36].”
BackgroundGiosan, C., Cobeanu, O., Mogoaşe, C., Szentágotai Tătar, A., Mureşan, V., & Boian, R. (2016) · Trials · doi:10.1186/s13063-016-1740-3 · Cited by 13
“Targeting risk factors for depression, such as cognitive vulnerability [27, 36, 37] and subthreshold depressive symptomatology [15], could represent a first step in building well-informed preventative online programs for this condition (see also [38]).”
Backgroundvan der Velden, P. G., Contino, C., Das, M., & Wittmann, L. (2022) · International Journal of Social Psychiatry · doi:10.1177/00207640221140287 · Cited by 13
Lin, Z., Zheng, J., Wang, Y., Su, Z., Zhu, R., Liu, R., Wei, Y., Zhang, X., & Wang, F. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-05638-x · Cited by 16
“Consequently, these unresolved issues can potentially develop into major depressive disorder (MDD) and generalized anxiety disorder (ANX) [12, 13], leading to an increased risk of suicide and functional impairment [14, 15].”
BackgroundMoschonis, G., Sarapis, K., Resciniti, S. M., Hall, R., Yim, K., Tonkovic, M., Fitzgerald, C., Anixiadis, F., Vinh, A., Dinh, Q. N., et al. (2024) · British Journal Of Nutrition · doi:10.1017/s0007114524001703 · Cited by 13
“GSH improvement suggests potential amelioration of oxidative stress previously linked to anhedonia severity in patients with MDD (52) .”
InfluentialShimada, K., Kasaba, R., Fujisawa, T. X., Sakakibara, N., Takiguchi, S., & Tomoda, A. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.12.031 · Cited by 13
“Major depressive disorder (MDD) is mainly characterised by distorted interpretations of other people's mental states, which leads to impaired interpersonal and social functioning (Cusi et al., 2012; Richman and Unoka, 2015).”
BackgroundMethodInfluentialEcological micro-expression recognition characteristics of young adults with subthreshold depression
Zhu, C., Yin, M., Chen, X., Zhang, J., & Liu, D. (2019) · PLoS ONE · doi:10.1371/journal.pone.0216334 · Cited by 13
Windle, M. T., & Mrug, S. (2015) · Frontiers in Psychology · doi:10.3389/fpsyg.2015.01322 · Cited by 15
“…because some studies have indicated high levels of continuity between depression in adolescence and young adulthood (Kandel and Davies, 1986; Cuijpers and Smit, 2004); without controlling for depression in adolescence, it would be difficult to know if the hypothesized G × E interaction…”
BackgroundUnderstanding subthreshold depression.
Juruena, M. F. (2012) · PubMed Central · doi:10.3969/j.issn.1002-0829.2012.05.009 · Cited by 13
“Despite the fluctuating operational criteria and the current lack of definitive biomarkers for subthreshold depressive states, it is clear that the various subthreshold depressive conditions have a high prevalence in the community and are all associated with psychosocial disability, poor quality of life, and high heal…”
Braimah, R. O., Ukpong, D. I., Ndukwe, K. C., & Akinyoola, A. L. (2017) · Clinical and Experimental Dental Research · doi:10.1002/cre2.90 · Cited by 13
“This in turn will affect the quality of life and recovery from the facial trauma (Cuijpers & Smit, 2004; Meningaud, Benadiba, Servant, Bertrand, & Pelicier, 2003).”
Background
Metadata
- Authors
- Cuijpers, P., & Smit, F.
- Affiliations
- Trimbos Institute (NL)
- Corresponding author
- Cuijpers, P.
- ORCID
- Venue
- Acta Psychiatrica Scandinavica
- Publisher
- Wiley
- Published
- 2004-03-28
- Volume
- 109
- Issue
- 5
- Pages
- 325-331
- ISSN
- 0001-690X (ISSN-L)
- 1600-0447
- OpenAlex
- W2139095467
- Cited by
- 595
- References
- 35
- Citations by year
- 2026: 34 · 2025: 40 · 2024: 32 · 2023: 26 · 2022: 41 · 2021: 36 · 2020: 29 · 2019: 28 · 2018: 21 · 2017: 35 · 2016: 30 · 2015: 37 · 2014: 24 · 2013: 27 · 2012: 27
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Acta Psychiatrica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- subthreshold depression, major depressive disorder, depression incidence, risk factors, prospective study, relative risk, community sample, vulnerable populations
- MeSH terms
- Major Depressive Disorder, Depressive Disorder, Major, Humans, Prospective Studies, Risk Factors, Severity of Illness Index
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