Predictors of recurrence of major depressive disorder
Open accessAbstract
A total of 201 patients with major depressive disorder from four hospitals in Malaysia were followed up for 5 years to determine the prognostic factors of recurrent major depressive disorder that could potentially contribute to improving the management of MDD patients. For each individual patient, at the time of recruitment as part of a case-control study, information was collected on recent threatening life events, personality and social and occupational functioning, while blood samples were collected to genotype single nucleotide polymorphisms of vitamin D receptor (VDR), zinc transporter-3 (ZnT3), dopamine transporter-1 (DAT1), brain-derived neurotropic factor (BDNF), serotonin receptor 1A (HT1A) and 2A (HT2A) genes. Kaplan-Meier and Cox-regression were used to estimate hazard functions for recurrence of major depressive disorder. Individuals with severe MDD in previous major depressive episodes had five and a half times higher hazard of developing recurrence compared to mild and moderate MDD (HR = 5.565, 95% CI = 1.631-18.994, p = 0.006). Individuals who scored higher on social avoidance had three and a half times higher hazard of recurrence of MDD (HR = 3.525, 95% CI = 1.349-9.209; p = 0.010). There was significant interaction between ApaI +64978C>A single nucleotide polymorphism and severity. The hazard ratio increased by 6.4 times from mild and moderate to severe MDD for A/A genotype while that for C/A genotype increased by 11.3 times. Social avoidance and severity of depression at first episode were prognostic of recurrence. Screening for personality factors at first encounter with MDD patients needs to be considered as part of the clinical practice. For those at risk of recurrence in relation to social avoidance, the psychological intervention prescribed should be customized to focus on this modifiable factor. Prompt and appropriate management of severe MDD is recommended to reduce risk of recurrence.
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Written from the paper’s full text.
TL;DR
In a 5-year follow-up of Malaysian patients with major depressive disorder, severe MDD at first episode and higher social avoidance predicted recurrence. The ApaI +64978C>A polymorphism interacted with severity to potentiate recurrence hazard.
Key findings
- Severe MDD at the first major depressive episode was associated with a 5.5-fold higher hazard of recurrence compared with mild/moderate MDD (HR = 5.565, 95% CI = 1.631–18.994, p = 0.006).
- Higher social avoidance was associated with a 3.5-fold higher hazard of recurrence (HR = 3.525, 95% CI = 1.349–9.209, p = 0.010).
- ApaI +64978C>A significantly interacted with severity: the hazard ratio increased by 6.4 times from mild/moderate to severe MDD for the A/A genotype and by 11.3 times for the C/A genotype.
- Age, gender, educational level, comorbidities, family history, and the other tested SNPs were not significant predictors in the Cox model.
Methods
- The study followed patients from an original case-control study across four hospitals in Malaysia; inclusion was ages 18–65 with single or recurrent non-psychotic MDD diagnosed less than 2 years prior, and 145 of 201 traced patients were available for survival analysis.
- Baseline data included sociodemographic characteristics, comorbidities, Lists of Threatening Events, Temperament and Personality questionnaire, and blood samples genotyped for VDR, ZnT3, DAT1, BDNF, HT1A, and HT2A SNPs.
- Kaplan-Meier analysis was used for univariate screening, and Cox proportional hazards regression estimated hazard ratios for recurrence, with censoring for patients without recurrent MDE by study end.
Limitations
- The authors state that the study inherits biases of a case-control design, including recall and selection bias, and that sample size was affected by loss to follow-up, although baseline profiles did not differ significantly between followed-up and missing cases.
- Evident in the text: the ApaI genotype–severity interaction is based on subgroup estimates; the A/A severe stratum had HR = 3.018 with p = 0.105 and a wide 95% CI (0.794–14.468), indicating limited precision.
- Evident in the text: recurrence was ascertained from clinical records and symptoms reported at visits, and the analysis had a relatively small number of recurrence events, which may limit power for subgroup and interaction findings.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
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Claims the paper makes
0 of 71 cited sources checked · 0 supported · 0 flagged
- Findingown data
Severe MDD at the first MDE was associated with a 5.565-fold higher hazard of recurrence compared to mild and moderate MDD (HR = 5.565, 95% CI = 1.631-18.994, p = 0.006).
“Individuals with severe MDD in previous major depressive episodes had five and a half times higher hazard of developing recurrence compared to mild and moderate MDD (HR = 5.565, 95% CI = 1.631–18.994, p = 0.006).”
- Also stated in: § Results · plain
“Individuals with severe MDD at the first MDE had five and a half times higher hazard of developing recurrence compared to mild and moderate MDD (HR = 5.565, 95% CI = 1.631–18.994, p = 0.006).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical record form endorsed by a psychiatrist accurately identifies recurrence of MDD as defined.
- Also stated in: § Results · plain
- Findingown data
There was a significant interaction between ApaI +64978C>A SNP and severity of first MDE on recurrence.
“There was significant interaction between ApaI +64978C>A single nucleotide polymorphism and severity.”
- Also stated in: § Results · plain
“Severity, social avoidance and interaction between ApaI polymorphism and severity significantly prognosticated recurrence (Table 3).”
- Also stated in: § Results · boosted
“ApaI +64978C>A was shown to significantly potentiate the effect of severity (Table 4).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical record form endorsed by a psychiatrist accurately identifies recurrence of MDD as defined.
- Also stated in: § Results · plain
- Findingown data
In depressed individuals, a higher tendency towards social avoidance is associated with greater risk of recurrence of MDD.
“Our study showed that depressed individuals with a higher tendency towards social avoidance were at greater risk of recurrence of MDD.”
Quote in the paperSubstantial claim - Findingown data
Higher social avoidance score was associated with a 3.525-fold higher hazard of recurrence of MDD (HR = 3.525, 95% CI = 1.349-9.209; p = 0.010).
“Individuals who scored higher on social avoidance had three and a half times higher hazard of recurrence of MDD (HR = 3.525, 95% CI = 1.349–9.209; p = 0.010).”
- Also stated in: § Results · plain
“Individuals with a higher score of social avoidance had three and a half times higher hazard of recurrence of MDD (HR = 3.525, 95% CI = 1.349–9.209; p = 0.010).”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical record form endorsed by a psychiatrist accurately identifies recurrence of MDD as defined.
- Rests on an assumption: The cut-off scores used for the T&P dimensions correctly classify the personality tendencies.
- Also stated in: § Results · plain
- Findingown data
In our study, family history of psychiatric illnesses was not associated with recurrence of MDD.
“Results regarding family history and recurrence also have been inconsistent–a number of previous studies have reported that a family history of psychiatric illnesses was not associated with recurrence of MDD [11, 44, 64, 65], similar to what we have found in our study.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [11] G Winokur, 1993, A prospective follow-up of patients with bipolar and primary unipolar affective disorder, Arch Gen Psychiatry source
Not checked in the free run.
- cites [44] EM Sendek, 2017, Modeling time-to-good control of hypertension using Cox proportional hazard and frailty models at Bahir-Dar Felege Hiwot Referral Hospital, Open Access Medical Statistics source
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- cites [64] PM Lewinsohn, 2000, Natural course of adolescent major depressive disorder in a community sample: Predictors of recurrence in young adults, Am J Psychiatry source
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- cites [65] N Kennedy, 2003, Remission and recurrence of depression in the maintenance era: long-term outcome in a Cambridge cohort, Psychol Med source
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- Findingown data
The interaction of ApaI +64978C>A genotype with severity at first MDE was significant in predicting recurrence of MDD.
“Although ApaI +64978C>A SNP by itself is not a predictor of recurrence in the present study, we found that the interaction of ApaI +64978C>A genotype with severity at first MDE to be significant in predicting its recurrence.”
Quote in the paperSubstantial claim - Findingown data
In the present study, ApaI +64978C>A SNP by itself was not a predictor of recurrence.
“Although ApaI +64978C>A SNP by itself is not a predictor of recurrence in the present study, we found that the interaction of ApaI +64978C>A genotype with severity at first MDE to be significant in predicting its recurrence.”
Quote in the paperSubstantial claim - Findingown data
The hazard of recurrence for carriers of the A/A and C/A genotypes of ApaI with a severe first episode of MDD is much higher than for a less severe episode.
“The hazard of recurrence for carriers of the A/A and C/A genotypes of ApaI with a severe first episode of MDD is much higher than for a less severe episode, indicating that ApaI +64978C>A polymorphisms potentiated the effect of severity on recurrence of MDD (Table 4).”
Quote in the paperSubstantial claim - Findingown data
In our study, severity at first MDE increased hazard of recurrence by five and a half times.
“Our study found that severity at first MDE increased hazard of recurrence by five and a half times.”
Quote in the paperSubstantial claim - Study design and conductown data
There was no difference between patients with data available for survival analysis and those for whom records were not available.
“Table 1 shows that there was no difference between the patients with data available for survival analysis and those for whom records were not available.”
Quote in the paperNot a substantial claim - Premisecitation
Results of studies on sociodemographic factors (age, gender, socioeconomic status, marital status) as risk factors for recurrence have been inconsistent.
“Many studies showed that sociodemographic factors such as younger age, women, and those who have never been married were at higher risk of recurrence [7, 11–15]; however, results of other studies on these risk factors have been inconsistent.”
- Also stated in: § Introduction · plain
“A systematic review by Hardeveld and colleagues (2009) did not find any association between sociodemographic factors such as age, gender, socioeconomic status, marital status and risk of recurrence [16, 17, 18].”
Quote in the paperNot a substantial claim0 of 9 sources checked- cites [7] TI Mueller, 1999, Recurrence after recovery from major depressive disorder during 15 years of observational follow-up, Am J Psychiatry source
Not checked in the free run.
- cites [11] G Winokur, 1993, A prospective follow-up of patients with bipolar and primary unipolar affective disorder, Arch Gen Psychiatry source
Not checked in the free run.
- cites [12] KM Holma, 2008, Long-term outcome of major depressive disorder in psychiatric patients is variable, J Clin Psychiatry source
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- cites [13] WW Eaton, 1997, Natural history of diagnostic interview schedule/DSM-IV major depression. The Baltimore Epidemiologic Catchment Area follow-up, Arch Gen Psychiatry source
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- cites [14] R Gueorguieva, 2017, Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis, Lancet Psy source
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- cites [15] G Serafini, 2019, Predictors of recurrence in a sample of 508 outpatients with major depressive disorder, J Psy Research source
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- cites [16] F Hardeveld, 2010, Prevalence and predictors of recurrence of major depressive disorder in the adult population, Acta Psychiatr Scand source
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- cites [17] PM Lewinsohn, 1989, Probability of relapse after recovery from an episode of depression, J Abnormal Psychol source
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- cites [18] M Kovac, 2003, Developmental changes in the phenomenology of depression in girls compared to boys from childhood onward, J Affect Disord source
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- Also stated in: § Introduction · plain
- Premisecitation
Patients with residual depression symptoms despite responding to treatment have a higher risk of recurrence.
“In addition, patients who had residual depression symptoms despite responding to treatment, had higher risk of recurrence (Serafini et al., 2018; Nierenberg et al., 2010; Judd et al., 1998) [19, 24, 25].”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationown data
ApaI +64978C>A genotypes act in synergy with severity in potentiating the hazard of recurrence.
“This study suggests that social avoidance and severity of previous MDD prognosticate recurrence, with ApaI +64978C>A genotypes acting in synergy with severity in potentiating the hazard of recurrence.”
Quote in the paperSubstantial claim - Study design and conductown data
The sample size was affected by loss to follow-up.
“The sample size undoubtedly was affected by loss to follow-up; however, there was no significant difference in the baseline profiles between those who were followed up and those lost to follow-up, indicating that the bias could have been kept to a minimum.”
Quote in the paperNot a substantial claim - Study design and conductown data
There was no significant difference in the baseline profiles between those who were followed up and those lost to follow-up.
“The sample size undoubtedly was affected by loss to follow-up; however, there was no significant difference in the baseline profiles between those who were followed up and those lost to follow-up, indicating that the bias could have been kept to a minimum.”
Quote in the paperSubstantial claim - Premisecitation
A more severe first MDE has consistently been shown to be related to recurrence.
“However, population and clinical studies that have been conducted used different classification systems for severity of first MDE which involved the duration of the first major depressive episode and number of symptoms present, but a more severe first MDE has consistently been shown to be related to recurrence [22].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] L Pintor, 2004, Is the type of remission after a major depressive episode an important risk factor to relapses in a 4-year follow up?, J Affect Disord source
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- Study design and conductown data
Representativeness of the sample was ensured as far as possible with the recruitment of patients who came from the catchment area of the hospital representative of the cross-section of the community as shown by their socio-demographic profiles (Table 2).
“Representativeness of the sample was ensured as far as possible with the recruitment of patients who came from the catchment area of the hospital representative of the cross-section of the community as shown by their socio-demographic profiles (Table 2).”
Quote in the paperNot a substantial claim - Interpretationown data
ApaI +64978C>A polymorphisms potentiated the effect of severity on recurrence of MDD.
“The hazard of recurrence for carriers of the A/A and C/A genotypes of ApaI with a severe first episode of MDD is much higher than for a less severe episode, indicating that ApaI +64978C>A polymorphisms potentiated the effect of severity on recurrence of MDD (Table 4).”
Quote in the paperSubstantial claim - Interpretationcitation
Differences in case mix could have partially accounted for some of the inconsistencies found in the published literature on family history and recurrence.
“This could have partially accounted for some of the inconsistencies found in the published literature.”
Quote in the paperNot a substantial claim - Interpretationown data
Severity of previous MDE predicts recurrence of MDD.
“The results consistently suggested that severity of previous MDE predicted recurrence and this was also demonstrated in our study.”
Quote in the paperSubstantial claim - Premisecitation
NEMESIS-2 showed that severity of the last depressive episode increased recurrence of MDD by almost two times.
“NEMESIS-2, a Dutch cohort study using the Sheehan Disability Scale (SDS) to classify severity of depression, showed that severity of the last depressive episode increased recurrence of MDD by almost two times [48].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [48] M ten Have, 2018, Recurrence and chronicity of major depressive disorder and their risk indicators in a population cohort, Acta Psychiatri Scand source
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- Premisecitation
Barkow et al. (2003) showed that severe MDD at baseline tripled the risk for development of subsequent depressive episodes in the primary care setting.
“Barkow et al. (2003) used ICD-10 criteria for severity to study the risk factors of recurrent MDE in the primary care setting and showed that severe MDD at baseline tripled the risk for development of subsequent depressive episodes [58].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [58] K Barkow, 2003, Risk factors for depression at 12-month follow-up in adult primary health care patients with major depression: An international prospective study, J Affect Disord source
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- The quote only partly states this claim. 1
- May combine two claims. 15
- Classified as probably not a substantial claim. 28
The quote only partly states this claim.
Findingown data20.9% of the MDD patients suffered a first recurrence over the five-year period.
“20.9% of the MDD patients suffered first recurrence; the rest were censored.”
- Also stated in: § Discussion · plain
“From our study, the proportion of first recurrence of MDD was 20.9%.”
Quote in the paperNot a substantial claim- Rests on an assumption: The clinical record form endorsed by a psychiatrist accurately identifies recurrence of MDD as defined.
- Also stated in: § Discussion · plain
May combine two claims.
Findingown dataFor the ApaI A/A genotype, the hazard of recurrence increased by 6.4 times when severity shifted from mild/moderate to severe; for the C/A genotype, the hazard ratio increased by a factor of 11.3.
“The hazard ratio increased by 6.4 times from mild and moderate to severe MDD for A/A genotype while that for C/A genotype increased by 11.3 times.”
- Also stated in: § Results · plain
“For A/A genotype, the hazard of recurrence increased by 6.4 times when the severity shifted from mild and moderate to severe; similarly, for the C/A genotype, the hazard ratio increased by a factor of 11.3.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical record form endorsed by a psychiatrist accurately identifies recurrence of MDD as defined.
- Also stated in: § Results · plain
May combine two claims.
FindingcitationIn our study, age at onset of first MDE and gender did not predict subsequent episode of MDE.
“In terms of age at onset and gender, the results of our study replicated results of several earlier studies showing that age at onset of first MDE [17, 18, 59–60] and gender [16, 18, 59–61] did not predict subsequent episode of MDE.”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [17] PM Lewinsohn, 1989, Probability of relapse after recovery from an episode of depression, J Abnormal Psychol source
Not checked in the free run.
- cites [18] M Kovac, 2003, Developmental changes in the phenomenology of depression in girls compared to boys from childhood onward, J Affect Disord source
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- cites [59] NWJ Wainwright, 2002, Childhood adversity, gender and depression over the life-course, J Affect Disord source
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- cites [60] RC Kessler, 1993, Childhood adversities and adult depression: Basic patterns of association in a US national survey, Psychol Med source
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- cites [16] F Hardeveld, 2010, Prevalence and predictors of recurrence of major depressive disorder in the adult population, Acta Psychiatr Scand source
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- cites [61] HB Simpson, 1997, First-episode major depression: Few sex differences in course, Arch Gen Psychiatry source
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Study design and conductown dataOf the 201 patients traced from case histories, 145 were available for survival analysis.
“Over the five-year period, of the 201 patients traced from the case histories, 145 patients were available for survival analysis.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductcitationThe T&P questionnaire has Cronbach's α coefficients ranging from 0.62 to 0.91 and intra-class correlations from 0.72 to 0.93.
“The T&P questionnaire consisted of 109 questions to capture information on eight personality dimensions and two personality functioning dimensions with Cronbach's α coefficients ranging from 0.62 to 0.91 and intra-class correlations from 0.72 to 0.93 [36, 39].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [36] Black Dog Institute. https://www.blackdoginstitute.org.au/clinical-resources/health-professional-resources/temperament-and-personality(t-p)-questionnaire. Assessed on: 3 August 2018
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- cites [39] L Spanemberg, 2014, Translation and cross-cultural adaptation of the Temperament & Personality Questionnaire into Brazilian Portuguese, Trends Psychiatry Psychother source
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Classified as probably not a substantial claim. May combine two claims.
PremisecitationFrequent avoidance of perceived unpleasant conditions by depressed individuals results in limited exposure to positively-reinforced behaviors and social activities, increasing the risk of recurrence.
“Ferster (1973) suggested that avoidance plays a role in which frequent avoidance of perceived unpleasant conditions by depressed individuals results in limited exposure to positively-reinforced behaviors and social activities [52, 53] hence increasing the risk of recurrence.”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductcitationThe English version of the 12-item LTE questionnaire has good internal consistency and test-retest reliability (Cronbach's alpha = 0.84; Cohen's kappa = 0.72), with sensitivity of 89% and specificity of 74%.
“The English version of the 12-item LTE questionnaire was reported to have good internal consistency and test-retest reliability (Cronbach's alpha = 0.84; Cohen's kappa = 0.72), with sensitivity of 89% and specificity of 74% [37]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [37] TS Bhugra, 1990, The list of threatening experiences: the relialibility and validity of a brief Life Events Questionaire, Acta Psychiatr Scand
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Study design and conductcitationThe Malay version of the LTE questionnaire is reliable (Kappa = 0.7 to 0.9).
“the Malay version by Ng et al. (2009) was shown to be reliable as well (Kappa ĸ = 0.7 to 0.9) [38].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Ng et al. (2009)
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- cites [38] CG Ng, 2009, The Reliability Of Malay Version Of List Of Threatening Experiences Questionnaire: A Study On A Group Of Medical Students In Malaysia, Malaysian Journal of Psychiatry
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSNPs of DAT1 gene increase risk of MDD.
“together with evidence that SNPs of dopamine transporter-1 gene increased risk of MDD[34, 35]”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [34] A Felten, 2011, Genetically determined dopamine availability predicts disposition for depression, Brain Behav source
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- cites [35] GJ Haeffel, 2008, Association between polymorphisms in the dopamine transporter gene and depression: Evidence for a gene-environment interaction in a sample of juvenile detainees, Psychol Sci source
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Classified as probably not a substantial claim. May combine two claims.
PremisecitationSNPs of VDR and ZnT3 genes are associated with MDD.
“findings by Kuningas et al. (2009) [32] and Lye et al. [33] that single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) and zinc transporter-3 (SLC30A3) genes were respectively associated with MDD”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [32] M Kuningas, 2009, VDR gene variants associate with cognitive function and depressive symptoms in old age, Neurobiol Aging source
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- cites [33] MS Lye, 2019, Zinc transporter-3 [SLC30A3 (rs11126936)] polymorphism is associated with major depressive disorder in Asian Subjects, Neuroscience Research Notes source
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Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).
PremisecitationVulnerability to recurrent MDD has a genetic component.
“Burcasa and Iacono in their review suggested that vulnerability to recurrent MDD has a genetic component [28].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] SL Burcusa, 2007, Risk for Recurrence in Depression, Clin Psychol Rev source
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Classified as probably not a substantial claim.
PremisecitationMutations in BDNF and serotonin receptor genes are associated with recurrent MDD.
“Mutations in the brain-derived neurotropic factor (BDNF) [29, 30] and serotonin receptor genes [31] were shown to be associated with recurrent MDD.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [29] KS Na, 2016, Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder, Sci Rep source
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- cites [30] ZM Xiao, 2011, Interaction between CRHR1 and BDNF genes increases the risk of recurrent major depressive disorder in Chinese population, PLoS ONE source
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- cites [31] WC Drevets, 2007, Serotonin-1A Receptor Imaging in Recurrent Depression: Replication and Literature Review, Nucl Med Biol source
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May combine two claims.
PremisecitationPersonality functioning is a predictor of incidence, relapse, and recurrence of depressive disorder, not only a modifier or sequela.
“Empirical evidence has been accumulated to show that personality functioning is not only a modifier or a sequela of depressive disorder, but also a predictor of its incidence [49], relapses and recurrences [50, 51].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [49] DN Klein, 2011, Personality and depression: explanatory models and review of the evidence, Annu Rev Clin Psychol source
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- cites [50] GA Fava, 2007, The concept of recovery in major depression, Psychol Med source
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- cites [51] D Huber, 2017, Change in personality functioning during psychotherapy for depression predicts long-term outcome, Psychoanalytic Psychology source
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May combine two claims.
Interpretationown dataSocial avoidance and severity of depression at first episode were prognostic of recurrence.
“Social avoidance and severity of depression at first episode were prognostic of recurrence.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical record form endorsed by a psychiatrist accurately identifies recurrence of MDD as defined.
- Rests on an assumption: The cut-off scores used for the T&P dimensions correctly classify the personality tendencies.
May combine two claims.
PremisecitationClinical variables such as number of previous episodes, severity of last episode, and family history of MDD are strong predictors of recurrence.
“However, clinical variables such as number of previous episodes [7, 11, 19–22], severity of last episode [21, 22] and family history of MDD [21– 23] were strong predictors of recurrence.”
Quote in the paperSubstantial claim0 of 7 sources checked- cites [7] TI Mueller, 1999, Recurrence after recovery from major depressive disorder during 15 years of observational follow-up, Am J Psychiatry source
Not checked in the free run.
- cites [11] G Winokur, 1993, A prospective follow-up of patients with bipolar and primary unipolar affective disorder, Arch Gen Psychiatry source
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- cites [19] LL Judd, 1998, Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse, J Affect Disord source
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- cites [20] M Maj, 1992, Pattern of recurrence of illness after recovery from an episode of major depressive episodes: A Prospective Study, Am J Psychiatry source
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- cites [21] L Pintor, 2003, Relapse of major depression after complete and partial remission during a 2-year follow-up, J Affect Disord source
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- cites [22] L Pintor, 2004, Is the type of remission after a major depressive episode an important risk factor to relapses in a 4-year follow up?, J Affect Disord source
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- cites [23] PM Lewinsohn, 2000, Natural course of adolescent major depressive disorder in a community sample: Predictors of recurrence in young adults, Am J Psychiatry source
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Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe limitations of the study include those inherent in the design of a case-control study from which data for this study was derived.
“The limitations of the study include those inherent in the design of a case-control study from which data for this study was derived.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe propensity of the A allele to increase risk of depression could possibly play a role in the interaction between ApaI polymorphism and severity.
“This propensity of the A allele to increase risk of depression could possibly play a role in the interaction between ApaI polymorphism and severity.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.
InterpretationreasoningThese differences could possibly apply to recurrence and explain inconsistent findings between studies conducted in different countries and with different age groups.
“We postulate that these differences could possibly apply to recurrence, and explain the inconsistent findings between studies conducted in different countries and with different age groups studied.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationBuckman et al. (2018) reported very limited and inconsistent evidence that family history of depression is prognostic of recurrence.
“In a recent systematic review and meta-analysis, Buckman et al. (2018) [66] reported that “there was very limited and inconsistent evidence that family history of depression is prognostic of recurrence”.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [66] JEJ Buckman, 2018, Risk factors for relapse and recurrence of depression in adults and how they operate: A four-phase systematic review and meta-synthesis, Clin Psychol Rev source
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Probably not a substantial claim: may not pass S2 (checkable).
Interpretationown dataThis study adds new information to the body of knowledge on modifiable risk factors and predictors for recurrence of MDD.
“This study adds new information to the body of knowledge on modifiable risk factors and predictors for recurrence of MDD; future studies could further examine the role of genetic biomarkers in prognosticating recurrence in assisting health care workers in early identification and preventive management of major depressive disorder.”
Quote in the paperNot a substantial claim- Rests on an assumption: Studies regarding the influence of personality functioning on recurrence of MDD are limited.
- Rests on an assumption: No previous study has reported social avoidance as a predictor of recurrence of MDD.
May combine two claims.
PremisecitationIn Buckman et al.'s meta-analysis, the pooled odds ratio for family history and recurrence was 1.36 (95% CI 0.92, 2.01) for 3 studies and was not statistically significant.
“In their meta-analysis, the pooled effect size of an odds ratio of 1.36 (95% CI = 0.92, 2.01) for 3 studies was not statistically significant.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [66] JEJ Buckman, 2018, Risk factors for relapse and recurrence of depression in adults and how they operate: A four-phase systematic review and meta-synthesis, Clin Psychol Rev source
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductreasoningEnumerators were on standby to ensure that any questions the patients may have were adequately addressed, with intimations from non-verbal communication from interviewers kept to a minimum.
“Since the questionnaires were self-administered, enumerators were on standby to ensure that any questions the patients may have were adequately addressed, with intimations from non-verbal communication from interviewers kept to a minimum.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationSome other studies found that age at onset and gender predict recurrence.
“This is contrary to what some other studies have found [7, 11–15].”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [7] TI Mueller, 1999, Recurrence after recovery from major depressive disorder during 15 years of observational follow-up, Am J Psychiatry source
Not checked in the free run.
- cites [11] G Winokur, 1993, A prospective follow-up of patients with bipolar and primary unipolar affective disorder, Arch Gen Psychiatry source
Not checked in the free run.
- cites [12] KM Holma, 2008, Long-term outcome of major depressive disorder in psychiatric patients is variable, J Clin Psychiatry source
Not checked in the free run.
- cites [13] WW Eaton, 1997, Natural history of diagnostic interview schedule/DSM-IV major depression. The Baltimore Epidemiologic Catchment Area follow-up, Arch Gen Psychiatry source
Not checked in the free run.
- cites [14] R Gueorguieva, 2017, Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis, Lancet Psy source
Not checked in the free run.
- cites [15] G Serafini, 2019, Predictors of recurrence in a sample of 508 outpatients with major depressive disorder, J Psy Research source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSalk et al. put forward Eagly and Wood's social-structural theory that larger gender differences should be observed in nations with more gender inequality.
“In a meta-analysis of the effect of gender and age on depressive symptoms, Salk et al. put forward Eagly and Wood’s social-structural theory [62] that “larger gender differences should be observed in nations with more gender inequality”.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [62] W Wood, 2012, Biosocial construction of sex differences and similarities in behavior, Advances in Experimental Social Psychology source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningInconsistencies in findings regarding age and gender could possibly be due to socio-cultural differences in the populations studied.
“The inconsistencies in findings regarding age and gender could possibly be due to the effect of socio-cultural differences in the populations studied.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationKuningas et al. found that Dutch patients with the baT haplotype of the Vitamin D receptor (VDR) gene were less prone to depression compared with carriers of BAt.
“Kuningas et al. (32) found that Dutch patients with the baT haplotype of the Vitamin D receptor (VDR) gene were less prone to depression compared with carriers of BAt.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] M Kuningas, 2009, VDR gene variants associate with cognitive function and depressive symptoms in old age, Neurobiol Aging source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHigher tendency towards neuroticism is associated with a higher risk of recurrence of MDD.
“Individuals with a higher tendency towards neuroticism, which was not measured in our study, were being consistently reported to be associated with a higher risk of recurrence [56, 57].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [56] J Ormel, 2004, Neuroticism: a non-informative marker of vulnerability to psychopathology, Soc Psychiatry Psychiatr Epidemiol source
Not checked in the free run.
- cites [57] DN Klein, 2002, Clinical features of major depressive disorder in adolescents and their relatives: Impact on familial aggregation, implications for phenotype definition, and specificity of transmission, J Abnormal Psychol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAnticipation of previously experienced discrimination may cause depressed individuals to avoid participation in certain life areas, leading to greater isolation and social marginalization.
“In addition, anticipation of previously experienced discrimination may further cause depressed individuals to avoid participation in certain life areas, leading to greater isolation and social marginalization [54].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [54] S Farrelly, 2014, Anticipated and experienced discrimination amongst people with schizophrenia, bipolar disorder and major depressive disorder: a cross-sectional study, BMC Psychiatry
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDepression may manifest differently in different cultures.
“Depression may also manifest differently in different cultures [63].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [63] JL Tsai, 2002
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe tools of measurement of personality dimension and personality functioning in Kudo et al. and our study were slightly different.
“However, the tools of measurement of the personality dimension (such as anxious worrying, personal reserve and perfectionism) and personality functioning (such as cooperativeness and effectiveness) in both studies were slightly different (Black Dog Institute, 2017).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Black Dog Institute, 2017
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOther studies reported that family history significantly predicted recurrence.
“Other studies [21–23] have reported that family history significantly predicted recurrence.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [21] L Pintor, 2003, Relapse of major depression after complete and partial remission during a 2-year follow-up, J Affect Disord source
Not checked in the free run.
- cites [22] L Pintor, 2004, Is the type of remission after a major depressive episode an important risk factor to relapses in a 4-year follow up?, J Affect Disord source
Not checked in the free run.
- cites [23] PM Lewinsohn, 2000, Natural course of adolescent major depressive disorder in a community sample: Predictors of recurrence in young adults, Am J Psychiatry source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationBuckman et al. reported that many studies fail to discriminate patients in their first episode from those with a history of multiple previous depressive episodes, and that differences in case mix across studies can lead to spurious conclusions.
“The authors reported that “many studies fail to discriminate patients in their first episode from those with a history of multiple previous depressive episodes” and that “differences in the case mix across studies can lead to spurious conclusions”.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [66] JEJ Buckman, 2018, Risk factors for relapse and recurrence of depression in adults and how they operate: A four-phase systematic review and meta-synthesis, Clin Psychol Rev source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenWe attempted to minimize recall bias by administering the questionnaires using enumerators trained in interviewing patients.
“We attempted to minimize recall bias by administering the questionnaires using enumerators trained in interviewing patients.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSalk et al. found quadratic trends for gender differences in interaction with age and age-related factors.
“In addition, Salk et al. found quadratic trends for gender differences in its interaction with age and age-related factors such as “stressors in adolescence and the hormonal and neurodevelopmental changes that vary by sex and peaking at ages 13–15 years and declining in the 20s”.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [62] W Wood, 2012, Biosocial construction of sex differences and similarities in behavior, Advances in Experimental Social Psychology source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationKudo et al. (2017) did not observe a significant association between the self-criticism personality domain and recurrence of MDD.
“Similar to the results of our study, Kudo et al. (2017) did not observe a significant association between the self-criticism personality domain and recurrence of MDD [55].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [55] Y Kudo, 2017, Temperament, personality, and treatment outcome in major depression: a 6-month preliminary prospective study, Neuropsychiatric Dis Treat source
Not checked in the free run.
May combine two claims.
Interpretationown dataSocial avoidance and severity of previous MDD prognosticate recurrence.
“This study suggests that social avoidance and severity of previous MDD prognosticate recurrence, with ApaI +64978C>A genotypes acting in synergy with severity in potentiating the hazard of recurrence.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The clinical record form endorsed by a psychiatrist accurately identifies recurrence of MDD as defined.
“A clinical record form endorsed by a psychiatrist (NI) (S1 Appendix) was used to identify recurrence based on the definition mentioned above and the symptoms reported at each visit”
The paper relies on this without support.
The cut-off scores used for the T&P dimensions correctly classify the personality tendencies.
“Items measuring each dimension add up to a scaled score, in which different cut off values were used to determine the tendencies of the dimensions.”
The paper relies on this without support.
Social avoidance is a modifiable factor and targeting it with psychological intervention reduces risk of recurrence.
“For those at risk of recurrence in relation to social avoidance, the psychological intervention prescribed should be customized to focus on this modifiable factor.”
The paper relies on this without support.
Studies regarding the influence of personality functioning on recurrence of MDD are limited.
“Studies regarding the influence of personality functioning on recurrence of MDD is limited.”
The paper relies on this without support.
No previous study has reported social avoidance as a predictor of recurrence of MDD.
“To the best of our knowledge, no previous study has reported on social avoidance as a predictor of recurrence of MDD.”
The paper relies on this without support.
Social avoidance is a modifiable risk factor for recurrence of MDD.
“We believe that this new finding has the potential to inform the management of MDD in which clinicians can now be alerted to potential recurrence from a fore knowledge of social avoidance and severity of a previous episode of MDD, both of which are modifiable risk factors.”
The paper relies on this without support.
Severity of a previous episode of MDD is a modifiable risk factor for recurrence.
“We believe that this new finding has the potential to inform the management of MDD in which clinicians can now be alerted to potential recurrence from a fore knowledge of social avoidance and severity of a previous episode of MDD, both of which are modifiable risk factors.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
This finding is consistent with other studies where few clinical factors predicted relapse in patients after treatment for MDD.
“This is consistent with other studies where few clinical factors predicted relapse in patients after treatment for MDD.15,20–23”
The relapse rate in this cohort is similar to those reported in other clinical settings and in meta-analyses of RCTs, which have shown relapse rates of 21% to 49%.
“This relapse rate is similar to those reported in other clinical settings7,22 and in meta-analyses of RCTs,6,8 which have shown that those who remain on antidepressants following remission had relapse rates of 21% to 49%.”
After treatment, a higher risk of relapse has been associated with the number and severity of previous episodes, the persistence of residual symptoms, and a history of childhood maltreatment.
“after treatment, a higher risk of relapse has been associated with the number and severity of previous episodes, the persistence of residual symptoms and a history of childhood maltreatment.9,15,19–23”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Table 2 contains 196 patients, not 145
MajorThe two age-group rows total 196 patients (24 + 89 + 17 + 66), although the table labels the study population as n = 145. Table 3 is also labeled n = 145 but repeats these age-group counts.
Reported 145 · recomputed 196
“Table: Table 2 Sociodemographic characteristics of study population by recurrence (n = 145). | Variables | Recurrencen (%) | Recurrencen (%) | No Recurrence n (%) | No Recurrence n (%) | χ 2 | p value | | --- | --- | --- | --- | --- | --- | --- | | Age (years old) | | | | | 0.017 | 0.898 | | 18–39 | 24 | 21.2 | 89 | 78.8 | | | | 40–65 | 17 | 20.5 | 66 | 79.5 | | |”
Follow-up comparison totals 300 rather than 201 patients
MajorTable 1 lists 196 followed-up and 104 missing patients, totaling 300, despite the Results describing 201 patients traced. The text identifies Table 1 as the comparison of patients with and without records available for survival analysis.
Reported 201 · recomputed 300
“Over the five-year period, of the 201 patients traced from the case histories, 145 patients were available for survival analysis.”
TaqI genotype counts change between Tables 1 and 3
MinorTable 1's followed-up group has 139 T/T and 44 T/C patients; Table 3's recurrence and no-recurrence counts give 138 T/T and 45 T/C patients. Both sets total 196, but one patient has shifted genotype category.
“| T/T | 139 | 70.9 | 78 | 75.0 | | | | T/C | 44 | 22.4 | 21 | 20.2 | | |”
“| TaqI | T/T | 33 | 23.9 | 105 | 76.1 | 1 | | | | TaqI | T/C | 7 | 15.6 | 38 | 84.4 | 0.700 | (0.258–1.900) | 0.483 |”
Family-history recurrence columns conflict with the rest of Table 3
MinorThe family-history rows put 160 patients in the recurrence column and 41 in the no-recurrence column. The severity rows in the same table put 41 in recurrence and 155 in no recurrence, indicating that the family-history outcome columns are reversed or otherwise mislabeled.
“| Family History of psychiatric illness | Yes | 45 | 83.3 | 9 | 16.7 | 1 | | | | Family History of psychiatric illness | No | 102 | 79.1 | 27 | 20.9 | 1.937 | (0.804–4.666) | 0.141 | | Family History of psychiatric illness | Unsure | 13 | 72.2 | 5 | 27.8 | 1.756 | (0.478–6.448) | 0.397 |”
“| Severity | Mild to Moderate | 20 | 17.4 | 95 | 82.6 | 1 | | | | Severity | Severe | 21 | 25.9 | 60 | 74.1 | 5.565 | (1.631–18.994) | 0.006* |”
Table 3 comorbidity groups exceed its age-group population
MinorTable 3's comorbidity rows contain 201 patients, while its age-group rows contain 196. Both are presented as counts for the same Cox-analysis population.
“| Comorbidities | Yes | 10 | 14.3 | 60 | 85.7 | 1 | | | | Comorbidities | No | 31 | 23.7 | 100 | 76.3 | 0.936 | (0.376–2.334) | 0.888 |”
“| Age group | 18–39 | 24 | 21.2 | 89 | 78.8 | 1 | | | | Age group | 40–65 | 17 | 20.5 | 66 | 79.5 | 0.778 | (0.323–1.874) | 0.575 |”
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Number of illness episodes as predictor of residual symptoms in major depressive disorder
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Predictors of recurrence in a sample of 508 outpatients with major depressive disorder
Serafini, G., Santi, F., Gonda, X., Aguglia, A., Fiorillo, A., Pompili, M., Carvalho, A. F., & Amore, M. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.04.015 · Cited by 6 · see citing works
Aldoghachi, A. F., Yusof, H. H. M., Abidin, S. Z., Habib, O., Cheah, P.-S., Stanslas, J., Ibrahim, N., Lye, M. S., Veerakumarasivam, A., Rosli, R., et al. (2018) · Universiti Putra Malaysia Institutional Repository (Universiti Putra Malaysia) · Cited by 4 · see citing works
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Self-citation
Flagged first, then by citations
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- RC Kessler, 2009, Handbook of Depression 2, 5
- JL Tsai, 2002, Handbook of depression, 467
- PM Lewinsohn, 2000, Natural course of adolescent major depressive disorder in a community sample: Predictors of recurrence in young adults, Am J Psychiatry, 157, 1584, 10.1176/appi.ajp.157.10.1584 · DOI · Paper page
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- Authors
- Lye, M.-S., Tey, Y.-Y., Tor, Y.-S., Shahabudin, A. F., Ibrahim, N., Ling, K.-H., Stanslas, J., Loh, S.-P., Rosli, R., Lokman, K. A., Badamasi, I. M., Faris-Aldoghachi, A., & Abdul Razak, N. A.
- Affiliations
- Universiti Putra Malaysia (MY)
- Corresponding author
- Lye, Munn-Sann
- Tey, Yin-Yee
- Tor, Yin-Sim
- Shahabudin, Aisya Farhana
- Ibrahim, Normala
- Ling, King-Hwa
- Stanslas, Johnson
- Loh, Su-Peng
- Rosli, Rozita
- Lokman, Khairul Aiman
- Badamasi, Ibrahim Mohammed
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2020-03-19
- Volume
- 15
- Issue
- 3
- Pages
- e0230363
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC7082055
- OpenAlex
- W3012504469
- Cited by
- 43
- References
- 68
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 12 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 1
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Universiti Putra Malaysia Institutional Repository (Universiti Putra Malaysia) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Greater South Information System
- Funders
- Universiti Putra Malaysia (GP-IPB/2013/9415700)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- major depressive disorder, recurrence, prognostic factors, social avoidance, depression severity, ApaI polymorphism, vitamin D receptor, single nucleotide polymorphisms, personality traits, brain-derived neurotrophic factor, dopamine transporter, serotonin receptors, genetic risk
- MeSH terms
- Adolescent, Adult, Aged, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Recurrence, Proportional Hazards Models, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Young Adult
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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