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Cited by 482Mental Health Treatment and AccessTreatment of Major DepressionAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature

Open access
Remes, Olivia, Mendes, João Francisco, Templeton, Peter·2021·Brain Sciences
DOI 10.3390/brainsci11121633PMC PMC8699555
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Abstract

Depression is one of the leading causes of disability, and, if left unmanaged, it can increase the risk for suicide. The evidence base on the determinants of depression is fragmented, which makes the interpretation of the results across studies difficult. The objective of this study is to conduct a thorough synthesis of the literature assessing the biological, psychological, and social determinants of depression in order to piece together the puzzle of the key factors that are related to this condition. Titles and abstracts published between 2017 and 2020 were identified in PubMed, as well as Medline, Scopus, and PsycInfo. Key words relating to biological, social, and psychological determinants as well as depression were applied to the databases, and the screening and data charting of the documents took place. We included 470 documents in this literature review. The findings showed that there are a plethora of risk and protective factors (relating to biological, psychological, and social determinants) that are related to depression; these determinants are interlinked and influence depression outcomes through a web of causation. In this paper, we describe and present the vast, fragmented, and complex literature related to this topic. This review may be used to guide practice, public health efforts, policy, and research related to mental health and, specifically, depression.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesized recent literature on biological, psychological, and social determinants of depression, including 470 documents published between 2017 and 2020. It concludes that risk and protective factors are interlinked across individual and wider ecological levels and influence depression through a complex web of causation.

Key findings

  • From 6335 identified documents, 470 papers were included. Determinants spanned biological factors (genetics, microbiome, inflammation, HPA-axis dysfunction, kynurenine pathway, cognition), psychological factors (rumination, neuroticism, negative self-concept, low self-esteem, maladaptive coping), and social factors (socioeconomic status, social support, adverse childhood experiences, gender, diet, and others).
  • Women were found to be twice as likely to have depression as men, and depression was estimated to have a prevalence of 5% among adults.
  • Biological findings included links between depression and pro-inflammatory cytokines such as TNF-alpha, BDNF (including the rs6265 allele A with major depressive disorder), HPA-axis dysregulation, and the kynurenine pathway.
  • Social and psychological findings included associations between low education and low income and depression, high education and income as protective, adverse childhood experiences increasing risk, and rumination acting as both a risk factor and mediator.

Methods

  • Literature review of biological, psychological, and social determinants of depression, focusing on documents published 2017–2020. Searches were conducted in PubMed, Medline, Scopus, and PsycInfo; inclusion covered primary studies, reviews, systematic reviews, meta-analyses, reports, and commentaries on human and/or rodent research, while treatment-focused studies and studies assessing depression as a comorbidity or secondary disorder were excluded.
  • Titles and abstracts were screened, then full texts were assessed. Screening was conducted by O.R., with a subsample screened by J.M.; discrepancies were resolved through communication. A data charting form was piloted on 20 studies, and narrative analysis was used to identify key themes.
  • The review attempted to follow PRISMA guidelines in several aspects.

Limitations

  • Stated in the paper: the review may have missed potentially important studies, though this is described as unavoidable for literature reviews; the aim was not to identify every study on depression risk and protective factors but to gain insight into the breadth of literature and key themes.
  • Evident from the text: heterogeneity in study design and measurement, and lack of standardization for measuring depression and its determinants, make comparison across studies difficult; findings in some areas, such as genetics, remain mixed.
  • Evident from the text: the review is a narrative synthesis and does not describe a formal quality appraisal or meta-analytic pooling of results.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/brainsci11121633

Cites

485 of 485 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 126 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    There are many risk and protective factors relating to biological, psychological, and social determinants that are related to depression.

    “The findings showed that there are a plethora of risk and protective factors (relating to biological, psychological, and social determinants) that are related to depression”
    Quote in the paperSubstantial claim
  • Findingcitation

    Bladder outlet obstruction has been linked to inflammation and depressive behaviour in rodent research.

    “For example, bladder outlet obstruction has been linked to inflammation and depressive behaviour in rodent research [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Hughes, 2020, A possible mechanism underlying mood disorders associated with LUTS: Chronic bladder outlet obstruction causes NLRP3-dependent inflammation in the hippocampus and depressive behavior in rats, Neurourol. Urodyn. source

      Not checked in the free run.

  • Findingcitation

    A disordered gut microbiota can play a role in the onset of depression.

    “a disordered gut microbiota can play a role in the onset of this mental health problem”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [158] Winter, 2018, Gut microbiome and depression: What we know and what we need to know, Rev. Neurosci. source

      Not checked in the free run.

  • Findingcitation

    Another study found no association between specific polymorphisms and major depressive disorder.

    “Another study found no association between specific polymorphisms and major depressive disorder [132].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [132] Hu, 2018, No association of GRIN2A polymorphisms with the major depressive disorder in the Chinese Han origin, Psychiatr. Genet. source

      Not checked in the free run.

  • Findingcitation

    The presence of head and neck cancer seemed to be related to an increased risk for depressive disorder.

    “The presence of head and neck cancer also seemed to be related to an increased risk for depressive disorder [45].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Fan, 2017, Risk of depressive disorder among patients with head and neck cancer: A nationwide population-based study, Head Neck source

      Not checked in the free run.

  • Classified as probably not a substantial claim. 35
  • May combine two claims. 39

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The review included 470 documents.

    “We included 470 documents in this literature review.”
    • Also stated in: § 3. Results · plain
      “After applying the inclusion and exclusion criteria, 470 papers were included in this review (Supplementary Table S1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    BDNF plays an important role in depression.

    “The brain-derived neurotrophic factor (BDNF) plays an important role in depression”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    The presence of a physical health condition can increase the risk for depression.

    “The presence of a physical health condition can increase the risk for depression”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Gestational diabetes mellitus has been linked to depressive symptoms in the postpartum period, but no association has been found with depression in the third pregnancy trimester.

    “Gestational diabetes mellitus has been linked to depressive symptoms in the postpartum period (but no association has been found with depression in the third pregnancy trimester) [50]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Varela, 2017, Association between gestational diabetes and perinatal depressive symptoms: Evidence from a Greek cohort study, Prim. Health Care Res. Dev. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Findingnone given

    There are possible links between the gut microbiome, host liver metabolism, brain inflammation, and depression.

    “There are possible links between the gut microbiome, host liver metabolism, brain inflammation, and depression”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Links exist between major histocompatibility complex region genes, various gene polymorphisms, and depression.

    “Links exist between major histocompatibility complex region genes, as well as various gene polymorphisms and depression”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Through the searches, 6335 documents were identified.

    “Through the searches, 6335 documents, such as primary studies, literature reviews, systematic reviews, meta-analyses, reports, and commentaries, were identified.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Findingnone given

    A disordered microbiome can lead to inflammation, which can then lead to depression.

    “A disordered microbiome can lead to inflammation, which can then lead to depression”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The results from genetics studies are compelling, but findings remain mixed.

    “The results from genetics studies are compelling; however, the findings remain mixed.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    A study reported a link between the BDNF rs6265 allele (A) and major depressive disorder.

    “a study reported a link between the BDNF rs6265 allele (A) and major depressive disorder [117].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [117] Aldoghachi, A.F., Tor, Y.S., Redzun, S.Z., Bin Lokman, K.A., Razaq, N.A.A., Shahbudin, A.F., Badamasi, I.M., Cheah, P.-S., Stanslas, J., and Veerakumarasivam, A. (2019). Screening of brain-derived neurotrophic factor (BDNF) single nucleotide polymorphisms and plasma BDNF levels among Malaysian major depressive disorder patients. PLoS ONE, 14. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Research has shown associations between depression and BDNF, candidate SNPs of the BDNF gene, polymorphisms of the BDNF gene, and the interaction of these polymorphisms with other determinants such as stress.

    “Research has shown associations between depression and BDNF (as well as candidate SNPs of the BDNF gene, polymorphisms of the BDNF gene, and the interaction of these polymorphisms with other determinants, such as stress) [129,144,145].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [129] Manukyan, 2018, Interactions Among Polymorphisms of Susceptibility Loci for Alzheimer’s Disease or Depressive Disorder, Med. Sci. Monit. source

      Not checked in the free run.

    • cites [144] He, 2018, Interaction between job stress and the BDNF Val66Met polymorphism affects depressive symptoms in Chinese healthcare workers, J. Affect. Disord. source

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    • cites [145] Hing, 2018, A comprehensive review of genetic and epigenetic mechanisms that regulate BDNF expression and function with relevance to major depressive disorder, Am. J. Med. Genet. B Neuropsychiatr Genet. source

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    Findingcitation

    When there is an imbalance in the intestinal bacteria, this can interfere with emotional regulation and contribute to harmful inflammatory processes and mood disorders.

    “When there is an imbalance in the intestinal bacteria, this can interfere with emotional regulation and contribute to harmful inflammatory processes and mood disorders [148,151,153,155,157].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [148] Stower, 2019, Depression linked to the microbiome, Nat. Med.

      Not checked in the free run.

    • cites [151] Ma, 2019, Chronic paradoxical sleep deprivation-induced depression-like behavior, energy metabolism and microbial changes in rats, Life Sci. source

      Not checked in the free run.

    • cites [153] Kuo, 2018, Moody microbiome: Challenges and chances, J. Formos. Med Assoc. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Early life stress has been linked to systemic inflammation, and this can increase the risk for depression.

    “Various determinants, such as early life stress, have also been linked to systemic inflammation, and this can increase the risk for depression [186].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [186] Hashimoto, 2020, Early life stress from allergic dermatitis causes depressive-like behaviors in adolescent male mice through neuroinflammatory priming, Brain Behav. Immun. source

      Not checked in the free run.

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    Findingcitation

    Chronic stress can impact the dendrites and synapses of various neurons, and may be implicated in the pathway leading to major depressive disorder.

    “Chronic stress can impact the dendrites and synapses of various neurons, and may be implicated in the pathway leading to major depressive disorder [114].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [114] Uchida, 2017, Epigenetic mechanisms of major depression: Targeting neuronal plasticity, Psychiatry Clin. Neurosci. source

      Not checked in the free run.

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    Findingcitation

    Stress has been linked to the release of inflammatory factors, as well as the development of depression.

    “Stress has been linked to the release of inflammatory factors, as well as the development of depression [204].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [204] Wu, 2018, PI3K/AKT/GSK3β/CRMP-2-mediated neuroplasticity in depression induced by stress, NeuroReport source

      Not checked in the free run.

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    Findingcitation

    The kynurenine pathway has been implicated in general depressed mood (inflammation-induced depression) and postpartum depression.

    “The kynurenine pathway has been implicated not only in general depressed mood (inflammation-induced depression) [184,214,219] but also postpartum depression [120].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [184] Dantzer, 2016, Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches, Curr. Top. Behav. Neurosci. source

      Not checked in the free run.

    • cites [214] Jeon, 2017, Inflammation-induced depression: Its pathophysiology and therapeutic implications, J. Neuroimmunol. source

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    • cites [219] Kruse, 2019, Kynurenine metabolism and inflammation-induced depressed mood: A human experimental study, Psychoneuroendocrinology source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    There are links between inflammation-induced activation of IDO, the kynurenine metabolism pathway, and depression.

    “Another review by Danzer et al. suggests links between the inflammation-induced activation of indolamine 2,3-dioxegenase (the enzyme that converts tryptophan to kynurenine), the kynurenine metabolism pathway, and depression”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [184] Dantzer, 2016, Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches, Curr. Top. Behav. Neurosci. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    There is a link between impairment of the kynurenine pathway and inflammation-induced depression (triggered by treatment for various physical diseases, such as malignancy).

    “A review by Jeon et al. notes a link between the impairment of the kynurenine pathway and inflammation-induced depression (triggered by treatment for various physical diseases, such as malignancy).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [214] Jeon, 2017, Inflammation-induced depression: Its pathophysiology and therapeutic implications, J. Neuroimmunol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    There are many affective risk factors linked to depression.

    “There are many affective risk factors linked to depression”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Low-level cognitive ability and cognitive vulnerability have been linked to depression.

    “In addition to cognitive deficits, low-level cognitive ability [231] and cognitive vulnerability [232] have also been linked to depression.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [231] Nissen, 2019, Low-level cognitive ability in young adulthood and other risk factors of depression in an observational cohort study among deployed Danish soldiers, Soc. Psychiatry Psychiatr. Epidemiol. source

      Not checked in the free run.

    • cites [232] Liu, 2018, A Latent Structure Analysis of Cognitive Vulnerability to Depression in Adolescence, Behav. Ther. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    Family history of cognitive impairment is linked to depression.

    “Family history of cognitive impairment is linked to depression”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Findingnone given

    Determinants of depression include negative self-concept, sensitivity to rejection, neuroticism, rumination, negative emotionality, and others.

    “Determinants of depression include negative self-concept, sensitivity to rejection, neuroticism, rumination, negative emotionality, and others”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Cognitive reserve appears to act as a moderator and can magnify the impact of certain determinants on poor mental health.

    “The cognitive reserve appears to act as a moderator and can magnify the impact of certain determinants on poor mental health.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Lower scores in cognition were related to depression in individuals attending outpatient stroke clinics; cognitive impairment appears to be associated with depressive symptomatology.

    “A study on individuals attending outpatient stroke clinics showed that lower scores in cognition were related to depression; thus, cognitive impairment appears to be associated with depressive symptomatology [226].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [226] Vermeer, 2016, Correlates of depressive symptoms in individuals attending outpatient stroke clinics, Disabil. Rehabil. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Factors such as age, social or socioeconomic status, social support, financial strain and deprivation, food insecurity, education, employment status, living arrangements, marital status, race, childhood conflict and bullying, violent crime exposure, abuse, discrimination, (self)-stigma, ethnicity and migrant status, working conditions, adverse or significant life events, illiteracy or health liter

    “Factors such as age, social or socioeconomic status, social support, financial strain and deprivation, food insecurity, education, employment status, living arrangements, marital status, race, childhood conflict and bullying, violent crime exposure, abuse, discrimination, (self)-stigma, ethnicity and migrant status, working conditions, adverse or significant life events, illiteracy or health liter”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [52] Lee, 2017, Gender differences in the trajectories and the risk factors of depressive symptoms in later life, Int. Psychogeriatr. source

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    • cites [133] Geisler, 2018, Immunometabolism in the Pathogenesis of Depressive Disorders-Therapeutic Considerations, Curr. Top. Med. Chem. source

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    • cites [235] Valmisa, 2018, Prevalence and correlates of major depression in Granada, Spain: Results from the GranadΣp study, Int. J. Soc. Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Social support and cohesion, as well as structural social capital, have been identified as determinants of depression.

    “Social support and cohesion, as well as structural social capital, have also been identified as determinants [140,228,239,269,293,372,373,374,375,376,377,378,379].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [140] Brouillard, 2016, Links Between the Mother–Adolescent and Father–Adolescent Relationships and Adolescent Depression: A Genetically Informed Study, J. Clin. Child Adolesc. Psychol. source

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    • cites [228] Hankin, 2018, Cognitive and Interpersonal Vulnerabilities to Adolescent Depression: Classification of Risk Profiles for a Personalized Prevention Approach, J. Abnorm. Child Psychol. source

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    • cites [239] Kim, 2016, The Impacts of Social Support and Cognitive Function on Depression among Community-Dwelling Older Japanese Americans, Soc. Work. Public Health source

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    Determinants can be at the individual, social network, community, and societal levels.

    “Determinants can be at the individual, social network, community, and societal levels”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Rumination has been presented as a mediator but also as a risk factor for depression.

    “Rumination has been presented as a mediator but also as a risk factor for depression [57,210,259].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [57] Zhang, 2019, Association between fatigue and depressive symptoms among kidney transplantation recipients: The mediating role of rumination, J. Adv. Nurs. source

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    • cites [210] Connolly, 2017, Rumination interacts with life stress to predict depressive symptoms: An ecological momentary assessment study, Behav. Res. Ther. source

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    • cites [259] Trick, 2019, Perseverative negative thinking predicts depression in people with acute coronary syndrome, Gen. Hosp. Psychiatry source

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  • May combine two claims.

    Findingcitation

    High levels of education and income are protective against depression.

    “By contrast, high levels of education and income are protective [335].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [335] Park, 2018, Association of depression with socioeconomic status, anticardiolipin antibodies, and organ damage in patients with systemic lupus erythematosus: Results from the KORNET registry, Clin. Exp. Rheumatol.

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Low levels of education have been shown to be linked to post-stroke depression (but not severe or clinical depression outcomes).

    “In a study, part of the findings showed that low levels of education have been shown to be linked to post-stroke depression (but not severe or clinical depression outcomes) [299].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [299] Backhouse, E.V., McHutchison, C.A., Cvoro, V., Shenkin, S.D., and Wardlaw, J.M. (2018). Cognitive ability, education and socioeconomic status in childhood and risk of post-stroke depression in later life: A systematic review and meta-analysis. PLoS ONE, 13. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    A number of factors arose in this review that were related to depression.

    “A number of factors arose in this review that were related to depression”
    Quote in the paperNot a substantial claim

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    Findingnone given

    Air pollution and nighttime shift work have been found to increase the risk for depression.

    “the latter determinants have been found to increase the risk for depression.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    The review finds important themes among the determinants of depression: the microbiome, dysregulation of the HPA axis, inflammatory reactions, the kynurenine pathway, and psychological and social factors.

    “The findings from this review show that there are important themes when it comes to the determinants of depression, such as: the microbiome, dysregulation of the HPA axis, inflammatory reactions, the kynurenine pathway, as well as psychological and social factors.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingcitation

    There are myriad ways of measuring depression and its determinants.

    “This review highlighted the myriad ways of measuring depression and its determinants [66,85,281,298,451,485].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [66] Trindade, 2017, An 18-month study of the effects of IBD symptomatology and emotion regulation on depressed mood, Int. J. Color. Dis. source

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    • cites [85] Treutlein, 2017, Association between neuropeptide Y receptor Y2 promoter variant rs6857715 and major depressive disorder, Psychiatr. Genet. source

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    • cites [281] Rudolph, 2017, Cognition–emotion interaction as a predictor of adolescent depressive symptoms, Dev. Psychol. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These determinants are interlinked and influence depression outcomes through a web of causation.

    “these determinants are interlinked and influence depression outcomes through a web of causation.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    The evidence base on the determinants of depression is fragmented, making interpretation of results across studies difficult.

    “The evidence base on the determinants of depression is fragmented, which makes the interpretation of the results across studies difficult.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The review was attempted to be conducted according to PRISMA guidelines.

    “In several aspects, we attempted to conduct this review according to PRISMA guidelines [18].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Tricco, 2018, PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation, Ann. Intern. Med. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The gut bacteria and the brain communicate via both direct and indirect pathways called the gut-microbiota-brain axis, which plays an important role in maintaining homeostasis.

    “The gut bacteria and the brain communicate via both direct and indirect pathways called the gut-microbiota-brain axis (the bidirectional communication networks between the central nervous system and the gastrointestinal tract; this axis plays an important role in maintaining homeostasis).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The data charting form was piloted on a subset of documents and refined.

    “The data charting form was piloted on a subset of documents, and refinements to it were made.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    A subsample of documents underwent double screening by two authors (O.R., J.M.), with discrepancies resolved through communication.

    “A subsample of documents underwent double screening by two authors (O.R., J.M.); again, any discrepancies were resolved through communication.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Screening of documents was conducted by O.R., and a subsample was screened by J.M.; discrepancies were resolved through communication.

    “Screening of documents was conducted by O.R., and a subsample was screened by J.M.; any discrepancies were resolved through a communication process.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Key themes were verified by a second author (J.M.), and discrepancies were resolved through communication.

    “This process (a subsample) was verified by a second author (J.M.), and the two authors resolved any discrepancies through communication.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Key themes were checked for major significance to public mental health and at the forefront of public health discourse according to stakeholder consultations.

    “Key themes were also checked as to whether they were of major significance to public mental health and at the forefront of public health discourse according to consultations we held with stakeholders”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    Determinants are interlinked in a complex web of causation.

    “Determinants are interlinked in a complex web of causation”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Early stress may play a role in the hyperactivation of the HPA axis, creating a predisposition towards a maladaptive reaction to stress; when this predisposition meets an acute stressor, depression may ensue.

    “it could be that early stress plays a role in the hyperactivation of the HPA axis, thus creating a predisposition “towards a maladaptive reaction to stress”. When this predisposition then meets an acute stressor, depression may ensue”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [213] Dean, 2017, The neurobiology of depression: An integrated view, Asian J. Psychiatry source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    A potential underpinning mechanism of depression relates to HPA axis abnormalities involved in chronic stress.

    “One review indicates that a potential underpinning mechanism of depression relates to “HPA axis abnormalities involved in chronic stress” [213].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [213] Dean, 2017, The neurobiology of depression: An integrated view, Asian J. Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Cognitive deficits can be both causal and resultant in depression.

    “Cognitive deficits can be both causal and resultant in depression.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    According to the 'cognitive neuropsychological' model of depression, negative affective biases play a central part in the development of depression.

    “according to the ‘cognitive neuropsychological’ model of depression, negative affective biases play a central part in the development of depression [222,241].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [222] Halahakoon, 2019, Cognitive Impairment and Depression-Cause, Consequence, or Coincidence?, JAMA Psychiatry source

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    • cites [241] Roiser, 2011, Cognitive Mechanisms of Treatment in Depression, Neuropsychopharmacology source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Social determinants are the conditions in the environments where people are born, live, learn, work, play, etc.; these influence (mental) health.

    “Social determinants are the conditions in the environments where people are born, live, learn, work, play, etc.; these influence (mental) health [291]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [291] Marmot, M., Allen, J., Boyce, T., Goldblatt, P., and Morrison, J. (2020). Health Equity in England: The Marmot Review 10 Years On, in The Health Foundation, Institute of Health Equity. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Determinants may present in several forms: as moderators or mediators, risk factors or outcomes, and this is why disentangling the relationships between the various factors linked to depression is a complex task.

    “This shows that determinants may present in several forms: as moderators or mediators, risk factors or outcomes, and this is why disentangling the relationships between the various factors linked to depression is a complex task.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Being exposed to deprivation, hardship, or adversity may increase the risk for air pollution exposure and nighttime shift work.

    “being exposed to deprivation, hardship, or adversity may increase the risk for air pollution exposure and nighttime shift work, among others”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Perceived parental support interacts with genes GABRR1 and GABRR2 and is associated with depressive symptoms in adolescence.

    “Perceived parental support has been found to interact with genes (GABRR1, GABRR2), and this appears to be associated with depressive symptoms in adolescence [480].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [480] Moons, 2017, Gene-based interaction analysis shows GABAergic genes interacting with parenting in adolescent depressive symptoms, J. Child Psychol. Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Determinants have an influence on risk behaviours, and this, in turn, can affect mood (i.e., depression), body processes (e.g., can increase inflammation), and may negatively influence brain structure and function.

    “The determinants have an influence on risk behaviours, and this, in turn, can affect the mood (i.e., depression), body processes (ex. can increase inflammation), and may negatively influence brain structure and function.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    All of these factors are interlinked and influence one another in a complex web of causation.

    “Nevertheless, all of these factors are interlinked and influence one another in a complex web of causation, as mentioned elsewhere in the paper.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Air pollution could also be regarded as an ecologic-level (environmental) determinant of mental health.

    “Air pollution could also be regarded as an ecologic-level (environmental) determinant of mental health.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Chronic stress is linked to glucocorticoid receptor resistance and problems with regulation of the inflammatory response.

    “Previous literature has shown that chronic stress (associated with depression) is also linked to glucocorticoid receptor resistance, as well as problems with the regulation of the inflammatory response [484].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [484] Cohen, 2012, Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The determinants of depression are interlinked and influence one another.

    “These determinants are interlinked and influence one another.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Physical factors may be proximal determinants of depression, acted on by more distal social factors such as deprivation, environmental events, and social capital.

    “It may be that physical factors are proximal determinants of depression, which, in turn, are acted on by more distal social factors, such as deprivation, environmental events, and social capital.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Study design and conductreasoning

    An exhaustive discussion of all risk factors and determinants linked to depression and their mechanisms is not possible in one journal article.

    “an exhaustive discussion of all the risk factors and determinants linked to depression and their mechanisms is not possible in one journal article—which, by its very nature, a single paper cannot do.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The review may have missed potentially important studies.

    “The limitations of the review include missing potentially important studies; however, this is a weakness that cannot be avoided by literature reviews.”
    Quote in the paperNot a substantial claim
60 of 60

  • The paper relies on this without support.

    Previous syntheses on depression are limited in scope and focus exclusively on social or biological factors, population sub-groups, or examine depression as a comorbidity rather than an independent disorder.

    “The previous syntheses on depression are limited in scope and focus exclusively on social or biological factors, population sub-groups, or examine depression as a comorbidity (rather than an independent disorder).”

  • The paper relies on this without support.

    Research on the determinants and causal pathways of depression is fragmented and heterogeneous, and this has not helped to stimulate progress in prevention and intervention.

    “The research on the determinants and causal pathways of depression is fragmentated and heterogeneous, and this has not helped to stimulate progress when it comes to the prevention and intervention of this condition—specifically unravelling the complexity of the determinants related to this condition and thus refining the prevention and intervention methods.”

  • The paper relies on this without support.

    Early life is a critical period during the lifespan at which cognitive processes develop.

    “Early life is a critical period during the lifespan at which cognitive processes develop.”

  • The paper relies on this without support.

    Older people are at a heightened risk of losing their social networks.

    “Older people are at a heightened risk of losing their social networks”
4 of 4

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?

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.

  • Stress-5-HTTLPR claim cites a different interaction

    Minor

    Reference 480 is titled as a study of GABAergic genes interacting with parenting, not stress interacting with 5-HTTLPR. The listed reference on stress and 5-HTTLPR is 479.

1 of 1

Cites

Flagged first, then by citations

2 of the 487 references couldn’t be matched to a known paper.

Research works printed but not linked: 5

  1. Lima, 2019, Depressive Symptoms among the Elderly in Sao Paulo city, Brazil: Prevalence and Associated Factors (SABE Study), Rev. Bras. De Epidemiol., 21, e180014
  2. Wang, 2020, Advance in relationship between receptor gene abnormality and depression, Yaoxue Xuebao, 55, 384
  3. Salgado, 2018, A new theory of depression based on the serotonin/kynurenine relationship and the hypothalamicpituitary- adrenal axis, Biomedica, 38, 437
  4. Ortiz, 2017, Determinants associated with chronic and incident depression in Mexican older adults, Gac. Med. De Mex., 153, S102
  5. Pramod, 2019, Lifestyle and substance use-an important cause for treatment-resistant depression and major depressive disorders, Drug Invent. Today, 11, 284

Cited by

Sorted by citations

Related

Authors
Remes, O., Mendes, J. F., & Templeton, P.
Affiliations
  • University of Cambridge (GB)
  • Universidade Nova de Lisboa (PT)
Corresponding author
Remes, Olivia
ORCID
Venue
Brain Sciences
Publisher
MDPI AG
Published
2021-12-10
Volume
11
Issue
12
Pages
1633
ISSN
2076-3425 (ISSN-L)
DOI
10.3390/brainsci11121633
PMC
PMC8699555
OpenAlex
W4200206491
Cited by
482
References
487
Citations by year
2026: 127 · 2025: 173 · 2024: 117 · 2023: 53 · 2022: 12
FWCI
7.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo
  • Apollo (cc-by)
Funders
  • The William Templeton Foundation for Young People's Mental Health (NA)
  • Cambridge Philosophical Society (NA)
  • Aviva Foundation (NA)
Topics
  • Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
depression, biological determinants, psychological factors, social determinants, risk factors, protective factors, depression outcomes, suicide risk, mental health

About these checks

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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