Regular Research Article|Articles in Press

Stability of the Subtypes of Major Depressive Disorder in Older Adults and the Influence of Mild Cognitive Impairment on the Stability

Published:February 14, 2023DOI:


      • What is the primary question addressed by this study?
        Are the subtypes of major depressive disorder according to the diagnostic and statistical manual of mental disorders (DSM-IV) specifiers stable in advanced age and what is the influence of mild cognitive impairment on this stability?
      • What is the main finding of this study?
        Longitudinal stability into advanced age of the atypical and the combined subtypes but not of the melancholic subtype of major depressive disorder according to the DSM-IV specifiers and absence of the effect of mild cognitive impairment on this stability.
      • What is the meaning of the finding?
        Additional support for the validity of the atypical subtype of major depressive disorder according to the DSM-IV specifier in older age.



      To assess 1) the longitudinal stability of the atypical, melancholic, combined atypical-melancholic and the unspecified subtypes of major depressive disorder (MDD) according to the diagnostic and statistical manual of mental disorders (DSM –IV) specifiers in older adults, and 2) the effect of mild cognitive impairment (MCI) on the stability of these subtypes.


      Prospective cohort study with a 5.1 year-follow-up.


      Population-based cohort from Lausanne, Switzerland.


      A total of 1,888 participants (mean age: 61.7 years, women: 69.2%) with at least two psychiatric evaluations, one after the age of 65 years.


      Semistructured diagnostic interview to assess lifetime and 12-month DSM-IV Axis-1 disorders at each investigation and neuro-cognitive tests to identify MCI in participants aged 65 years and over. Associations between lifetime MDD status before and 12-month depression status after the follow-up were assessed using multinomial logistic regression. The effect of MCI on these associations was assessed by testing interactions between MDD subtypes and MCI status.


      1) Associations between depression status before and after the follow-up were observed for atypical (adjusted OR [95% CI] = 7.99 [3.13; 20.44]), combined (5.73 [1.50; 21.90]) and unspecified (2.14 [1.15; 3.98]), but not melancholic MDD (3.36 [0.89; 12.69]). However, there was a certain degree of overlap across the subtypes, particularly between melancholic MDD and the other subtypes. 2) No significant interactions were found between MCI and lifetime MDD subtypes regarding depression status after follow-up.


      The strong stability of the atypical subtype in particular highlights the need for identifying this subtype in clinical and research settings, given its well-documented links to inflammatory and metabolic markers.

      Key Words

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      1. World Health Organization. The global burden of disease: 2004 update, Geneva, 2008. Available at:

        • Penninx BWJH
        • Nolen WA
        • Lamers F
        • et al.
        Two-year course of depressive and anxiety disorders: results from the Netherlands Study of Depression and Anxiety (NESDA).
        J Affect Disord. 2011; 133: 76-85
        • Spijker J
        • De Graaf R
        • Bijl RV
        • et al.
        Duration of major depressive episodes in the general population: results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS).
        Br J Psychiatry. 2002; 181: 208-213
        • Antonijevic IA
        Depressive disorders – is it time to endorse different pathophysiologies?.
        Psychoneuroendocrinology. 2006; 31: 1-15
        • Ghaemi SN
        • Vohringer PA
        The heterogeneity of depression: an old debate renewed.
        Acta Psychiatr Scand. 2011; 124: 497
        • Kendler KS
        • Gardner CO
        • Prescott CA
        Toward a comprehensive developmental model for major depression in women.
        Am J Psychiatry. 2002; 159: 1133-1145
        • Baune BT
        • Stuart M
        • Gilmour A
        • et al.
        The relationship between subtypes of depression and cardiovascular disease: a systematic review of biological models.
        Transl Psychiatry. 2012; 2: e92
        • Harald B
        • Gordon P
        Meta-review of depressive subtyping models.
        J Affect Disord. 2012; 139: 126-140
        • Kaestner F
        • Hettich M
        • Peters M
        • et al.
        Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity.
        J Affect Disord. 2005; 87: 305-311
        • Penninx BW
        • Milaneschi Y
        • Lamers F
        • et al.
        Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile.
        BMC Med. 2013; 11: 129
        • Lamers F
        • Cui L
        • Hickie IB
        • et al.
        Familial aggregation and heritability of the melancholic and atypical subtypes of depression.
        J Affect Disord. 2016; 204: 241-246
        • Angst J
        • Gamma A
        • Benazzi F
        • et al.
        Melancholia and atypical depression in the Zurich study: epidemiology, clinical characteristics, course, comorbidity and personality.
        Acta Psychiatr Scand. 2007; 115: 72-84
        • Lamers F
        • Rhebergen D
        • Merikangas KR
        • et al.
        Stability and transitions of depressive subtypes over a 2-year follow-up.
        Psychol Med. 2012; 42: 2083-2093
        • Veltman E
        • Kok A
        • Lamers F
        • et al.
        Stability and transition of depression subtypes in late life.
        J Affect Disord. 2020; 265: 445-452
        • Simões do Couto F
        • Lunet N
        • Ginó S
        • et al.
        Depression with melancholic features is associated with higher long-term risk for dementia.
        J Affect Disord. 2016; 202: 220-229
        • Firmann M
        • Mayor V
        • Vidal PM
        • et al.
        The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome.
        BMC Cardiovasc Disord. 2008; 8: 6
        • Preisig M
        • Waeber G
        • Vollenweider P
        • et al.
        The PsyCoLaus study: methodology and characteristics of the sample of a population-based survey on psychiatric disorders and their association with genetic and cardiovascular risk factors.
        BMC Psychiatry. 2009; 9: 9
        • Leboyer M
        • Barbe B
        • Gorwood P
        • et al.
        Interview diagnostique pour les études génétiques.
        INSERM, Paris1995
        • Nurnberger JI
        Diagnostic interview for genetic studies: rationale, unique features, and training.
        Arch Gen Psychiatry. 1994; 51: 849
        • Preisig M
        • Fenton BT
        • Matthey M-L
        • et al.
        Diagnostic interview for genetic studies (DIGS): inter-rater and test-retest reliability of the French version.
        Eur Arch Psychiatry Clin Neurosci. 1999; 249: 174-179
        • Berney A
        • Preisig M
        • Matthey M-L
        • et al.
        Diagnostic interview for genetic studies (DIGS): inter-rater and test-retest reliability of alcohol and drug diagnoses.
        Drug Alcohol Depend. 2002; 65: 149-158
        • Leboyer M
        • Maier W
        • Teherani M
        • et al.
        The reliability of the SADS-LA in a family study setting.
        Eur Arch Psychiatry Clin Neurosci. 1991; 241: 165-169
        • Endicott J
        A diagnostic interview: the schedule for affective disorders and schizophrenia.
        Arch Gen Psychiatry. 1978; 35: 837
        • American Psychiatric Association
        4th ed. Diagnostic and Statistical Manual of Mental Disorders. 179. Author. Br J Psychiatry, Washington, DC2000 (text rev85-85)
      2. Hollingshead AB: Four factor index of social status, New Haven, CT, 1975

        • Buschke H
        • Sliwinski MJ
        • Kuslansky G
        • et al.
        Diagnosis of early dementia by the double memory test: encoding specificity improves diagnostic sensitivity and specificity.
        Neurology. 1997; 48: 989-996
      3. Deloche G, Hannequin, D: DO 80 : Epreuve de Dénomination Orale d'images, Paris, 1997

        • Stroop JR
        Studies of interference in serial verbal reactions.
        J Exp Psychol. 1935; 18: 643
        • Morris JC
        • Heyman A
        • Mohs RC
        • et al.
        The consortium to establish a registry for Alzheimer’s disease (CERAD): I. Clinical and neuropsychological assessment of Alzheimer’s disease.
        Neurology. 1989; 39: 1159-1165
        • Morris JC
        The clinical dementia rating (cdr): current version and scoring rules.
        Neurology. 1993; 43: 2412-2414
      4. Kosmidis I: brglm2: bias reduction in generalized linear Models., R package version 0.8.2. 2021

        • Yu O-C
        • Jung B
        • Go H
        • et al.
        Association between dementia and depression: a retrospective study using the Korean National Health Insurance Service-National Sample Cohort database.
        BMJ Open. 2020; 10e034924
        • Lasserre AM
        • Strippoli MF
        • Glaus J
        • et al.
        Prospective associations of depression subtypes with cardio-metabolic risk factors in the general population.
        Mol Psychiatry. 2017; 22: 1026-1034
        • Glaus J
        • von Känel R
        • Lasserre AM
        • et al.
        The bidirectional relationship between anxiety disorders and circulating levels of inflammatory markers: results from a large longitudinal population-based study.
        Depress Anxiety. 2018; 35: 360-371