Familiality of major depressive disorder and patterns of lifetime comorbidity. The NEMESIS and GenMood studies

A comparison of three samples
  • Maaike Verhagen
  • Annemarie van der Meij
  • Barbara Franke
  • Wilma A. M. Vollebergh
  • Ron de Graaf
  • Jan K. Buitelaar
  • Joost G. E. Janzing



Major depressive disorder (MDD) aggregates in families and is associated with high rates of lifetime axis-I comorbidity. This study examined whether familiality of MDD is associated with the presence of specific comorbid disorders, which might be an important factor to be taken into account in MDD treatment and research into MDD etiology.


A population sample was divided into subjects with familial (f-MDD; n = 432) and nonfamilial MDD (nf-MDD; n = 454). Since, more comorbidity was expected in clinical cases, a clinical sample with f-MDD (n = 120) was also studied. Subjects were assessed with the Composite International Diagnostic Interview and family history methods. Binary logistic regression analyses were carried out to examine the influence of familiality of MDD on comorbidity. Analyses were adjusted for potential confounders, including MDD characteristics such as severity and age of onset.


Dysthymia, anxiety disorders, and alcohol use disorders were significantly more prevalent in subjects with f-MDD than in subjects with nf-MDD. Clinical f-MDD was associated with more anxiety disorders and fewer alcohol use disorders than population f-MDD. After adjustment for MDD characteristics including age at onset, severity, and disease course, comorbid disorders remained more prevalent in f-MDD than in nf-MDD.


The instruments used in the population and the clinical samples were not identical, however, they were comparable to a substantial degree.


F-MDD, especially in clinical cases, appears to increase the risk of development of comorbid disorders, regardless of MDD characteristics. The link between familiality and comorbidity is important because it will aid a better understanding of the MDD phenotype, and it contributes to planning of effective treatment and to molecular genetic studies.


major depressive disorder familiality comorbidity clinical features 


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Copyright information

© Springer 2008

Authors and Affiliations

  • Maaike Verhagen
    • 1
  • Annemarie van der Meij
    • 1
  • Barbara Franke
    • 2
  • Wilma A. M. Vollebergh
    • 3
    • 4
  • Ron de Graaf
    • 3
  • Jan K. Buitelaar
    • 1
  • Joost G. E. Janzing
    • 1
  1. 1.Department of Psychiatry (966)Radboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.Department of Human Genetics (855) and Department of Psychiatry (966)Radboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Netherlands Institute of Mental Health and AddictionUtrechtThe Netherlands
  4. 4.Faculty of Social and Behavioral SciencesUniversity of UtrechtUtrechtThe Netherlands

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