Familial aggregation and heritability of the melancholic and atypical subtypes of depression

Femke Lamers, Lihong Cui, Ian B Hickie, Catherine Roca, Rodrigo Machado-Vieira, Carlos A Zarate, Kathleen R Merikangas

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20 Citations (Scopus)


BACKGROUND: The heterogeneity of mood disorders has been a challenge to our understanding of their underlying biologic and genetic pathways. This report examines the specificity of the familial aggregation of atypical and melancholic subtypes of depression and their clinical correlates in a large community based family study of affective spectrum disorders.

METHODS: The sample includes 457 probands and their directly interviewed adult first degree relatives from the National Institute of Mental Health (NIMH) Family Study of Affective Spectrum Disorder. Depression subtypes were based on best estimate diagnoses using information from semi-structured diagnostic interviews by experienced clinical interviews and multiple family history reports.

RESULTS: Atypical depression in probands was significantly associated with the atypical subtype of depression in relatives (OR 1.75 [95%CI 1.02-3.02], p=0.04), independent of proband and relative comorbid disorders. Melancholic depression in probands was not associated with melancholic depression in relatives (OR 1.25 [95%CI 0.62-2.55], p=.53). The familial heritability of the atypical subtype was 0.46 (95%CI 0.21-0.71), whereas that of the melancholic subtype was 0.33 (95%CI 0.21-0.45). Melancholic depression was associated with greater severity in terms of treatment, global functioning, suicide attempts, comorbid disorders, and an earlier age at onset of depression.

LIMITATIONS: The subsample of interviewed relatives necessary to assess specific subtypes of depression reduced the power to detect the specificity of mood disorder subtypes.

CONCLUSION: The results indicate that the atypical subtype should be incorporated in future treatment, genetic and other etiologic studies of major depression. Findings further suggest that melancholic subtype may be an indicator of clinical severity of depression.

Original languageEnglish
Pages (from-to)241-6
Number of pages6
JournalJournal of affective disorders
Publication statusPublished - 1 Nov 2016


  • Journal Article

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