Families at high and low risk for depression: A three-generation startle study

Christian Grillon, Virginia Warner, Jeffrey Hille, Kathleen R. Merikangas, Gerard E. Bruder, Craig E. Tenke, Yoko Nomura, Paul Leite, Myrna M. Weissman

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Background: Anxiety symptoms might be a vulnerability factor for the development of major depressive disorder (MDD). Because elevated startle magnitude in threatening contexts is a marker for anxiety disorder, the present study investigated the hypothesis that enhanced startle reactivity would also be found in children and grandchildren of individuals with MDD. Methods: The magnitude of startle was investigated in two tests (anticipation of an unpleasant blast of air and during darkness) in children (second generation) and grandchildren (third generation) of probands with (high risk) or without (low risk) MDD (first generation). Results: Startle discriminated between the low- and high-risk groups. In the probands' children, the high-risk group showed increased startle magnitude throughout the fear-potentiated startle test. In the probands' grandchildren, a gender-specific abnormality was found in the high-risk group with high-risk girls, but not boys, exhibiting elevated startle magnitude throughout the procedure. Conclusions: Increased startle reactivity in threatening contexts, previously found in patients with anxiety disorder and in children of parents with an anxiety disorder, might also constitute a vulnerability marker for MDD. These findings suggest that there might be common biologic diatheses underlying depression and anxiety.

Original languageEnglish
Pages (from-to)953-960
Number of pages8
JournalBiological Psychiatry
Issue number9
StatePublished - 1 May 2005
Externally publishedYes


  • Anxiety
  • High risk
  • Major depressive disorder
  • Psychophysiology
  • Startle


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