Early adversity in chronic depression: Clinical correlates and response to pharmacotherapy

Daniel N. Klein, Bruce A. Arnow, Jennifer L. Barkin, Frank Dowling, James H. Kocsis, Andrew C. Leon, Rachel Manber, Barbara O. Rothbaum, Madhukar H. Trivedi, Stephen R. Wisniewski

Research output: Contribution to journalArticlepeer-review

123 Scopus citations


Background: There is growing evidence suggesting that early adversity may be a marker for a distinct pathway to major depressive disorder (MDD). We examined associations between childhood adversity and a broad variety of clinical characteristics and response to pharmacotherapy in a large sample of patients with chronic forms of MDD. Methods: Subjects included 808 patients with chronic forms of MDD (chronic MDD, double depression, or recurrent MDD with incomplete recovery between episodes and a total continuous duration of >2 years) who were enrolled in a 12-week open-label trial of algorithm-guided pharmacotherapy. Baseline assessments included a semistructured diagnostic interview, and clinician- and self-rated measures of depressive symptoms, social functioning, depressotypic cognitions, and personality traits, and childhood adversity. Patients were re-evaluated every 2 weeks. Results: A longer duration of illness; earlier onset; greater number of episodes, symptom severity, self-rated functional impairment, suicidality, and comorbid anxiety disorder; and higher levels of dysfunctional attitudes and self-criticism were each associated with multiple forms of childhood adversity. A history of maternal overcontrol, paternal abuse, paternal indifference, sexual abuse, and an index of clinically significant abuse each predicted a lower probability of remission. Among patients completing the 12-week trial, 32% with a history of clinically significant abuse, compared to 44% without such a history, achieved remission. Conclusions: These findings indicate that a history of childhood adversity is associated with an especially chronic form of MDD that is less responsive to antidepressant pharmacotherapy.

Original languageEnglish (US)
Pages (from-to)701-710
Number of pages10
JournalDepression and anxiety
Issue number8
StatePublished - Aug 2009


  • Childhood maltreatment
  • Clinical features
  • Major depression
  • Mood disorders
  • Treatment response

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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