Antecedents of New-Onset Major Depressive Disorder in Children and Adolescents at High Familial Risk

Frances Rice, Ruth Sellers, Gemma Hammerton, Olga Eyre, Rhys Bevan Jones, Ajay K Thapar, Stephan Collishaw, Gordon T Harold, Anita Thapar

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Importance  Early-onset major depressive disorder (MDD) is common in individuals at high familial risk of depression and is associated with poor long-term mental health, social, and educational outcomes.

Objectives  To examine the developmental pathways that lead to first-episode adolescent-onset MDD (incident cases) in those at high familial risk and to postulate a theoretically informed model that enables simultaneous testing of different pathways to incident adolescent-onset MDD composed of contributions from familial/genetic and social risk factors, as well as effects via specific clinical antecedents.

Design, Setting, and Participants  This investigation was a 4-year longitudinal study (April 2007 to March 2011) among offspring of depressed parents in the general community. Analyses were conducted between September 1, 2015, and May 27, 2016. Participants were 337 families in whom the index parent (315 mothers and 22 fathers) had experienced at least 2 episodes of MDD (recruited through primary care) and among whom there was a biologically related child in the age range of 9 to 17 years living with the index parent (197 girls and 140 boys with a mean [SD] age of 12.4 [2.0] years) at baseline. Offspring with MDD before the study or at baseline (n = 27), offspring with an episode of MDD that had remitted by follow-up (n = 4), and offspring with missing baseline MDD data (n = 2) were excluded. Ninety-two percent (279 of 304) of families completed the follow-up.

Main Outcomes and Measures  The primary outcome was new-onset offspring MDD, and the secondary outcome was the total DSM-IV MDD symptom score.

Results  On average, children and adolescents had a mean (SD) of 1.85 (1.74) (range, 0-8.5) DSM-IV symptoms of MDD at follow-up. Twenty (6 males and 14 females) had new-onset MDD, with a mean (SD) age at onset of 14.4 (2.0) years (range, 10-18 years). Irritability (β = 0.12, P = .03) and fear and/or anxiety (β = 0.38, P < .001) were significant independent clinical antecedents of new adolescent-onset MDD, but disruptive behavior (β = −0.08, P = .14) and low mood (β = −0.03, P = .65) were not. The results were similar for the DSM-IV symptom count at follow-up. All the measured familial/genetic and social risk indicators directly influenced risk for new-onset MDD rather than indirectly through acting on dimensional clinical antecedents.

Conclusions and Relevance  There are multiple pathways to first-onset adolescent depression in individuals at familial risk. Irritability and fear/anxiety may be additional clinical phenomena to be included as targets in primary preventive interventions focusing on the child. In addition to targeting these phenomena in parents and children, depression prevention methods in high-risk groups may need to take into consideration social risks, such as poverty and psychosocial adversity.

Original languageEnglish
Pages (from-to)153-160
Number of pages8
JournalJAMA Psychiatry
Issue number2
Early online date7 Dec 2016
Publication statusPublished - Feb 2017


  • adolescence
  • depression
  • incidence
  • risk
  • social
  • familial
  • genetic
  • antecedent


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