The phenotypic and genetic structure of depression and anxiety disorder symptoms in childhood, adolescence, and young adulthood

JAMA Psychiatry. 2014 Aug;71(8):905-16. doi: 10.1001/jamapsychiatry.2014.655.

Abstract

Importance: The DSM-5 classifies mood and anxiety disorders as separate conditions. However, some studies in adults find a unidimensional internalizing factor that underpins anxiety and depression, while others support a bidimensional model where symptoms segregate into distress (depression and generalized anxiety) and fear factors (phobia subscales). However, little is known about the phenotypic and genetic structure of internalizing psychopathology in children and adolescents.

Objective: To investigate the phenotypic associations between depression and anxiety disorder symptom subscales and to test the genetic structures underlying these symptoms (DSM-5-related, unidimensional and bidimensional) across 3 developmental stages: childhood, adolescence, and early adulthood.

Design, setting, and participants: Two population-based prospective longitudinal twin/sibling studies conducted in the United Kingdom. The child sample included 578 twins (mean age, approximately 8 and 10 years at waves 1 and 2, respectively). The adolescent and early adulthood sample included 2619 twins/siblings at 3 waves (mean age, 15, 17, and 20 years at each wave).

Main outcomes and measures: Self-report symptoms of depression and anxiety disorders.

Results: Phenotypically, when controlling for other anxiety subscales, depression symptoms were only associated with generalized anxiety disorder symptoms in childhood (r = 0.20-0.21); this association broadened to panic and social phobia symptoms in adolescence (r = 0.17-0.24 and r = 0.14-0.16, respectively) and all anxiety subscales in young adulthood (r = 0.06-0.19). The genetic associations were in line with phenotypic results. In childhood, anxiety subscales were influenced by a single genetic factor that did not contribute to genetic variance in depression symptoms, suggesting largely independent genetic influences on anxiety and depression. In adolescence, genetic influences were significantly shared between depression and all anxiety subscales in agreement with DSM-5 conceptualization. In young adulthood, a genetic internalizing factor influencing depression and all anxiety subscales emerged, alongside a small significant genetic fear factor.

Conclusions and relevance: These results provide preliminary evidence for different phenotypic and genetic structures of internalizing disorder symptoms in childhood, adolescence, and young adulthood, with depression and anxiety becoming more associated from adolescence. The results inform molecular genetics research and transdiagnostic treatment approaches. The findings affirm the need to continue examining the classification of mood and anxiety disorders in diagnostic systems.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Anxiety Disorders / classification*
  • Anxiety Disorders / genetics*
  • Child
  • Depression / classification*
  • Depression / genetics*
  • Depressive Disorder / classification
  • Depressive Disorder / genetics
  • Diseases in Twins / genetics
  • Female
  • Humans
  • Male
  • Models, Statistical
  • Phenotype
  • Prospective Studies
  • United Kingdom
  • Young Adult