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Original Investigation |

The Phenotypic and Genetic Structure of Depression and Anxiety Disorder Symptoms in Childhood, Adolescence, and Young Adulthood ONLINE FIRST

Monika A. Waszczuk, MSc1; Helena M. S. Zavos, PhD1; Alice M. Gregory, PhD2; Thalia C. Eley, PhD1
[+] Author Affiliations
1King’s College London, MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, London, England
2Department of Psychology, Goldsmiths, University of London, London, England
JAMA Psychiatry. Published online June 11, 2014. doi:10.1001/jamapsychiatry.2014.655
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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.

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Multivariate Model Diagrams

The diagrams present the 3 multivariate models fitted to the data: correlated factors solution (DSM-5 conceptualization) (A), 1-factor independent pathway model (unidimensional conceptualization) (B), and 2-factor independent pathway model (bidimensional distress and fear conceptualization) (C). The figure is for illustrative purposes only; only the genetic and nonshared environmental associations are shown. The diagram in part A illustrates only the genetic and nonshared environmental correlations between depression and anxiety subscales. Ac and Ac1 indicate additive genetic influences acting via a common factor on all variables; Ac2, additive genetic influences acting via a common factor on 3 fear variables; As, additive genetic influences acting on a specific variable; Ec, nonshared environmental influences acting via a common factor on all variables; and Es, nonshared environmental influences acting on a specific variable.

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