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J Affect Disord. 2010 Oct;126(1-2):14-38. doi: 10.1016/j.jad.2009.11.006. Epub 2009 Dec 11.

Genetic and environmental influences on psychiatric comorbidity: a systematic review.

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Center for Urban Epidemiologic Studies, New York Academy of Medicine, New York, NY, 10029, USA.



The purpose of this review is to systematically appraise the peer-reviewed literature about the genetic and environmental determinants of psychiatric comorbidity, focusing on four of the most prevalent types of psychopathology: anxiety disorders, depression, conduct disorder and substance abuse.


We summarize existing empirical research on the relative contribution that genetic, nonshared and shared environmental factors make to the covariance between disorders, and evidence about specific genes and environmental characteristics that are associated with comorbidity.


Ninety-four articles met the inclusion criteria and were assessed. Genetic factors play a particularly strong role in comorbidity between major depression and generalized anxiety disorder or posttraumatic stress disorder, while the non-shared environments make an important contribution to comorbidity in affective disorders. Genetic and non-shared environmental factors also make a moderate-to-strong contribution to the relationship between CD and SA. A range of candidate genes, such as 5HTTLPR, MAOA, and DRD1-DRD4, as well as others implicated in the central nervous system, has been implicated in psychiatric comorbidity. Pivotal social factors include childhood adversity/life events, family and peer social connections, and socioeconomic and academic difficulties.


Methodological concerns include the use of clinical case-control samples, the focus on a restricted set of individual-level environmental risk factors, and restricted follow-up times.


Given the significant mental health burden associated with comorbid disorders, population-based research on modifiable risk factors for psychiatric comorbidity is vital for the design of effective preventive and clinical interventions.

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