Cannabis and Depression: A Twin Model Approach to Co-morbidity

Abstract

Cannabis use disorder (CUD) co-occurs with major depressive disorder (MDD) more frequently than would be expected by chance. However, studies to date have not produced a clear understanding of the mechanisms underlying this co-morbidity. Genetically informative studies can add valuable insight to this problem, as they allow the evaluation of competing models of co-morbidity. This study uses data from the Australian Twin Registry to compare 13 co-morbidity twin models initially proposed by Neale and Kendler (Am J Hum Genet 57:935–953, 1995). The analysis sample comprised 2410 male and female monozygotic and dizygotic twins (average age 32) who were assessed on CUD and MDD using the SSAGA-OZ interview. Data were analyzed in OpenMx. Of the 13 different co-morbidity models, two fit equally well: CUD causes MDD and Random Multiformity of CUD. Both fit substantially better than the Correlated Liabilities model. Although the current study cannot differentiate between them statistically, these models, in combination, suggest that CUD risk factors may causally influence the risk to develop MDD, but only when risk for CUD is high.

Cannabis and Mood Disorders

“…This meta-analysis grouped heavy users as those fitting the criteria for CUD or weekly users in attempt to create more consistency across the studies, but it is important that future researchers work to create a validated measure of cannabis use across the research discipline [19**]. Finally, a recent twin study has helped to elucidate the temporal relationship of the association, and provided a model for understanding the development of this comorbidity [20]. They found that CUD risk factors lead to MDD symptoms using a model fitting approach [20].…”

“…Finally, a recent twin study has helped to elucidate the temporal relationship of the association, and provided a model for understanding the development of this comorbidity [20]. They found that CUD risk factors lead to MDD symptoms using a model fitting approach [20]. …”

US Epidemiology of Cannabis Use and Associated Problems

“…A study of polygenic risk suggested that cannabis use or CUD shared genetic risk with major depression ( Carey et al , 2016 ), as did a study of cannabis dependence using a genome-wide association approach ( Sherva et al , 2016 ). Additional genetic studies suggest either common causes underlying the comorbidity between CUD and major depression ( Hodgson et al , 2017 ) or a causal effect of CUD on major depression ( Smolkina et al , 2017 ). Thus, the nature of the relationship between cannabis use or CUD and psychiatric comorbidity remains a topic of debate.…”

Prevalence and correlates of major depression in Granada, Spain: Results from the GranadΣp study

“…Cannabis has been frequently linked to psychosis, but its association with depression is not as well studied and the direction of causality is not completely clear. However, cannabis use has been described as a risk factor for developing depression in a sufficient number of studies, while there is less evidence supporting the opposite (Degenhardt, 2002; Lev-Ran et al, 2013; Smolkina et al, 2017). Mechanisms by which cannabis could lead to depression include neurochemical alterations of monoamines, impaired cognitive performance and psychosocial failure (Marmorstein & Iacono, 2011; Nader & Sanchez, 2017; Van de Giessen et al, 2016).…”