Not all individuals exposed to childhood adversity develop depression and genotype may moderate the relationship between childhood adversity and mental health outcomes10;47. For instance, a polymorphism, rs1360780, in the FKBP5 gene (which regulates glucocorticoid regulator sensitivity) reportedly enhances risk for depression only in the presence of moderate/severe (but not mild) physical abuse48. Similarly, Cichetti et al found that maltreated individuals with the high activity genotype of the monoamine oxidase (MAOA) gene reported fewer depressive symptoms in the presence of self-coping strategies, indicating that the high activity allele produces a substrate, even in maltreated individuals, where receptivity to coping strategies is enhanced49. Our study demonstrates a similar stress-adaptive role for CNR1- this is important because the endogenous cannabinoid system, in rodent paradigms, has been found to afford stress buffering directly as well as indirectly, via modulation of HPA-axis activity.
