the modulation of the AAO such as solar insolation, light exposure737475 or exposure to stimulants76, as well as antidepressants77. Among investigated environmental factors that modulate the AAO of BD, the role of early cannabis misuse has been widely proposed47879808182. The picture is further complicated by the possibility of significant additive effects evident between cannabis abuse and childhood abuse on an earlier AAO in BD81, suggesting the existence of a complex pathway that includes gene-environment modulation and environment/environment interactions. Finally other hypotheses are also relevant to be studied using potential interactions between 5HTTLPR and childhood trauma such as those concerning psychosis or suicidality in BD1783.
