Many factors and their interaction are linked to the aetiology of schizophrenia, leading to the development of animal models of multiple risk factors and adverse exposures. Differentiating between separate and combined effects for each factor could better elucidate schizophrenia pathology, and drive development of preventative strategies for high-load risk factors. An epidemiologically valid risk factor commonly associated with schizophrenia is adolescent cannabis use. The aim of this review is to evaluate how early-life adversity from various origins, in combination with adolescent cannabinoid exposure interact, and whether these interactions confer main, synergistic or protective effects in animal models of schizophrenia-like behavioural, cognitive and morphological alterations. Patterns emerge regarding which models show consistent synergistic or protective effects, particularly those models incorporating early-life exposure to maternal deprivation and maternal immune activation, and sex-specific effects are observed. It is evident that more research needs to be conducted to better understand the risks and alterations of interacting factors, with particular interest in sex differences, to better understand the translatability of these preclinical models to humans.

许多因素及其相互作用与精神分裂症的病因相关，从而导致了多种风险因素和不良暴露的动物模型的发展。区分每种因素的单独和联合作用可以更好地阐明精神分裂症的病理状况，并推动针对高负荷危险因素的预防策略的发展。通常与精神分裂症相关的流行病学有效危险因素是青少年使用大麻。这篇综述的目的是评估各种来源的早期逆境与青少年大麻素暴露如何相互作用，以及这些相互作用是否在精神分裂症样行为，认知和形态改变的动物模型中产生主要，协同或保护作用。关于哪些模型显示出一致的协同或保护作用，尤其是那些结合了生命早期暴露于母体剥夺和母体免疫激活的模型，并观察到了性别特异性效应，出现了一些模式。显然，需要进行更多的研究来更好地理解相互作用因素的风险和改变，尤其是对性别差异的兴趣，以便更好地理解这些临床前模型对人类的可翻译性。