Nevertheless, the dualistic nature of IGF-1 is a big challenge of applying IGF-1 treatment to clinical trials [31]. Recent studies proposed that in humans, optimal cognitive functioning required an optimum level of IGF-1 and both low and high levels of IGF-1 may impair cognition [32, 33]. Chigogoraet al. discovered that both low and high levels of IGF-1 might be associated with higher risk of depression in humans [33]. Moreover, a recent report proposed pro-epileptic effect of IGF-1 and showed that long-term IGF-1 exacerbated epileptogenesis in vitroafter brain injury [31]. Further researches are needed to determine the optimum dose of IGF-1 required in human.