Insulin Like Growth Factor 1 Moderates the Influence of the BDNF P.Val66Met Variant on Depression Severity in Adolescent Depression

Abstract

Background: A genetic influence for adolescent depression has been described in numerous studies. The product of the brain-derived neurotrophic factor gene (BDNF; rs6265 c.196G>A; p.Val66Met) has been identified playing an important role in genesis and course of depression. It interacts with serological BDNF and other growth factors such as the Insulin-like-Growth Factor 1 (IGF-1), influencing memory-associated brain regions (i.e. hippocampus, parahippocampal gyrus and entorhinal cortex) as well as reward-related brain circuits (cf. nucleus accumbens, amygdala and frontal areas). Methods: 40 patients with adolescent depression aged 13 to 17 years, were included. Assuming a significant influence of the BDNF p.Val66Met variant on depression severity, we performed moderation analyses to further examine the interplay between BDNF p.Val66Met variant, serological IGF-1, regional brain volume and depression severity. Results: IGF-1 was found to moderate significantly the influence of BDNF p.Val66Met variant on depression severity. Brain volumes of (para) hippocampal, and amygdala as well as the nucleus accumbens moderated the same only in combination with IGF-1. Conclusions: We discuss the significant influence of serological IGF-1 and BDNF p.Val66Met variant in terms of neuroplasticity. We interpret the role of changes in memory and reward-related brain circuits as hints towards the localization of the interaction between BDNF p.Val66Met variant and IGF-1. Our findings point to a potential mechanism in juvenile depression which differs from actual models in adult depression and could in a further step contribute to targeted therapies for depressive adolescents.