Adolescence, characterized by important brain physiological maturation and reorganization under the influence of sex hormones, is a period of great vulnerability to stress, which can damage brain structures and lead to the emergence of psychopathologies.
Anxiety and depressive symptoms (internalizing disorders) increase and show sexual dimorphism during adolescence.
Stress induces activation of the hypothalamic-pituitary-adrenal (HPA) axis, which also activates inflammation and oxidative stress in interaction with each other. These mechanisms were found to be associated with internalizing disorders. The interaction between inflammation and oxidative stress was found to involve the matrix metalloproteinase 9 (MMP-9), which was also linked to depression and anxiety symptoms.
This study aims to explore the putative link between MMP-9 and internalizing disorders, as well as the influence of sex and pubertal status, under inflammatory, oxidative stress and stress conditions.
We used clinical and biological data from adolescents of the general population, with anxiety and depressive symptoms (Mindfulteen Study). We extracted Peripheral Blood Mononuclear Cells (PBMCs), which were stimulated by pro-inflammatory, pro-oxidative challenges, and/or hydrocortisone, and then measured MMP-9 activity.
Our results reported significantly higher levels of MMP-9 activity in females than in males after a pro- inflammatory challenge. Moreover, females showed a significant association between MMP-9 activity and depressive symptoms, under the pro-inflammatory and the pro-oxidative conditions, and a significant associations between MMP-9 activity and anxiety symptoms under the combination of both challenges. Males showed an association between MMP9 and anxiety only under the control condition. Our study suggests the involvement of MMP-9 in the inflammation/oxidative stress/HPA loop linked to internalizing symptoms, in a sex-dependent manner. No major effect of the pubertal status was observed.
Sexual dimorphism in the HPA/inflammation/oxidative stress/MMP-9 potentiation loop could underlie sex differences in vulnerability to internalizing disorders in adolescents. Further studies are needed to explore the role of puberty within this mechanism