Sex-hormone fluctuations as a risk model of mood disorders; GnRH-agonist model
Gonadotrophin Releasing Hormone agonists (GnRHa)
The endavour of this series of experiments is to uncover possible associations between fluctuations in sex-steroid hormone levels and brain biology, brain structure and architecture, stress and inflammatory responses, and neurocognitive functions of importance in neuropsychiatric disorders.
Sex matters in normal brain function as in neuropsychiatric and neurodegenerative disorders. The vulnerability to mood and anxiety disorders is considerably greater in women, e.g major depression is twice as prevalent in women as in men. In particular, women going through phases in life where endogenous sex hormone levels decline rapidly from high levels as postpartum or during menopausal transition are more vulnerable to psychiatric disorders. However, the neurobiological mechanisms involved are unclear. Interestingly, increased variability of plasma levels of estradiol is associated with the risk of developing depressive symptoms or major depression in the menopausal transition period. Therefore, a biphasic ovarian sex-steroid hormone response induced pharmacologically provides a unique opportunity to study how sex-hormone fluctuations provoke mood state changes and increase vulnerability to neuropsychiatric disorders.
In the GnRH-agonist model work we investigate neuropsychobiological effects of sex-steroid hormone fluctuations in a group of healthy female volunteers in a placebo controlled doubleblinded study design. Further, we work with translational rodent designs.
Research in neuropsychobiological correlates of vulnerability related to sex-steroid hormone changes is pivotal to improve the etiological understanding of brain disorders with gender differences. Such research may contribute to improve treatment of neuropsychiatric diseases, and, ideally, shed light on possible preventive strategies in vulnerable phases of women’s lives.