Stress, particularly during childhood (juvenile period of life), is a major risk factor for depression, a psychiatric disorder with a two-fold higher prevalence in women compared with men. Thus, in addition to juvenile stress, biological sex is an important contributor of depression susceptibility. However, the neurobiology underlying how stress during childhood differentially affects the female and male brain thus resulting in increased risk for females to develop depression in later in adulthood remains unknown.
Current antidepressant drugs are suboptimal as they have a slow onset of action, unwanted side-effects and are ineffective in many individuals. The development of new more effective antidepressants has been hampered by our lack of understanding of the pathophysiology underlying depression and how stress contributes to this. Moreover, 80% of animal drug discovery studies investigating this issue have neglected to include females and analyse biological sex as a variable. This startling inattention to the female brain is impeding antidepressant drug discovery and may partly explain the poor translation of discoveries made exclusively in male animal models to successful new treatments used to treat both women and men. This project aims to bridge these fundamental gaps in knowledge by identifying the areas of the brain that underlie sex-dependent and sex-independent susceptibility to juvenile stress-induced depression later in adult life. These findings will drive antidepressant drug development forward by identifying the brain regions that should undergo future molecular analysis in a sex-independent and/or sex-dependent manner for the purpose of identifying novel targets for future antidepressant drug development.
