The effects of Effort-Based Reward (EBR) training and chemogenetic activation of the lateral habenula on behavioral and neuroendocrine responses in stressful contexts

The effects of Effort-Based Reward training and chemogenetic activation of the lateral habenula on behavioral and neuroendocrine responses in stressful contexts Major Depressive Disorder (MDD), commonly referred to as depression, is an affective psychiatric illness that impacts approximately 280 million people worldwide (World Health Organization, 2021). It is the leading cause of disability globally. Its prevalence increased three-fold during the COVID-19 pandemic (Winkler et al., 2020). More specifically, pandemic-related negative psychological states like fear of infection, financial stress, and loneliness were closely associated with symptoms of MDD (Hoffart et al., 2021). MDD is primarily characterized by depressed mood states, diminished pleasure in daily activities, feelings of worthlessness, fatigue, and loss of concentration (American Psychiatric Association, 2013). These symptoms significantly impede social and occupational functioning. Furthermore, neuropsychiatric disorders like MDD are the most relevant risk factors for death by suicide (Bachmann et al., 2018). As such, we must act with urgency to mitigate predispositions to this pervasive disorder. Additionally, it is crucial to elucidate the role of environmental and genetic risk factors in MDD pathophysiology, implement effective preventative strategies, characterize early behavioral, cognitive, and neurobiological markers, and develop novel diagnostic measures and therapeutic interventions