An understanding of the neurobiology of anxiety and depression and alcohol use disorder and response to medications

Project Description

Psychiatric disorders such as anxiety and depression are often observed in patients with alcohol use disorder (AUD). The high likelihood of the co-occurrence of experiencing anxiety and depression, and AUD, likely reflects common pathophysiological mechanisms and neurobiological adaptations. The treatment options for patients with anxiety and depression and AUD are limited, and there can be progression of AUD as a coping mechanism due to a limited response to first-line anti-anxiety or anti-depression medication. Hence, improved pharmacotherapeutic approaches will require a better understanding of the underlying neurobiology. In order to investigate this further, this project will consider gene and protein changes in brain tissue from patients with AUD, depression, and both AUD and depression and compare them with age, and sex-matched control subjects. Brain tissue macroscopically dissected (post-mortem) from the pre-frontal cortex will be used for the studies. In addition, AUD changes and responses to anti-anxiety and anti-depression medications will be modelled in vitro using pluripotent stem cells and 3D organoid cultures and compared with gene and protein changes established using the ex vivo approach. The identification of the gene and proteomic changes in neurobiological pathways that have been altered in these patient cohorts will help direct future medical interventions.