Grant: Project Grant

Major depressive disorder (MDD) affects 20% of the population and females are twice more likely to develop MDD compared with males. Furthermore, cognitive symptoms of depression, including negative cognitive bias, are more severe in females than in males. Negative cognitive bias is the increased perception of ambiguous situations as negative and predicts the onset of future depressive episodes. Current treatments to reduce MDD symptoms are only effective for a subset of the population and are not effective for reducing negative cognitive bias. The discovery of underlying mechanisms of negative cognitive bias would facilitate the development of new effective treatments for MDD and a focus on sex differences would allow for improved precision treatments for MDD. Our work to date suggests that negative cognitive bias might be influenced by activity in the hippocampus, a region that is known to be important for memory and is comprised with MDD. In these experiments we will begin to understand the brain representation of negative cognitive bias and how it might change with sex and exposure to chronic unpredictable stress (CUS) which is a reliable model of stimulating depressive-like symptoms. We expect that males and females will differ in not only where in the brain that negative cognitive bias is expressed but in the different cells that express this symptom of depression. In addition, we will examine the role of neurogenesis and inflammation in negative cognitive bias and how it may be different between the sexes. Ultimately, we understand that determining the association among the activation of different brain regions and cell types, neuroinflammation, neuroplasticity and negative cognitive bias will result in tailored precision treatments for cognitive dysfunction in females and males with MDD.