Background, Aims, and Methods:

Depression is among the most prevalent of all psychiatric disorders, accounting for over 20% of economic costs for all mental illness. An important public health priority is the development of methods for identifying vulnerability to this disorder. The general aim of this project is to investigate the role of cognitive biases in the onset and course of major depression, including an examination, for the first time, of the neurobiological concomitants of these biases. More specifically, we are using multiple indicators of information-processing biases to examine the functional role of cognitive processing in Major Depression by predicting the course of depression over a one-year period.

We have identified a "High-Cognitive-Bias" subtype of depressed patient, which is characterized by strong and consistent negative biases across a range of information-processing tasks and stimuli, as well as by an elevated vulnerability to experiencing both ready activation of these negative biases and increased depressive symptoms when exposed to a sad mood induction procedure. Equally important, in this project we are localizing the neurobiological substrates of these cognitive biases and examining changes in brain activation in High- and Low-Bias depressed patients as a function of episode status. In addressing these issues and questions in this grant, we are conducting intensive evaluations of cognitive information-processing biases with state-of-the-art computerized assessments, and we are examining localized brain activation in response to emotional stimuli using functional Magnetic Resonance Imaging (fMRI), with patients diagnosed with Major Depressive Disorder, Panic Disorder, and Social Phobia.

We have now successfully developed and implemented a protocol and analytic procedure to allow us to identify a "High-Cognitive-Bias" subtype of depressed patient. Although these depressed patients do not differ in severity from their "Low-Cognitive-Bias" counterparts, we have found that they do demonstrate dramatically different psychosocial and biological functioning. We also now have promising data from a small number of participants suggesting that cognitive bias is related to treatment response.