Thursday, April 3, 2025
4/3/2025
Neural and Behavioral Mechanisms of Angry Hostility in Depression - ABSTRACT Despite the fact that multiple different treatments for depression have been available for decades, the global burden of the illness has grown steadily. Depression is now one of the leading causes of disability worldwide. Current treatment strategies for depression remain largely trial-and-error, and fewer than 40% of patients respond to a given treatment and sustain that response for a year, even when treatment is continued. A central barrier to improving these outcomes is the need to characterize better phenotypes of depressive illness that are more closely aligned to modifiable neurobiological targets than are current symptom constellations and diagnostic codes. Findings from our group, and from others, suggest that one such phenotype involves the propensity to experience anger, hostility, and irritability following negative experiences and to respond in an aggressive, overly hostile manner (hereafter denoted Angry Hostility). Our preliminary data suggest that the Angry Hostility phenotype is associated with a particular pattern of altered functioning in neural regions that support emotion processing and emotion regulation. Furthermore, Angry Hostility appears to be strongly associated with hostile, aggressive behaviors following provocation and with real-world interpersonal and work- functioning impairments that can exacerbate depressive symptoms. The primary goal of this project is to test a novel model through which higher levels of Angry Hostility among adults with depression are associated with specific patterns of abnormal neural function and behavior, leading to poor functional outcomes and future symptoms. To achieve these goals, 150 adults (18-45 years old) with at least mild symptoms of depression will be recruited, as will 100 demographically matched, psychiatrically healthy individuals. Participants will complete clinical, neuroimaging, and laboratory behavioral assessments, as well as 4-, 8-, and 12-month follow-up assessments and four 10-day ecological momentary assessment protocols. The project will examine 1) whether Angry Hostility is associated with abnormal neural function in emotion processing and emotion regulation regions; 2) whether Angry Hostility is associated with aggressive behaviors in the laboratory and in real-world settings; and 3) whether abnormalities in a-priori neural systems and behaviors prospectively predict poorer real- world functioning and psychiatric symptoms over the 12-month follow-up. The aims of the project match well with the strategic goals of the National Institute of Mental Health. Moreover, the results of this study have the potential to describe the neurobiological bases, behavioral mechanisms, and real-world consequences of elevated Angry Hostility among adults with depression. Future work will aim to develop personalized treatments to target the neural mechanisms identified in this study in order to reduce symptoms and improve functional outcomes for adults with depression who have higher levels of Angry Hostility.
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