Skip to main content

Kean University

Apply
Visit
Exclamation_Point_2_x2C__Caution_2_x2C__Warning_2 Created with Sketch.

Weather Alert

Due to the winter weather forecast, all classes that begin at 6 p.m. or later at Kean’s main campus in Union will be conducted remotely today, Tuesday, February 11. Classes that begin before 6 p.m. will operate as normal.

Only essential personnel should report to work as required after 6 p.m. today. Employees with questions about their status should consult their supervisors. Kean Ocean will follow the Ocean County College schedule. All students and employees at Kean Ocean are encouraged to visit the OCC website for updates.

DNA

Stress, Immune Function and Reward Learning  

According to the Centers for Disease Control and Prevention, nearly 57% U.S. teen girls felt persistently sad or hopeless in 2021, which is double that of boys, representing a nearly 60% increase and the highest level reported over the past decade. These sex differences in the prevalence of depression occur only after the onset of adolescence. Anhedonia – the loss of pleasure or lack of reactivity to pleasurable stimuli is a core feature and highly promising endophenotype of depression. According to the NIH’s recent update on the construct of anhedonia within the Positive Valence Systems of the Research Domain Criteria, anhedonia has been postulated to reflect impairments of reinforcement learning (RL) (i.e., the ability to learn stimulus-outcome associations from reward feedback to guide future behavior), which is supported by the corticostriatal dopaminergic (DA) reward circuit.  Attenuated reward responsivity in anhedonia has been extensively examined by the Reward Positivity (RewP) ERP, a fronto-central, event-related potential (ERP) component at the receipts of reward feedback. Many ERP studies consistently found that even asymptomatic adolescents of parents with depression show attenuated RewP amplitudes responding to reward feedback7. Accumulating evidence indicates that such blunted RewP ERP appears to be driven by more anticipatory aspects of reward deficits, “wanting”, which is essential for understanding how reward value deficits manifest in depression risk. Also, anhedonia is associated with impaired DA signals of reward prediction error and low learning rates8. However, the conventional RL tasks used in adults might not fully capture key aspect of RL, which is an incentive motivation that is central to anhedonia, which involves difficulties with the drive to pursue rewards, rather than just the enjoyment of them.  

One promising but understudied pathophysiological pathway that may drive reward deficits in anhedonia is stress-induced inflammation. Accumulating evidence indicates an association between inflammation and anhedonia9. In adults with depression, elevated markers of inflammation have been linked to anhedonia and dysregulated reward corticostriatal circuitry10. Administration of endotoxin and typhoid vaccination induce release of proinflammatory mediators such as interleukin-6 (IL-6) and blunted neural reactivity to monetary reward11-13 and reduce willingness to work for monetary reward14. One of the most relevant biobehavioral sources of elevated inflammation in anhedonia is stress15. Stress can activate the immune system, leading to the release of pro-inflammatory cytokines such as IL-616-18. These cytokines not only promote inflammation but also alter the DAergic corticostriatal circuitry involved in RL and motivation by decreasing DA release, reducing sensitivity to DA, or disrupting the communication between the prefrontal cortex and striatum, which leads to impaired reward learning, and motivation18 19 . Indeed, stress is a strong predictor of depression onset and has been specifically linked to anhedonia5 20 21. A widely used method to examine the influence of stress on behavioral responses in adults involves the use of acute laboratory stress 22-24. Acute psychosocial stress, as measured by laboratory-based, Trier Social Stress Test (TSST), increases inflammatory signaling, and this effect is associated with increased reward response bias scores in female adults25. This demonstrates the DAergic RL system to be highly sensitive to inflammatory signaling, including the relatively mild alterations that occur following a single episode of acute psychosocial stress. However, little is known about the mechanistic relationship of stress-induced inflammatory function to RL processes and depression in girls. Such information would be extremely useful for developing sex-specific interventions for depression that could ameliorate this highly treatment-resistant disorder. Despite the prominence of anhedonic symptoms in depression, and increased vulnerability for girls with higher levels of social stress than boys during early adolescence26 27, there are no approved therapeutics designed to attenuate the loss of responsivity to previously rewarding stimuli. 

This project aims to determine a mechanistic relationship of stress-induced inflammation and key RL processes in adolescent girls. The central hypothesis of this project is that a stress-induced inflammatory dysfunction in girls may impair normal DA signaling of reward representation (i.e., RewP ERP), and reward learning, resulting in increasing risk for depression.