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[Preprint]. 2026 Mar 10:2026.01.27.26344962. Originally published 2026 Jan 30. [Version 2] doi: 10.64898/2026.01.27.26344962

The Neuroendocrine Profile During the Trier Social Stress Test in College Freshmen Offers Insights into the Emergence of Anxiety and Depression Symptoms

Huzefa Khalil, Cortney A Turner, Virginia Murphy-Weinberg, Linda Gates, Fei Li, Alexandra Onica, Keiko Arakawa, Lauren Weinberg, Clare Stack, Juan F Lopez, Stanley J Watson, Huda Akil
PMCID: PMC12870633  PMID: 41646822

Abstract

Background

The Michigan Freshman Study on Stress and Resilience aims to identify factors that predict the emergence of depression and/or anxiety symptoms in college freshmen. We previously showed that a combination of psychiatric instruments (Affect Score) strongly predicts who will develop such symptoms during the freshman year. Here, we ask: a) Can we replicate the predictive power of the Affect Score in an independent cohort? and b) Can the neuroendocrine profile during the Trier Social Stress Test (TSST) serve as an additional predictor?

Methods

A new cohort of subjects (N= 357) was used for Affect Score replication. The TSST study involved 337 subjects (Females 184, Males 153). Self-report questionnaires at the start of the year were used to derive the Affect Score. GAD-7 and PHQ-9 were used to monitor anxiety and depression, respectively. TSST measures involved plasma ACTH and Cortisol and heart rate monitoring.

Results

The Affect Score proved to be a highly replicable predictor of future depression and anxiety. In the TSST, subjects not currently depressed but who developed depression at another timepoint during the year showed a higher and delayed peak of the CORT response. Female subjects not currently anxious but who developed anxiety at another timepoint had an elevated CORT response throughout the TSST. This hyperresponsiveness was not correlated with Affect Score and was an independent predictor of anxiety.

Present address

Michigan Neuroscience Institute, University of Michigan, A. Alfred Taubman Biomedical Science Research Building, Rm 2009, Ann Arbor, MI, 48109-9901, USA

Author Contributions

HK performed research, analyzed data, wrote the paper; CAT designed research, performed research, wrote the paper; VM-W designed research, performed research; LG, FL, AO, KA and LW performed research; CS coded and analyzed data; JFL designed research; SJW Jr designed research; HA designed research, wrote the paper.

Funding

This work was supported by the Office of Naval Research (ONR) Grant N00014-09-1-0598, N00014-12-1-0366 and N00014-19-1-2149, the Pritzker Neuropsychiatric Disorders Research Consortium Fund, LLC and the Hope for Depression Research Foundation. This project was also supported by Grant Number P30DK020572 (MDRC) from the National Institute of Diabetes and Digestive and Kidney Diseases.

Competing interests

The authors declare no competing interests.

Conclusions

The Affect Score is a powerful predictor of depression and anxiety in college freshmen. The combination of Affect Score and TSST is strongly predictive of anxiety in females.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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