Examining HPA-axis functioning as a mediator of the relationship between depression and cognition across the adult lifespan

ABSTRACT

Altered HPA-axis functioning is a hypothesized mechanism for worsened cognition in depression. The current study examines the indirect effects of depression on processing speed, executive functioning, and memory as a function of the HPA-axis. 38 individuals with a depression diagnosis and 50 healthy controls (HCs) aged 18–86 underwent neuropsychological testing and at-home diurnal salivary cortisol collection. Depression was assessed via structured clinical interviews and rating scales. Cognitive composite scores were derived from factor analysis. Daytime cortisol exposure was estimated using area under the curve (AUC). Depression was associated with higher cortisol levels and slower processing speed . A significant suppression effect of AUC was present on the relationship between depression and processing speed. Limitations include the cross-sectional design and limited sample heterogeneity. Though poorly modulated HPA-axis is one proposed mechanism of cognitive alterations in depression, our results did not support this conclusion for processing speed. Alternative mechanisms should be considered to inform interventions to target cognitive alterations in depression.

KEYWORDS:

• Depression
• cortisol
• memory
• speeded processing
• cognition
• HPA-axis

Acknowledgments

We would like to thank all of those who contributed to data collection and processing including Laura Gabriel, Michael-Paul Schallmo, Brennan Haase, Katie Hazlett, Rachel Kay, Hadia Leon, Alyssa Barba, Viginia Murphy-Weinberg, Nadia M Huq, Leslie Guidotti Breting, Benjamin Long, Lawrence Own, and Arpita Mohanty. Thank you to our participants whom without this study would not be possible. This work was presented in part at the 2017 Annual Meeting of the International College of Geriatric Psychoneuropharmacology.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors have nothing to disclose. This work was supported by the following grants: RO1 (SAL, MH 091811), K-23 NIMH (SAL, MH 074459), K-12 RR017607 (SAL), Rachel Upjohn Clinical Scholars Award (SAL, SLW), UMMC Psychiatry Protocol Review Committee (SAL), Meader Research Fund for Depression/Genetics/Pain (SAL/SLW), PO1 MH 42251 (HA, JKZ, EAY), MO1 RR00042 General Clinical Research Center (SAL), Heinz C. Prechter Longitudinal Bipolar Project (MGM), NARSAD (SAL), MADRC Investigation of Neuroanatomical Networks to Understand Late Onset Depression, (SAL/SLW); Brain and Behavior Research Foundation [NARSAD Young Investigator Award]; National Institute of Health [K-12 RR017607,K-23 MH 074459]; University of Michigan [Heinz C. Prechter Longitudinal Bipolar Project, Investigation of Neuroanatomical Networks to Under,MO1 RR00042 General Clinical Research Center, Meader Research Fund for Depression/Genetics/Pain, Psychiatry Protocol Review Committee, Rachel Upjohn Clinical Scholars Award].