Associations between Saliva Alpha-Amylase, Heart Rate Variability, Saliva Cortisol and Cognitive Performance in Individuals at Ultra High-Risk for Psychosis

Abstract

Background: Cognitive impairments are present in individuals at ultra-high risk (UHR) of psychosis and UHR individuals exhibit a hyperactive and dysfunctional HPA-axis. Increasing stress levels could potentially lead to cognitive impairments and no previous studies have examined the association between physiological stress biomarkers and cognition in UHR individuals. This study aims to examine the association between saliva alpha-amylase (SAA), heart rate variability (HRV), saliva cortisol, and cognition in UHR individuals.

Method: We included 72 UHR individuals, aged 18-40, fulifilling criteria of the comprehensive assessment of at-risk mental state (CAARMS). Cognitive tests indexed the 7 core domains as stated by Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS). Physiological stress levels were observed for one day: saliva was collected at awakening, 30 min and 60 min after awakening and at bedtime. HRV was measured during sleep and before awakening. We used generalized linear model and controlled for multiple testing using false discovery rate (FDR).

Results: Higher levels of SAA were significantly associated with lower cognitive performance in the domains of verbal and visual learning and memory, sustained attention, working memory and global neurocognition looking at unadjusted data. Controlling for FDR visual memory, sustained attention and global neurocognition remained significant assoicated with SAA. We discovered no associations between cortisol and cognition.

Conclusion: Visual learning and memory, sustained attention and global neurocognition remained significantly associated with SAA. This finding support our hypothesis that an association between abnormal stress biomarkers and impaired cognition might be present in UHR individuals.

Note:
Clinical Trial Registration Details: The trial was registered at ClinicalTrial.gov (NCT02098408).

Funding Information: The study was supported by the Lundbeck Foundation (grant no R25-A2701 and grant no R287-2018-1485), the Mental Health Services, Capital Region of Denmark and Lundbeck Foundation, Scholarship in Psychiatry (grant no R355-2020-945).

Declaration of Interests: The authors have declared that there are no conflicts of interest.

Ethical Approval Statement: The Committee on Health Research Ethics of the Capital Region Denmark (study: H-6-2013-015) and the Danish Data Protection Agency (RHP-2014-009-02670) approved the protocol.

Keywords: Ultra High-Risk, cognition, Stress, Saliva-alpha-amylase, Heart-rate-variability, Cortisol