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, fulfilling 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 associated 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 supports our hypothesis that an association between abnormal stress biomarkers and impaired cognition might be present in UHR individuals.