Diurnal salivary alpha-amylase and not cortisol differentiates major depressive disorder in out-patients

Introduction To date, there are few putative biomarkers specifically for MDD. Such biomarkers could help improve our understanding of MDD pathophysiology, and aid in the refinement of current MDD criteria. Research has shown that the stress hormone cortisol in saliva, a non-invasive marker of hypothalamus pituitary adrenal (HPA) axis activity, can differentiate between healthy controls and patients with psychiatric disorders on a group level. Another interesting system for putative biomarkers is the autonomic nervous system (ANS). Animal studies have indicated the involvement of the ANS, and specifically the sympathetic nervous system (SNS) in the release of the enzyme alpha amylase in saliva (sAA), whereby sAA has been proposed to be an index of sympathoadrenal medullary (SAM) activity. This theory is based on the premise that the (para-)sympathetic branches of the autonomic nervous system innervate salivary glands, whereby sympathetic stimulation increases salivary protein secretion [1]. In line with these findings, sAA has been positively correlated with the acute SNS stress response in adults [2]. Many studies have since demonstrated that MDD patients generally have higher sAA in comparison to healthy controls within experimental settings [i.e.3]. However, what remains unknown is the natural diurnal sAA profile of MDD patients in comparison to patients with other psychiatric disorders and healthy controls. Aims To determine the diurnal profiles of sAA and salivary cortisol in out-patients with MDD, patients with other affective disorders, and healthy controls. Methods sAA and salivary cortisol levels were determined from 7 saliva samples collected over the course of the day from 833 participants that partook in our Routine Outcome Monitoring [4] measurement (i.e., 97 MDD patients, 142 patients with other psychiatric problems, and 594 controls). ANOCVAs were conducted to examine the differences in both diurnal sAA and salivary cortisol between the MDD patient group, the other psychiatric disorder group, and healthy controls. In this, covariates were entered into the model in accordance with factors that have been found to be influential on these markers in previous research. Results On average, MDD patients had higher sAA levels upon awakening and (Area under the Curve) AUC i in comparison to both controls and patients with other psychiatric problems. Elevated evening cortisol levels were found in MDD patients in comparison to both controls and patients with other psychiatric problems. Cortisol values in MDD patients and patients with other psychiatric problems were higher after ingestion of dexamethasone upon awakening on day 2. Conclusion sAA levels were found to be higher in MDD patients at awakening and with respect to the AUC i , whereas no time-point measured indicated elevated sAA levels in the other affective disorders group or the healthy controls. Salivary cortisol was unable to differentiate between MDD and other affective disorders as successfully as sAA, suggesting that sAA levels at awakening may have stronger differentiating qualities for MDD specifically.