Central serotonergic activity correlates with salivary cortisol after waking in depressed patients

Abstract

Aberrant patterns of cortisol secretion and serotonergic dysfunction are important features of major depressive disorder (MDD). A multitude of studies investigated the relationship between cortisol and serotonin. Increased salivary cortisol was found after waking in depressed patients (Bhagwagar et al. 2005, 2003). It is assumed that this cortisol awakening reaction (CAR) may be a more exact marker of depression instead of the general assumption of hypercortisolism (Bhagwagar et al. 2005). The present study aimed at investigating the relationship between cortisol and serotonergic function from a new angle. Loudness dependence of auditory-evoked potentials (LDAEP) indicates the activity of synaptically released serotonin. It measures the amplitude change of the auditoryevoked N1/P2 component in response to different stimulus intensities. A low LDAEP indicates a high serotonergic activity and vice versa (Juckel et al. 1996, 1997, 2004, 2007). After excluding four patients with insufficient cortisol data, 12 non-medicated MDD patients [seven females, mean age 47.9±8.6 years, mean Beck Depression Inventory (BDI-II) score 27.4±7.5, all outpatients] were compared to 16 healthy controls (nine females, mean age 50.1± 7.3 years). Structured clinical interview for DSM-IV and BDI-II were used as diagnostic instruments. Salivary cortisol samples were collected in salivettes. CAR was measured by subtracting the cortisol concentration upon waking from the cortisol concentration 30 min after getting up. A time-resolved immunoassay with fluorescence detection was used for cortisol analysis (Lederbogen et al. 2010). Auditory-evoked potentials were tested using a standard procedure. Three hundred fifty sinus tones of five different intensities (60–100 dB SPL) were presented in a pseudorandomised way using Presentation 11.3® (Neurobehavioral Systems Inc., Albany, CA, USA). Artifact-free stimuli were averaged with BrainVision Analyzer® (Brain Products GmbH, Munich, Germany). The N1 amplitude was regarded as the lowest point between 50 and 150 ms after the stimulus, P2 as the highest point between 100 and 250 ms post-stimulus and the N1/P2 amplitude was calculated as the amplitude difference. The LDAEP was calculated as the median slope of the single loudness levels (for further details see Roser et al. 2009). There were no significant differences between patients and controls regarding CAR levels (patients, 7.06±10.07; controls, 13.19±9.70; t test, p=0.129). There was a nonsignificant tendency towards a decreased LDAEP in depressed patients (0.13±0.18) compared to healthy controls (0.24±0.17; t test, p=0.089). I. Uhl (*) : C. Norra :G. Juckel Department of Psychiatry, Psychotherapy and Preventive Medicine, Ruhr University Bochum, LWL University Hospital Bochum, Alexandrinenstrasse 1-3, 44791 Bochum, Germany e-mail: idun.uhl@wkp-lwl.org