Background There is a central belief that depression is associated with hyperactivity of the HPA-axis, resulting in higher cortisol levels. However, results are inconsistent. We examined whether there is an association between depression and cortisol levels in a large cohort.Implications - Dysregulation of the HPA axis is hypothesized to be one of the key mechanisms underlying depression. This study can provide more insight into this pathophysiological process. - Medication involved in HPA axis regulation is already being developed, however the exact role of the HPA axis in depression is unclear as is which patients would benefit from it. This study will give more evidence for the indication of such medication.Products - Papers - ThesisMethods Data are from 1,655 adults (18-65 years) of the NESDA cohort of 2,981 participants. Major depressive disorder (MDD): Based on MDD diagnosis (using the CIDI interview) and on scoring on the IDS (Inventory of Depressive Symptoms), participants were divided into three groups: -453 controls (no anxiety/depression diagnosis, IDS < 14, no psycho-active medication) -794 persons with MDD lifetime (MDD prior in their life, no current MDD ) -438 persons with MDD current (MDD in the past month, IDS >22 ) Cortisol saliva samples: collected at awakening, 30, 45 and 60 minutes later, at 22.00h, at 23.00h and at awakening the next morning after 0.5 mg dexamethasone ingestion. Samples were analyzed using the E-170 random access analyzer (Roche), competitive Electro Chemil Luminescence Immunoassay (ECLIA). SA Vreeburg 1, BP Kruijtzer 2, J van Pelt 2, R van Dyck 1, FG Zitman 3, RH de Rijk 3, WJ Hoogendijk 1, BW Penninx 1 1 Department of psychiatry and EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands 2 Laboratory for Clinical Chemistry and 3 Department of Psychiatry, LUMC Medical Center, Leiden, The Netherlands Depression and dysregulation of the HPA-axis Preliminary results of the Netherlands Study of Depression and Anxiety Preliminary results Table 1: Demographics Controls n=453 MDD lifetime n=794 MDD current n=438 p Mean age % Female Mean educational level Mean awakening time % Working (sampling day) % Smoking : : : < <0.001 The three groups show significant differences in sex, educational level, smoking and working on the day of cortisol measurement (see Table 1). Using Generalized Equations Estimation (GEE) analysis there was a significant group by time interaction (overall p>0.001) for the Cortisol Awakening Rise (CAR), indicating a different CAR for the three groups. These findings are adjusted for sex, age, smoking, season, awakening time, use of antidepressants, BMI, weekday and working on the day of cortisol measurement. As shown in figure 1 the four morning cortisol values comprising the CAR differed significantly between the three groups (overall p=0.03), with the highest values for respondents with current MDD and MDD prior in their life. No differences were observed for evening cortisol levels.Conclusion Preliminary results of this large cohort study indicate that depression is associated with modest, significant differences in the Cortisol Awakening Rise. Figure 1: cortisol values on the 6 sampling times Cortisol nmol/l min 22.00u 23.00u Time MDD lifetime MDD current Controls p overall.03 p overall >0.20