Co-morbid depression and sexual abuse during childhood as confounding factors in the analysis of glucocorticoid-receptor supersensitivity in patients with posttraumatic stress disorder Marcelo F. Mello, Andrea A. F. Mello, Juliana E. Ruiz, Victor Fossaluza, Jose Paulo Fiks, Rodrigo A. Bressan, Sergio B. Andreoli, Mariana C. P. Costa, Deborah Suchecki, Jair J. Mari INTRODUCTION Evidence shows t hat posttraumatic st r ess disorder (PTSD) patients have low basal cortisol levels and glucocorticoid-receptor (GR) supersensitivity following a pharmacological challenge. These findings, however, are controversial, partially due to the presence of confounding factors, such as co-morbidity with major depressive disorder (MDD) and childhood trauma. In the present study, salivary cortisol levels of victims of violence with and without PTSD were assessed following a prednisolone suppression t est (PST), controlling for the presence of MDD and sexual abuse during childhood. METHOD The sample was nested in an epidemiological study performed in São Paulo City. The subjects with a diagnosis of PTSD (PTSD+) and a matched control group (PTSD-) were submitted to SCID-I; after which Ear l y Trauma Invent ory (ETI), Clinician-Administered PTSD Scale (CAPS), Beck Depression (BDI) and Anxiety Inventory (BAI) and the Peritraumatic Dissociative Experiences Questionnaire (PDEQ) were used. Saliva samples were collected before and after 1,5 mg of prednisolone, administered at 10 PM. Discussion These results confirm previous findings that PTSD patients have lower cortisol levels by showing a blunted response to exogenous GC), which is likely due to increased GR responsiveness. Separating the patients with PTSD alone from those with co-morbid MDD showed that hypocortisolism is specific to PTSD, and the presence of MDD counterbalances PTSD-related dysfunction to “normalize” the curve of patients with both diagnoses. The presence of sexual abuse during childhood correlated negatively with lower the salivary cortisol concentrations. Early sexual abuse, but not other types of trauma such as general, physical, and psychological traumas, was correlated with cortisol dysfunction. The presence of sexual abuse during childhood is a potent risk factor for developing an Axis I diagnosis during adulthood [1]. Some authors find a correlation between early abuse and lower cortisol concentrations after a psychosocial stressor test and pharmacological challenge, an effect that is independent of the presence of an Axis I diagnostics [2-3]. The question raised here is whether the presence of severe sexual abuse during childhood and HPA axis response to stress is an endophenotype. Another aspect to consider is whether subjects with a particular type of HPA axis response are at a greater risk for PTSD development after a severe adulthood stressor. PTSD related to increased GR supersensitivity should be investigated further. Research also should address whether the presence of different endophenotypes depends on the timing of the trauma (considering epigenetic phenomenon). Interestingly, we did not find differences between controls and PTSD patients. Despite the fact that 40% of our sample had PTSD+MDD, the presence of PTSD symptoms had a predominant effect on HPA axis by lowering cortisol concentrations, as demonstrated by our comparison of PTSD+ (either with or without MDD) with controls. References 1. Green, J.G., et al., Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry, 2010. 67(2): p. 113-23. 2. Carpenter, L.L., et al., Cerebrospinal fluid corticotropin-releasing factor and perceived early-life stress in depressed patients and healthy control subjects. Neuropsychopharmacology, 2004. 29(4): p. 777-84. 3. Fries, A.B., E.A. Shirtcliff, and S.D. Pollak, Neuroendocrine dysregulation following early social deprivation in children. Dev Psychobiol, 2008. 50(6): p. 588-99. PTSD (Posttraumatic Stress Disorder), CAPS (Clinician-Administered PTSD Scale), BDI (Beck Depression Inventory), BAI (Beck Anxiety Inventory), ETI (Early Trauma Inventory), PDEQ (Peritraumatic Dissociative Experiences Questionnaire) . X 2 chi-square test, T=T test * p<.05 The red line represents salivary cortisol means at time points for PTSD patients, the blue line represents PTSD+MDD patients and green line represents control subjects. Night before 20h Wake-up (wu) 30min after wu 12h 16h PTSD+MDD (19) .157 .625 .542 .358 .232 PTSD alone (15) .167 .442 .381 .285 .346 Controls (14) .167 .607 .539 .252 .216 Table 3: Cortisol means ( µg/dL) at different time points on victims of violence with PTSD+MDD, PTSD alone and without axis I psychopathology Table 2: Non Parametric ANOVA Ordinal data for repeated measures Table 4: General linear Model regression (GLM) This study was partly funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant: 2004/15039-0, 2010/07432-5), and partly by a grant from the National Council of Research (CNPq – grant: 420122/2005-2). AFS received a scholarship from CNPq (133485/2006-9); AAFM and MCPC, from the Ministry of Education (CAPES grants: 02772/09-4 and 27909024886, respectively. Profs. Jair Mari, Marcelo F Mello, Rodrigo A. Bressan, Sergio B. Andreoli, and Deborah Suchecki are CNPq Researchers. RESULTS Table 1: Demographics and clinical characteristics of victims of assault with and without PTSD right protected. F1000 Po Posters. Copyright protected. F1000 Posters. Copyrig cted. F1000 Posters. Copyright protected. F1000 Posters. Copyright protected. opyright protected. F1000 Posters. Copyright protected. F1000 Posters. Copyright protected. F1000 Poster osters. Copyright protected. F1000 Posters. Copyright protected. F1000 Posters. Copyright protected. F1000 Posters. Copyr ght protected. F1000 Posters. Copyright protected. F1000 Posters. Copyright protected. F1000 P F1000 Posters. Copyright protected. F1000 Posters. Copyright protec rs. Copyright protected. F1000 Posters. Co protected. F100