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  1. 1. CORTISOL AND PTSD Hypothalamic-pituitary-adrenal axis function in dissociative disorders, post-traumatic stress disorder, and healthy volunteers. Author Simeon, Daphne; Knutelska, Margaret; Yehuda, Rachel; Putnam, Frank; Schmeidler, James; Smith, Lisa M Affiliation Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. Source Biological psychiatry, 2007 Apr 15, 61(8):966-73. Epub: 2006 Nov 29 ISSN 0006-3223 Effects of parental PTSD on the cortisol response to dexamethasone administration in their adult offspring. Yehuda, Rachel; Blair, William; Labinsky, Ellen; Bierer, Linda M The American journal of psychiatry, 2007 Jan, 164(1):163-6 ... dexamethasone suppression test to examine the effect of a PTSD risk factor, parental PTSD, on cortisol negative feedback inhibition in adult offspring of Holocaust survivors with PTSD (N=13) versus without ... Enhanced cortisol suppression to dexamethasone associated with Gulf War deployment Golier, Julia A1; Schmeidler, James2; Legge, Juliana1; Yehuda, Rachel1 Psychoneuroendocrinology. Vol 31(10), Nov 2006, pp. 1181-1189 Objective: To examine whether PTSD or post-deployment health symptoms in veterans of the first Gulf War (Operation Desert Shield/Storm) are associated with enhanced suppression of the pituitary-adrenal axis to low-dose dexamethasone (DEX). Method: Plasma cortisol and lymphocyte glucocorticoid receptor (GR) number were measured at 08:00 h on two consecutive days, before and after administration of 0.5 mg of DEX at 23:00 h in 42 male Gulf War veterans (14 without psychiatric illness, 16 with PTSD only, and 12 with both PTSD and MDD) and 12 healthy male veterans not deployed to the Gulf War or another war zone. Results: In the absence of group differences in basal cortisol levels or GR number, Gulf War veterans without psychiatric illness and Gulf War veterans with PTSD only had significantly greater cortisol suppression to DEX than non-deployed veterans and Gulf War veterans with both PTSD and MDD. Gulf War deployment was associated with significantly greater cortisol suppression to DEX controlling for weight, smoking status, PTSD, and MDD; PTSD was not associated with response to DEX. Among Gulf War veterans musculoskeletal symptoms were significantly associated with cortisol suppression and those who reported taking anti- nerve gas pills (i.e., pyridostigmine bromide) during the war had significantly greater DEX-induced cortisol suppression than those who did not. Conclusions: The data demonstrate that alterations in neuroendocrine function are associated with deployment to the Gulf War and post-deployment musculoskeletal symptoms, but not PTSD. Additional studies are needed to examine the relationship of enhanced glucocorticoid responsivity to deployment exposures and chronic unexplained medical symptoms in Gulf War veterans. (PsycINFO Database Record (c) 2006 APA, all rights reserved) (journal abstract)
  2. 2. PTSD and the HPA axis: Differences in response to the cold pressor task among individuals with child vs. adult trauma Santa Ana, Elizabeth J1; Saladin, Michael E2; Back, Sudie E1; Waldrop, Angela E1; Spratt, Eve G3; McRae, Aimee L1; LaRowe, Steven D4; Timmerman, Mary Ann1; Upadhyaya, Himanshu1; Brady, Kathleen T1 Psychoneuroendocrinology. Vol 31(4), May 2006, pp. 501-509 Hypothalamic pituitary adrenal (HPA) axis and subjective stress response to a cold-water immersion task, the cold pressor task (CPT), in individuals (N=89) with post-traumatic stress disorder (PTSD) were examined. All tests were conducted at 08:00 h after an overnight hospital stay. Plasma adrenocorticotrophin hormone (ACTH), cortisol, and subjective stress were examined at baseline and five post-task time points in controls (n=31), subjects with PTSD as a result of an index trauma during childhood (i.e. before age 18; n=25), and subjects with PTSD as a result of an index trauma as an adult (n=33). Approximately, 50% of individuals in both trauma groups were alcohol dependent, and the impact of this comorbidity was also examined. Subjects with PTSD, regardless of age of index trauma, had a less robust ACTH response as compared to controls. Regardless of the presence or absence of comorbid alcohol dependence, subjects with childhood trauma had lower cortisol at baseline and at all post-task measurement points and did not demonstrate the decrease in cortisol over the course of the 2 h monitoring period seen in subjects with adult index trauma and controls. The findings reveal differences in the neuroendocrine response to the CPT in individuals with PTSD compared to control subjects, and differences in PTSD subjects when examined by age of index trauma. (PsycINFO Database Record (c) 2006 APA, all rights reserved) (journal abstract) Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder Yehuda, Rachel1; Halligan, Sarah L1; Golier, Julia A1; Grossman, Robert1; Bierer, Linda M1 Psychoneuroendocrinology. Vol 29(3), Apr 2004, pp. 389-404 To evaluate cortisol suppression following 0.5 mg of dexamethasone (DEX) in trauma survivors (N = 52) with posttraumatic stress disorder (PTSD), major depressive disorder (MDD), both, or neither disorder, and in subjects never exposed to trauma (N = 10), in order to examine interactions between diagnosis and trauma history on cortisol negative feedback inhibition. Lifetime trauma exposure and psychiatric diagnoses were assessed and blood samples were obtained at 8:00 a.m. for the determination of baseline cortisol. Participants ingested 0.5 mg of DEX at 11:00 p.m. and blood samples for determination of cortisol and DEX were obtained at 8:00 a.m. the following day. PTSD was associated with enhanced cortisol suppression in response to DEX. Among trauma survivors, the presence of a traumatic event prior to the focal trauma had a substantial impact on cortisol suppression in subjects with MDD. Such subjects were more likely to show cortisol alterations similar to those associated with PTSD, whereas subjects with MDD with no prior trauma were more likely to show alterations in the opposite direction, i.e. relative non-suppression. Cortisol hypersuppression in PTSD appears not to be dependent on the presence of traumatic events prior to the focal trauma. (PsycINFO Database Record (c) 2006 APA, all rights reserved)
  3. 3. Cortisol response to a cognitive stress challenge in posttraumatic stress disorder (PTSD) related to childhood abuse Bremner, J D1; Vythilingam, M2; Vermetten, E1; Adil, J1; Khan, S1; Nazeer, A1; Afzal, N1; McGlashan, T3; Elzinga, B1; Anderson, G M4; Heninger, G3; Southwick, S M3; Charney, D S2 Psychoneuroendocrinology. Vol 28(6), Aug 2003, pp. 733-750 Patients with posttraumatic stress disorder (PTSD) have been found to have normal or decreased function of the hypothalamic-pituitary-adrenal (HPA) axis, however no studies have looked at the HPA response to stress in PTSD. This study assessed cortisol responsivity to a stressful cognitive challenge in patients with PTSD related to childhood abuse. Salivary cortisol levels, as well as heart rate and blood pressure, were measured before and after a stressful cognitive challenge in patients with abuse-related PTSD (N=23) and healthy comparison Ss (N=18). PTSD patients had 61% higher group mean cortisol levels in the time period leading up to the cognitive challenge, and 46% higher cortisol levels during the time period of the cognitive challenge, compared to controls. Both PTSD patients and controls had a similar 66-68% increase in cortisol levels from their own baseline with the cognitive challenge. Following the cognitive challenge, cortisol levels fell in both groups and were similar in PTSD and control groups. PTSD patients appeared to have an increased cortisol response in anticipation of a cognitive challenge relative to controls. Although cortisol has been found to be low at baseline, there does not appear to be an impairment in cortisol response to stressors in PTSD. (PsycINFO Database Record (c) 2006 APA, all rights reserved) Low cortisol and risk for PTSD in adult offspring of Holocaust survivors Yehuda, Rachel1; Bierer, Linda M; Schmeidler, James; Aferiat, Daniel H; Breslau, Ilana; Dolan, Susan American Journal of Psychiatry. Vol 157(8), Aug 2000, pp. 1252-1259 Examined the association between cortisol and putative risk factors for posttraumatic stress disorder (PTSD) in a sample of Ss at increased risk for the development of PTSD. 24-hr urinary cortisol excretion was measured in 35 26-50 yr old adult offspring of Holocaust survivors and 15 23-51 yr old healthy comparison Ss who were not offspring of Holocaust survivors. Ss were also characterized with regard to clinical symptoms, presence or absence of psychiatric diagnoses including PTSD, and presence or absence of PTSD in their parents. The results show that low cortisol levels were significantly associated with both PTSD in parents and lifetime PTSD in Ss, whereas having a current psychiatric diagnosis other than PTSD was relatively, but nonsignificantly, associated with higher cortisol levels. Offspring with both parental PTSD and lifetime PTSD had the lowest cortisol levels of all study groups. It is concluded that parental PTSD, a putative risk factor for PTSD, appears to be associated with low cortisol levels in offspring, even in the absence of lifetime PTSD in the offspring. The findings suggest that low cortisol levels in PTSD may constitute a vulnerability marker related to parental PTSD as well as a state-related characteristic associated with acute or chronic PTSD symptoms. (PsycINFO Database Record (c) 2006 APA, all rights reserved)
  4. 4. Phenomenology and psychobiology of the intergenerational response to trauma Yehuda, Rachel1; Schmeidler, Jim; Elkin, Abbie; Wilson, Skye; Siever, Larry; Binder- Brynes, Karen; Wainberg, Milton; Aferiot, Dan Danieli, Yael (Ed). (1998). International handbook of multigenerational legacies of trauma. The Plenum series on stress and coping. (pp. 639-655). New York, NY, US: Plenum Press. xxiii, 710 pp. From the chapter) This chapter examines preliminary findings from 3 studies in progress on the phenomenology and neurobiology of posttraumatic adaptations in Holocaust survivors and their offspring. Study 1 examined the relationship between posttraumatic stress disorder (PTSD) symptoms in 19 parents and their offspring. Results indicated that the level of severity of some PTSD symptoms in parents and their children are correlated and provide support that offspring may be influenced by the symptoms of their parents. Study 2 compared 24 1st- and 2nd-generation survivors on biological variables (urinary cortisol excretion). This group was compared to a sample of Holocaust survivors who were further subgrouped according to the presence (31 Ss) or absence (34 Ss) of PTSD. Many of the offspring had extremely low cortisol levels. Study 3 compared urinary cortisol excretion in 23 offspring of Holocaust survivors to that of demographically matched normals. Results indicate that low cortisol levels in offspring were associated with the tendency of these individuals to indicate distress about the trauma of the Holocaust and to have PTSD symptoms. These studies provide the first biological validation that the symptoms described by offspring as being related to the Holocaust appear to reflect a type of posttraumatic response. (PsycINFO Database Record (c) 2006 APA, all rights reserved) Biological factors associated with susceptibility to posttraumatic stress disorder Yehuda, Rachel1 Canadian Journal of Psychiatry. Vol 44(1), Feb 1999, pp. 34-39 Because only a proportion of persons exposed to traumatic events develop posttraumatic stress disorder (PTSD), it has become important to elucidate the factors that increase the risk for the development of PTSD following trauma exposure as well as the factors the might serve to protect individuals from developing this condition. Putative risk factors for PTSD may describe the index traumatic event or characteristics of persons who experience those events. Recent data have implicated biological and familial risk factors for PTSD. For example, recent studies have demonstrated an increased prevalence of PTSD in the adult children of Holocaust survivors, even though these children, as a group, do not report a greater exposure to life-threatening events. These studies are reviewed. It is difficult to know to what extent the increased vulnerability to PTSD in family members of trauma survivors is related to biological or genetic phenomena, as opposed to experimental ones, because of the large degree of shared environment in families. In particular, at-risk family members, such as children, may be more vulnerable to PTSD as a result of witnessing the extreme suffering of a parent with chronic PTSD rather than because of inherited genes. (PsycINFO Database Record (c) 2006 APA, all rights reserved) *I have in PDF form
  5. 5. Salivary cortisol and psychopathology in children bereaved by the september 11, 2001 terror attacks. Author Pfeffer, Cynthia R; Altemus, Margaret; Heo, Moonseong; Jiang, Hong Affiliation Department of Psychiatry, Weill Medical College of Cornell University, New York, 10605 USA. Source Biological psychiatry, 2007 Apr 15, 61(8):957-65. Epub: 2006 Nov 29 ISSN 0006-3223 Abstract BACKGROUND: Studies suggest that stressful events increase risk for childhood anxiety and depression and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This prospective longitudinal study evaluated relationships among severe psychosocial stress, psychiatric morbidity, and HPA axis function in children. METHODS: Forty-five children (mean age: 8.9 +/- 2.9 years) suffering parent death from September 11, 2001 terror attacks and 34 nonbereaved children (mean age: 9.3 +/- 2.5 years) were evaluated prospectively at 6-month intervals in this 2-year study. Assessments involved diagnostic interviews (Child Schedule for Affective Disorders and Schizophrenia [K-SADS]) for psychopathology and 3 days of baseline salivary cortisol and a salivary dexamethasone suppression test for HPA axis function. RESULTS: Bereaved children, but not nonbereaved children, had significantly increased rates of psychiatric disorders involving anxiety disorders, especially posttraumatic stress disorder (PTSD), after September 11, 2001 compared with retrospective assessments before September 11, 2001. Morning (AM) and 4:00 pm baseline cortisol were significantly and persistently higher for bereaved than nonbereaved children. Compared with bereaved children without psychopathology, bereaved children with PTSD had significantly lower 4:00 pm baseline cortisol and significantly greater 4:00 pm cortisol suppression. Children with generalized anxiety disorder had significantly less AM cortisol suppression than children without psychopathology. CONCLUSIONS: Children bereaved by sudden, unexpected parent death had persistent psychological dysfunction and HPA axis dysregulation in this study. Higher Levels of Basal Serial CSF Cortisol in Combat Veterans With Posttraumatic Stress Disorder Baker, Dewleen G; Ekhator, Nosa N; Kasckow, John W; Dashevsky, Boris; Horn, Paul S; Bednarik, Ludmila; Geracioti, Thomas D Jr. American Journal of Psychiatry. Vol 162(5), May 2005, pp. 992-994 Objective: Results of basal peripheral cortisol measures in posttraumatic stress disorder (PTSD) have been variable. The authors' goal was to measure CSF cortisol concentrations, which more accurately reflect brain glucocorticoid exposure, in ... Basal and Dexamethasone Suppressed Salivary Cortisol Concentrations in a Community Sample of Patients with Posttraumatic Stress Disorder Lindley, Steven E1; Carlson, Eve B1; Benoit, Maryse1 Biological Psychiatry. Vol 55(9), May 2004, pp. 940-945 Posttraumatic stress disorder (PTSD) has been associated with lower concentrations of cortisol and enhanced suppression of cortisol by dexamethasone, although discrepancies exist among reports. The objective of the study was to determine the pattern ... The cortisol and glucocorticoid receptor response to low dose dexamethasone administration in aging combat veterans and Holocaust survivors with and without
  6. 6. posttraumatic stress disorder Yehuda, Rachel1; Halligan, Sarah L1; Grossman, Robert; Golier, Julia A1; Wong, Cheryl1 Biological Psychiatry. Vol 52(5), Sep 2002, pp. 393-403 Because alterations in cortisol negative feedback inhibition associated with aging are generally opposite of those observed in posttraumatic stress disorder (PTSD), we examined the cortisol and glucocorticoid receptor (GR) response to dexamethasone .. Assessment of HPA-axis function in posttraumatic stress disorder: Pharmacological and non-pharmacological challenge tests, a review de Kloet, C S1; Vermetten, E1; Geuze, E1; Kavelaars, A2; Heijnen, C J2; Westenberg, H G M3 Journal of Psychiatric Research. Vol 40(6), Sep 2006, pp. 550-567 ... the HPA axis, and in vitro leukocyte glucocorticoid receptor studies in adult PTSD subjects. Studies using a non-pharmacological stress paradigm (cognitive stress, trauma reminders) to stimulate the HPA axis showed an exaggerated cortisol ... View Record | 1 Duplicate | References Hypocortisolism and increased glucocorticoid sensitivity of pro-inflammatory cytokine production in Bosnian war refugees with posttraumatic stress disorder Rohleder, Nicolas1; Joksimovic, Ljiljana2; Wolf, Jutta M1; Kirschbaum, Clemens1 Biological Psychiatry. Vol 55(7), Apr 2004, pp. 745-751 ... basal hormone levels, and changes in glucocorticoid receptor (GR) numbers on lymphocytes. The functional significance of these latter changes remains elusive. Twelve Bosnian war refugees with PTSD and 13 control subjects were studied. On 2 ... Flow cytometric determination of glucocorticoid receptor (GCR) expression in lymphocyte subpopulations: lower quantity of GCR in patients with post-traumatic stress disorder (PTSD) Gotovac, K; Sabioncello, A*; Rabatic, S; Berki, T; Dekaris, D Clinical and Experimental Immunology [Clin. Exp. Immunol.]. Vol. 131, no. 2, pp. 335-339. Feb 2003. Assessment of the intracellular glucocorticoid receptor (GCR) level may be useful in monitoring functional disturbances of the hypothalamic-pituitary-adrenocortical axis or effects of prolonged steroid therapy. Cytosolic ligand binding assays have recently been supplemented by flow cytometric determination of receptor expression in individual cells. A method based on multiparametric analysis of whole blood by simultaneous labelling of intracellular GCRs and surface markers of lymphocyte subsets is described. We examined 25 healthy male volunteers and 35 age- and sex-matched post-traumatic stress disorder (PTSD) patients within 8 years from traumatic event. PTSD patients had a lower relative quantity of GCR in all lymphocyte populations tested as compared with healthy volunteers. NK cells of both groups showed higher expression of GCR than other lymphocyte subsets. In PTSD patients, the expression of GCR in B lymphocytes was also higher than in T cell. Although serum cortisol level was lower in PTSD patients, there was no correlation between cortisol level and GCR expression. Multiparameter flow cytometric determination of GCR expression in lymphocyte subpopulations may provide a useful tool for monitoring immunoregulatory action of glucocorticoids.
  7. 7. *have a copy in the folder, electronic Lymphocyte glucocorticoid receptor number in posttraumatic stress disorder Yehuda, Rachel1; Lowy, Martin T; Southwick, Steven M; Shaffer, Dottie; et al American Journal of Psychiatry. Vol 148(4), Apr 1991, pp. 499-504 Investigated the possibility that glucocorticoid receptor (GCR) changes may be involved in the dysregulation of the hypothalamic-pituitary-adrenal axis in posttraumatic stress disorder (PTSD) by measuring the number of lymphocyte cytosolic ... Glucocorticoid-Induced Inhibition of Memory Retrieval: Implications for Posttraumatic Stress Disorder DE Quervain, Dominique J-F Annals of the New York Academy of Sciences [Ann. N. Y. Acad. Sci.]. Vol. 1071, pp. 216-220. Jul 2006. Posttraumatic stress disorder (PTSD) is characterized by traumatic memories that can manifest as daytime recollections, traumatic nightmares, or flashbacks in which components of the event are relived. These symptoms reflect excessive retrieval of ... *ordered through ILL Can Posttraumatic Stress Disorder Be Prevented with Glucocorticoids? Schelling, Gustav1; Roozendaal, Benno1; de Quervain, Dominique J -F1 Yehuda, Rachel (Ed); McEwen, Bruce (Ed). (2004). Biobehavioral stress response: Protective and damaging effects. Annals of the New York Academy of Sciences, Vol. 1032. (pp. 158-166). New York, NY, US: New York Academy of Sciences. xvi, 331 pp. ... traumatic memories and PTSD development. Studies in long-term survivors of ICU treatment demonstrated a clear and vivid recall of different categories of traumatic memory such as nightmares, anxiety, respiratory ... *ordered from CC Relationship between cortisol and age-related memory impairments in Holocaust survivors with PTSD Yehuda, Rachel1; Golier, Julia A1; Harvey, Philip D1; Stavitsky, Karina1; Kaufman, Shira1; Grossman, Robert A1; Tischler, Lisa1 Psychoneuroendocrinology. Vol 30(7), Aug 2005, pp. 678-687 ... evidenced by their performance on tests of explicit memory, and also show more exaggerated patterns on age-related alterations in cortisol release over the diurnal cycle than Holocaust survivors without PTSD and nonexposed subjects. To investigate ... *ordered from CC 5-7 Low-Dose Cortisol Reduces Traumatic Memories in PTSD Ginsberg, David L1 Primary Psychiatry. Vol 11(10), Oct 2004, pp. 27 Patients with chronic posttraumatic stress disorder (PTSD) often show low basal cortisol levels, and individuals with reduced cortisol excretion in response to a traumatic event have a higher risk of developing subsequent PTSD. There is also research demonstrating
  8. 8. that an elevation of glucocorticoid levels inhibits memory retrieval in animals and healthy human subjects by acting in the medial temporal lobe and that prolonged administration of stress doses of cortisol during intensive care treatment reduces the risk of later PTSD. Moreover, by inhibiting memory retrieval, cortisol may weaken traumatic memory trace over time and thereby reduce symptoms even beyond the treatment period. Alternatively, cortisol administration may reduce PTSD symptoms by altering cortisol feedback regulation. *ILL ordered 5-7 Low-dose cortisol for symptoms of posttraumatic stress disorder Aerni, Amanda; Traber, Rafael; Hock, Christoph; Roozendaal, Benno; Schelling, Gustav; Papassotiropoulos, Andreas; Nitsch, Roger M; Schnyder, Ulrich; de Quervain, Dominique J -F1 American Journal of Psychiatry. Vol 161(8), Aug 2004, pp. 1488-1490 Objective: Because elevated cortisol levels inhibit memory retrieval in healthy human subjects, the present study investigated whether cortisol administration might also reduce excessive retrieval of traumatic memories and related symptoms in patients with chronic posttraumatic stress disorder (PTSD). Method: During a 3-month observation period, low-dose cortisol (10 mg/day) was administered orally for 1 month to three patients with chronic PTSD in a double-blind, placebo-controlled, crossover design. Results: In each patient investigated, there was a significant treatment effect, with cortisol-related reductions of at least 38% in one of the daily rated symptoms of traumatic memories, as assessed by self-administered rating scales. In accordance, Clinician-Administered PTSD Scale ratings assessed after each month showed cortisol-related improvements for reexperiencing symptoms and, additionally, in one patient for avoidance symptoms. Conclusions: The results of this pilot study indicate that low-dose cortisol treatment reduces the cardinal symptoms of PTSD. (PsycINFO Database Record (c) 2006 APA, all rights reserved) (journal abstract)