The role of corticosterone in human hypothalamic– pituitary–adrenal axis feedback

Objective  In humans, the glucocorticoid corticosterone circulates in blood at 10–20-fold lower levels than cortisol, but is found in higher relative amounts in postmortem brain samples. Access of cortisol and corticosterone to the central nervous system may not be equal. Additionally, the relative affinities for the glucocorticoid and mineralocorticoid receptors differ, such that corticosterone may play a significant role in human brain function. Design  We measured cortisol and corticosterone levels in paired plasma and cerebrospinal fluid (CSF) samples. To test the relative potency of cortisol vs. corticosterone on hypothalamic–pituitary–adrenal (HPA) feedback, subjects underwent a three-phase, single-blind, randomized study assessing the postmetyrapone ACTH response over 3 h to an intravenous bolus of vehicle, cortisol or corticosterone (0·15 mg/kg and 0·04 mg/kg). Participants  Outpatients undergoing diagnostic lumbar puncture who were subsequently deemed to be free of disease. Feedback was tested in healthy male volunteers. Measurements  Plasma and CSF corticosterone to cortisol ratio was calculated and the ACTH response over time after the bolus glucocorticoid measured. Results  Plasma corticosterone : cortisol was 0·069 ± 0·007; CSF corticosterone : cortisol was 0·387 ± 0·050 ( P <  0·001). Cortisol and corticosterone (0·15 mg/kg) suppressed ACTH vs. vehicle ( P =  0·002); there was no difference between corticosterone and cortisol. The 0·04 mg/kg dose had no effect on ACTH despite supraphysiological plasma corticosterone levels. Conclusions  Corticosterone contributes almost 40% of total active glucocorticoids (cortisol and corticosterone) in the CSF. Significant effects on HPA axis suppression were only seen with supraphysiological levels of corticosterone, suggesting that corticosterone is not important in this model of nonstress-induced ACTH hypersecretion, in which the effect of cortisol predominates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72329/1/j.1365-2265.2006.02540.x.pd

Narrative Exposure Therapy for Posttraumatic Stress Disorder associated with repeated interpersonal trauma in patients with Severe Mental Illness: a mixed methods design

Background: In the Netherlands, most patients with severe mental illness (SMI) receive flexible assertive community treatment (FACT) provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD) are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET) within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. Objectives: The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1) PTSD and dissociative symptoms changes and (2) changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients’ experiences with NET and to identify influencing factors on treatment results. Methods: This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25) with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results enhance the understanding of quantitative outcomes. Discussion: The results of this study will provide more insight into influencing factors for clinical changes in this population

Intolerance of uncertainty and meta-worry: relative importance in discriminating GAD

This study explored whether intolerance of uncertainty and/or meta-worry discriminate between non-clinical individuals and those diagnosed with generalised anxiety disorder (GAD group). The participants were 107 GAD clients and 91 university students. The students were divided into two groups (high and low GAD symptom groups). A multivariate analysis of covariance (MANCOVA) adjusting for age indicated that intolerance of uncertainty distinguished between the low GAD symptom group and the high GAD symptom group, and between the low GAD symptom group and the GAD group. Meta-worry distinguished all three groups. A discriminant function including intolerance of uncertainty and meta-worry classified 94.4% of the GAD group and 97.9% of the low GAD symptom group. Only 6.8% of the high GAD symptom group was classified correctly, 77.3% of the high GAD symptom group was classified as GAD. Findings indicated that intolerance of uncertainty and meta-worry may assist with the diagnosis and treatment of GAD