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ABSTRACT: The authors aimed to examine central glucocorticoids effects by measuring relative glucose metabolic rate (rGMR) in the hippocampus, amygdala, and anterior cingulate cortex (ACC) and the relationship between amygdala and ACC activity. The participants were male combat veterans with and without PTSD, 52 to 81 years old. The authors utilized randomized, double-blind, placebo-controlled examinations of the rGMR response to 17.5 mg hydrocortisone (HCORT) using 2-Deoxy-2-[(18)F]fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) neuroimaging. Group differences in hemispheric laterality of rGMR were observed following placebo administration, reflecting lower rGMR in the right hippocampus and ventral amygdala, and higher rGMR in the left ventral amygdala in the PTSD+ group compared to the PTSD- group. HCORT reduced these group differences in laterality. The net effect of HCORT was to restore a normal inverse association between the ACC and amygdala in the PTSD+ group, but disrupt this neural network in the PTSD- group. The magnitude of improvement in working memory correlated with greater hemispheric laterality in the dorsal amygdala following HCORT in both groups. The restorative effects of HCORT on metabolism and working memory provide a rationale for examining the therapeutic benefits of glucocorticoid manipulation in aging PTSD patients.
The Journal of neuropsychiatry and clinical neurosciences 02/2009; 21(2):132-43. · 2.34 Impact Factor
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ABSTRACT: Lower cortisol levels in posttraumatic stress disorder (PTSD) may reflect a preexisting vulnerability associated with developing the disorder after trauma exposure. Because offspring of trauma survivors with PTSD have a greater prevalence of PTSD after their own life events than offspring of trauma survivors without PTSD and offspring of nonexposed persons, examination of patterns of basal cortisol secretion in such offspring provides an opportunity to test this hypothesis.
To characterize the patterns of basal cortisol secretion in offspring of Holocaust survivors with and without parental PTSD and children of nonexposed parents.
Cortisol secretion was measured every 30 minutes for 24 hours. The raw hormonal data were subjected to a chronobiological analysis by applying single-oscillator and multioscillator cosinor analyses, a nonlinear least squares curve-fitting program, to determine circadian and ultradian regulatory dynamics.
The study was conducted under controlled conditions at the General Clinical Research Center at the Mount Sinai School of Medicine.
Twenty-three Holocaust offspring with parental PTSD and 10 without parental PTSD were compared with 16 children of nonexposed parents. No participant had PTSD.
Mean cortisol levels during the 24-hour cycle and other chronobiological parameters (amplitude, acrophase, circadian quotient, and goodness-of-fit coefficient) derived from single-oscillator and multioscillator models.
Offspring with parental PTSD displayed lower mean cortisol levels, reflected by the circadian mesor and reduced cortisol amplitude, compared with offspring without parental PTSD and children of nonexposed parents. This effect seemed to be specifically related to the presence of maternal PTSD.
Low cortisol levels and other chronobiological alterations in offspring are associated with the risk factor of maternal PTSD, raising the possibility that these alterations are acquired via glucocorticoid programming either from in utero exposures or in response to maternal behaviors early in life.
Archives of General Psychiatry 10/2007; 64(9):1040-8. · 12.02 Impact Factor
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ABSTRACT: We developed a short questionnaire--Parental PTSD Questionnaire--(PPQ), designed to assess the presence of posttraumatic stress disorder (PTSD) symptoms in parents. Fifty-eight adult offspring of Holocaust survivors (23 men and 35 women) completed the questionnaire about a parent who was independently evaluated by a trained clinician using the Clinician Administered PTSD Scale (CAPS). Only 5.2% of the offspring reported, "not knowing" if their parent had experienced 10 or fewer symptoms, while 56.9% provided estimates for all 17 items. There were no significant differences between lifetime frequencies of the individual symptoms as endorsed on the PPQ compared to the CAPS when subjects with completed PPQs were compared with CAPS. Interrater reliability between offspring and clinician was highly significant for each of the items when evaluated separately so as to include data for subjects who endorsed not knowing if a certain symptom had been present. Further studies are warranted to examine the psychometric properties of this measure.
Annals of the New York Academy of Sciences 08/2006; 1071:484-7. · 3.15 Impact Factor
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ABSTRACT: This study examined the effects of sertraline (SER) on glucocorticoid sensitivity in mononuclear leukocytes (MNL) from eight subjects with current post-traumatic stress disorder (PTSD) and nine comparison subjects. In all, 60 ml of blood was withdrawn by venipuncture at 0800, and MNL were isolated from blood and divided into two portions: the first contained live cells incubated with a series of concentrations of dexamethasone (DEX); the second contained cells incubated with similar concentrations of DEX+2 muM SER. Group difference in the concentrations of DEX required to inhibit lysozyme activity by 50% were evaluated under conditions of DEX-only and DEX+SER using analysis of covariance (ANCOVA). A significant Group x Condition interaction reflected that SER altered the lysozyme IC(50-DEX) in the direction of decreasing sensitivity to glucocorticoids in PTSD while having no uniform effect in cells from comparison subjects. The data provide support for the idea that glucocorticoid receptors might be more responsive to antidepressants in PTSD than in persons without PTSD. Insofar as increased sensitivity to glucocorticoids has been linked with PTSD, the actions of SER on the lysozyme IC(50-DEX) suggest that this medication may target a biologic alteration associated with PTSD pathophysiology.
Neuropsychopharmacology 02/2006; 31(1):189-96. · 7.99 Impact Factor
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ABSTRACT: Holocaust survivors with PTSD appear to show an accelerated aging effect as 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 the implications of age-related HPA axis alterations on cognition, we examined correlations between parameters reflecting circadian cortisol release and implicit and explicit memory performance.
Nineteen Holocaust survivors with PTSD (7 men, 12 women), 16 Holocaust survivors without PTSD (7 men, 9 women), and 28 non-exposed healthy comparison subjects (13 men, 15 women) collected salivary samples at six times over the diurnal cycle, and were tested with Paired Associates and Word Stem Completion Tests.
Negative correlations were observed between several measures of salivary cortisol concentrations and explicit memory in Holocaust survivors with PTSD after adjusting for IQ, years of education and current age reflecting poorer performance in association with higher cortisol levels. This relationship was absent in Holocaust survivors without PTSD and in demographically-comparable subjects who were not exposed to the Holocaust or other extremely traumatic events.
The significantly different relationship between cortisol and memory performance in these groups suggests that the neuropsychological impairments observed in Holocaust survivors with PTSD may reflect an interaction of PTSD and aging effects.
Psychoneuroendocrinology 09/2005; 30(7):678-87. · 5.81 Impact Factor
