Robert Grossman

Childhood trauma and risk for PTSD:relationship to intergenerational effects of trauma, parental PTSD and cortisol excretion

Among the adverse mental health consequences of childhood trauma is the risk related to the development of posttraumatic stress disorder (PTSD) in adulthood. Other risk factors for PTSD. including parental trauma exposure and parental PTSD, can also contribute to the experience of child trauma. We examined associations between childhood trauma and PTSD in 51 adult children of Holocaust survivors and 41 comparison subjects. in consideration of parental trauma exposure and parental PTSD. We also examined these variables in relation to 24-hr urinary cortisol levels. Adult offspring of Holocaust survivors showed significantly higher levels of self-reported childhood trauma, particularly emotional abuse and neglect. relative to comparison subjects. The difference was largely attributable to parental PTSD. Self-reported childhood trauma was also related to severity of PTSD in subjects, and emotional abuse was significantly associated with 24-hr mean urinary cortisol secretion. We conclude that the experience of childhood trauma may be an important factor in the transmission of PTSD from parent to child.

The cortisol and glucocorticoid receptor response to low dose dexamethasone administration in aging combat veterans and holocaust survivors with and without posttraumatic stress disorder

BACKGROUND 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 (DEX) in older trauma survivors. METHODS Twenty-three Holocaust survivors (9 men, 14 women), 27 combat veterans (all male), and 10 comparison subjects (7 men, 3 women) provided samples for plasma or salivary cortisol and glucocorticoid receptor determination in mononuclear leukocytes at 8:00 AM on the day of, and following, 0.5 mg of DEX at 11:00 PM. RESULTS Greater percent suppression of cortisol and lymphocyte GR was observed in older trauma survivors with PTSD compared to survivors without PTSD and comparison subjects. There was a significant main effect of depression in the direction of reduced suppression following DEX, consistent with the effects of DEX in major depressive disorder patients. Responses to DEX were uncorrelated with PTSD symptom severity, but cortisol suppression was associated with years elapsed since the most recent, but not focal, traumatic event. CONCLUSIONS The response to DEX is generally similar in older and younger trauma survivors, but the findings suggest that age, symptom severity, and lifetime trauma exposure characteristics may influence this response.

Longitudinal Assessment of Cognitive Performance in Holocaust Survivors with and without PTSD

BACKGROUND There are currently no longitudinal studies of cognitive performance in older patients with Posttraumatic Stress Disorder (PTSD). It is therefore unclear whether relationships between memory and symptoms differ over time among older persons with and without PTSD. METHODS Twenty-eight Holocaust survivors and nineteen comparison subjects were evaluated 5 years after they had received a memory assessment including paired-associates learning and the California Verbal Learning Test (CVLT). RESULTS While Holocaust survivors with PTSD showed a diminution in symptom severity (t = 2.99, df = 12, p = .011), they still manifested a decline in paired associates learning, suggesting an acceleration in age-related memory impairment (related word pairs: t = 2.87, df = 13, p = .013; unrelated word pairs: t = 2.06, df = 13, p = .060). The survivors with PTSD showed improvements on several CVLT measures over time. These improvements correlated with symptom improvements, such that group differences at the follow-up were no longer detected. CONCLUSIONS The discrepancy in the pattern of performance on these two tests of memory following symptom improvement suggests possible differentiation between of aspects of memory functions associated with aging and trauma exposure and those associated with the severity of PTSD symptoms. Performance on the CVLT appeared related to clinical symptom severity while paired associate learning worsened over time in Holocaust survivors with PTSD, consistent with earlier cross-sectional findings.

The Relationship Between Hippocampal Volume and Declarative Memory in a Population of Combat Veterans With and Without PTSD

Abstract:  Both reduced hippocampal volume and cognitive alterations have been found in posttraumatic stress disorder (PTSD). The purpose of this article was to examine the relationship between hippocampal volume, combat exposure, symptom severity, and memory performance in a sample of combat veterans with and without a history of PTSD. Subjects were 33 male veteran volunteers (16 PTSD+, 17 PTSD−) who underwent an MRI and neuropsychological testing with the California Verbal Learning Test (CVLT), a measure of declarative memory. Relationships between hippocampal volume (i.e., right + left hippocampal volume/whole brain volume) and performance on the CVLT were determined using partial correlational analysis controlled for age and Wechsler Adult Intelligence Scale, Third Edition (WAIS‐III) vocabulary scores. Percent hippocampal volume for the entire sample was positively associated with several aspects of memory performance as reflected by the CVLT. In the PTSD+ group, CVLT performance was negatively correlated with lifetime, but not current CAPS symptoms. CVLT performance appears to be strongly correlated with hippocampal volume in a group of trauma survivors with and without PTSD. Insofar as CVLT performance in the PTSD group was negatively associated with worst episode, but not to current PTSD symptoms, memory performance in combat veterans may reflect some aspect of risk related to the magnitude of the psychological response to trauma, rather than current symptoms that may be interfering with cognitive performance. It will be of interest to study cognitive abilities that may relate to the likelihood of specific PTSD symptoms and to track changes in CVLT performance and hippocampal volume over time in persons with and without a history of trauma exposure.

Ten-year follow-up study of PTSD diagnosis, symptom severity and psychosocial indices in aging holocaust survivors.

Objective:  We performed a longitudinal study of holocaust survivors with and without post‐traumatic stress disorder (PTSD) by assessing symptoms and other measures at two intervals, approximately 10 years apart.

Relationship between cortisol and age-related memory impairments in Holocaust survivors with PTSD

RATIONALE 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. METHODS 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. RESULTS 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. CONCLUSION 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.

Childhood trauma and basal cortisol in people with personality disorders

This study examined the influence of various forms of childhood abuse on basal cortisol levels in a sample of adults with Axis II personality disorders. Participants included 63 adults (n = 19 women) who provided basal plasma cortisol samples and completed the Childhood Trauma Questionnaire. Linear regression analyses that included all 5 subscales (ie, sexual abuse, physical abuse, emotional abuse, physical neglect and emotional neglect) demonstrated that physical abuse was related to lower cortisol levels (beta = -.43, P = .007), consistent with prior literature. In contrast, physical neglect was associated with higher cortisol (beta = .36, P = .02), after controlling for other forms of abuse. Results are consistent with the view that childhood trauma has long-lasting neurobiological effects and suggest that different forms of trauma may have distinct biological effects.

Neuroimaging studies in post-traumatic stress disorder.

The authors review some of the advances that have been made in understanding the structural, biochemical, and functional neuroanatomy of post-traumatic stress disorder (PTSD). First, the authors review the primary brain regions that had been hypothesized a priori, from the phenomenology and neurobiology of PTSD, to be implicated in the pathophysiology. Next, they review findings from neuroimaging studies of these brain regions in PTSD, and explain the various experimental methods and imaging technologies used in these studies. A broader perspective, including a discussion of additional brain areas that may be involved in PTSD, is synthesized. The authors conclude with a rationale and approach for studies testing sharply defined hypotheses and those using multidisciplinary strategies that integrate neuroimaging data with other cognitive, biologic, and genetic tools to study this complex disorder.

Cognitive Effects of Intravenous Hydrocortisone in Subjects with PTSD and Healthy Control Subjects

Abstract:  On the basis of peripheral (nonbrain) neuroendocrine findings in subjects with posttraumatic stress disorder (PTSD), it has been hypothesized that these individuals also have a greater central (brain) sensitivity to glucocorticoids. In nonpsychiatric subjects, it has been found that working and declarative memory performance is selectively impaired by acute glucocorticoid administration. We hypothesized that subjects with PTSD, as compared to nonpsychiatric controls, would show greater impairments in verbal declarative memory and working memory, but not attention, following exogenous glucocorticoid administration. These data are part of a larger study using functional neuroimaging and peripheral HPA axis measures in these same subjects. Subjects underwent a 0.5‐mg dexamethasone suppression test and measurement of basal cortisol, basal plasma lymphocyte glucocorticoid receptor number, and postdexamethasone cortisol on a separate day. Under double‐blind randomized crossover conditions, 17‐mg hydrocortisone or placebo was administered by intravenous (i.v.) bolus to 15 medication‐free PTSD subjects (4 female) and 12 nonpsychiatric control subjects (4 female) matched by age, sex, and education level. Participants then underwent positron emission tomography (PET) scanning and 90 min after the initial drug/placebo administration, cognitive testing was then performed. By repeated measures ANCOVA (covaried for baseline performance on that neuropsychological test), neither attention tasks of digit span forward nor backward showed significant change. However, there were significant drug (F= 17.644, df= 1,25 P < 0.001), group (F = 4.383, df= 1,25 P= 0.048), and drug by group interactions (F= 4.756, df= 1,25 P= 0.040) for verbal declarative memory. By t‐test, there was not a difference in baseline performance on this measure between subject groups. The subject group with PTSD experienced a greater decline in verbal declarative memory performance following hydrocortisone administration. For working memory, there were significant group (F= 6.048, df= 1,25 P= 0.022) and drug by group interactions (F= 6.048, df= 1,25 P= 0.022) for verbal declarative memory. By t‐test, there was not a difference in baseline performance on this measure between subject groups. The hydrocortisone administration led to impairment in working memory in the group of subjects with PTSD, but not in the control subject group. Exploratory correlations between percent cortisol suppression following dexamethasone and baseline plasma lymphocyte glucocorticoid receptor number with declarative and working memory measures among subject groups separately and in a combined way revealed a negative correlation between lymphocyte glucocorticoid receptor density and working memory (r=−0.54, df= 25, P= 0.008). Brain sensitivity to glucocorticoids appears to be greater in subjects with PTSD. Heightened vulnerability of declarative memory in subjects with PTSD may indicate hippocampal involvement, whereas working memory vulnerability suggests additional brain regions (prefrontal, cingulate, temporal, and parietal cortices) and neurotransmitter systems (dopamine and serotonin) particularly sensitive to glucocorticoids in persons with PTSD.

Effect of sertraline on glucocorticoid sensitivity of mononuclear leukocytes in post-traumatic stress disorder

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 μM 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 × Condition interaction reflected that SER altered the lysozyme IC50-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 IC50-DEX suggest that this medication may target a biologic alteration associated with PTSD pathophysiology.