Trauma-Related Altered States of Consciousness (TRASC) and Functional Impairment I: Prospective Study in Acutely Traumatized Persons.

A theoretical framework referred to as a 4-D model has been described for classifying posttraumatic stress symptoms into those potentially occurring within normal waking consciousness (NWC) versus those thought to intrinsically exemplify dissociative experiences, specifically, trauma-related altered states of consciousness (TRASC). As a further test of this theoretical distinction, this prospective study evaluated whether TRASC and NWC forms of distress incrementally and prospectively predicted functional impairment at 6 and 12 weeks following presentation at hospital emergency departments in the acute aftermath of traumatic events in 180 persons. Establishing the clinical significance of both TRASC and NWC-distress symptoms, we found that 6-week markers of TRASC and NWC-distress independently predicted 12-week self-reported levels of social and occupational impairment. We also observed broad support for various predictions of the 4-D model except that, in contrast with hypotheses, childhood trauma history was generally more strongly correlated with symptoms of NWC-distress than with TRASC. Future research directions are discussed.

Decreased prefrontal Myo-inositol in major depressive disorder.

BACKGROUND: Postmortem studies have shown robust prefrontal cortex glial losses and more subtle neuronal changes in major depressive disorder (MDD). Earlier proton magnetic resonance spectroscopy (1H-MRS) studies of the glial marker myo-inositol in MDD were subject to potential confounds. The primary hypothesis of this study was that MDD patients would show reduced prefrontal/anterior cingulate cortex levels of myo-inositol. METHODS: Thirteen nonmedicated moderate-severe MDD patients and 13 matched control subjects were studied (six male, seven female per group). Proton magnetic resonance spectroscopy stimulated echo acquisition mode spectra (3.0 T; echo time=168 msec; mixing time=28 msec; repetition time=3000 msec) were obtained from prefrontal/anterior cingulate cortex. Metabolite data were adjusted for tissue composition. RESULTS: Patients with MDD showed significantly lower myo-inositol/creatine ratios (.94+/-.23) than control subjects (1.32+/-.37) [F(1,23)=6.9; p=.016]. CONCLUSIONS: These data suggest a reduction of myo-inositol in prefrontal/anterior cingulate cortex in MDD, which could be a consequence of glial loss or altered glial metabolism. Additional in vivo studies of glial markers could add to the understanding of the pathophysiology of MDD.

Increased beclomethasone-induced vasoconstriction in women with posttraumatic stress disorder.

It has been hypothesized that patients with posttraumatic stress disorder (PTSD) show increased glucocorticoid sensitivity. The study tested beclomethasone-induced vasoconstriction (BIV), a measure of peripheral glucocorticoid sensitivity, in women with PTSD. A case-control design was employed in 33 PTSD patients and 33 healthy controls. BIV was tested using beclomethasone dipropionate (1-100 micro g/ml). Vasoconstriction was assessed after 15-18 h. Waking and afternoon salivary cortisol concentrations were measured. BIV ratings were significantly increased in PTSD at beclomethasone concentrations from 10-100 micro g/ml. Salivary cortisol concentrations did not differ between groups or correlate with BIV. Preliminary evidence has been found for increased peripheral glucocorticoid sensitivity in PTSD. Further study is required to replicate this finding and assess its relationship to the pathophysiology of the disorder.

Increased sympathetic response to standing in panic disorder.

Although autonomic function has been investigated in panic disorder (PD), previous studies have not used non-invasive beat by beat blood pressure (BP) monitoring to assess the rapid dynamics of BP during autonomic reflex tests. The hypothesis of the current study was that patients with PD would show increased cardiovascular sympathetic reactivity compared with healthy or anxious controls, as assessed by the initial overshoot of diastolic BP during the immediate response to standing. Patients with PD (n=56), social phobia (n=28) and healthy volunteers (n=56) were tested using finger photoplethysmography during an orthostatic challenge. Panic disorder patients showed an increased BP overshoot compared with both control groups. Moreover, in a preliminary assessment of selective serotonin reuptake inhibitor treatment effects, the BP overshoot was significantly reduced towards normal values. These findings are consistent with recent evidence for increased sympathetic baroreflex function in PD and may be relevant to the pathophysiology of the disorder.

Neural correlates and predictive power of trait resilience in an acutely traumatized sample: a pilot investigation.

OBJECTIVE: Resilience refers to the ability to thrive despite adversity and is defined as a multidimensional phenomenon, spanning internal locus of control, sense of meaning, social problem-solving skills, and self-esteem. We aimed to investigate the predictive value of resilience for the development of posttraumatic stress disorder (PTSD) and to examine the neural correlates mediating the relationship between resilience and recovery from a traumatic event in acutely traumatized subjects. We hypothesized that resilience would mediate the relationship between childhood trauma and posttraumatic recovery. METHOD: We conducted a prospective study with 70 acutely traumatized subjects with DSM-IV PTSD recruited at the emergency department, assessing PTSD symptom severity at 3 time points within the first 3 months posttrauma. Scores for childhood trauma as assessed with the Childhood Trauma Questionnaire and trait resilience as assessed with the Connor-Davidson Resilience Scale were used as predictors of symptom severity. A subsample of 12 subjects additionally underwent a functional 4 Tesla magnetic resonance imaging scan 2 to 4 months posttrauma. We employed the traumatic script-driven imagery paradigm to assess the correlations between trait resilience and blood oxygen level-dependent (BOLD) response. The study was conducted from 2003 to 2007. RESULTS: Resilience predicted PTSD symptom severity at 5 to 6 weeks (ß = -0.326, P = .01) as well as at 3 months (ß = -0.423, P = .003) posttrauma better than childhood trauma. Resilience essentially mediated the relationship between childhood trauma and posttraumatic adjustment. Resilience scores were positively correlated with BOLD signal strength in the right thalamus as well as the inferior and middle frontal gyri (Brodmann area 47). CONCLUSIONS: This pilot investigation revealed a significant relationship between resilience and emotion regulation areas during trauma recall in an acutely traumatized sample. Resilience was established as a significant predictor of PTSD symptom severity and mediated the influence of childhood trauma on posttraumatic adjustment.

Neural and behavioral correlates of peritraumatic dissociation in an acutely traumatized sample.

OBJECTIVE: Peritraumatic dissociative responses have been identified as strong predictors of subsequent posttraumatic stress disorder development. We aimed to clarify the mechanism by which peritraumatic dissociation is related to PTSD development by exploring the neural correlates of peritraumatic dissociation during posttraumatic adjustment. METHOD: We combined a prospective questionnaire study with a neuroimaging paradigm in an acutely traumatized sample recruited from the emergency department from 2004 until 2009. 121 acutely traumatized subjects were assessed for acute stress disorder, PTSD, and dissociative symptoms at 3 time points within the first 3 months post trauma. A subsample of 21 subjects underwent a script-driven 4-Tesla functional magnetic resonance imaging scan 2 to 4 months post trauma. RESULTS: Peritraumatic dissociation predicted PTSD diagnostic status at 5-6 weeks and 3 months over and above childhood trauma (Wald = 4.035, P = .045; Wald = 4.793, P = .029, respectively). Peritraumatic dissociation scores were positively correlated with activation in the right occipital lobe, ie, the lingual (Brodmann area [BA] 18, z = 3.37), fusiform (BA 19, z = 3.64), and parahippocampal (BA 19, z = 3.25) gyri. After covariation of dissociation at the time of the scan, peritraumatic dissociation remained positively correlated with activation in the right lingual (BA 18, z = 3.21) and fusiform (BA 19, z = 3.55) gyri. CONCLUSIONS: The neuroimaging findings indicate that peritraumatic dissociation is associated with greater activation of the right occipital lobe (BAs 18 and 19), a region previously implicated in vivid autobiographical memory recall of highly emotional events. These results suggest that peritraumatic dissociation directly leads to the formation of intrusive memories. Peritraumatic dissociation and childhood trauma emerged as valuable predictors of PTSD development and therefore can guide the identification of individuals at risk.

Beclomethasone-induced vasoconstriction in women with major depressive disorder.

OBJECTIVE: It has been hypothesized that abnormal negative feedback of cortisol release in major depressive disorder (MDD) may involve impaired central glucocorticoid receptor (GR) function. Beclomethasone-induced vasoconstriction (BIV) was recently used to test the hypothesis that impaired GR function generalizes to peripheral tissues, and it was reported that BIV was decreased in medicated patients with MDD. The objective was to test the hypothesis that BIV would be reduced in unmedicated women with MDD compared with healthy controls. DESIGN: Case-control. SETTING: A university womens' mental health research unit. PARTICIPANTS: Women aged 18-65 years (n=19) diagnosed, according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, with MDD after a structured interview and clinical assessment. Healthy women pair-matched for age, reproductive and smoking status. PROCEDURES: BIV was tested using a range of beclomethasone dipropionate concentrations (1-100 microg/mL) applied to the forearm, with vasoconstriction scored visually after 15-18 hours by raters blinded to diagnosis and the randomization of the application sites. OUTCOME MEASURE: Visual scores for BIV at each beclomethasone concentration. RESULTS: No significant differences between patients with MDD and controls were found. Postmenopausal women showed less of a response than premenopausal women or women taking sex-hormone preparations. CONCLUSION: The study did not concur with the previous finding that BIV is decreased in MDD. Further research is needed to determine whether the difference in findings is due to medication or to other factors that may have distinguished the samples, including sex, age, reproductive status, illness severity, treatment resistance and setting.

Effects of diazepam on facial emotion recognition.

OBJECTIVE: There have been few studies of the pharmacologic modulation of facial emotion recognition. The present study aimed to replicate and extend the finding that recognition of facial anger was selectively impaired by diazepam. The hypothesis was that, in comparison with placebo, diazepam would impair the recognition of facial anger in healthy volunteers, but not the recognition of 5 other basic emotions: happiness, surprise, fear, sadness and disgust. DESIGN: A randomized, counterbalanced, double-blind, placebo-controlled, within-subjects comparison of diazepam with placebo. SETTING: A university psychopharmacology research unit. PARTICIPANTS: Healthy male (n = 6) and female (n = 22) volunteers, aged 18-45 years. PROCEDURES: Subjects were tested on 2 tasks following the administration of diazepam, 15 mg, and placebo on separate occasions. In the first "multimorph" task, images of facial expressions were morphed to produce continua between the neutral and full expressions of 6 basic emotions. Accuracy and identification thresholds were assessed for stimuli in which the intensity of expression gradually increased. In the second "emotional hexagon" task, facial expressions were morphed between pairs of emotions. Single images were presented, and accuracy and speed of response were assessed. RESULTS: Diazepam produced broad impairments in response accuracy, recognition thresholds and response speed on the facial emotion tasks that were not limited to angry expressions. CONCLUSIONS: The present study found that diazepam, 15 mg, impaired facial emotion recognition, but not selectively. In the emotional hexagon task, a reaction-time analysis suggested that the identification of facial anger might be differentially sensitive to variations in stimulus duration, complicating the interpretation of this paradigm.