Renal BOLD-MRI does not reflect renal function in chronic kidney disease.

Renal blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) is a noninvasive fast technique to characterize renal function. Here we evaluated the impact of renal function on the relaxation rate (R2(*)) in the cortex and medulla to provide baseline data for further use of renal BOLD-MRI. This parameter was evaluated in 400 patients scheduled for abdominal imaging who underwent transversal blood oxygen level-dependent measurements with a multi-echo gradient-echo sequence with 12 echo times. The loss of phase coherence (T2(*)) maps were generated in which kidney regions of interest were selected to differentiate the medulla and cortex, and R2(*) was equated to 1/T2(*). Individual R2(*) values were, in turn, correlated to the eGFR (MDRD formula of 280 patients with available serum creatinine measurements), age, and gender each for 1.5 and 3.0 T field-strength scans of 342 patients. At both the field strengths, no significant differences in R2(*) of the cortex and medulla were found between patient gender, age, eGFR, or between different stages of chronic kidney disease determined using the KDOQI system. Thus, BOLD-MRI of a non-specific patient population failed to discriminate between the patients with various stages of chronic kidney disease.

Basal and suppressed salivary cortisol in female Vietnam nurse veterans with and without PTSD.

It has been suggested that discrepant findings regarding low basal cortisol levels and enhanced suppression of cortisol in response to dexamethasone (DEX) administration in post-traumatic stress disorder (PTSD) may reflect individual differences in gender, trauma type, stage of development at trauma occurrence (e.g., childhood vs. adulthood), early pre-traumatic risk factors, or other individual differences. This study examined salivary cortisol levels at 08.00h and 16.00h as well as cortisol response to 0.50 mg DEX in 40 female Vietnam nurse veterans who had current, chronic PTSD (Current) vs. 43 who never had PTSD (Never). Repeated measures analyses of covariance did not reveal significant group differences in cortisol levels or cortisol suppression. Given that nurses who served in Vietnam had similar exposures, ages at exposure, and duration since exposure to previously studied male Vietnam combat veterans, the present lack of evidence for low cortisol and cortisol hyper-suppression in nurses with PTSD suggests that previous findings of low cortisol and cortisol hyper-suppression in male Vietnam veterans, females sexually abused as children, and other populations may reflect risk factors beyond simply having PTSD.

Subtle neurologic compromise as a vulnerability factor for combat-related posttraumatic stress disorder: results of a twin study.

CONTEXT: Previous studies have demonstrated subtle neurologic dysfunction in chronic posttraumatic stress disorder (PTSD) manifest as increased neurologic soft signs (NSSs). The origin of this dysfunction is undetermined. OBJECTIVE: To resolve competing origins of increased NSSs in PTSD, namely, preexisting vulnerability factor vs acquired PTSD sign. DESIGN: Case-control study of identical twins. SETTING: A Veterans Affairs and academic medical center (ambulatory). PARTICIPANTS: A convenience sample of male Vietnam veteran twins with (n = 25) and without (n = 24) PTSD and their combat-unexposed identical (monozygotic) co-twins. INTERVENTIONS: Neurologic examination for 45 NSSs. MAIN OUTCOME MEASURE: Average scores for 45 NSSs, each scored on an ordinal scale from 0 to 3, masked to diagnosis and combat exposure status. RESULTS: There was a significant between-pair main effect of PTSD diagnosis (as determined in the combat-exposed twin) on average NSS score in the absence of a significant combat exposure main effect or diagnosis x exposure interaction. Combat veterans with PTSD had significantly higher NSS scores than combat veterans without PTSD. The "high-risk," unexposed co-twins of the former also had significantly higher NSS scores than the "low-risk," unexposed co-twins of the latter. This result could not be explained by age, number of potentially traumatic lifetime noncombat events, alcoholism, or the presence of a comorbid affective or anxiety disorder. The average NSS score in unexposed co-twins was not significantly associated with combat severity in combat-exposed twins. CONCLUSIONS: These results replicate previous findings of increased NSSs in Vietnam combat veterans with PTSD. Furthermore, results from their combat-unexposed identical co-twins support the conclusion that subtle neurologic dysfunction in PTSD is not acquired along with the trauma or PTSD but rather represents an antecedent familial vulnerability factor for developing chronic PTSD on exposure to a traumatic event.

Clarifying the origin of biological abnormalities in PTSD through the study of identical twins discordant for combat exposure.

A biological abnormality found to be associated with posttraumatic stress disorder (PTSD) may be, among other things, a pretrauma vulnerability factor, that is, it may have been present prior to the event's occurrence and increased the individual's likelihood of developing PTSD upon traumatic exposure. Alternately, it may be an acquired PTSD sign, that is, it may have developed after the traumatic exposure, along with the PTSD. We have studied pairs of Vietnam combat veterans and their noncombat-exposed, identical twins in an effort to resolve these competing origins. Combat veterans were diagnosed as current PTSD or non-PTSD (i.e., never had). Average heart rate responses (HRRs) to a series of sudden, loud-tone presentations were larger in Vietnam combat veteran twins with PTSD, but these larger responses were not shared by their noncombat-exposed cotwins, whose responses were similar to those of the non-PTSD combat veterans and their noncombat-exposed cotwins. These results suggest that larger HRRs to sudden, loud tones represent an acquired sign of PTSD. In contrast, increased neurological soft signs (NSSs), diminished hippocampal volume, and presence of abnormal cavum septum pellucidum (CSP) were found in Vietnam combat veteran twins with PTSD and their "high-risk," unexposed cotwins compared to Vietnam combat veteran twins without PTSD and their "low-risk," unexposed cotwins. These results support the conclusion that the latter abnormalities represent antecedent, familial vulnerability factors for developing chronic PTSD upon exposure to a traumatic event.

Effects of beta blockade, PTSD diagnosis, and explicit threat on the extinction and retention of an aversively conditioned response.

An aversively conditioned SC response was assessed in 18 males meeting DSM-IV criteria for chronic posttraumatic stress disorder (PTSD) and 10 trauma-exposed males who never developed PTSD. Effects of beta blockade on acquisition and retention of a conditioned response (CR) were examined by administering propranolol HCl before acquisition or following extinction trials. Retention of the CR was assessed 1 week following acquisition under conditions of non-threat and threat. Conditioned stimuli were colored circles and the unconditioned stimulus (UCS) was a "highly annoying" electrical stimulus. The propranolol failed to produce any measurable effects on acquisition or retention of the CR and there was no evidence of increased conditionability in individuals diagnosed with PTSD. One week following acquisition, the differential CR to the reinforced stimulus was evident only in the threat condition. This suggests that belief in the presence of a threat is necessary and sufficient for activating a previously established CR.

Physiologic responses to sudden, loud tones in monozygotic twins discordant for combat exposure: association with posttraumatic stress disorder.

BACKGROUND: Larger heart rate responses to sudden, loud (startling) tones represent one of the best-replicated psychophysiologic markers for posttraumatic stress disorder (PTSD). This abnormality may be a pretrauma vulnerability factor, ie, it may have been present prior to the event's occurrence and increased the individual's likelihood of developing PTSD on traumatic exposure. Alternately, it may be an acquired PTSD sign, ie, it may have developed after the traumatic exposure, along with the PTSD. Studying identical twins discordant for traumatic exposure offers an opportunity to resolve these competing origins. METHODS: Subjects included pairs of Vietnam combat veterans and their non-combat-exposed, monozygotic twins. Combat veterans were diagnosed as having current PTSD (n = 50) or non-PTSD (ie, never had) (n = 53). All subjects listened to a series of 15 sudden, loud tone presentations while heart rate, skin conductance, and orbicularis oculi electromyogram responses were measured. RESULTS: Consistent with previous reports, averaged heart rate responses to the tones were larger in Vietnam combat veterans with PTSD. These larger responses were not shared by their non-combat-exposed co-twins, whose responses were similar to those of the non-PTSD combat veterans and their non-combat-exposed co-twins. This result remained significant after adjusting for a number of potentially confounding factors. CONCLUSIONS: The results suggest that larger heart rate responses to sudden, loud tones represent an acquired sign of PTSD rather than a familial vulnerability factor.

Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD.

CONTEXT: Theoretical neuroanatomic models of posttraumatic stress disorder (PTSD) and the results of previous neuroimaging studies of PTSD highlight the potential importance of the amygdala and medial prefrontal regions in this disorder. However, the functional relationship between these brain regions in PTSD has not been directly examined. OBJECTIVE: To examine the relationship between the amygdala and medial prefrontal regions during symptom provocation in male combat veterans (MCVs) and female nurse veterans (FNVs) with PTSD. DESIGN: Case-control study. SETTING: Academic medical center. PARTICIPANTS: Volunteer sample of 17 (7 men and 10 women) Vietnam veterans with PTSD (PTSD group) and 19 (9 men and 10 women) Vietnam veterans without PTSD (control group). MAIN OUTCOME MEASURES: We used positron emission tomography and the script-driven imagery paradigm to study regional cerebral blood flow (rCBF) during the recollection of personal traumatic and neutral events. Psychophysiologic and emotional self-report data also were obtained to confirm the intended effects of script-driven imagery. RESULTS: The PTSD group exhibited rCBF decreases in medial frontal gyrus in the traumatic vs neutral comparison. When this comparison was conducted separately by subgroup, MCVs and FNVs with PTSD exhibited these medial frontal gyrus decreases. Only MCVs exhibited rCBF increases in the left amygdala. However, for both subgroups with PTSD, rCBF changes in medial frontal gyrus were inversely correlated with rCBF changes in the left amygdala and the right amygdala/periamygdaloid cortex. Furthermore, in the traumatic condition, for both subgroups with PTSD, symptom severity was positively related to rCBF in the right amygdala and negatively related to rCBF in medial frontal gyrus. CONCLUSIONS: These results suggest a reciprocal relationship between medial prefrontal cortex and amygdala function in PTSD and opposing associations between activity in these regions and symptom severity consistent with current functional neuroanatomic models of this disorder.

PTSD arousal and depression symptoms associated with increased right-sided parietal EEG asymmetry.

Researchers have proposed that depression and particular types of anxiety are associated with unique patterns of regional brain activation. The authors examined the relationship among posttraumatic stress disorder (PTSD), anxiety, and depressive symptoms and frontal, temporal, and parietal EEG alpha asymmetry in female Vietnam War nurse veterans. The results indicate that PTSD arousal symptoms are associated with increased right-sided parietal activation. However, the combination of arousal, depression, and their interaction explain more than twice the variance in parietal asymmetry compared with arousal alone. The results support the contention that the association between anxiety and right-sided posterior activation is specific to the anxious arousal subtype. These findings underscore the importance of isolating, both theoretically and statistically, emotional subcomponents in studies of regional brain activation.

Psychophysiology of post-traumatic stress disorder.

In general, the results of psychophysiologic research on PTSD support the presence of a variety of autonomic, sensory, and cognitive processing differences between individuals with and without the disorder. The findings are diverse and include heightened responsiveness to trauma reminders; exaggerated startle; increased conditionability and autonomic responsiveness to aversive, high-intensity stimuli; and elevated tonic or baseline physiologic activity. Increased sensitivity of the central nervous system is suggested by electrophysiologic evidence for a failure to habituate to redundant information, over-responsiveness to novel information, and reduced cortical responsiveness to overstimulation. Cognitive processing abnormalities are suggested by electrophysiologic evidence for a reduced ability to attend to task-relevant information and increased attention to task-irrelevant, trauma-related information in individuals with PTSD. Some findings, such as the heightened physiologic and P300 response amplitude responses to trauma-related stimuli and increased HR response to loud tones, have been highly replicable and appear to be as reliable as any biologic finding in the psychiatric literature. Other findings, such as increased eye-blink startle responses and tonic or baseline physiologic activity, have been less consistently replicated and have led investigators to explore how stressful or threatening experimental contexts might produce phasic alterations in the psychophysiology of individuals with PTSD. We hope that the broad range of psychophysiologic investigations and findings in PTSD will inspire others to consider possible applications of these methodologies to their own clinical and research endeavors.

Absence of selected neurological soft signs in Vietnam nurse veterans with post-traumatic stress disorder.

This study examined eight neurological soft signs (NSSs), which had previously proved successful in discriminating medication-free post-traumatic stress disorder (PTSD) from non-PTSD combat veterans and sexually abused women, in 82 unmedicated female nurse Vietnam veterans, 32 with and 50 without PTSD. The increased NSSs observed in the previously studied PTSD samples were not found in the nurses with PTSD. The results fail to support the hypothesis that the stress of a traumatic event and/or resultant PTSD damages the nervous system.

Performance on visuospatial copying tasks in individuals with chronic posttraumatic stress disorder.

The ability to copy figures was evaluated in 41 subjects with chronic posttraumatic stress disorder (PTSD) and 27 trauma-exposed, non-PTSD comparison subjects. Individuals with PTSD demonstrated significantly impaired performance. However, after adjusting for pre-trauma variables, there was only a marginally significant association between figure-copying performance and PTSD. These findings are consistent with pre-trauma visual-spatial impairment as being among the risk factors for chronic PTSD.

The relationship between Hippocampal asymmetry and working memory processing in combat-related PTSD - a monozygotic twin study.

BACKGROUND: PTSD is associated with reduction in hippocampal volume and abnormalities in hippocampal function. Hippocampal asymmetry has received less attention, but potentially could indicate lateralised differences in vulnerability to trauma. The P300 event-related potential component reflects the immediate processing of significant environmental stimuli and has generators in several brain regions including the hippocampus. P300 amplitude is generally reduced in people with PTSD. METHODS: Our study examined hippocampal volume asymmetry and the relationship between hippocampal asymmetry and P300 amplitude in male monozygotic twins discordant for Vietnam combat exposure. Lateralised hippocampal volume and P300 data were obtained from 70 male participants, of whom 12 had PTSD. We were able to compare (1) combat veterans with current PTSD; (2) their non-combat-exposed co-twins; (3) combat veterans without current PTSD and (4) their non-combat-exposed co-twins. RESULTS: There were no significant differences between groups in hippocampal asymmetry. There were no group differences in performance of an auditory oddball target detection task or in P300 amplitude. There was a significant positive correlation between P300 amplitude and the magnitude of hippocampal asymmetry in participants with PTSD. CONCLUSIONS: These findings suggest that greater hippocampal asymmetry in PTSD is associated with a need to allocate more attentional resources when processing significant environmental stimuli.

Event-related potentials to auditory stimuli in monozygotic twins discordant for combat: association with PTSD.

Studies have demonstrated ERP abnormalities related to concentration difficulties in post-traumatic stress disorder (PTSD). We used an identical-twin, case-control design to investigate whether these abnormalities reflect pre-trauma vulnerability or the acquired consequence of PTSD. Vietnam combat veterans and their non-combat-exposed, identical twins completed a three-tone oddball task. Veterans with PTSD had delayed target N2 latencies compared to veterans without PTSD. In a small nonmedicated, nonsmoking subsample, veterans with PTSD also had significantly diminished target P3b amplitudes. A mixed-model, random-effects analysis on the nonmedicated, nonsmoking subsample that included the combat-unexposed co-twins showed a significant Diagnosis x Combat Exposure interaction for target P3b amplitude. Results replicate increased N2 latency and diminished P3b amplitude in PTSD and suggest that diminished P3b amplitude is an acquired condition in PTSD.

Intensity dependence of auditory P2 in monozygotic twins discordant for Vietnam combat: associations with posttraumatic stress disorder.

Two studies have reported decreased intensity dependence of the P2 event-related potential (ERP) in male combat veterans with posttraumatic stress disorder (PTSD), a response pattern presumed to reflect central nervous system-induced protective inhibition and heightened central serotonergic activity. We used an identical twin, case-control design to investigate whether intensity dependence abnormalities reflect pretrauma vulnerability or are an acquired consequence of PTSD. ERPs were measured in male Vietnam combat veterans and their noncombat-exposed monozygotic twin brothers during a four-tone, stimulus-intensity modulation procedure. Contrary to previous findings in male veterans, the PTSD group had significantly steeper P2 amplitude intensity slopes, similar to those reported for female veterans and abused children with PTSD. Additionally, increased P2 amplitude intensity slope was associated with increased PTSD symptom severity, particularly the severity of reexperiencing symptoms. A mixed-model, random-effects analysis that included the combat-unexposed twins revealed a significant diagnosis by combat exposure interaction. Inspection of group means suggests that the observed increased P2 intensity dependence is a consequence of PTSD. Our findings further suggest that low serotonergic tone may emerge as one potential consequence of this disorder.

Physiologic reactivity to startling tones in female Vietnam nurse veterans with PTSD.

Posttraumatic stress disorder (PTSD) is associated with larger heart rate (HR), skin conductance (SC), and eyeblink responses to sudden, loud tones. The present study tested this association in female nurse veterans with PTSD related to witnessing patients' death, severe injury and/or suffering during their Vietnam service. Nurses with current, past but not current, or who never had PTSD listened to 15 consecutive 95-dB, 500-ms, 1000-Hz tones with sudden onsets, while HR, SC, and eyeblink responses were measured. Nurses with current PTSD produced significantly larger averaged HR, but not SC or eyeblink responses across tone trials. A larger HR response to loud tones is one of the most robust physiologic findings in PTSD and may reflect increased defensive responding.

Neurobehavioral effects of exposure to trichloroethylene through a municipal water supply.

We studied a population-based sample of 143 residents of a community in which the municipal water supply had been contaminated with trichloroethylene (TCE) and related chemicals from several adjacent hazardous waste sites between 1981 and 1986. A hydraulic simulation model was used in conjunction with a geographic information system (GIS) to estimate residential water supply exposures to TCE; 80% of the participants had potential TCE exposure exceeding the maximum contaminant level (5 ppb). The Neurobehavioral Core Test Battery (NCTB), tests of visual contrast sensitivity, and the profile of mood states (POMS) were administered approximately 6 years following peak concentrations of TCE in municipal drinking water. Multivariate analysis of variance adjusted for potential confounders was used to compare mean test scores of residents classified by estimated TCE exposure (< or =5, >5-10, >10-15, >15 ppb). TCE exposure >15 ppb was associated with poorer performance on the digit symbol, contrast sensitivity C test, and contrast sensitivity D test and higher mean scores for confusion, depression, and tension. We found evidence of a strong interaction between exposure to TCE and alcohol consumption; the associations for the NCTB and POMS among persons in the high-exposure group who also consumed alcohol were stronger and were statistically significant for the Benton, digit symbol, digit span, and simple reaction time tests, as well as for confusion, depression, and tension. This study adds to the evidence that long-term exposure to low concentrations of TCE is associated with neurobehavioral deficits and demonstrates the usefulness of GIS-based modeling in exposure assessment.

Event-related potentials to auditory stimuli in female Vietnam nurse veterans with posttraumatic stress disorder.

Individuals with posttraumatic stress disorder (PTSD) have been found to show several event-related brain potential (ERP) abnormalities including reduced target P3b amplitude, P50 suppression, and P2 amplitude/intensity slope. Female Vietnam nurse veterans with (n = 29) and without (n = 38) current PTSD completed P50 paired-click, three-tone "oddball" and four-tone stimulus-intensity modulation procedures. Opposite to previous findings, the current PTSD group had larger target P3b amplitudes and increased P2 amplitude/intensity slopes. Reduced P50 suppression was associated with increased severity of general psychopathology, but not with PTSD diagnosis. Findings suggest that target P3b amplitude and P2 amplitude/intensity slope abnormalities reflect different pathophysiological processes. Future research is needed to determine whether the opposite ERP abnormalities observed in this PTSD sample reflect gender-, trauma-, or sample-specific findings.