Thomas C. Neylan

Association of Mental Health Disorders With Prescription Opioids and High-Risk Opioid Use in US Veterans of Iraq and Afghanistan

CONTEXT Record numbers of Iraq and Afghanistan veterans survive their war injuries and yet continue to experience pain and mental health problems, particularly posttraumatic stress disorder (PTSD). Little is known about the association of mental health disorders and prescription opioid use. OBJECTIVE To investigate the effect of mental health disorders, particularly PTSD, on risks and adverse clinical outcomes associated with prescription opioid use. DESIGN Retrospective cohort study involving 141,029 Iraq and Afghanistan veterans who received at least 1 non-cancer-related pain diagnosis within 1 year of entering the Department of Veterans Affairs (VA) health care system from October 1, 2005, through December 31, 2010. MAIN OUTCOME MEASURES Independent association of mental health disorders and the prescription of opioids, higher risk opioid use, and adverse clinical outcomes (eg, accidents and overdose) within 1 year of receiving a pain-related diagnosis. RESULTS A total of 15,676 veterans were prescribed opioids within 1 year of their initial pain diagnosis. Compared with 6.5% of veterans without mental health disorders, 17.8% (adjusted relative risk [RR], 2.58; 95% CI, 2.49-2.67) of veterans with PTSD and 11.7% (adjusted RR, 1.74; 95% CI, 1.67-1.82) with other mental health diagnoses but without PTSD were significantly more likely to receive opioids for pain diagnoses. Of those who were prescribed pain medication, veterans with PTSD were more likely than those without mental health disorders to receive higher-dose opioids (22.7% vs 15.9%, adjusted RR, 1.42; 95% CI, 1.31-1.54), receive 2 or more opioids concurrently (19.8% vs 10.7%, adjusted RR, 1.87; 95% CI, 1.70-2.06), receive sedative hypnotics concurrently (40.7% vs 7.6%, adjusted RR, 5.46; 95% CI, 4.91-6.07), or obtain early opioid refills (33.8% vs 20.4%; adjusted RR, 1.64; 95% CI, 1.53-1.75). Receiving prescription opioids (vs not) was associated with an increased risk of adverse clinical outcomes for all veterans (9.5% vs 4.1%; RR, 2.33; 95% CI, 2.20-2.46), which was most pronounced in veterans with PTSD. CONCLUSION Among US veterans of Iraq and Afghanistan, mental health diagnoses, especially PTSD, were associated with an increased risk of receiving opioids for pain, high-risk opioid use, and adverse clinical outcomes.

Posttraumatic Stress Disorder and Risk of Dementia Among US Veterans

CONTEXT Posttraumatic stress disorder (PTSD) is highly prevalent among US veterans because of combat and may impair cognition. OBJECTIVE To determine whether PTSD is associated with the risk of developing dementia among older US veterans receiving treatment in the Department of Veterans Affairs medical centers. DESIGN A stratified, retrospective cohort study conducted using the Department of Veterans Affairs National Patient Care Database. SETTING Department of Veterans Affairs medical centers in the United States. PARTICIPANTS A total of 181 093 veterans 55 years or older without dementia from fiscal years 1997 through 2000 (53 155 veterans with and 127 938 veterans without PTSD). MAIN OUTCOME MEASURES During the follow-up period between October 1, 2000, and December 31, 2007, 31 107 (17.2%) veterans were ascertained to have newly diagnosed dementia according to International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS The mean baseline age of the veterans was 68.8 years, and 174 806 (96.5%) were men. Veterans with PTSD had a 7-year cumulative incident dementia rate of 10.6%, whereas those without had a rate of 6.6% (P < .001). With age as the time scale, Cox proportional hazards models indicated that patients with PTSD were more than twice as likely to develop incident dementia compared with those without PTSD (hazard ratio, 2.31; 95% confidence interval, 2.24-2.39). After multivariable adjustment, patients with PTSD were still more likely to develop dementia (hazard ratio, 1.77; 95% confidence interval, 1.70-1.85). Results were similar when we excluded those with a history of head injury, substance abuse, or clinical depression. CONCLUSIONS In a predominantly male veteran cohort, those diagnosed as having PTSD were at a nearly 2-fold-higher risk of developing dementia compared with those without PTSD. Mechanisms linking these important disorders need to be identified with the hope of finding ways to reduce the increased risk of dementia associated with PTSD.

Decreased hippocampal N-acetylaspartate in the absence of atrophy in posttraumatic stress disorder

BACKGROUND Previous magnetic resonance imaging studies of posttraumatic stress disorder reported hippocampal volume loss. The goals of this study were 1) to determine the relationship between hippocampal atrophy and posttraumatic stress disorder in the absence of alcohol abuse, and 2) to test if loss of N-acetylaspartate (a neuron marker) in the hippocampus of posttraumatic stress disorder occurs separate from atrophy. In addition, volume changes in the entorhinal cortex were also explored. METHODS Eighteen male patients with combat-related posttraumatic stress disorder (mean age 51.2 +/- 2.5 years) and 19 male control subjects (mean age 51.8 +/- 3.2 years) were studied using magnetic resonance imaging and Proton magnetic resonance spectroscopic imaging. Both groups had no alcohol and drug abuse during the past 5 years. RESULTS Posttraumatic stress disorder and control subjects had similar volumes of hippocampus and entorhinal cortex. In contrast to volume, N-acetylaspartate was significantly reduced by about 23% bilaterally in the hippocampus of posttraumatic stress disorder when compared with control subjects, and creatine-containing compounds were reduced by 26% in the right hippocampus of posttraumatic stress disorder. CONCLUSIONS N-acetyl asparate and creatine reductions imply that there are hippocampal abnormalities in posttraumatic stress disorder. Furthermore, these metabolite changes seem to be better indicators of posttraumatic stress disorder pathology than volume losses.

Childhood Trauma Associated with Short Leukocyte Telomere Length in Posttraumatic Stress Disorder

BACKGROUND Posttraumatic stress disorder (PTSD) is associated with increased risk for age-related diseases and early mortality. An accelerated rate of biological aging could contribute to this increased risk. To investigate, we assessed leukocyte telomere length (LTL), an emerging marker of biological age, in men and women with and without PTSD. We also examined childhood trauma, a risk factor for both PTSD and short LTL, as a potential contributor to short LTL in PTSD. METHODS Participants included 43 adults with chronic PTSD (n = 18 with multiple categories of childhood trauma) and 47 control subjects (none with multiple categories of childhood trauma) (mean age = 30.55, SD = 7.44). Exclusion criteria included physical illness, medication use, obesity, alcohol or substance abuse, and pregnancy. Structured clinical interviews were conducted to assess PTSD and other psychiatric disorders and childhood trauma exposure. LTL was measured with a quantitative polymerase chain reaction method. RESULTS As predicted, participants with PTSD had shorter age-adjusted LTL than control subjects. Exposure to childhood trauma was also associated with short LTL. In fact, childhood trauma seemed to account for the PTSD group difference in LTL; only participants with PTSD and exposure to multiple categories of childhood trauma had significantly shorter LTL than control subjects. CONCLUSIONS Childhood trauma is associated with short LTL in individuals with PTSD. Chronic exposure to the psychobiological sequelae of childhood trauma could increase risk for PTSD and short LTL. Thus, the lasting psychological impact of exposure to trauma in childhood might be accompanied by equally enduring changes at the molecular level.

Predictors of Posttraumatic Stress in Police and Other First Responders

Abstract:  We provide an overview of previous research conducted by our group on risk and resilience factors for PTSD symptoms in police and other first responders. Based on our work, the findings of other investigators on individual differences in risk for PTSD, and drawing on preclinical studies fear conditioning and extinction, we propose a conceptual model for the development of PTSD symptoms emphasizing the role of vulnerability and resilience to peritraumatic panic reactions. We tested this conceptual model in a cross‐sectional sample of police officers (n= 715). Utilizing an hierarchical linear regression model we were able to explain 39.7% of the variance in PTSD symptoms. Five variables remained significant in the final model; greater peritraumatic distress (β= 0.240, P < .001), greater peritraumatic dissociation (β= 0.174, P < .001), greater problem‐solving coping (β= 0.103, P < .01), greater routine work environment stress (β= 0.182, P < .001), and lower levels of social support (β=−0.246, P < .001). These results were largely consistent with the proposed conceptual model. Next steps in this line of research will be to test this model prospectively in a sample of 400 police academy recruits assessed during training and currently being followed for the first 2 years of police service.

Magnetic Resonance Imaging of Hippocampal Subfields in Posttraumatic Stress Disorder

CONTEXT Most neuroimaging studies of posttraumatic stress disorder (PTSD) have focused on potential abnormalities in the whole hippocampus, but the subfields of this structure, which have distinctive histological characteristics and specialized functions, have not been investigated. Studies of individual subfields may clarify the role of the hippocampus in PTSD. OBJECTIVE To determine if PTSD is associated with structural alterations in specific subfields of the hippocampus. DESIGN Case-control study. PARTICIPANTS A total of 17 male veterans with combat trauma and PTSD (mean [SD] age, 41 [12] years) and 19 age-matched male veterans without PTSD who were recruited from the outpatient mental health clinic of the San Francisco Veterans Affairs Medical Center and by advertising in the community. INTERVENTIONS High-resolution magnetic resonance imaging at 4 T. MAIN OUTCOME MEASURE Volumes of hippocampal subfields. RESULTS Posttraumatic stress disorder was associated with 11.4% (1.5%) (P = .02) smaller mean (SD) cornu ammonis 3 (CA3)/dentate gyrus subfield volumes, irrespective of age-related alterations, whereas other subfields were spared. Age was associated with reduced volume of the CA1 subfield (P = .03). Total hippocampal volume was also reduced in PTSD by a mean (SD) of 6.5% (0.6%) but, related to both PTSD (P = .05) and age (P = .01), was consistent with the measurements in the subfields. CONCLUSIONS The findings indicate for the first time in humans that PTSD is associated with selective volume loss of the CA3/dentate gyrus subfields, consistent with animal studies, implying that chronic stress suppresses neurogenesis and dendritic branching in these structures.

Rescuers at risk: a systematic review and meta-regression analysis of the worldwide current prevalence and correlates of PTSD in rescue workers

PurposeWe sought to estimate the pooled current prevalence of posttraumatic stress disorder (PTSD) among rescue workers and to determine the variables implicated in the heterogeneity observed among the prevalences of individual studies.MethodsA systematic review covering studies reporting on the PTSD prevalence in rescue teams was conducted following four sequential steps: (1) research in specialized online databases, (2) review of abstracts and selection of studies, (3) review of reference list, and (4) contact with authors and experts. Prevalence data from all studies were pooled using random effects model. Multivariate meta-regression models were fitted to identify variables related to the prevalences heterogeneity.ResultsA total of 28 studies, reporting on 40 samples with 20,424 rescuers, were selected. The worldwide pooled current prevalence was 10%. Meta-regression modeling in studies carried out in the Asian continent had, on average, higher estimated prevalences than those from Europe, but not higher than the North American estimates. Studies of ambulance personnel also showed higher estimated PTSD prevalence than studies with firefighters and police officers.ConclusionsRescue workers in general have a pooled current prevalence of PTSD that is much higher than that of the general population. Ambulance personnel and rescuers from Asia may be more susceptible to PTSD. These results indicate the need for improving pre-employment strategies to select the most resilient individuals for rescue work, to implement continuous preventive measures for personnel, and to promote educational campaigns about PTSD and its therapeutic possibilities.

PTSD symptoms predict waking salivary cortisol levels in police officers

This study examines whether pre- or post-dexamethasone salivary cortisol is related to cumulative critical incident exposure, peritraumatic responses, or post-traumatic stress disorder (PTSD) symptom severity. Thirty active duty police officers completed the study protocol, which included measures of peritraumatic emotional distress, peritraumatic dissociation, duty-related trauma exposure, and PTSD symptoms. Salivary cortisol was consolidated into three outcome variables: (1) pre-dexamethasone free cortisol levels at 1, 30, 45, and 60 min after awakening, (2) post-dexamethasone cortisol levels at the identical wake times, and (3) percentage of cortisol suppression. Control variables included age, gender, average daily alcohol use, night shift work, routine work environment stressors, and salivary dexamethasone levels. Zero order correlations showed that greater levels of PTSD symptoms, peritraumatic distress, and peritraumatic dissociation were associated with lower levels of pre-dexamethasone cortisol levels on awakening, but were not associated with the other two cortisol variables. A trend was also noted for older subjects to have lower pre-dexamethasone cortisol on awakening. When these four predictors were entered simultaneously in a regression analysis, only age and PTSD symptom severity significantly predicted pre-dexamethasone awakening cortisol levels. These results replicate previous research indicating a relationship between greater PTSD symptoms and lower levels of basal cortisol on awakening, and extend this finding to a previously unstudied non-treatment seeking population, urban police.

Critical Incident Exposure and Sleep Quality in Police Officers

Objective Police officers face many stressors that may negatively impact sleep quality. This study compares subjective sleep quality in police officers with that in control subjects not involved in police or emergency services. We examined the effects of critical incident exposure (trauma exposure) and routine (nontraumatic) work environment stressors on sleep quality after controlling for the effects of work shift schedule. Methods Subjective sleep disturbances were measured by the Pittsburgh Sleep Quality Index in police officers (variable-shift workers, N = 551; stable day-shift workers, N = 182) and peer-nominated comparison subjects (variable-shift workers, N = 98; stable day-shift workers, N = 232). The main predictor variables were 1) duty-related critical incident exposure to on-line policing and 2) work environment stress related to routine administrative and organizational aspects of police work. Results Police officers on both variable and stable day shifts reported significantly worse sleep quality and less average sleep time than the two corresponding control groups. Within police officers, cumulative critical incident exposure was associated with nightmares but only weakly associated with poor global sleep quality. In contrast, the stress from officers’ general work environment was strongly associated with poor global sleep quality. Sleep disturbances were strongly associated with posttraumatic stress symptoms and general psychopathology. Conclusions A large percentage of police officers report disturbances in subjective sleep quality. Although the life-threatening aspects of police work are related to nightmares, the routine stressors of police service seem to most affect global sleep quality in these subjects. These findings may have implications for health and occupational performance.

Sensory gating in chronic posttraumatic stress disorder: reduced auditory P50 suppression in combat veterans.

BACKGROUND Posttraumatic stress disorder (PTSD) may be associated with a general impairment of cognitive function that extends beyond the processing of trauma-specific stimuli. Suppression of the auditory P50 response to repeated stimuli occurs in normal subjects and reflects the central nervous systems ability to screen out repetitive stimuli, a phenomenon referred to as sensory gating. This study examines P50 sensory gating to nonstartle auditory stimuli in PTSD subjects and normal controls. METHODS P50 generation and gating were studied using a conditioning/testing paradigm in 15 male subjects with PTSD and 12 male controls. P50 test/conditioning (T/C) ratios were estimated using the Singular Value Decomposition method. RESULTS The amplitude of the P50 response to the conditioning stimulus did not differ in subjects with PTSD compared to normal controls. The P50 T/C ratio is increased in PTSD subjects (mean = .408, SD = .275) as compared to the controls (mean = .213, SD = .126, two tailed t, p = .024). CONCLUSIONS This study provides evidence that PTSD is associated with impaired gating to nonstartle trauma-neutral auditory stimuli.