Preliminary evidence for differential olfactory and trigeminal processing in combat veterans with and without PTSD.
ABSTRACT: Structural and functional changes in the olfactory system are increasingly implicated in the expression of PTSD. Still, very little is known about the neurobiological networks of trauma-related odor sensitivity or how they relate to other objective and subjective measures of olfaction and PTSD. The purpose of this study was to replicate prior findings and further characterize olfactory function in trauma-exposed combat veterans with and without PTSD. We also sought to extend this area of research by exploring the effects of time since the combat-related index trauma (TST) on post-trauma olfactory function, as well as by correlating odor-elicited brain activity to general olfactory ability and odor-elicited PTSD symptoms. Participants included combat veterans with PTSD (CV+PTSD; n = 21) or without any psychiatric disorder (CV-PTSD; n = 27). TST was coded as greater (n = 24) or less (n = 24) than 5 years. There were main effects and/or interaction for PTSD-status and TST across several parameters of olfactory function: odor detection, odor identification, ratings for trauma-related odor intensity and triggered PTSD symptoms, and trauma odor-elicited brain activation. Overall, results suggest olfactory impairment in chronic PTSD, but not necessarily in the earlier stages of the disorder, although some early-stage olfactory findings may be predictive of later olfactory impairment. Results also suggest that trauma-exposed individuals who never develop PTSD may demonstrate olfactory resiliency. Finally, results highlight a potentially unique role of trigeminal odor properties in the olfactory-PTSD relationship.
Project description:Intrusive re-experiencing of traumatic events is a hallmark symptom of posttraumatic stress disorder, characterized by rich and vivid sensory details as reported in "flashbacks". While prevailing models of trauma intrusions focus on dysregulated emotional processes, we hypothesize that a deficiency in intrinsic sensory inhibition could drive overactivation of sensory representations of trauma memories, precipitating sensory-rich intrusions. In a sample of combat veterans, we examined resting-state alpha (8-12?Hz) oscillatory activity (in both power and posterior?frontal connectivity), given its role in sensory cortical inhibition, in association with intrusive re-experiencing symptoms. Veterans further participated in an odor task (including both combat and non-combat odors) to assess olfactory trauma memory and emotional response. We observed an association between intrusive re-experiencing symptoms and attenuated resting-state posterior?frontal alpha connectivity, which were both correlated with olfactory trauma memory. Importantly, olfactory trauma memory was identified as a mediator of the relationship between alpha connectivity and intrusive re-experiencing, suggesting that deficits in intrinsic sensory inhibition contributed to intrusive re-experiencing of trauma via heightened trauma memory. Therefore, by permitting unfiltered sensory cues to enter information processing and activate sensory representations of trauma, sensory disinhibition can constitute a sensory mechanism of intrusive re-experiencing in trauma-exposed individuals.
Project description:<h4>Background</h4>Mild traumatic brain injury (mTBI) is a common injury among military personnel serving in Iraq or Afghanistan. The impact of repeated episodes of combat mTBI is unknown.<h4>Objective</h4>To evaluate relationships among mTBI, post-traumatic stress disorder (PTSD) and neurological deficits (NDs) in US veterans who served in Iraq or Afghanistan.<h4>Methods</h4>This was a case-control study. From 2091 veterans screened for traumatic brain injury, the authors studied 126 who sustained mTBI with one or more episodes of loss of consciousness (LOC) in combat. Comparison groups: 21 combat veterans who had definite or possible episodes of mTBI without LOC and 21 veterans who sustained mTBI with LOC as civilians.<h4>Results</h4>Among combat veterans with mTBI, 52% had NDs, 66% had PTSD and 50% had PTSD and an ND. Impaired olfaction was the most common ND, found in 65 veterans. The prevalence of an ND or PTSD correlated with the number of mTBI exposures with LOC. The prevalence of an ND or PTSD was >90% for more than five episodes of LOC. Severity of PTSD and impairment of olfaction increased with number of LOC episodes. The prevalence of an ND for the 34 combat veterans with one episode of LOC (4/34=11.8%) was similar to that of the 21 veterans of similar age and educational background who sustained civilian mTBI with one episode of LOC (2/21=9.5%, p-NS).<h4>Conclusions</h4>Impaired olfaction was the most frequently recognised ND. Repeated episodes of combat mTBI were associated with increased likelihood of PTSD and an ND. Combat setting may not increase the likelihood of an ND. Two possible connections between mTBI and PTSD are (1) that circumstances leading to combat mTBI likely involve severe psychological trauma and (2) that altered cerebral functioning following mTBI may increase the likelihood that a traumatic event results in PTSD.
Project description:<h4>Objective</h4>To examine the association between the 5-HTTLPR polymorphism of the serotonin transporter (SLC6A4) gene, combat exposure, and posttraumatic stress disorder (PTSD) diagnosis and among two samples of combat-exposed veterans.<h4>Method</h4>The first sample included 550 non-Hispanic Black (NHB) combat-exposed veterans. The second sample included 555 non-Hispanic White (NHW) combat-exposed veterans. Participants were genotyped for the 5-HTTLPR/rs25531 variants of the SLC6A4 gene. A structured clinical interview was used to diagnose PTSD. Combat and civilian trauma exposure were assessed with validated self-report instruments. Logistic regression was used to test for main effects of 5-HTTLPR on PTSD diagnosis as well as gene x environment (GxE) interactions after adjusting for sex, ancestry proportion scores, civilian trauma exposure, and combat exposure.<h4>Results</h4>Within the NHB sample, a significant additive effect was observed for 5-HTTLPR (OR = 1.502, p = .0025), such that the odds of having a current diagnosis of PTSD increased by 1.502 for each additional S' allele. No evidence for an association between 5-HTTLPR and PTSD was observed in the NHW sample. In addition, no evidence for combat x 5-HTTLPR effects were observed in either sample.<h4>Conclusion</h4>The present study suggests that there may be an association between 5-HTTLPR genotype and PTSD diagnosis among NHB veterans; however, no evidence for the hypothesized 5-HTTLPR x combat interaction was found.
Project description:Post-traumatic stress disorder (PTSD), a complex and chronic disorder caused by exposure to a traumatic event, is a common psychological result of current military operations. It causes substantial distress and interferes with personal and social functioning. Consequently, identifying the risk factors that make military personnel and veterans more likely to experience PTSD is of academic, clinical, and social importance. Four electronic databases (PubMed, Embase, Web of Science, and PsycINFO) were used to search for observational studies (cross-sectional, retrospective, and cohort studies) about PTSD after deployment to combat areas. The literature search, study selection, and data extraction were conducted by two of the authors independently. Thirty-two articles were included in this study. Summary estimates were obtained using random-effects models. Subgroup analyses, sensitivity analyses, and publication bias tests were performed. The prevalence of combat-related PTSD ranged from 1.09% to 34.84%. A total of 18 significant predictors of PTSD among military personnel and veterans were found. Risk factors stemming from before the trauma include female gender, ethnic minority status, low education, non-officer ranks, army service, combat specialization, high numbers of deployments, longer cumulative length of deployments, more adverse life events, prior trauma exposure, and prior psychological problems. Various aspects of the trauma period also constituted risk factors. These include increased combat exposure, discharging a weapon, witnessing someone being wounded or killed, severe trauma, and deployment-related stressors. Lastly, lack of post-deployment support during the post-trauma period also increased the risk of PTSD. The current analysis provides evidence of risk factors for combat-related PTSD in military personnel and veterans. More research is needed to determine how these variables interact and how to best protect against susceptibility to PTSD.
Project description:The present study examined lifespan and combat-related trauma exposure as predictors of alcohol use among male and female veterans. Posttraumatic stress and depressive symptoms were examined as mediators of the effects of trauma exposure on alcohol use.Data were examined from 1825 (1450 male, 375 female) veterans and active duty service members who took part in a multi-site research study conducted through the Department of Veterans Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center (VISN 6 MIRECC).For both men and women, depressive symptoms significantly mediated the effects of non-combat trauma exposure experienced before, during and after the military, as well as combat-exposure, on alcohol use. With posttraumatic stress symptoms, the models for men and women differed. For men, the effects of non-combat trauma exposure during and after military service, and combat exposure, on alcohol use were mediated by PTSD symptoms; however, for women, PTSD symptoms did not mediate these relationships.Findings are discussed in the context of potential gender differences in response to trauma such as use of alcohol to cope with traumatic events.
Project description:<h4>Background</h4>Complicated grief (CG) is a bereavement-specific syndrome distinct from but commonly comorbid with posttraumatic stress disorder (PTSD). While bereavement is common among military personnel (Simon et al., 2018), there is little research on the impact of CG comorbidity on PTSD treatment outcomes.<h4>Methods</h4>To evaluate the impact of comorbid CG on PTSD treatment outcomes we analyzed data from a randomized trial comparing prolonged exposure, sertraline, and their combination in veterans with a primary diagnosis of combat-related PTSD (n?=?194). Assessment of PTSD, trauma-related guilt, functional impairment, and suicidal ideation and behavior occurred at baseline and weeks 6, 12, and 24 during the 24-week trial.<h4>Results</h4>CG was associated with lower PTSD treatment response (odds ratio (OR)?=?0.29, 95% confidence interval (CI) [0.12, 0.69], p?=?0.005) and remission (OR?=?0.28, 95% CI [0.11, 0.71], p?=?0.007). Those with CG had greater severity of PTSD (p?=?0.005) and trauma-related guilt (<0.001) at baseline and endpoint. In addition, those with CG were more likely to experience suicidal ideation during the study (CG: 35%, 14/40 vs. no CG 15%, 20/130; OR?=?3.01, 95% CI [1.29, 7.02], p?=?0.011).<h4>Conclusions</h4>Comorbid CG is associated with elevated PTSD severity and independently associated with poorer endpoint treatment outcomes in veterans with combat-related PTSD, suggesting that screening and additional intervention for CG may be needed.
Project description:Post-traumatic stress disorder (PTSD) is an anxiety disorder that is associated with structural and functional alterations in several brain areas, including the anterior cingulate cortex (ACC). Here, we examine resting state functional connectivity of ACC subdivisions in PTSD, using a seed-based approach. Resting state magnetic resonance images were obtained from male veterans with (n?=?31) and without (n?=?25) PTSD, and healthy male civilian controls (n?=?25). Veterans with and without PTSD (combat controls) had reduced functional connectivity compared to healthy controls between the caudal ACC and the precentral gyrus, and between the perigenual ACC and the superior medial gyrus and middle temporal gyrus. Combat controls had increased connectivity between the rostral ACC and precentral/middle frontal gyrus compared to PTSD patients and healthy civilian controls. The resting state functional connectivity differences in the perigenual ACC network reported here indicate that veterans differ from healthy controls, potentially due to military training, deployment, and/or trauma exposure. In addition, specific alterations in the combat controls may potentially be related to resilience. These results underline the importance of distinguishing trauma-exposed (combat) controls from healthy civilian controls when studying PTSD.
Project description:Neuroimaging studies have revealed functional abnormalities in the anterior cingulate cortex in posttraumatic stress disorder (PTSD). The goal of this study was to determine whether hyperresponsivity of the dorsal anterior cingulate in PTSD is an acquired characteristic or a familial risk factor.Using a case-control twin design, the authors studied combat-exposed veterans with PTSD (N=12) and their identical combat-unexposed co-twins (N=12), as well as combat-exposed veterans without PTSD (N=14) and their identical combat-unexposed co-twins (N=14). Participants underwent functional MRI during completion of the Multi-Source Interference Task, which reliably activates the dorsal anterior cingulate.Combat-exposed veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and tended to have larger response time difference scores, as compared to combat-exposed veterans without PTSD and their co-twins. Dorsal anterior cingulate activation in the exposed twins was positively correlated with their PTSD symptom severity. Dorsal anterior cingulate activation in the unexposed twins was positively correlated with their combat-exposed co-twins' PTSD symptom severity, but not with depression or alcohol use severity in the combat-exposed co-twins.Hyperresponsivity in the dorsal anterior cingulate appears to be a familial risk factor for the development of PTSD following psychological trauma.
Project description:Background:Previously we reported a genetic risk score significantly improved PTSD prediction among a trauma-exposed civilian population. In the current study, we sought to assess this prediction among a trauma-exposed military population. Methods:We examined current PTSD diagnosis and PTSD symptom severity among a random sample of 1042 community-based US military veterans. Main effects and interaction effects were assessed for PTSD genetic risk by trauma exposure using cross-product terms for PTSD x trauma exposures, including combat, lifetime trauma, and adverse childhood exposures. The PTSD risk variants studied were within genetic loci previously associated with PTSD, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variants, which were used to calculate a total PTSD genetic risk score (range=0-8, mean=3.6, SD=1.4). Results:Based on DSM-5 PTSD criteria, 7.1% of veterans (95% CI=5.6-8.8) met criteria for current PTSD. The PTSD genetic risk count was significantly higher among PTSD cases vs non-cases (3.92 vs 3.55, p=0.027). Since the PTSD genetic risk score was not significant in the PTSD diagnosis model, we assessed this association using PTSD symptom severity. Because these symptom data were skewed (mean=9.54, SD=12.71, range=0-76), we used negative binomial regression to assess this outcome. This symptom model included a PTSD genetic risk score, demographic factors, trauma exposures, current insomnia, current depression, concussion history, and attention-deficit disorder, expressed as incident rate ratios (IRR), which is an estimate of one-unit increase in PTSD severity, given other variables are held constant. Variables in the final model included age and sex (both p<0.001), PTSD genetic risk (IRR=1.02, p=0.028), warzone tours (IRR=0.94, p=0.003), childhood abuse (IRR=1.50, p<0.0001), current depression (IRR=1.89, p<0.0001), current insomnia (IRR=2.58, p<0.0001), low social support (IRR=1.19, p<0.0001), attention-deficit disorder (IRR=1.51, p<0.0001), agreeable personality (IRR=0.77, p<0.0001), and concussion (IRR=1.38, p<0.0001). Significant interactions were detected for combat and lifetime trauma exposure by PTSD genetic risk (both p<0.0001), suggesting that the impact of trauma exposures on PTSD severity was lower when the PTSD genetic risk was higher. Conclusion:Both warzone and non-warzone factors predicted current PTSD symptoms among veterans, including a PTSD genetic risk score. Interaction effects were detected for combat exposure and lifetime trauma by genetic risk score for PTSD symptoms, suggesting that PTSD symptom manifestation was more dependent on PTSD risk variants than the level of trauma or combat exposure. This suggests that controlling for other factors, the absence of genetic risk variants may confer PTSD resilience. Further research is planned.
Project description:<h4>Background</h4>Post-traumatic stress disorder (PTSD) involves debilitating symptoms that can disrupt cognitive functioning. The emotional Stroop has been commonly used to examine the impact of PTSD on attentional control, but no published study has yet used it with Afghanistan and Iraq war veterans, and only one previous study has compared groups on habituation to trauma-related words.<h4>Methods</h4>We administered the emotional Stroop, the Beck Depression Inventory (BDI), and the PTSD Checklist (PCL) to 30 veterans with PTSD, 30 military controls, and 30 civilian controls. Stroop word types included Combat, Matched-neutral, Neutral, Positive and Negative.<h4>Results</h4>Compared to controls, veterans with PTSD were disproportionately slower in responding to Combat words. They were also slower and less accurate overall, did not show interference on Negative or Positive words relative to Neutral, and showed a trend for delayed but successful habituation to Combat words. Higher PCL and BDI scores also correlated with larger interference effects.<h4>Conclusions</h4>Because of its specificity in detecting attentional biases to trauma-related words, the emotional Stroop task may serve as a useful pre- and post task with intervention studies of PTSD patients.