Course and Predictors of Postdeployment Fatigue: A Prospective Cohort Study in the Dutch Armed Forces.

OBJECTIVE: The purpose of this study was to examine course and predictors of fatigue in military personnel deployed to Afghanistan. METHODS: A total of 906 soldiers in the Dutch Armed Forces who participated in a 4-month mission to Afghanistan were included in this study. Assessment took place prior to and 1, 6, 12, and 24 months after deployment. Data were collected between 2005 and 2011. The fatigue severity subscale of the Checklist Individual Strength was used to indicate the level of fatigue during the previous 2 weeks. Mixed models and logistic regression analysis were used to predict course and prevalence of fatigue after deployment. Predictors of postdeployment fatigue were assessed prior to deployment. RESULTS: The mean level of fatigue increased significantly following deployment (B = 0.58, P = .007). In total, 274 soldiers (30.2%) were severely fatigued at least once after deployment and 130 (14.3%) soldiers had recurrent levels of severe fatigue. Only a minority of the veterans with severe fatigue could be classified as having posttraumatic stress disorder (PTSD, per DSM-IV-TR criteria) or potential medical problems. Significant predeployment predictors of less favorable courses of fatigue after deployment were higher levels of fatigue (B = 0.46, P ≤ .001), emotional abuse during childhood (B = 0.99, P ≤ .001), and harm avoidance (B = 0.27, P = .012). These predeployment factors also predicted severe fatigue after deployment. CONCLUSIONS: Severe fatigue is a substantial problem in Afghanistan War veterans that does not seem to resolve over time. In a majority of cases, the symptoms cannot be attributed to medical problems or PTSD, whereas predeployment differences in psychosocial factors partially explain course and prevalence of postdeployment fatigue. These findings support assumptions that a complex interplay of various factors might be responsible for the symptoms.

Treatment Outcome-Related White Matter Differences in Veterans with Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a debilitating disorder that has been associated with brain abnormalities, including white matter alterations. However, little is known about the effect of treatment on these brain alterations. To investigate the course of white matter alterations in PTSD, we used a longitudinal design investigating treatment effects on white matter integrity using diffusion tensor imaging (DTI). Diffusion tensor and magnetization transfer images were obtained pre- and posttreatment from veterans with (n=39) and without PTSD (n=22). After treatment, 16 PTSD patients were remitted, and 23 had persistent PTSD based on PTSD diagnosis. The dorsal and hippocampal cingulum bundle, stria terminalis, and fornix were investigated as regions of interest. Exploratory whole-brain analyses were also performed. Groups were compared with repeated-measures ANOVA for fractional anisotropy (FA), and magnetization transfer ratio. Persistently symptomatic PTSD patients had increasing FA of the dorsal cingulum over time, and at reassessment these FA values were higher than both combat controls and the remitted PTSD group. Group-by-time interactions for FA were found in the hippocampal cingulum, fornix, and stria terminalis, posterior corona radiata, and superior longitudinal fasciculus. Our results indicate that higher FA of the dorsal cingulum bundle may be an acquired feature of persistent PTSD that develops over time. Furthermore, treatment might have differential effects on the hippocampal cingulum, fornix, stria terminalis, posterior corona radiata, and superior longitudinal fasciculus in remitted vs persistent PTSD patients. This study contributes to a better understanding of the neural underpinnings of PTSD treatment outcome.

Neural correlates of inhibition and contextual cue processing related to treatment response in PTSD.

Thirty to fifty percent of posttraumatic stress disorder (PTSD) patients do not respond to treatment. Understanding the neural mechanisms underlying treatment response could contribute to improve response rates. PTSD is often associated with decreased inhibition of fear responses in a safe environment. Importantly, the mechanism of effective treatment (psychotherapy) relies on inhibition and so-called contextual cue processing. Therefore, we investigate inhibition and contextual cue processing in the context of treatment. Forty-one male war veterans with PTSD and 22 healthy male war veterans (combat controls) were scanned twice with a 6- to 8-month interval, in which PTSD patients received treatment (psychotherapy). We distinguished treatment responders from nonresponders on the base of percentage symptom decrease. Inhibition and contextual cue processing were assessed with the stop-signal anticipation task. Behavioral and functional MRI measures were compared between PTSD patients and combat controls, and between responders and nonresponders using repeated measures analyses. PTSD patients showed behavioral and neural deficits in inhibition and contextual cue processing at both time points compared with combat controls. These deficits were unaffected by treatment; therefore, they likely represent vulnerability factors or scar aspects of PTSD. Second, responders showed increased pretreatment activation of the left inferior parietal lobe (IPL) during contextual cue processing compared with nonresponders. Moreover, left IPL activation predicted percentage symptom improvement. The IPL has an important role in contextual cue processing, and may therefore facilitate the effect of psychotherapy. Hence, increased left IPL activation may represent a potential predictive biomarker for PTSD treatment response.

Resting state functional connectivity of the anterior cingulate cortex in veterans with and without post-traumatic stress disorder.

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.

Impaired right inferior frontal gyrus response to contextual cues in male veterans with PTSD during response inhibition.

BACKGROUND: Posttraumatic stress disorder (PTSD) is often associated with impaired fear inhibition and decreased safety cue processing; however, studies capturing the cognitive aspect of inhibition and contextual cue processing are limited. In this fMRI study, the role of contextual cues in response inhibition was investigated. METHODS: Male medication-naive war veterans with PTSD, male control veterans (combat controls) and healthy nonmilitary men (healthy controls) underwent fMRI while performing the stop-signal anticipation task (SSAT). The SSAT evokes 2 forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping based on contextual cues). RESULTS: We enrolled 28 veterans with PTSD, 26 combat controls and 25 healthy controls in our study. Reduced reactive inhibition was observed in all veterans, both with and without PTSD, but not in nonmilitary controls, whereas decreased inhibition of the left pre/postcentral gyrus appeared to be specifically associated with PTSD. Impaired behavioural proactive inhibition was also specific to PTSD. Furthermore, the PTSD group showed a reduced right inferior frontal gyrus response during proactive inhibition compared with the combat control group. LIMITATIONS: Most patients with PTSD had comorbid psychiatric disorders, but such comorbidity is common in patients with PTSD. Also, the education level (estimate of intelligence) of participants, but not of their parents, differed among the groups. CONCLUSION: Our findings of reduced proactive inhibition imply that patients with PTSD show reduced contextual cue processing. These results complement previous findings on fear inhibition and demonstrate that contextual cue processing in patients with PTSD is also reduced during cognitive processes, indicating a more general deficit.

The role of stress sensitization in progression of posttraumatic distress following deployment.

PURPOSE: Military personnel exposed to combat are at risk for experiencing post-traumatic distress that can progress over time following deployment. We hypothesized that progression of post-traumatic distress may be related to enhanced susceptibility to post-deployment stressors. This study aimed at examining the concept of stress sensitization prospectively in a sample of Dutch military personnel deployed in support of the conflicts in Afghanistan. METHOD: In a cohort of soldiers (N = 814), symptoms of post-traumatic stress disorder (PTSD) were assessed before deployment as well as 2, 7, 14, and 26 months (N = 433; 53 %) after their return. Data were analyzed using latent growth modeling. Using multiple group analysis, we examined whether high combat stress exposure during deployment moderated the relation between post-deployment stressors and linear change in post-traumatic distress after deployment. RESULTS: A higher baseline level of post-traumatic distress was associated with more early life stressors (standardized regression coefficient = 0.30, p < 0.001). In addition, a stronger increase in posttraumatic distress during deployment was associated with more deployment stressors (standardized coefficient = 0.21, p < 0.001). A steeper linear increase in posttraumatic distress post-deployment (from 2 to 26 months) was predicted by more post-deployment stressors (standardized coefficient = 0.29, p < 0.001) in high combat stress exposed soldiers, but not in a less combat stress exposed group. The group difference in the predictive effect of post-deployment stressors on progression of post-traumatic distress was significant (χ²(1) = 7.85, p = 0.005). CONCLUSIONS: Progression of post-traumatic distress following combat exposure may be related to sensitization to the effects of post-deployment stressors during the first year following return from deployment.

Police officers: a high-risk group for the development of mental health disturbances? A cohort study.

OBJECTIVES: Policing is generally considered a high-risk profession for the development of mental health problems, but this assumption lacks empirical evidence. Research question of the present study is to what extent mental health disturbances, such as (very) severe symptoms of anxiety, depression and hostility are more prevalent among police officers than among other occupational groups. DESIGN: Multicomparative cross-sectional study using the data of several cross-sectional and longitudinal studies in the Netherlands. PARTICIPANTS: Two samples of police officers (N=144 and 503), employees of banks (N=1113) and employees of banks who were robbed (N=144); employees of supermarkets (N=335), and a psychiatric hospital (N=219), employees of a governmental social welfare organisation (N=76), employees who followed a training based on rational-motive therapy to strengthen their assertiveness (N=710), soldiers before deployment (N=278) and before redeployment (N=236) and firefighters (N=123). The numbers refer to respondents with complete data. PRIMARY OUTCOMES: Prevalence of severe (subclinical level) and very severe symptoms (clinical level) were computed using the Dutch norm tables (80th percentile and 95th percentile, respectively) of the Symptom Check List Revised (SCL-90-R). All comparisons were controlled for age, gender and education. RESULTS: Multivariate logistic regression and analyses showed that the prevalence of clinical and subclinical levels of symptoms of anxiety, depression and hostility among police officers were not significantly higher than among comparison groups. The same pattern was found for the other SCL-90-R subscales. CONCLUSIONS: We found no indications that self-reported mental health disturbances were more prevalent among police officers than among groups of employees that are not considered high-risk groups, such as employees of banks, supermarkets, psychiatric hospital and soldiers before deployment.

Neural correlates of personality: an integrative review.

This review examines the neural correlates of Gray's model (Gray and McNaughton, 2000; McNaughton and Corr, 2004), supplemented by a fourth dimension: constraint (Carver, 2005). The purpose of this review is to summarize findings from fMRI studies that tap on neural correlates of personality aspects in healthy subjects, in order to provide insight into the neural activity underlying human temperament. BAS-related personality traits were consistently reported to correlate positively to activity of the ventral and dorsal striatum and ventral PFC in response to positive stimuli. FFFS and BIS-related personality traits are positively correlated to activity in the amygdala in response to negative stimuli. There is limited evidence that constraint is associated with PFC and ACC activity. In conclusion, functional MRI research sheds some light on the specific neural networks underlying personality. It is clear that more sophisticated task paradigms are required, as well as personality questionnaires that effectively differentiate between BAS, FFFS, BIS, and constraint. Further research is proposed to potentially reveal new insight in the neural subsystems governing basic human behavior.

Altered functional connectivity in posttraumatic stress disorder with versus without comorbid major depressive disorder: a resting state fMRI study.

Posttraumatic stress disorder (PTSD) is an anxiety disorder that is often diagnosed with comorbid depressive disorder. Therefore, neuroimaging studies investigating PTSD typically include both patients with and without comorbid depression. Differences in activity of the anterior cingulate cortex (ACC) and insula have been shown to differentiate PTSD patients with and without major depressive disorder (MDD). Whether or not comorbid MDD affects resting state functional connectivity of PTSD patients has not been investigated to our knowledge. Here, resting state functional connectivity of PTSD patients with (PTSD+MDD; n=27) and without (PTSD-MDD; n=23) comorbid MDD was investigated. The subgenual ACC and insula were investigated as seed regions. Connectivity between the subgenual ACC and perigenual parts of the ACC was increased in PTSD+MDD versus PTSD-MDD. Reduced functional connectivity of the subgenual ACC with the thalamus was found in the PTSD+MDD group versus the PTSD-MDD group. These results remained significant after controlling for PTSD severity. In addition, the PTSD+MDD group showed reduced functional connectivity of the insula with the hippocampus compared to the PTSD-MDD group. However, this cluster was no longer significantly different when controlling for PTSD severity. Thus, resting state functional connectivity of the subgenual ACC may distinguish PTSD+MDD from PTSD-MDD. As PTSD patients with comorbid MDD are more treatment resistant, this result may be important for treatment development.

Symptom structure of PTSD: support for a hierarchical model separating core PTSD symptoms from dysphoria.

BACKGROUND: As of yet, no collective agreement has been reached regarding the precise factor structure of posttraumatic stress disorder (PTSD). Several alternative factor-models have been proposed in the last decades. OBJECTIVE: The current study examined the fit of a hierarchical adaptation of the Simms et al. (2002) dysphoria model and compared it to the fit of the PTSD model as depicted in the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV), a correlated four-factor emotional numbing, and a correlated four-factor dysphoria model. METHODS: Data were collected using the Clinician-Administered PTSD Scale in a mixed-trauma sample of treatment-seeking PTSD patients (N=276). RESULTS: All examined models provided superior fit to the three-factor model of DSM-IV. The hierarchical four-factor solution provided a better fit than competing models. CONCLUSION: The present study provides empirical support for a conceptualization of PTSD that includes a higher-order PTSD factor that encompasses re-experiencing, arousal, and effortful avoidance sub-factors and a dysphoria factor.

Neuroendocrine and immune responses to a cognitive stress challenge in veterans with and without PTSD.

BACKGROUND: PTSD has been associated with altered hypothalamus-pituitary-adrenal-axis (HPA-axis), immune and sympathetic nervous system (SNS) regulation. The purpose of this study was to evaluate the effect of cognitive stress on these systems in PTSD patients and controls. METHODS: The subjective units of distress score (SUDS), NK-cell response, plasma levels of noradrenalin and ACTH in response to cognitive stress were assessed in male veterans with PTSD (n=15) and age, region and year of deployment matched veterans without psychopathology (n=15). RESULTS: The challenge induced an increase in SUDS, noradrenalin, ACTH and NK-cell response in both groups. Baseline levels of ACTH were lower in PTSD patients. The test was experienced as more stressful by PTSD patients and resulted in an augmented ACTH response in patients. The noradrenalin and NK-cell responses showed no group differences. The ACTH response correlated with the severity of symptoms in patients, and the noradrenalin response correlated with the ACTH and NK-cell response in controls, but not in patients. DISCUSSION: PTSD patients experience more distress and present with an exaggerated pituitary response to this stressor. In addition, our results suggest an altered interaction between the HPA-axis, SNS and immune system in PTSD.

Glucocorticoid receptor number predicts increase in amygdala activity after severe stress.

INTRODUCTION: Individuals who are exposed to a traumatic event are at increased risk of developing psychiatric disorders such as posttraumatic stress disorder (PTSD). Studies have shown that increased amygdala activity is frequently found in patients with PTSD. In addition, pre-trauma glucocorticoid receptor (GR) number in peripheral blood mononuclear cells (PBMCs) has been found to be a significant predictor for the development of PTSD symptoms. Research in rodents has shown that the response of basolateral amygdala neurons to corticosterone is mediated by GR. However, to the best of our knowledge, no previous study has investigated GR number in PBMCs and amygdala function in humans. METHODS: To investigate whether peripheral GR number is related to amygdala functioning, we assessed GR number in PBMCs of healthy soldiers before their deployment to Afghanistan. Amygdala functioning was assessed with fMRI before and after deployment. RESULTS: We found that pre-deployment GR number was significantly negatively correlated to pre-deployment amygdala activity. More importantly, pre-deployment GR number predicted the increase in amygdala activity by deployment. DISCUSSION: Our results demonstrate that peripheral GR number is associated with amygdala functioning and predicts the increase in amygdala activity following military deployment in healthy individuals who did not develop PTSD. It is uncertain how this relationship is mediated mechanistically, but future studies should examine the relation of GR and amygdala activity to determine whether this is part of a common pathway leading to increased vulnerability to stress-related disorders.

A prospective study on personality and the cortisol awakening response to predict posttraumatic stress symptoms in response to military deployment.

Few prospective studies on pre-trauma predictors for subsequent development of posttraumatic stress disorder (PTSD) have been conducted. In this study we prospectively investigated whether pre-deployment personality and the cortisol awakening response (CAR) predicted development of PTSD symptoms in response to military deployment. Furthermore, we hypothesized that potential effects of age, childhood trauma and previous deployment on development of PTSD symptoms were mediated via pre-deployment personality, CAR and PTSD symptoms. Path analysis was performed on data from 470 male soldiers collected before and six months after a 4-month deployment to Afghanistan. Before deployment, personality was assessed with the short-form Temperament-Character Inventory and the Cook-Medley Hostility scale. In addition, pre-deployment saliva sampling for assessment of the CAR was performed immediately after awakening and 15, 30 and 60min thereafter. Pre-deployment high hostility and low self-directedness represented intrinsic vulnerabilities for development of PTSD symptoms after deployment. The CAR assessed before deployment did not predict PTSD symptoms after deployment. Pre-deployment low-to-moderate PTSD symptoms were associated with PTSD symptoms after deployment. As hypothesized, the effects of age and childhood trauma on PTSD symptoms after deployment were mediated via personality and pre-deployment PTSD symptoms. However, the number of previous deployments was not related to development of PTSD symptoms. The total model explained 24% of variance in PTSD symptoms after military deployment.

Type D personality and the development of PTSD symptoms: a prospective study.

Psychological trauma and prolonged stress may cause mental disorders such as posttraumatic stress disorder (PTSD). Pretrauma personality is an important determinant of posttraumatic adjustment. Specifically, trait neuroticism has been identified as a risk factor for PTSD. Additionally, the combination of high negative affectivity or neuroticism with marked social inhibition or introversion, also called Type D personality (Denollet, 2000), may compose a risk factor for PTSD. There is no research available that examined pretrauma Type D personality in relation to PTSD. The present study examined the predictive validity of the Type D personality construct in a sample of Dutch soldiers. Data were collected prior to and 6 months after military deployment to Afghanistan. Separate multiple regression analyses were performed to examine the predictive validity of Type D personality. First, Type D personality was defined as the interaction between negative affect and social inhibition (Na × Si). In a second analysis, Type D was defined following cutoff criteria recommended by Denollet (2000). Results showed that negative affectivity was a significant predictor of PTSD symptoms. Social inhibition and the interaction Na × Si did not add to the amount of explained variance in postdeployment PTSD scores over the effects of childhood abuse, negative affectivity, and prior psychological symptoms. A second analysis showed that Type D personality (dichotomous) did not add to the amount of explained variance in postdeployment PTSD scores over the effects of childhood abuse, and prior psychological symptoms. Therefore, Type D personality appears to be of limited value to explain development of combat-related PTSD symptoms.

Investigating the MMPI-2 trauma profile in treatment-seeking peacekeepers.

Most available research on MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) scores in combat veterans suffering from posttraumatic stress disorder (PTSD) has focused on Vietnam veterans. No data are available from peacekeepers suffering from PTSD. The aim of this study was to investigate the relationship between PTSD and the MMPI-2 in a sample of 120 treatment seeking peacekeeping veterans. Results show that relative to a non-PTSD reference group, veterans who screened positive for PTSD scored higher on Scales F, 2 (D), 4 (Pd), 6 (Pa), 7 (Pt), 8 (Sc), and 0 (Si) of the MMPI-2. Scales 2 (D), 7 (Pt), and 8 (Sc) were highest in the mean PTSD profile but no 2- or 3-point code type could be defined. Moderate correlations were found between a self-report measure for PTSD symptoms and scores on MMPI-2 clinical scales 1 (Hs), 2 (D), 6 (Pa), 7 (Pt), and 8 (Sc). The MMPI-2 proved to be useful in assessing the broad range of symptoms typically present in trauma populations as well as the severity of posttraumatic morbidity.

Personality dimensions harm avoidance and self-directedness predict the cortisol awakening response in military men.

To account for individual differences in vulnerability for stress-related disorders, studies have examined the relationship between hypothalamic-pituitary-adrenal (HPA) axis functioning and personality. The present study examined the relationship between the free fraction of cortisol in saliva after awakening and personality as measured with Cloninger's Temperament and Character Inventory [Cloninger, C.R., Przybeck, T.R., Svrakic, D.M., Wetzel, R.D., 1994. The Temperament and Character Inventory (TCI): A Guide to its Development and Use. Washington University, Center for Psychobiology of Personality, St. Louis, MO] in 107 healthy male soldiers. Harm avoidance explained 9% of variance in cortisol levels after awakening (AUCG), and harm avoidance and self-directedness predicted 10% of variance in mean cortisol increase. The cortisol awakening response (CAR) was lower in participants with low scores on harm avoidance, and mean cortisol increase after awakening was higher in soldiers high on self-directedness and harm avoidance. These results show that the CAR is related to personality and that it can be used to examine individual differences in HPA (re)activity.

Self-reported early trauma as a predictor of adult personality: a study in a military sample.

Exposure to early trauma has frequently been linked to adult psychopathology, including personality disorders. This cross-sectional study explored the relationship between personality and retrospectively rated levels of early trauma in 242 soldiers. Multiple regression analyses showed a significant relationship between early trauma and adult personality as exposure to emotional trauma predicted levels of self-directedness and cooperativeness on the Temperament and Character Inventory (TCI; C. R. Cloninger, T. R. Przybeck, D. M. Svrakic, & R. D. Wetzel, 1994). Overall, these results suggest that early emotional trauma may be related to personality dimensions associated with poor impulse control and interpersonal behavior. These results are noteworthy considering that they were obtained in a healthy sample. They show that early trauma may become ingrained in personality and hamper the potential to effectively engage in social interactions, increasing the risk of emotional and cognitive problems.