Faculty Bibliography

OBJECTIVE: Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n=85), and war trauma-exposed individuals with current PTSD (n=113), with life-time PTSD (n=61) and without PTSD (trauma controls; n=88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD. METHODS: Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting. RESULTS: Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (Bmax) in PBMCs. Hormone-binding potential (Bmax/KD ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between Bmax and KD that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting Bmax data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD. CONCLUSIONS: Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between Bmax and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecule population in PBMCs.

BACKGROUND: A significant proportion of soldiers return from deployment with symptoms of fatigue, sleep difficulties, and posttraumatic complaints. Disrupted sleep has been proposed as a contributing factor for the development of posttraumatic stress disorder (PTSD). This study investigates the impact of impaired sleep and nightmares before deployment on the development of PTSD symptoms. METHOD: We collected reports on insomnia symptoms and nightmares in 453 Dutch service members prior to military deployment to Afghanistan. PTSD symptoms were assessed at 6 months postdeployment. The predictive value of insomnia symptoms and nightmares on the development of PTSD symptoms was assessed with a logistic regression analyses, in which was controlled for predeployment mood and anxiety symptoms. RESULTS: Self-reported predeployment nightmares predicted PTSD symptoms at 6 months (odds ratio 2.992, 95% confidence interval (CI) 1.096-8.551, P < .05), while predeployment insomnia complaints did not (odds ratio 0.976, 95% CI 0.862-1.155, P > .05). CONCLUSION: In conclusion, this prospective longitudinal cohort study indicates that the existence of predeployment nightmares is associated with an increased risk for the development of PTSD symptoms. Nightmares may be related to hampered fear extinction memory consolidation, which has been associated with REM sleep.

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.

BACKGROUND: Nightmares and insomnia in PTSD are hallmark symptoms, yet poorly understood in comparison to the advances toward a biological framework for the disorder. According to polysomnography (PSG), only minor changes in sleep architecture were described. This warrants alternative methods for assessing sleep regulation in PTSD. METHODS: After screening for obstructive sleep apnea and period limb movement disorder, veterans with PTSD (n=13), trauma controls (TCs, n=17) and healthy controls (HCs, n=15) slept in our sleep laboratory on two consecutive nights with an IV catheter out of which blood was sampled every 20min from 22:00h to 08:00h. Nocturnal levels of plasma adrenocorticotropic hormone (ACTH), cortisol, melatonin were assessed in conjunction with PSG registration, as well as subjective sleep parameters. RESULTS: PTSD patients showed a significant increase in awakenings during sleep in comparison to both control groups. These awakenings were correlated with ACTH levels during the night, and with the subjective perception of sleep depth. Also, heart rate (HR) was significantly increased in PTSD patients as compared with both control groups. The diurnal regulation of ACTH, cortisol and melatonin appeared undisturbed. PTSD patients exhibited lower cortisol levels at borderline significance (p=0.056) during the first half of the night. ACTH levels and cortisol levels during the first half of the night were inversely related to slow wave sleep (SWS). CONCLUSION: This study suggests that hypothalamo-pituitary-adrenal (HPA) axis activity is related to sleep fragmentation in PTSD. Also, activity of the sympathetic nervous system (SNS) is increased during sleep in PTSD. Further research is necessary to explore the potential causal relationship between sleep problems and the activity of the HPA-axis and SNS in PTSD.

The contribution to psychotrauma literature from Dutch authors has a long tradition. The relatively high lifetime prevalence of trauma and posttraumatic stress disorder (PTSD) is not unique for the Netherlands and does not fully explain the interest in trauma and its consequences. In this overview of psychotraumatology in the Netherlands, we will discuss some of the key events and processes that contribute to the current interest. We outlined the historical basis and development of the field in the Netherlands, including the impact of World War II, the effects of major man-made or natural disasters, engagement in military conflicts, as well as smaller scale traumatic events like sexual abuse and traffic accidents. The liberal and open culture may have reduced stigma to trauma, while other sociocultural aspects may have contributed to increased prevalence. Finally, we describe Dutch psychotraumatology today and how history and culture have shaped the current scientific basis.

One of the goals in research in the clinical neuroscience of trauma-related disorders is to apply findings related to the effects of traumatic stress in the brain on animals and patients with trauma and stressor-related disorders e.g. PTSD. The paradigm of translational neuroscience has been an avenue that has contributed much to a model of the neural circuitry of PTSD that is currently used in studies. In general, the neural circuits and systems mediating symptoms of all PTSD, trauma and stressor-related disorders can be studied by registering en assessing behavioral and biochemical responses to environmental/pharmacological challenge to specific neurochemical systems measuring neurotransmitters and hormone levels in blood, urine, and saliva; measuring key brain structures with neuroimaging (Magnetic Resonance Imaging, MRI), provoking disease-specific symptoms in conjunction with (functional) neuroimaging (functional MKT, fMRI), or using imaging (Positron Emission Tomography, PET) to measure neuroreceptors. The findings of the studies (research designs, methodologies, and some of the techniques) will be discussed in this chapter varying to a great extent. Three key mechanisms seen in PTSD are: stress sensitization, fear conditioning and failure of extinction. This chapter thither focuses on the functional neuroimaging research conducted in PTSD. It covers various techniques (SPECT, PET and fMRI) that are used in different kinds of paradigms (resting, active tasks and stimulus presentation) and provides a global overview of the brain circuits that currently, are used to explain the phenomenology in PTSD. The disorder showed remarkable heterogeneity in some recent studies. These give consideration to speculate on two models for the disorder that can alternate and coexist together. These two models will be presented, one, in which the amygdala is hyperactive, in line with fear circuitry, being the most common and dominant situation. In another model the amygdala is hypoactive, in line with predominance of symptoms of derealisation and depersonalization symptoms that are accompanying the other PTSD symptoms. Finally, the need for longitudinal studies is emphasized. Studies that assess patients before as well as after treatment are the paradigm that will be new and promising.