Agorastos

Assessment of Plasma C-Reactive Protein as a Biomarker of Posttraumatic Stress Disorder Risk

IMPORTANCE Posttraumatic stress disorder (PTSD) has been associated in cross-sectional studies with peripheral inflammation. It is not known whether this observed association is the result of PTSD predisposing to inflammation (as sometimes postulated) or to inflammation predisposing to PTSD. OBJECTIVE To determine whether plasma concentration of the inflammatory marker C-reactive protein (CRP) helps predict PTSD symptoms. DESIGN, SETTING, AND PARTICIPANTS The Marine Resiliency Study, a prospective study of approximately 2600 war zone-deployed Marines, evaluated PTSD symptoms and various physiological and psychological parameters before deployment and at approximately 3 and 6 months following a 7-month deployment. Participants were recruited from 4 all-male infantry battalions imminently deploying to a war zone. Participation was requested of 2978 individuals; 2610 people (87.6%) consented and 2555 (85.8%) were included in the present analysis. Postdeployment data on combat-related trauma were included for 2208 participants (86.4% of the 2555 included) and on PTSD symptoms at 3 and 6 months after deployment for 1861 (72.8%) and 1617 (63.3%) participants, respectively. MAIN OUTCOMES AND MEASURES Severity of PTSD symptoms 3 months after deployment assessed by the Clinician-Administered PTSD Scale (CAPS). RESULTS We determined the effects of baseline plasma CRP concentration on postdeployment CAPS using zero-inflated negative binomial regression (ZINBR), a procedure designed for distributions, such as CAPS in this study, that have an excess of zeroes in addition to being positively skewed. Adjusting for the baseline CAPS score, trauma exposure, and other relevant covariates, we found baseline plasma CRP concentration to be a highly significant overall predictor of postdeployment CAPS scores (P = .002): each 10-fold increment in CRP concentration was associated with an odds ratio of nonzero outcome (presence vs absence of any PTSD symptoms) of 1.51 (95% CI, 1.15-1.97; P = .003) and a fold increase in outcome with a nonzero value (extent of symptoms when present) of 1.06 (95% CI, 0.99-1.14; P = .09). CONCLUSIONS AND RELEVANCE A marker of peripheral inflammation, plasma CRP may be prospectively associated with PTSD symptom emergence, suggesting that inflammation may predispose to PTSD.

The role of melatonin in glaucoma: implications concerning pathophysiological relevance and therapeutic potential

Abstract:  Glaucoma is a frequent ophthalmologic condition leading to chronic progressive optic neuropathy, which can result in visual impairment and blindness. In addition, glaucoma is associated with a dysregulation of circadian rhythms, as well as with a high incidence of sleep disorders, depression, and anxiety. However, because of their high comorbidity in older age, these conditions have not received much scientific attention and are often undertreated. In the current paper, we review the available literature on the role of melatonergic mechanisms in glaucoma, regulation of circadian rhythms, and depression. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. Recently, there has been evidence for a progressive loss of intrinsically photosensitive retinal ganglion cells (ipRGC) because of oxidative stress in glaucoma. As ipRGC are responsible for the photic transduction to the circadian system and subsequent melatonin secretion, and melatonin is involved in the pathophysiology of circadian desynchronization, sleep disorder, and depression, an impairment of photo‐dependent melatonergic signaling may be a common pathway connecting glaucoma with these comorbidities. This fact, as well as the proven retinal neuroprotective role of melatonin, suggests that melatonergic drugs provide a potentially promising treatment strategy supplementing the management of intraocular pressure by pharmacological and surgical measures. Additionally, multidisciplinary treatment focusing on depression and normalization of circadian rhythms might be beneficial for glaucoma patients. Furthermore, glaucoma might be a useful model for studying the pathophysiological interactions between the melatonergic, circadian, and mood systems.

Immediate and early behavioral interventions for the prevention of acute and posttraumatic stress disorder.

Purpose of review The development of acute and posttraumatic stress symptoms after a traumatic event is common and often leads to personal distress, functional impairment, and economic consequences in trauma victims and their loved ones. Hence, the prevention of acute and chronic posttraumatic stress is an important public health priority. This article aims to review the current evidence regarding immediate (within hours) and early (within days and weeks) psychological and behavioral interventions to prevent posttraumatic stress symptoms. Recent findings Acute distress management, psychological debriefing and other immediate unspecific interventions within the first hours following a traumatic event have so far not demonstrated efficacy in preventing posttraumatic stress symptoms. So far, there are no randomized controlled trials (RCTs) that have examined immediate trauma-focused cognitive behavioral interventions. In contrast, some, but not many, studies have shown that cognitive behavioral interventions are efficacious if administered within days or weeks after a traumatic event. For other early interventions after trauma exposure, there is no, or only weak, evidence in support of their efficacy. However, conclusions are limited by the small numbers of trials examining immediate and early interventions. Summary Today, there is no empirical evidence to support any immediate intervention within hours after the traumatic event to prevent posttraumatic stress symptoms. With regard to early interventions in the first days or weeks after trauma, literature is also sparse, but supports brief cognitive behavioral interventions as a first choice. There is an urgent need for RCTs to examine if behavioral interventions immediately following a traumatic event might be able to reduce the burden of acute and posttraumatic stress symptoms.

Diminished vagal activity and blunted diurnal variation of heart rate dynamics in posttraumatic stress disorder

Affected autonomic heart regulation is implicated in the pathophysiology of cardiovascular diseases and is associated with posttraumatic stress disorder (PTSD). However, although sympathetic hyperactivation has been repeatedly shown in PTSD, research has neglected parasympathetic function. The objective of this study is the long-term assessment of heart rate (HR) dynamics and its diurnal changes as an index of autonomic imbalance in PTSD. Since tonic parasympathetic activity underlies long-range correlation of heartbeat interval fluctuations in the healthy state, we included nonlinear (unifractal) analysis as an important and sensitive readout to assess functional alterations. We conducted electrocardiogram recordings over a 24-h period in 15 deployed male subjects with moderate to high levels of combat exposure (PTSD: n = 7; combat controls: n = 8) in the supine position. HR dynamics were assessed in two 5-h sub-epochs in the time and frequency domains, and by nonlinear analysis based on detrended fluctuation analysis. Psychiatric symptoms were assessed using structured interviews, including the Clinician Administered PTSD Scale. Subjects with PTSD showed significantly higher baseline HR, higher LF/HF ratio in the frequency domain, blunted differences between day and night-time measures, as well as a higher scaling coefficient αfast during the day, indicating diminished tonic parasympathetic activity. Diminished diurnal differences and blunted tonic parasympathetic activity altering HR dynamics suggest central neuroautonomic dysregulation that could represent a possible link to increased cardiovascular disease in PTSD.

Circadian rhythmicity, variability and correlation of interleukin-6 levels in plasma and cerebrospinal fluid of healthy men.

BACKGROUND Interleukin-6 (IL-6) is a cytokine with pleiotropic actions in both the periphery of the body and the central nervous system (CNS). Altered IL-6 secretion has been associated with inflammatory dysregulation and several adverse health consequences. However, little is known about the physiological circadian characteristics and dynamic inter-correlation between circulating and CNS IL-6 levels in humans, or their significance. METHODS Simultaneous assessment of plasma and cerebrospinal fluid (CSF) IL-6 levels was performed hourly in 11 healthy male volunteers over 24h, to characterize physiological IL-6 secretion levels in both compartments. RESULTS IL-6 levels showed considerable within- and between-subject variability in both plasma and CSF, with plasma/CSF ratios revealing consistently higher levels in the CSF. Both CSF and plasma IL-6 levels showed a distinctive circadian variation, with CSF IL-6 levels exhibiting a main 24h, and plasma a biphasic 12h, circadian component. Plasma peaks were roughly at 4 p.m. and 4 a.m., while the CSF peak was at around 7 p.m. There was no correlation between coincident CSF and plasma IL-6 values, but evidence for significant correlations at a negative 7-8h time lag. CONCLUSIONS This study provides evidence in humans for a circadian IL-6 rhythm in CSF and confirms prior observations reporting a plasma biphasic circadian pattern. Our results indicate differential IL-6 regulation across the two compartments and are consistent with local production of IL-6 in the CNS. Possible physiological significance is discussed and implications for further research are highlighted.

Depression, Anxiety, and Disturbed Sleep in Glaucoma

Although it has been suggested that glaucoma is associated with circadian misalignment, sleep disorder, anxiety, and depression, these comorbid conditions have not received much attention. This study provides evidence for a significantly higher prevalence of depression, trait anxiety, and sleep disturbances in patients with progressed glaucoma, as compared with glaucoma patients with no or minor visual field defects (VFD). Logistic-regression analyses suggest that severe VFD constitute a significant predictor of depression, trait-anxiety, and sleep disturbance. Results indicate the necessity of regular screening and psychochronobiological treatment in glaucoma patients.

Potential pleiotropic beneficial effects of adjuvant melatonergic treatment in posttraumatic stress disorder

Loss of circadian rhythmicity fundamentally affects the neuroendocrine, immune, and autonomic system, similar to chronic stress and may play a central role in the development of stress‐related disorders. Recent articles have focused on the role of sleep and circadian disruption in the pathophysiology of posttraumatic stress disorder (PTSD), suggesting that chronodisruption plays a causal role in PTSD development. Direct and indirect human and animal PTSD research suggests circadian system‐linked neuroendocrine, immune, metabolic and autonomic dysregulation, linking circadian misalignment to PTSD pathophysiology. Recent experimental findings also support a specific role of the fundamental synchronizing pineal hormone melatonin in mechanisms of sleep, cognition and memory, metabolism, pain, neuroimmunomodulation, stress endocrinology and physiology, circadian gene expression, oxidative stress and epigenetics, all processes affected in PTSD. In the current paper, we review available literature underpinning a potentially beneficiary role of an add‐on melatonergic treatment in PTSD pathophysiology and PTSD‐related symptoms. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. We conclude that adjuvant melatonergic treatment could provide a potentially promising treatment strategy in the management of PTSD and especially PTSD‐related syndromes and comorbidities. Rigorous preclinical and clinical studies are needed to validate this hypothesis.

Sex differences of salivary cortisol secretion in patients with major depression

Depression is associated with increased cortisol secretion and occurs more often in women than in men. Thus, it has been hypothesized that differences in cortisol secretion might, in part, be responsible for the greater risk of developing depression in women. However, only few studies have examined sex differences in baseline cortisol secretion in depressed patients and healthy controls. We examined sex effects on cortisol secretion in 52 medication-free patients with major depression (37 women, 15 men, mean ± SD age 35 ± 11 years, Hamilton Depression Scale mean score 27 ± 5) and 50 healthy age- and sex-matched control subjects. Salivary cortisol concentrations were measured at 8:00, 12:00, 16:00, and 22:00 h. Repeated measures analysis of covariance revealed a group × sex interaction (p = 0.05). Post hoc tests revealed higher cortisol concentrations in depressed compared to healthy men [F(1;29) = 7.5, p = 0.01]. No differences were found between depressed and non-depressed women. Our results do not support the hypothesis that differences in cortisol secretion between depressed and non-depressed subjects are more pronounced in women than in men. Study characteristics and methods as well as sex-specific confounding variables such as menstrual cycle, menopause and the use of oral contraceptives may account for inconclusive results across studies.

Influence of religious aspects and personal beliefs on psychological behavior: focus on anxiety disorders

The current paper presents literature relevant to the relationship of religiosity, spirituality, and personal beliefs with mental health and, in particular, anxiety disorders as an empirical narrative review, providing an overview on the most important and clinically relevant research results on the topic. The relationship between religiosity/spirituality, personal beliefs (ie, magical ideation and paranormal beliefs), and mental health has lately been studied extensively, and results have indicated significant associations among these variables. However, scientific approaches to this field are complex and multidimensional, partly leading to poor operationalization, incomparable data, and contradictory results. Literature demonstrates that higher religiosity/spirituality and magical ideation scores have often been associated with increased obsessive–compulsive traits. Similar results could not be confidently replicated for other anxiety disorders. However, it is still unclear if these differences suggest a specific association with obsessive–compulsive traits and reflect deviating etiopathogenetic and cognitive aspects between obsessive–compulsive disorder and other anxiety disorders, or if these results are biased through other factors. Religiosity/spirituality and personal beliefs constitute important parameters of human experience and deserve greater consideration in the psychotherapeutic treatment of psychiatric disorders.

Association between cortisol awakening response and memory function in major depression

BACKGROUND While impaired memory and altered cortisol secretion are characteristic features of major depression, much less is known regarding the impact of antidepressant medication. We examined whether the cortisol awakening response (CAR) is increased in depressed patients with and without medication compared with healthy controls (HC) and whether CAR is associated with memory function in each group. METHOD We examined 21 patients with major depression without medication, 20 depressed patients on antidepressant treatment, and 41 age-, sex- and education-matched healthy subjects. We tested verbal (Auditory Verbal Learning Task) and visuospatial (Rey figure) memory and measured CAR on two consecutive days. RESULTS Patient groups did not differ in severity of depression. We found a significant effect of group (p = 0.03) for CAR. Unmedicated patients exhibited a greater CAR compared with medicated patients (p = 0.04) with no differences between patient groups and HC. We found a significant effect of group for verbal (p = 0.03) and non-verbal memory (p = 0.04). Unmedicated patients performed worse compared with medicated patients and HC in both memory domains. Medicated patients and HC did not differ. Regression analyses revealed a negative association between CAR and memory function in depressed patients, but not in HC. CONCLUSIONS While in unmedicated depressed patients the magnitude of CAR is associated with impaired memory, medicated patients showed a smaller CAR and unimpaired cognitive function compared with HC. Our findings are compatible with the idea that antidepressants reduce CAR and partially restore memory function even if depressive psychopathology is still present.