Dissociation, forced normalization and dynamic multi-stability of the brain

Dissociated states represent pathological conditions where psychological trauma may emerge in a variety of forms such as psychic dissociative symptoms (hallucinations, derealization etc.) or on the other hand as somatoform symptoms (paroxysms, loss of motor control, involuntary movements etc.). Recent findings suggest that neurophysiological level of dissociative phenomena may be linked to the same neurophysiological principles that emerge in multi-stable perception of ambiguous stimuli likely caused by competing interpretations with mutual exclusivity. At this time there is evidence that temporal lobe seizure activity can produce dissociative syndrome and from these findings may be inferred that temporal lobe epileptic activity existing independently of neurological focal may share common neurobiological mechanism with dissociative symptoms. This conceptualization of dissociative phenomena is also in accordance with findings that originate from the study of the relationship between epilepsy and mental illness. The relationship was for the first time described in Meduna's concept of antagonism between epilepsy and psychosis and from the study of forced normalization introduced by Landolt in 1950s. The findings reported similar pathological conditions as in dissociative states when psychopathological symptoms and paroxysms may represent two different forms of the pathological process. Following the concept of forced normalization Tellenbach in 1965 introduced the term alternative psychosis implicating that stopping seizures does not mean vanishing or inactivity of the pathological state and that the epilepsy is still active subcortically and supplies energy for psychopathological symptoms. In the present review chaos in brain neural networks as a possible explanation of the relationship between dissociation and epileptic activity has been suggested that represents testable hypothesis for future research.     

Global perceived stress level as a moderator of the relationship between negative life events and depression

The present research investigated the proposal that global perceived stress level moderates the degree of relationship between negative life events and depression. Accordingly, subjects in this study completed the Beck Depression Inventory (BDI), the Life Experiences Survey (LES), and the Perceived Stress Scale (PSS). The PSS provides a measure of global perceived stress level, or the general tendency to view one's life as being unpredictable, out of control, and overwhelming. Consistent with past research, the findings revealed an increase in depression level as negative life change scores increased. Of special importance, however, was the finding that global level of stress significantly moderated the relationship between depression and negative life events. For those low on perceived stress, negative life changes had only a minimal impact on depression level. In contrast, for those high on perceived stress, the relationship was more pronounced. These findings were then discussed with regard to the possible role of cognitive appraisals in enhancing the symptoms of psychopathology experienced by individuals high on global level of perceived stress.     

Effects of biofeedback-assisted attention training in a college population

A program of stress management employing open-focus attention-training workshops was developed at Baruch College to bring the benefits of stress reduction to students. The purpose of the research reported here was to evaluate the results of the open-focus attention-training technique. Open-focus technique without biofeedback training was used for two semesters. Biofeedback training was incorporated in the third semester. In the first study, changes in grade point average (GPA), stress-related symptoms, and physiological measures were examined. The experimental subjects' stress data for this study was reported previously (Valdés, 1985). In the second study, changes in the same variables for experimental and control subjects were evaluated. Students in the control group showed decreased GPA, while those who participated in open-focus training showed a trend toward improved GPA. Stress-related symptoms associated with anxiety and management of emotional problems showed significant posttraining improvement, as did physiological measures in all of the biofeedback modalities in which the experimental subjects were specifically trained. The results support the hypothesis that the workshops were successful in reducing stress levels, and suggest that further controlled research be conducted to verify these findings, and to identify the most effective components of the training procedure.     

Co-Morbid Symptoms of depression and conduct disorder in first nations children: Some findings from the flower of two soils project

The prominence of co-morbidity in children and adolescents has increased over the past decade as new empirical research data has accumulated. Yet little epidemiological data of any kind exists for First Nations Children. Following a brief literature review on co-morbidity in children and adolescents, the authors analyzed data from the Flower of Two Soils Project (M. Beiser, principal investigator) to examine more closely the relationship between self-reported depressive symptoms and parent/teacher reported conduct symptoms. Such a relationship has been consistently found in a number of studies. Children aged 7 to 10 were found to show more academic and social problems when rated as having high conduct symptoms. Children in the co-morbid group were found to have the highest rates of family stress and help-seeking behavior. Suicidal ideation was as high in the conduct and co-morbid groups as it was in the high depression group. More First Nations children were found in the high conduct-low depression group. The significance of these findings is discussed.     

The long-term costs of traumatic stress: intertwined physical and psychological consequences

The gradual emergence of symptoms following exposure to traumatic events has presented a major conceptual challenge to psychiatry. The mechanism that causes the progressive escalation of symptoms with the passage of time leading to delayed onset post-traumatic stress disorder (PTSD) involves the process of sensitization and kindling. The development of traumatic memories at the time of stress exposure represents a major vulnerability through repeated environmental triggering of the increasing dysregulation of an individual’s neurobiology. An increasing body of evidence demonstrates how the increased allostatic load associated with PTSD is associated with a significant body of physical morbidity in the form of chronic musculoskeletal pain, hypertension, hyperlipidaemia, obesity and cardiovascular disease. This increasing body of literature suggests that the effects of traumatic stress need to be considered as a major environmental challenge that places individual’s physical and psychological health equally at risk. This broader perspective has important implications for developing treatments that address the underlying dysregulation of cortical arousal and neurohormonal abnormalities following exposure to traumatic stress.     

Psychosocial stress and the menstrual cycle.

The relationship between mood states, urinary stress hormone output (adrenaline, noradrenaline and cortisol) and adequacy of the menstrual cycle was examined in 120 recorded non-conception cycles from 34 women. It was hypothesized that women with higher stress levels would be more likely to experience abnormal cycles and that within women higher stress levels would positively relate to follicular phase length and inversely relate to luteal phase length. There was a non-significant trend for women to report higher stress levels during oligomenorrhoeic and unclear cycles compared with normal cycles. Analysis of covariance indicated that there was no consistent relationship between the measures of stress used here and follicular or luteal phase length within women. There was also no consistent pattern of relationship between reported mood states and stress hormone excretion within women. Further research is warranted to understand the role of stress and subtle menstrual cycle abnormalities in female fertility.     

A population based twin study of sex differences in depressive symptoms.

Depressive symptoms reflect depressed mood over a relatively short period of time and are measured using symptom checklists such as the SCL-90. There is some evidence that depressive symptoms are associated with major depression (MD), which is a clinically diagnosed psychiatric illness. Genetic studies of depressive symptomatology suggest a role for genetic factors as well as unique environmental influences. While epidemiological research suggests that depressive symptoms may be influenced by sex-specific factors, few genetically informative findings support this result entirely. We used data from male and female same sex and opposite-sex twin pairs to assess the extent to which genetic, shared and unique environmental factors influence depressive symptoms. Furthermore, we tested for the presence of qualitative and quantitative sex differences in depressive symptoms. Our results suggest that similar to other studies, depressive symptomatology is moderately heritable (31%) with no evidence for shared environmental factors. Our best fitting model suggests that there are no qualitative or quantitative sex differences in depressive symptoms. Our analyses suggest that while there may be mean differences in the levels of depressive symptoms across sexes, the genetic and environmental factors that predispose males and females to depressive symptoms are not different.     

Decreased plasma and cerebrospinal fluid ascorbate levels in patients with septic encephalopathy

Septic encephalopathies rapidly affect brain function without the involvement of a specific area causing a broad range of reversible neurologic symptoms. Capillary leakage including dysfunction of the blood-brain barrier has been proposed as a potential pathogenic mechanism in this entity. We tested the hypothesis that oxidative stress measured in plasma and cerebrospinal fluid (CSF) of patients suffering from septic encephalopathy could be linked to the neurologic symptoms of the disease. The neurologic symptoms of eleven patients with septic encephalopathy were described semiquantitatively through a score system. The ascorbate levels were significantly lower in both plasma and CSF from patients with septic encephalopathy than controls, and in CSF but not plasma this decrease correlated with the severity of neurologic symptoms. No significant changes were found for alpha-tocopherol. Our findings suggest that the short-term oxidative stress may be an important factor in the development of septic encephalopathy, possibly through dysregulation of the blood-brain barrier.     

Changes in the Serum Urate Level Can Predict the Development of Parkinsonism in the 6-Hydroxydopamine Animal Model

Epidemiological studies indicate that a higher plasma level of uric acid (UA) associates with the reduced risk of Parkinson’s disease (PD). To confirm the role of UA as a biomarker for PD, we evaluated changes in the serum UA level in the 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonism in rat. For this purpose, 6-OHDA was administered in the medial forebrain bundle by stereotaxic surgery. According to the apomorphine-induced rotational test, the increased intensity of behavioral symptoms as a function of time was associated with the further reduction of UA level. On the other hand, the level of UA increased in the midbrain of the injured hemisphere. The level of reduction in the serum UA level of rats with severe and moderate symptoms was significantly higher than that of rats with mild symptoms. The immunohistofluorescence and biochemical analyses showed that the serum UA level was also correlated with the death of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc), reduced level of striatal dopamine, and severity of oxidative stress in the midbrain. The rats with mild symptoms also showed a significant decrease in TH-positive neurons and striatal dopamine level. These findings suggest a positive correlation between the level of reduction in the serum urate level and severity of 6-OHDA-induced Parkinsonism. In addition, our findings indicated that UA had no marked neuroprotective effects, at least at concentrations obtained in this study. On the other hand, UA was introduced as a biomarker for PD, as a significant decline was observed in the serum UA level of rats with mild behavioral symptoms but with significant dopaminergic cell death in the SNc.     

Teleconference versus Face-to-Face Scientific Peer Review of Grant Application: Effects on Review Outcomes

Teleconferencing as a setting for scientific peer review is an attractive option for funding agencies, given the substantial environmental and cost savings. Despite this, there is a paucity of published data validating teleconference-based peer review compared to the face-to-face process.Our aim was to conduct a retrospective analysis of scientific peer review data to investigate whether review setting has an effect on review process and outcome measures.We analyzed reviewer scoring data from a research program that had recently modified the review setting from face-to-face to a teleconference format with minimal changes to the overall review procedures. This analysis included approximately 1600 applications over a 4-year period: two years of face-to-face panel meetings compared to two years of teleconference meetings. The average overall scientific merit scores, score distribution, standard deviations and reviewer inter-rater reliability statistics were measured, as well as reviewer demographics and length of time discussing applications.The data indicate that few differences are evident between face-to-face and teleconference settings with regard to average overall scientific merit score, scoring distribution, standard deviation, reviewer demographics or inter-rater reliability. However, some difference was found in the discussion time.These findings suggest that most review outcome measures are unaffected by review setting, which would support the trend of using teleconference reviews rather than face-to-face meetings. However, further studies are needed to assess any correlations among discussion time, application funding and the productivity of funded research projects.     

Influence of fibril taper on the function of collagen to reinforce extracellular matrix

Collagen fibrils provide tensile reinforcement for extracellular matrix. In at least some tissues, the fibrils have a paraboloidal taper at their ends. The purpose of this paper is to determine the implications of this taper for the function of collagen fibrils. When a tissue is subjected to low mechanical forces, stress will be transferred to the fibrils elastically. This process was modelled using finite element analysis because there is no analytical theory for elastic stress transfer to a non-cylindrical fibril. When the tissue is subjected to higher mechanical forces, stress will be transferred plastically. This process was modelled analytically. For both elastic and plastic stress transfer, a paraboloidal taper leads to a more uniform distribution of axial tensile stress along the fibril than would be generated if it were cylindrical. The tapered fibril requires half the volume of collagen than a cylindrical fibril of the same length and the stress is shared more evenly along its length. It is also less likely to fracture than a cylindrical fibril of the same length in a tissue subjected to the same mechanical force.     

New onset and persistent symptoms of post-traumatic stress disorder self reported after deployment and combat exposures: prospective population based US military cohort study

Objective To describe new onset and persistence of self reported post-traumatic stress disorder symptoms in a large population based military cohort, many of whom were deployed in support of the wars in Iraq and Afghanistan.Design Prospective cohort analysis.Setting and participants Survey enrolment data from the millennium cohort (July 2001 to June 2003) obtained before the wars in Iraq and Afghanistan. Follow-up (June 2004 to February 2006) data on health outcomes collected from 50 184 participants.Main outcome measures Self reported post-traumatic stress disorder as measured by the posttraumatic stress disorder checklist—civilian version using Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria.Results More than 40% of the cohort were deployed between 2001 and 2006; between baseline and follow-up, 24% deployed for the first time in support of the wars in Iraq and Afghanistan. New incidence rates of 10-13 cases of post-traumatic stress disorder per 1000 person years occurred in the millennium cohort. New onset self reported post-traumatic stress disorder symptoms or diagnosis were identified in 7.6-8.7% of deployers who reported combat exposures, 1.4-2.1% of deployers who did not report combat exposures, and 2.3-3.0% of non-deployers. Among those with self reported symptoms of post-traumatic stress disorder at baseline, deployment did not affect persistence of symptoms.Conclusions After adjustment for baseline characteristics, these prospective data indicate a threefold increase in new onset self reported post-traumatic stress disorder symptoms or diagnosis among deployed military personnel who reported combat exposures. The findings define the importance of post-traumatic stress disorder in this population and emphasise that specific combat exposures, rather than deployment itself, significantly affect the onset of symptoms of post-traumatic stress disorder after deployment.     

Decreased Plasma and Cerebrospinal Fluid Ascorbate Levels in Patients With Septic Encephalopathy

Septic encephalopathies rapidly affect brain function without the involvement of a specific area causing a broad range of reversible neurologic symptoms. Capillary leakage including dysfunction of the blood-brain barrier has been proposed as a potential pathogenic mechanism in this entity. We tested the hypothesis that oxidative stress measured in plasma and cerebrospinal fluid (CSF) of patients suffering from septic encephalopathy could be linked to the neurologic symptoms of the disease. The neurologic symptoms of eleven patients with septic encephalopathy were described semiquantitatively through a score system. The ascorbate levels were significantly lower in both plasma and CSF from patients with septic encephalopathy than controls, and in CSF but not plasma this decrease correlated with the severity of neurologic symptoms. No significant changes were found for &#102 -tocopherol. Our findings suggest that the short-term oxidative stress may be an important factor in the development of septic encephalopathy, possibly through dysregulation of the blood-brain barrier.     

Psychological processes mediating the association between developmental trauma and specific psychotic symptoms in adults: a systematic review and meta‐analysis

Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta‐analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty‐two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post‐traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross‐sectional research. Our findings suggest that there may be distinct psy­chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis.     

Elevated zeaxanthin bound to oligomeric LHCII enhances the resistance of Arabidopsis to photooxidative stress by a lipid-protective, antioxidant mechanism

The xanthophyll cycle has a major role in protecting plants from photooxidative stress, although the mechanism of its action is unclear. Here, we have investigated Arabidopsis plants overexpressing a gene encoding beta-carotene hydroxylase, containing nearly three times the amount of xanthophyll cycle carotenoids present in the wild-type. In high light at low temperature wild-type plants exhibited symptoms of severe oxidative stress: lipid peroxidation, chlorophyll bleaching, and photoinhibition. In transformed plants, which accumulate over twice as much zeaxanthin as the wild-type, these symptoms were significantly ameliorated. The capacity of non-photochemical quenching is not significantly different in transformed plants compared with wild-type and therefore an enhancement of this process cannot be the cause of the stress tolerant phenotype. Rather, it is concluded that it results from the antioxidant effect of zeaxanthin. 80-90% of violaxanthin and zeaxanthin in wild-type and transformed plants was localized to an oligomeric LHCII fraction prepared from thylakoid membranes. The binding of these pigments in intact membranes was confirmed by resonance Raman spectroscopy. Based on the structural model of LHCII, we suggest that the protein/lipid interface is the active site for the antioxidant activity of zeaxanthin, which mediates stress tolerance by the protection of bound lipids.     

Stress and psychophysiological dysregulation in patients with fibromyalgia syndrome

Fibromyalgia syndrome (FMS) is a prevalent musculoskeletal pain disorder characterized by diffuse pain and associated psychophysiological symptoms. Despite extensive research in the past 3 decades, the etiology and pathophysiology of FMS and effective treatment approaches are yet to be delineated. Recently, it has been suggested that FMS may be related to hypofunctional stress systems, particularly in the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. Studies have demonstrated that patients with FMS exhibit lowered sympathoadrenal reactivity to stress. These findings seem to be consistent with the large volume of research indicating the inverse relationship between pain sensitivity and sympathetic reactivity. In this paper, we discuss the role of stress in the pain experience in general, stress in patients with FMS, and review the studies evaluating the ANS and HPA functions in response to various stressors.     

Applying the digital image correlation method to estimate the mechanical properties of bacterial biofilms subjected to a wall shear stress

A digital image correlation (DIC) method was applied to characterize the mechanical behavior of Pseudomonas aeruginosa biofilms in response to wall shear stress using digital video micrographs taken from biofilm flow cells. The appearance of the biofilm in the transmitted light photomicrographs presented a natural texture which was highly conducive to random encoding for DIC. The displacement fields were calculated for two biofilm specimens. The DIC method concurred with previous analysis showing that biofilms exhibit viscoelastic behavior, but had the advantage over simple length measurements of longitudinal strain that it could precisely measure local strains in length (x) and width (y) within biofilm clusters with a 2 μm resolution as a function of time and wall shear stress. It was concluded that DIC was more accurate at measuring elastic moduli than simple length measurements, but that time-lapse 3D images would enable even more accurate estimates to be performed.     

Formulation of pre-extension in a practical stress-relaxation measurement of the plant cell wall

In practical measurement of stress-relaxation, a certain length of time is required to apply the initial stress to a specimen. We refer to this process as pre-extension. In the stress-relaxation analysis of the plant cell wall which we developed, a wall specimen is stretched at a constant rate in pre-extension. The condition of pre-extension, such as the length of the pre-extension period, affects the subsequent stress-relaxation process. Thus, the stress-relaxation time spectrum calculated directly from the stress-relaxation process is an approximation. In this study, the condition during pre-extension was formulated in a stress-relaxation function and the stress-relaxation time spectrum, H(τ), was calculated as H(τ) = b·exp(−T_o/τ) −exp(−T_m/τ) / r·τ·(1−exp(−T_p/τ)) where T_o and T_m are the minimum and maximum relaxation times, τ is the relaxation time, b is the relaxation rate, r is the extension rate in pre-extension and T_p is the pre-extension time. The effect of the pre-extension condition on the spectrum is discussed.     

Changes in interface pressures and shear stresses over time on trans-tibial amputee subjects ambulating with prosthetic limbs: comparison of diurnal and six-month differences

For trans-tibial amputees maintenance over time of a quality fit of the prosthesis to the residual limb is an important clinical challenge. The purpose of this research was to compare diurnal and long-term (5 weeks to 6 months) interface stress changes as well as variance in the change in cross-sectional area down the length of the residual limb. If long-term changes were simply accentuated diurnal fluctuations then this result would suggest similar treatment methods should be used for both conditions. Interface pressures and shear stresses at 13 sites and residual limb shape were measured on eight trans-tibial amputee subjects using patellar-tendon-bearing prostheses. Data were collected at diurnal intervals (within the same day at least 5 h apart) as well as at long-term intervals (5, 10, 15, 20, and 25 weeks apart). Absolute diurnal interface stress changes were not significantly different from those at 5-weeks intervals but were significantly smaller than those at 15, 20, and 25-weeks intervals. Mean interface stress changes increased significantly (p<0.05) for increased session-to-session intervals. Variance of the change in cross-sectional area down the length of the residual limb was significantly smaller for diurnal intervals than for 6-months intervals, indicating that long-term changes were more localized than diurnal changes. These results indicate that long-term changes are not simply accentuated diurnal fluctuations, suggesting that different treatment methods should be used to treat each condition.     

A Putatively Functional Polymorphism in the HTR2C Gene is Associated with Depressive Symptoms in White Females Reporting Significant Life Stress

Psychosocial stress is well known to be positively associated with subsequent depressive symptoms. Cortisol response to stress may be one of a number of biological mechanisms that links psychological stress to depressive symptoms, although the precise causal pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also been shown to be associated with depression and with clinical response to antidepressant medications. We recently demonstrated that variation in a single nucleotide polymorphism on the HTR2C gene, rs6318 (Ser23Cys), is associated with different cortisol release and short-term changes in affect in response to a series of stress tasks in the laboratory. Based on this observation, we decided to examine whether rs6318 might moderate the association between psychosocial stress and subsequent depressive symptoms. In the present study we use cross-sectional data from a large population-based sample of young adult White men (N = 2,366) and White women (N = 2,712) in the United States to test this moderation hypothesis. Specifically, we hypothesized that the association between self-reported stressful life events and depressive symptoms would be stronger among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers. In separate within-sex analyses a genotype-by-life stress interaction was observed for women (p = .022) but not for men (p = .471). Homozygous Ser23 C women who reported high levels of life stress had depressive symptom scores that were about 0.3 standard deviations higher than female Cys23 G carriers with similarly high stress levels. In contrast, no appreciable difference in depressive symptoms was observed between genotypes at lower levels of stress. Our findings support prior work that suggests a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms in White women with a history of significant life stress.