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Module 7 – Oral lectures:

 


7A_01_S

Predator Stress, Memory and Brain Plasticity

Diamond, David M.

Departments of Psychology, Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida 33620 USA

e-mail: ddiamond@mail.usf.edu

It is well-known that the hippocampus is critically involved in the formation of new memories. However, extensive research has provided strong support for the view that hippocampal functioning is impaired in times of strong emotionality. For example, studies have shown that stress suppresses the induction of long-term potentiation (LTP), a well-accepted physiological model of memory, in rats. Moreover, research on people indicates that in times of strong emotionality there is a suppression of hippocampal functioning. Thus, despite the importance of the hippocampus in processes involved in memory formation, in times of stress the hippocampus appears to be inhibited from participating in the formation of emotional memories, including flashbulb and traumatic memories. In this talk I will incorporate rodent and human studies to provide an alternative interpretation of the findings. I will suggest that conditions of strong emotionality actually produce enhanced neuroplasticity in the hippocampus (and amygdala), which underlies the declarative component of emotional memories. The hyperactivation phase of plasticity, which is then followed by an inhibitory phase of hippocampal plasticity, underlies well-described psychological phenomena in emotional memory processing, such as the great durability of flashbulb and traumatic memories, as well as stress-induced amnesia.



7A_02_S

Hyper- and hypo-arousal int he control of aggressiveness: the role of glucocorticoids

Haller J, Halasz J, Mikics E, Toth M, Barsy B.

Institute of Experimental Medicine, Budapest, Hungary

We will show that - beyond chronic HPA-axis hyperfunction -, decreased glucocorticoid production also leads to psychopathologies. This point will be exemplified by studies on aggressive behavior. Psychopathology-associated human aggression types are induced by a variety of conditions, are behaviorally variable, and show a differential pharmacological responsiveness. Thus, there are several types of abnormal human aggression. This diversity was not reflected by conventional laboratory approaches that focused on the quantitative aspects of aggressive behavior. Recently, several laboratory models of abnormal aggression were proposed, which mainly model hyperarousal-driven aggressiveness (characteristic to intermittent explosive disorder, posttraumatic stress disorder, depression, chronic burnout, etc.) and hypoarousal-driven aggressiveness (characteristic mainly to antisocial personality disorder and its childhood antecedent conduct disorder). Findings obtained with these models suggest that hyperarousal-driven aggressiveness has at its roots an excessive acute glucocorticoid stress response (and probably an exaggerated response of other stress-related systems), whereas chronic hypoarousal-associated aggressiveness is due to glucocorticoid deficits that affect brain function on the long term. In hypoarousal-driven aggressiveness, serotonergic neurotransmission appears to lose its impact on aggression (which it has in normal aggression), certain prefrontal neurons are weakly activated, whereas the central amygdala (no, or weakly involved in the control of normal aggression) acquires important roles. We suggest that the specific study of abnormal aspects of aggressive behavior would lead to important developments in understanding the specific mechanisms underlying different forms of aggression, and may ultimately lead to the development of better treatment approaches.



7A_04_S

A systems-level model of stress effects on cognition

Jeansok J. Kim and Taejib Yoon

Department of Psychology and Program in Neurobiology & Behavior, University of Washington, Seattle, Washington, U.S.A.

Stress is a biologically significant social-environmental factor that plays a pervasive role in our lives, from impacting our daily behaviors to producing and exacerbating myriad physical and mental illness. An accumulating body of evidence from human and animal studies reveals that while the acute response to stress (i.e., heightened cognition) is an adaptive mechanism, exposures to uncontrollable (unpredictable and inescapable) stress can subsequently produce detrimental neurocognitive effects, particularly in the hippocampus. Rodent studies further indicate that stress impairs long-term potentiation (LTP), a leading candidate cellular mechanism of information storage, in the hippocampus. We have recently discovered that amygdalar lesions/inactivation and prefrontal cortex lesions block and exacerbate, respectively, stress-induced impairments in hippocampal LTP and spatial memory. Moreover, single unit recording data indicate that stress alters the firing rate of place cells recorded from dorsal hippocampus, providing an empirical bridge between stress effects on synaptic plasticity and spatial memory. Based on these findings, we will present a conceptual model of the central stress mechanism (a neural-endocrine network comprising of amygdala, prefrontal cortex and glucocorticoids) regulating hippocampal functioning.



7A_05_S

Stress coping strategies in a 3D escape maze reveal two distinct types of social fear learning

Cliff H Summers, Russ E Carpenter

Biology, Neuroscience Group, University of South Dakota, Vermillion, SD 57069 USA, cliff@usd.edu

Rainbow trout interact aggressively, and form distinct social hierarchies. We hypothesized that social interaction against a larger opponent provides the impetus and information necessary to stimulate goal-oriented learning in subordinate individuals. A small (~100 g) juvenile rainbow trout in one tank compartment was adjacent to a large fish (~300 g; US) in another. A small (5 cm) hole leading to an empty compartment, large enough only for the smaller fish to pass was only available when the larger fish was present. Once a day the water inflow was turned off (CS); 15s later dividers were removed and fish interacted for 15 min. Larger fish were aggressive, and the learning curve for subordinate fish was dramatic (600%) over seven days. Escape time improved daily until fish escaped in approximately one minute. Plasma was taken 3 days before and 1 day after social interaction and learning trials. For samples taken after the trials, fish were presented with inflow water off but no large fish challenge. Fish learning to escape showed no change in plasma cortisol. However, fish that did not learn to escape exhibited a four-fold increase in cortisol, although no large fish was presented as a social challenge. Turning off inflow water acts as a conditioned stimulus to provoke increased cortisol, and elevated dopamine and serotonin in amygdala, hypothalamus and raphé. Increased anxiety induced by CRF stimulates increased attacks, but also increased retreat and escape behavior. Coping strategies appear to be influenced by CRF1 receptor activity. Fear conditioning in non-escaping fish is manifest by increased neural and hormonal stress responsiveness, whereas those that learn to escape utilize spatial learning to cope with social stress.



7A_06_S

Are extremes in anxiety linked to cognitive abilities?

1Bunck M., 2Sartori SB, 1Zurmühlen R., 1Wotjak CT., 2Singewald N. and 1Landgraf R.

1Max Planck Institute of Psychiatry, Munich, Germany, 2Department of Pharmacology and Toxicology, University of Innsbruck, Austria; Bunck@mpipsykl.mpg.de

Anxiety and learning/memory are hypothesized to be linked phenomena, as patients suffering from anxiety disorders and depression display changes in cognitive abilities. To mimic the clinical situation, wild type CD1 mice (NAB) were selected and inbred for extremes in anxiety-related behaviour in the elevated plus maze test to generate (HAB) versus low anxiety-related behaviour (LAB) mice. To study the interplay between emotionality and cognition, HAB, NAB and LAB mice were subjected to various social and non-social learning tasks. The general ability to recognise a familiar stimulus animal was assessed by the social recognition test. As a more sophisticated measure of social memory, the social discrimination task (SD) was performed. Furthermore, we used a contextual and cued fear-conditioning (FC) paradigm to investigate extinction abilities. The results clearly indicate that all three lines show social recognition abilities with a similar decline in olfactory investigation of the same stimulus. Remarkably, in the SD only HAB mice succeeded in identifying a familiar animal even after 120 min interexposure interval, indicating that the SD can be used to reveal differences in cognitive abilities between the mouse lines. Interestingly, in both FC paradigms HAB mice displayed delayed extinction compared to both, NAB and LAB animals. The data suggest that hyper-anxiety typical of HABs is linked to enhanced social memory abilities and resistance to extinction.

Further analyses of the interaction between emotionality and cognition will focus on anxiety- and cognition-related neuropeptide systems, the effects of antidepressants and extinction-facilitating drugs.



7B_01_S

Stress and common health complaints

Holger Ursin

Unifob health, University of Bergen, Norway

According to the Cognitive Activation Theory of Stress (CATS – Ursin and Eriksen 2004), a formal system of systematic definitions, the term “stress” is used for stress stimuli, the stress experience, the non-specific, general stress response, and the experience of the stress response. The stress response is normal, healthy, and necessary alarm. If sustained there may be a risk of illness and disease. The level and duration of the alarm depends on the expectancy of the outcome of stimuli and the specific responses available for coping.

The most common health complaints are subjective health complaints like muscle pain, tiredness and mood changes. These are normal aches of short duration and low intensity for most people. For some the pains and complaints are substantial and long-lasting with serious implications for functioning. There are no sharp or obvious limits in the distribution of health complaints, separating ‘normal’ and endurable pain and complaints, and intolerable complaints that need professional help. These conditions are most often unspecific, and are the most common reason for encounters with health professionals, and the most frequent reason for sick leave and disability. There is a striking comorbidity for all these conditions. This may be explained by psychobiological sensitization within neural loops, which has been suggested as a mechanism for these conditions (Ursin 1997).



7B_02_S

Low-energy stress-related disorders. Diagnostic utility of bio-psychosocial markers

Bengt B. Arnetz1,2 , Ulla Maria Anderberg2, Ingrid Anderzen2, and Christina Halford2

1Division of Occupational and Environmental Health, Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan 48009, USA. barnetz@med.wayne.edu

2 Division of Social Medicine, Department of Public Health Sciences, Uppsala University, Uppsala Sciences Park, 751 05 Uppsala, Sweden

It is commonly difficult to differentiate low energy states due to stress-related disorders from depression.1 The aim of the present study was to evaluate possible differences in symptoms, psychiatric co-diagnosis, and biological stress markers in patients suffering from stress-related disorders versus depression. 150 patients that had been referred by primary care physicians to an academic stress medicine center were evaluated by a physician using structured psychiatric tools, the center’s validated stress-assessment visual analogue scales, biological stress markers, blood pressure, and Body Mass Index. Patients with depression, >20 points on MADRS, scored significantly lower on the global energy scale, self rated health, and quality of sleep as compared to patients suffering from stress-related disorders. Depressed patients scored higher on the global stress scale. Depressed patients rated themselves to be less rested following a night’s sleep. Depressed patients scored lower with regard to satisfaction with their family and job situations. It is suggested that studies involving either stress-related disorders or depression more carefully screen the participants with regard to biopsychosocial characteristics. A substantial number of patients being referred for stress-related disorders also suffer from psychiatric co-morbidity.

1 Arnetz, BB, Ekman R. (Eds). Stress in health and disease. Wiley-VCH. Weinheim, Germany. ISBN-13 978-3-527-31221-4.



7B_03_S

Stress and the heart: The physiological basis for the development of cardiac risk in depression and anxiety disoders

Gavin Lambert

Baker Heart Research Institute, Melbourne, Australia (gavin.lambert@baker.edu.au )

Until recently it was thought that no more than 50% of clinical coronary heart disease was explicable in terms of classical cardiac risk factors such as dyslipidemia, cigarette smoking, high blood pressure and diabetes. Recent large scale epidemiological studies have increased our understanding of the mechanisms generating cardiac risk and have provided evidence indicating that psychosocial factors, particularly depressive illness (MDD), anxiety states, and acute and chronic mental stress are involved here, “triggering” clinical cardiovascular events, and possibly also contributing to hypertension and atherosclerosis development. Although the underlying mechanisms in play are most likely multi factorial in origin the sympathetic nervous system is undoubtedly paramount in many cases. Using noradrenaline isotope dilution methodology and direct nerve recording coupled with invasive blood sampling techniques we have examined cardiac sympathetic activity in patients with MDD and also panic disorder (PD). By sampling blood also from the internal jugular vein we have been able to gain insight into brain monoamine turnover in these conditions and have directly evaluated the effects of SSRI therapy on brain monoamines in these conditions. The pattern of sympathetic activation is very different in patients with MDD (bimodal) or PD (normal). Brain monomaine turnover is different in each group, with brain noradrenaline turnover being reduced in MDD yet normal in PD. Interestingly, in both MDD and PD brain serotonin turnover, surprisingly, is markedly elevated before treatment and is significantly diminished following SSRI therapy. Clearly, the role of brain monoamines and their relation to generating increased cardiac risk merits further attention.



7B_04_S

Intermittent neurogenic stress delays onset of diabetes in rats: Selye’s eustress?

Holly E. Bates, A Sirek, MA Kiraly, JTY Yue, D Goche Montes, SG Matthews, and M Vranic

University of Toronto, Toronto, Canada. holdoug@yahoo.ca

Acute stress deteriorates glycemic control in diabetes. We hypothesized that chronic intermittent restraint stress (1hr/d, 5d/wk for 13wks) of male ZDF rats, a model of Type 2 Diabetes, would accelerate development of diabetes. Intermittent stress lowered food intake by 15%. Thus, pair fed rats were included to distinguish between the effects of reduced food intake and of stress per se. Surprisingly, intermittent stress delayed development of fed and fasting hyperglycemia, effects mediated partly by reduced food intake, but also by intermittent stress per se. The stress-induced reduction in food intake improved insulin secretion and ß-cell mass, suggesting these as mechanisms for reduced food intake to improve glycemia. However, intermittent stress per se also led to HPA axis adaptations. Although basal ACTH levels did not differ, intermittent stress prevented the 30% increase in basal corticosterone (CORT) with food restriction, which could predict 20% of the variation in fed glycemia. In addition, intermittent stress led to habituation of restraint-induced CORT responses to lower levels than those induced by food removal. These CORT adaptations with intermittent stress were consistent with adaptation of mRNA levels for hippocampal MR, paraventricular nucleus AVP, and anterior pituitary POMC. Thus, intermittent restraint stress per se delays hyperglycemia, presumably via adaptations in the HPA axis that prevent the hypercorticosteronemia caused by food restriction. Since hypercortisolemia deteriorates glycemic control, adaptation to repetitive, predictable stress may be beneficial for glucose regulation. Thus, as Hans Selye noted when coining eustress, not all stress is deleterious.



7B_05_S

STRESS, QUALITY OF LIFE AND MULTIPLE CHRONIC DISEASES: Patterns Emerging From a Large National Sample, Australia

Agnes Walker

Australian Centre for Economic Research on Health, Australian National University CANBERRRA 0200 AUSTRALA, Agnes.Walker@anu.edu.au

OBJECTIVES: to study the associations between multiple chronic diseases and quality of life and psychological distress scores.

METHODS: analysis of unit record cross sectional data from Australian national surveys for the population aged 20 years or more. Identification of an appropriate indicator of multiple chronic diseases (ie comorbidities). Use of logistic regression techniques to study associations between (a) comorbidities and demographic, socioeconomic and risk factor variables and (b) quality of life (general and psychological distress) and demographic, socioeconomic and health status indicators.

RESULTS: older people, obese persons, women, persons with low socioeconomic status and those living alone had significantly greater probability of having three or more chronic illnesses than did other 20+ year olds (p<0.0001). Also people with comorbidities and/or with poor self-rated general health; those living alone; people with low educational qualifications; and persons with low socioeconomic status were more likely to feel dissatisfied, unhappy or terrible about their lives and of having moderate, high or very high psychological distress scores than did the rest of the 20+ year old population (p<0.0001).

CONCLUSIONS: age and obesity were found to be major risk factors for comorbidities. In turn, comorbidities and self-rated health were negatively associated with quality of life - whether indicated by how people felt about their lives generally, or by the extent of their psychological distress.



7B_06_S

The long-term impact of perceived stress on sleep quality

Leif W. Rydstedt

University West, Trollhättan, Sweden

Jason J. Devereux, Mark Cropley, Georgia Michalianou

University of Surrey, Guildford, UK

The purpose of the present study was to investigate the long-term impact of perceived stress on sleep quality. The sample consisted of 70 British white-collar workers (age m=42, 31% females) that participated in a survey study and also volunteered for a field study about 4 years later. Hierarchic regression analysis was used with age and gender entered in the first step and an indicator of baseline sleep quality in the second step of the equation, while perceived stress at baseline (measure by the 10-item version of PSS, aiming at stress the last month) was entered in the third step. The result showed that perceived stress level at baseline significantly predicted (R2 =.049, p<.05) sleep quality (measured by PSQI) 4 years later. This finding suggest that even more momentarily perceived stress may reflect a more chronic strain influence.



7C_01_S

Alterations of the catecholamine-cytokine balance in depression

Szelényi J. and Vizi E.S.

Institute of Experimental Medicine, Laboratory of Neuroimmunology, 43. Szigony str., H-1083 Budapest, Hungary

Cytokines are involved both in various immune reactions and in controlling certain events in the central nervous system. In our earlier studies it was shown that monoamine neurotransmitters, released in stress situations, represent a tonic sympathetic control on cytokine production and on the balance of proinflammatory/antiinflammatory cytokines. Basic and clinical studies have provided evidence that the biophase level of monoamines, determined by the balance of their release and uptake, is involved in the pathophysiology and treatment of depression, while inflammatory mediators might also have role in its etiology. In this work we studied the role of changes in norepinephrine (NE) level on the LPS evoked TNF-a and IL-10 response both in the plasma and in the hippocampus of mice. We demonstrated that the LPS induced TNF-a response is in direct correlation with the biophase level of NE as it is significantly higher when the release of NE of vesicular origin was completely inhibited in an animal model of depression (reserpine treatment) and it is significantly lower in case of increasing biophase level of NE by genetical (NETKO) or chemical (desipramine) disruption of NE reuptake. IL-10 was changed inversely to the TNF-a level only in the desipramine treated animals. Our results showed that depression is related both to changes in peripheral and in hippocampal inflammatory cytokine production and to monoamine neurotransmitter levels. Since several antiinflammatory drugs have also antidepressant effect we hypothesized that inhibitors of the monoamine uptake system might have multiple targets and are also able to modulate the LPS-induced inflammatory responses, which might contribute to their antidepressant effect.

This work was supported by grants OTKA T-046896 and ETT 298/2006



7C_02_S

Cytokine actions in the brain mediate the increased prevalence of depression in diseases with an inflammatory component

Robert Dantzer

Integrative Immunology & Behavior Program, University of Illinois at Urbana-Champaign, USA

Physically ill patients experience a high prevalence of affect disorders that are exacerbated by relatively minor infections. Activation of the peripheral innate immune system induces signs of sickness that culminate in depressive-like behavior in adult mice. This response is exaggerated in aged mice whose innate immune system is chronically activated. Peripheral inflammation is relayed to the brain by both the sensory nerves that innervate the site of inflammation and the overflow of inflammatory mediators that enters the general circulation. In response to these stimuli, brain macrophage-like cells produces cytokines that directly or indirectly affect neuronal function. Activation of indoleamine 2,3 dioxygenase (IDO), a key enzyme in the metabolism of tryptophan, is an important mechanism for the depressive-like effects of immune activation. Enhanced activity of this enzyme in response to tumor necrosis factor-alpha and/or interferon-gamma induces the production of neurotoxic kynurenine metabolites and decreases the bioavailability of tryptophan, which ultimately impacts on serotoninergic neurotransmission. The development of depressive-like behavior in mouse in response to acute or chronic activation of the peripheral innate immune system is temporarily correlated with IDO activation in the brain and at the periphery. Furthermore pretreatment with 1-methyl-tryptophan, a competitive antagonist of IDO, abrogates depressive-like behavior but not sickness behavior in mice during the course of inflammation. These preclinical findings emphasize the role of cytokines and their metabolic effects in the pathophysiology of inflammation-associated depression. Supported by NIMH (R01 MH-71349 and MH-079829).



7C_03_S

Long photoperiod-iduced glucocorticoid resistance and decreased negative selection in double-positive thymocytes of female but not male mice. Mechanisms and possible implication in the geographical distribution of autoimmune diseases

Georges Maestroni

The mammalian immune response is circadian and is regulated through daily alterations of darkness and recently defined specific pathway of non-visual light. The endogenous pace maker that drives this circadian cycle is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Light reaches the SCN through non-rod, non-cone intrinsically photosensitive retinal ganglion cells. The nervous pathway connecting the non-visual light detection in the SCN of the hypothalamus leads to a release of neurohormones from the pituitary, pineal, adrenal glands, and the gonads that finally reach the lymphoid organs. We found that exposure of adult female but not male mice to long photoperiod (22 hours light: 2 hours dark, LP) for 8 days decreased the glucocorticoid sensitivity of the thymus gland. Dexamethasone –induced apoptosis was decreased in double positive thymocytes and this effect was apparent only in vivo but not in vitro. This effect was not observed in prebubertal female mice and in adult gonadectomized mice as well as in beta-2 adrenergic receptor gene deficient mice. We exposed to the LP DO11.10 mice transgenic for a T cell receptor recognizing an ovalbumin peptide. The peptide was then injected intraperitoneally to induce intrathymic negative selection. The LP-exposed mice showed a significantly reduced negative selection of double positive thymocytes. Intrathymic negative selection is mediated by endogenous glucocorticoids and generates tolerance to self –antigens. As the seasonal variation of the photoperiod increases with the latitude, we might have disclosed a basic mechanism explaining the gender and geographical distribution of autoimmune disorders which are more frequent in women and show a north-south gradient of incidence.



7C_04_S

Maternal stress and the prenatal programming of infant immunity

Christopher L. Coe, Gabriele R. Lubach

University of Wisconsin, 22 N. Charter Street, Madison, WI, USA, ccoe@wisc.edu

Background. While stress can influence immune responses at any point in the life span, our research has shown that the effects are larger and more lasting in the young and aged host. In particular, during fetal and infant development, the maturational trajectory of immunity can be permanently altered. This presentation will focus on changes seen after manipulation of the in utero environment and the role of placental and neuroendocrine processes in mediating the immune alterations. Methods. Pregnancy conditions of rhesus monkeys were manipulated in several ways, including by psychological disturbance of the gravid female, administration of dexamethasone acutely, dietary treatments, or viral infection. The impact on the infants’ immune, endocrine, brain, and behavioral development was assessed.

Results. Maternal stress, or antenatal administration of corticosteroids, significantly affected immune responses at birth and continued to have an effect on lymphocyte proliferation and cytokine responses up to 2 years of age. These immune changes were associated with changes in the gut microbiota (including reduced Lactobacilli and Bifidobacter), which increased the risk for infection with enteric pathogens. A novel pathway mediating the effect of maternal stress on the fetus was also identified: a reduction in the placental transfer of iron. Lower iron stores at birth increased the risk for an iron deficiency anemia (IDA) in the growing infants. The anemia emerging at 4-8 months of age provided a second postnatal hit to the immune system. In addition, infant monkeys from stressed pregnancies evinced behavioral and neural changes, including immature neuromotor reflexes at birth, greater emotionality during the first year of life, and a smaller hippocampus as juveniles. Smaller hippocampal size was associated with less neurogenesis, and a more reactive hypothalamic-pituitary-adrenal axis. Conclusions. Stressful and challenging events during fetal life can significantly impact the development of immunity at a vulnerable point in ontogeny and change the regulatory set points for several physiological systems postnatally.



7C_06_S

Stress triggered neuronal plasticity in spleen in interaction with immunocytes

C. Liezmann1, M. Daniltchenko1, S. Pavlovic Masnikosa1, B. F. Klapp1, E. M. J. Peters1

1 University-Medicine Charité, Charité Center 12 for Internal Medicine and Dermatology, Psychoneuroimmunology, Campus Virchow, Berlin, Germany; eva.peters@charite.de

Stress is considered as a factor which induces or aggravates inflammatory skin diseases such as atopic dermatitis. An influence of stress on the interaction of peripheral nerve fibers with cells of the cutaneous immune system (mast cells, dendritic cells) with following modulation of an inflammation reaction could be proven recently. In this context, Substance P (SP) - a sensory neuropeptide - was revealed as an important stress mediator with its own stress axis in the skin. Here we postulate stress-dependent communication between nerve fibers and immune-competent cells with effect on the course of inflammatory skin diseases in the spleen. To address this question, we employed a combined mouse model of experimental allergic dermatitis (AD) and stress. AD was induced in C57BL/6 mice by double sensitization (i.p) and an intradermal challenge using chicken egg ovalbumin. Animals were additionally exposed to sonic stress for 24h prior to challenge. In this model stress leads to a relative hyperinnervation of the immune-competent areas of the spleen. At the same time, an increased number of antigen-presenting cells (APC) can be observed in these arreas and contacts between nerve fibers and APC were found. Further analysis of quality and function of neuro-immune interaction will reveal the role of the observed stress-induced alterations in the spleen in atopic disease .



7D_01_S

Socioeconomic and psychosocial determinants of chronic stress in a changing society

Maria S. Kopp

Institute of Behavioral Sciences, Semmelweis University, H-1089 Budapest, Nagyvárad t. 4, Hungary kopmar@net.sote.hu

In the last decades in the transforming societies of Central and Eastern Europe (CEE) premature mortality increased dramatically, especially among men. In Hungarostudy 2002 survey 12.640 persons were interviewed in their homes. They represent the Hungarian population according to age, sex and 150 sub-regions above age 18. Socioeconomic, psychosocial, work and family related factors, behavioral and self-reported health measures were recorded. From the latest Hungarostudy 2006 follow-up study 1130 men and 1529 women were included into the present study, who in 2002 were between the age of 40-69. By 2006 99 men (8.8%) and 53 women (3.6%) died in the 40-69 age group. After adjustment for traditional risk factors, work related measures, such as job insecurity and low social support from co-workers predicted significantly the all-cause mortality among men. Low education and low personal income were connected with premature mortality only among men. Living with the spouse was significant protective factor against early death only among men, whereas dissatisfaction with personal relations was a significant risk factor among women. Beck Depression score and self-rated health were much more important predictors of premature death among men than among women. In the transforming society of Hungary middle aged men are much more vulnerable to the work and socioeconomic deprivation related chronic stress factors than women in the same age groups. Chronic stress is proposed as an integrating model that can be applied to understand the gender differences in premature mortality during social transformation.



7D_02_S

Early ageing as a consequence of adverse psychosocial stress exposure

Peter M Nilsson, MD, PhD

Department of Clinical Sciences, Lund University, University Hospital, S-205 02 Malmö, Sweden. E-mail: Peter.Nilsson@med.lu.se

Normal ageing can be further divided into “successful” and “non-successful” ageing, the latter linked to different manifestations of early morbidity and mortality shaped by intricate gene-environmental interactions. There are well-known examples of pure genetic models of early ageing, such as the Hutchinson-Gilford syndrome (progeria in childhood) and Werner´s syndrome (progeria in mid-life). On the other end of the ageing spectrum there are many examples on how a detrimental mix of poor living conditions, increased psychosocial stress and unhealthy lifestyle habits add up to early biological ageing and a reduced lifespan. This is now obvious in many parts of the former Soviet Union, for example in some Russian cities with a decrease in male longevity to currently around 57 years.

One important consequence of early ageing is cardiovascular disease (CVD) caused by risk factor changes of arterial stiffening and endothelial dysfunction as part of the Early Vascular Ageing (EVA) syndrome. Normal vascular ageing is associated with a gradual change of the vascular structure and function, resulting in decreased arterial compliance and increased arterial stiffening. This is influenced by age-dependent structural and biochemical changes, e.g. in the content of elastin and collagen in the vessel wall. Superimposed on this more or less normal process is pathological arterial vascular ageing (atherosclerosis) with characteristic lesions and plaque formation, starting with subtle increased intima media thickening (IMT) in the vessel wall. In susceptible individuals the vascular ageing process seems to take a more rapid course, eventually resulting in premature CVD manifestations, including coronary heart disease (CHD), myocardial infarction, stroke and symptoms from peripheral arterial disease (PAD). Another aspect is the progressing vascular dementia with its clinical symptoms of impaired cognitive function, depression, and disturbed central regulation of physiological processes, e.g. blood pressure regulation. This early (premature) vascular ageing is both influencing a more rapid course of normal age-dependent arterial changes and the superimposed pathological vascular ageing based on atherosclerosis. The process is measurable directly by use of imaging devices such as ultrasound measurements of the arterial wall, for example in the carotid artery, the aorta, or the femoral artery, for evaluation of IMT and plaque formation. Another approach is to use physiological methods such as pulse wave velocity (PWV) or the arterial augmentation index, as markers of arterial stiffening. Other methods include the measurements of different biomarkers reflecting endothelial function, as an important part of the vascular ageing process, or the measurement of telomere length. Telomeres form the end cap of the DNA helix and are shortened by each cell division until the cell can divide no more. It has been repeatedly shown that telomere length is shorter (reflecting so called “mitotic senescence”) in subjects with arterial ageing, atherosclerosis, CHD, insulin resistance or reporting poor lifestyle habits as reflected in obesity and excessive smoking. Even psychosocial stress exposure has been shown to be associated with shorter telomere length, as well as with increased risk of CVD. Telomere length is even a predictor of mortality risk in subjects aged 60 years or older. No studies, however, have so far been able to show time-dependent changes in telomere length in relation to changes in vascular function or ultrasound imaging of arterial wall characteristics, for example the IMT, after repeated measurements. This could represent a fruitful approach in future studies of vascular changes in relation to age that is supposed to be heterogenous in subjects at different CVD risk.

In summary, differential ageing is influenced by genes and environmental factors, not at least increased psychosocial stress exposure. This will influence the risk of CVD, the major health hazard, in the EVA syndrome based on early vascular ageing and telomere attrition.

References

1. Adams JM, White M. Biological ageing. A fundamental, biological link between socio-economic status and health? Eur J Pub Health 2004; 14:331-334.

2. Artandi SE. Telomeres, telomerase, and human disease. N Engl J Med 2006;355:1195-7.

3. Aviv A, Levy D, Mangel M. Growth, telomere dynamics and successful and unsuccessful human aging. Mech Ageing Dev 2003;124:829-37.

4. Najjar SS, Scuteri A, Lakatta EG. Arterial aging: is it an immutable cardiovascular risk factor? Hypertension 2005;46:454-62.

5. Nilsson P. Premature ageing - the link between psychosocial risk factors and disease? Med Hypotheses 1996; 47:39-42.

6. Nilsson PM. Early vascular ageing and hypertension – A new model for understanding cardiovascular risk. Curr Hypertens Rev 2007;3:133-136.

7. Samani NJ, Boultby R, Butler R, Thompson JR, Goodall AH. Telomere shortening in atheroclerosis. Lancet 2001;358:472-3.



7D_03_S

Work stress and health in the cultural context of globalisation

Johannes Siegrist

University of Duesseldorf, Germany

Economic globalisation has far-reaching impact on the socio-cultural life and the health of populations in modern and rapidly developing societies. Technological progress goes along with the spread of a Western lifestyle that increases the risk of non-communicable diseases. Importantly, a globally expanding market of capital, goods and labour results in an increase of stressful working conditions among large parts of employed people, in addition to the afflictions of unemployment.

Based on the discoveries of two leading theoretical models, a wide range of health-adverse effects of stressful work has now been identified. In these models, stressful work is defined as either a combination of high demand and low control in one's job, and as an imbalance between high effort spent and low reward received in turn, where rewards include money, esteem, and promotion prospects including job security. This latter model is of particular interest in the context of globalisation as it points to violations of a fundamental principle of economic and social exchange, reciprocity.

Major research findings from epidemiological and experimental studies of work stress and health are demonstrated, with special emphasis on rapidly transforming societies. In the final part, policy implications of current scientific evidence are discussed, with a focus on worksite health promotion, and promising preliminary findings from intervention studies are reported. Yet, given the scale of challenge, coordinated international strategies towards healthy work will be needed.



7D_04_S

Psychosocial Stress Management Programs in Transforming Societies

Redford B. Williams, M.D.

Duke University Medical Center, Durham, NC, USA

Populations living in societies undergoing major transition can be subjected to mounting levels of stress that have the potential to produce serious health problems in some or all segments of the population. Since the breakup of the Soviet Union in 1989, for example, there has been a marked increase in annual mortality in countries of the former Soviet Block, most marked in Russia where the annual mortality increased from 600/100,000 to 900/100,000 – producing an excess of 400,000 deaths per year. Another example is India, where a continuing dramatic expansion of the economy has created another set of social, political and economic upheavals. A recent WHO report estimates that by 2010, 65% of the world’s cardiac cases will be persons of Indian descent, both in India and elsewhere. It is likely that a significant proportion of these increasing mortality and cardiac problems are a result of the stresses encountered in these transforming societies. While all might agree that the ideal solution would be to ameliorate the social, political, and economic conditions that are creating the health-damaging stress, that may be a solution that is easier to contemplate than to implement. In this presentation I will review experiences with one structured stress management program, the Williams LifeSkills Workshop, that has been implemented, with appropriate adaptations to the different cultures, in the Far East and Hungary. In both regions, results indicate that training in coping skills can be implemented with results that clearly document reduced stress levels. To have a favorable impact on the health problems in these regions at the public health level, however, it will be necessary to develop and implement delivery systems that can disseminate this training on a mass scale. I will conclude by considering how mass media and the internet might be used to do this.



7D_05_S

Psychosocial stress at work and outside work and problem drinking: the HAPIEE Study

Pikhart H1, Bobak M1, Pajak A2, Malyutina S3, Kubinova R4, Peasey A1, Marmot M1.

1Department of Epidemiology and Public Health, UCL, UK; 2Department of Epidemiology and Population Studies, Jagiellonian University, Krakow, Poland; 3Institute of Internal Medicine, RAMS, Novosibirsk, Russia; 4NIPH, Prague, Czech Republic

Background: It has been shown in the past that psychosocial factors (at work and outside work) are associated with various health outcomes. It is thought that they influence health partly through health behaviours. Aims: To examine the association between the effort-reward imbalance (ERI), overcommitment and control over general life, and several alcohol related measures in three populations in Central and Eastern Europe in the HAPIEE Study. Methods: The sample of population aged 45–69 years old in Novosibirsk (Russia), Krakow (Poland), and 6 Czech towns completed a questionnaire in 2002-2005 that included ERI, overcommitment (OC), control over life, and a number of sociodemographic variables. Annual alcohol intake, annual number of drinking sessions, the mean dose of alcohol per drinking session, and binge drinking were calculated from graduated frequencies in the questionnaire. Data were also available on problem drinking (>2 positive answers on CAGE questionnaire). Only men who were full-time working at the time of interview were used for the analysis (N=6700). Results: After controlling for age and country, the measures of problem drinking were associated with ERI, OC and control over life. Adjustment for socioeconomic position did not substantially change the results. When all 3 psychosocial constructs were used at the same model, the estimated effects were reduced but still associated with the alcohol related outcomes. Conclusions: Stress at work and outside work expressed by ERI, OC and control over life is associated with problem drinking in these populations.



7E_01_S

ACHIEVING STRESSLESS PREDICTABLE PERIO / IMPLANT EXCELLENCE

Dr André P. SAADOUN, DDS, MS

The creation of an esthetic implant restoration with gingival architecture in harmony with the adjacent dentition is a formidable challenge. The process of soft and hard tissue healing must be understood and incorporated into a carefully coordinated sequence of therapy.

The essential prerequisites in order to establish an optimal aesthetic implant restoration should always remain a precise, comprehensive biological and prosthetic diagnosis as well as the choice of the most conservative, appropriate, and least traumatic treatment for the patient to prevent any injury to the periodontal and dental structure and achieve a successful outcome.

The final objective is to achieve an optimal crown restoration surrounded by its natural gingival environment, using delicate ossoeus and/or muco-gingival plastic surgery.

A major evolution in implantology has taken place with tapered and rough surface implants, inserted in a one-step, non-submerged surgical protocol.

It is important to identify complications and clinical mistakes and their implications on the final esthetic outcome.



7E_02_S

The role of stress in periodontal disease

B.Willershausen, A.Kasaj, A.Pistorius

Department of Operative Dentistry, Johannes Gutenberg University , Mainz Germany

In the last two decades several investigations have been carried out on associations between stress factors and periodontitis and a number pathogenesis models have been discussed and examined. As a physiologic measure of stress urin levels of corticosteroids have been used, and increased free cortisol levels in the urine of periodontitis patients as compared with controls have been encountered. It was shown that emotional stress may interfere with normal immune function and may result in increased levels of circulating hormones that can effect the periodontium. Stressful life events appear to lead to a greater prevalence of periodontal disease and individuals with financial worries, distress, depression or inadequate coping mechanisms have a more sever loss of clinical attachment. Furthermore, it could be demonstrated that anxiety and stress may have a negative influence on the response to periodontal therapy and that patients responding less well to periodontal treatment have more psychosocial strain and a more passivedependent personality. Although epidemiologic data on the association of stress and periodontal disease is still limited, it appears that stress may be a putative risk factor for periodontitis.

The purpose of this presentation is to provide an overview, based on own data obtained from controlled clinical studies, on the association of stress, distress and coping behaviours with periodontal disease.



7E_03_S

Hypnosis in dentistry

Krause W.R.

Dept. of Psychiatry and Psychotherapy, Harz-Klinikum Wernigerode-Blankenburg, Germany

psychiatrie@harz-klinikum.de

In daily practice dentists are faced with a wide array of psychological problems including dental fear, gagging, psychogenic denture intolerance, bruxism, atypical facial pain etc. Although several hypnotherapeutic methods can be used rather effectively to solve most of these problems [1,2], only few dentists use such techniques in his/her practice. Therefore the aim of the lecture is to introduce the possibilities of hypnotherapy in dentistry and to inspire the audience's effort to use this method in the dental practice. For this purpose author will summarize the theoretical background and basic clinical knowledge of hypnotherapy, and will describe how hypnosis can be used for a wide spectrum of dental problems. References: (1): Krause, W-R.: Hypnose und Autogenes Training. In Schultz, JH.: Hypnosetechnik. Praktische Anleitung zum Hypnotisieren für Ärzte. 9. Auflage, bearbeitet und ergänzt von G. Iversen und W-R. Krause. Gustav Fischer Verlag, Stuttgart, 1994. (2): Staats, J., Krause, W-R.: Hypnotherapie in der zahnärztlichen Praxis. Hüthig Verlag, Heidelberg, 1995.



7E_04_S

Psychosomatic dentistry in Hungary. Trends and progress in the last 10 years

Fábián T.K.

Clinic of Prosthetic Dentistry, Semmelweis University, Budapest, Hungary

Following a rather long brake, an increase of interest in psychosomatic dentistry occurred in the middle of nineties in Hungary. From this time up to the present 67 written publications were published from the Faculty of Dentistry of the Semmelweis University Budapest related to this topic. During this time all together 32 researchers participated in this multidisciplinary project including 13 dentists, 6 psychologists, 5 biochemists, 1 psychiatrist, 1 teacher, 5 dental student and 1 psychology student. Research topics included epidemiology of dental fear, clinical treatment of dental fear and several oro-facial psychogenic symptoms, and stress related biochemical changes of saliva. The lecture will summarize the most important data and results of this 10 years project and give a broad outline of research possibilities in the next future.



7E_05_S

Differential elicitation of the saliva level of 3-methoxy-4-hydroxyphenylglycol (MHPG) , a metabolite of noradrenaline, induced by mental stress testing

Satoshi Horiuchi, Akira Tsuda, Hisayoshi Okamura, Jumpei Yajima

Graduate School of Psychology, Kurume University

Address: 1635, Mii-machi, Kurume-shi, Fukuoka-ken, 839-8502, Japan

E-mail: satosato.007@nifty.com

3-methoxy-4-hydroxyphenylglycol (MHPG) is a principal metabolite of noradrenaline derived from the brain. Therefore, to assess the saliva levels of MHPG is considered as a non-invasive tool for measuring central noradrenergic activity. From previous findings, although it is suspected that changes in the saliva level of MHPG varies among modes of mental stress testing, very few studies have tested this possibility directly. Therefore, the purpose of this study was to test different elicitation of the saliva level of MHPG induced Stroop Color Word Conflict Test (SCWCT) and Uchida-Kraepelin Test (UKT) as modes of mental stress testing in ten male healthy volunteers. The participants performed these two tasks at about the same time on two different days according to their schedule available. The order of the tasks was counterbalanced. MHPG responses varied among tasks; only loading SCWCT resulted in the significant increase in MHPG level in the saliva even while both SCWCT and UKT induced similar degree of subjective stress state. These results provide evidence that mental work load induces increase in levels of MHPG specifically, suggesting that there are specific situational dimension(s) which activates the central noradrenergic nervous system. Combined with previous studies focusing on individual difference, future attempts to clarify the dimension (s) would improve our understanding of brain noradrenergic activity induced by acute stress.



7E_06_S

Autogenic training in the treatment of atypical facial pain.

1Krause M., 2Müller O., 3Nguyen M.T., 3Fábián T.K., 3Fejérdy P., 1Krause W.R..

1Dept. of Psychiatry and Psychotherapy, Harz-Klinikum Wernigerode-Blankenburg, Germany

2Clinic of Pediatric Dentistry and Orthodontics, Semmelweis University Budapest, Hungary

3Clinic of Prosthetic Dentistry, Semmelweis University, Faculty of Dentistry, Budapest, Hungary

In this study 10 female patients (age between 29-58 yr.) with atypical oro-facial pain (ICD-10 category: F40-48) were treated with autogenic training in a small group, once a week for 10 weeks. The method was administered as an initial therapy in the early phase of treatment. The first two basic exercises (feeling of heaviness and warmth) were practiced only, in sitting position [1]. Suggestions of the therapist [1,2]were given via microphone with the use of loud-speakers. A relaxing background music were also given. Symptom palliation was measured with numerical analogue scale. In 3 cases (30%) symptoms disappeared totally. At least partial symptom palliation occurred in another 4 cases (40%). In 3 cases (30%) the treatment was unsuccessful. Belief of the patients in psychotherapy and patient-therapist relationship strong enough for entering to the exploratory part of psychotherapy were developed in all cases (100%). References: (1): Krause, W-R.: Hypnose und Autogenes Training. In: Schultz, JH.: Hypnosetechnik. Praktische Anleitung zum Hypnotisieren für Ärzte. 9. Auflage, bearbeitet und ergänzt von G. Iversen und W-R. Krause. Gustav Fischer Verlag, Stuttgart, 1994 Pp. 71-80. (2): Staats, J., Krause, W-R.: Hypnotherapie in der zahnärztlichen Praxis. Hüthig Verlag, Heidelberg, 1995. Pp 120-123.



7F_01_S

Gene - environment interactions in PTSD and other stress-related disorders

Marcus Ising

Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany

ising@mpipsykl.mpg.de

Stress related disorders can be defined as illnesses whose causation, onset, or development is substantially influenced by stress and its neurobiological correlates. Among mental disorders, depression, anxiety, and post-traumatic stress disorder (PTSD) are typical examples for stress-related disorders. They are characterized by a moderate heritability suggesting the involvement of genetic vulnerability factors. Additionally, environmental influences including exposure to stressful life events and trauma contribute to the disease risk and can act as triggers for the onset of the disorder. Taking both into account, the investigation of gene – environment interactions is an important approach to elucidate the aetiology of stress-related disorders. We will discuss different approaches to examine gene – environment interactions in depression, anxiety, and PTSD, summarize the findings from the literature and present own results. The investigation of gene – environment interactions could prove as a promising approach to extend our knowledge about the aetiology and to identify new treatment targets in stress-related disorders.



7F_02_S

PREDICTORS OF RESPONSE TO A NOVEL NK-1 RECEPTOR ANTAGONIST IN PTSD

Sanjay J. Mathew, M.D., Kathryn Keegan, B.A., Kate Collins, LCSW, Jin Fan, Ph.D., Dennis Charney, M.D.

Mount Sinai School of Medicine, One Gustave L. Levy Place Box 1217, NY, NY 10029 sanjay.mathew@mssm.edu

Few robust predictors of response to pharmacological treatment of PTSD have been identified.  In this study, we sought to identify demographic, clinical, neurochemical (CSF), structural magnetic resonance imaging (MRI) moderators of response to a novel selective neurokinin-1 receptor antagonist (GR205171) or pill placebo in patients with PTSD who participated in a 8 week randomized placebo-controlled double-blind clinical trial.   Inasmuch as NKI receptors are highly expressed in medial temporal lobe (MTL) structures such amygdala and hippocampus, and elevated levels of CSF substance P have been reported in PTSD, we hypothesized that clinical response would be associated with morphometric changes in MTL regions and reductions in CSF levels of substance P.
Patients with PTSD related to a variety of traumas (childhood abuse, combat, witnessing violence) were treated for 8 weeks with GR205171 (5 mg fixed dose) or matching pill placebo.  All patients received 2 weeks of single-blind placebo prior to randomization, during which MRI and clinical ratings, using the Clinician Administered PTSD Scale (CAPS) and Montgomery Asberg Depression Rating Scale (MADRS) was performed.   MRI was repeated prior to the end of the study, while patients were taking active drug or placebo.   Lumbar punctures were also performed at the beginning and endpoint of the study.



7F_03_S

The search to cure PTSD: evidence for novel molecular targets

Christoph Czermak, MD, Alexander Neumeister, MD

Yale University, Dept of Psychiatry, West Haven, CT, USA, alexander.neumeister@yale.edu

Indirect support exists for an involvement of the noradrenergic system, the serotonergic system and nicotinic acetylcholine receptors in the pathophysiology of posttraumatic stress disorder (PTSD). To untangle the relative contribution of these transmitter systems to the pathophysiology of PTSD and to identify potential novel targets to treat PTSD, we conducted a series of functional imaging studies using positron emission tomography (PET) and single photon emission computed tomography (SPECT). Using novel radioligands we studied for the first time the expression of serotonin (5-HT) receptors types 1A and 1B, the norepinephrine transporter and nicotinic acetylcholine receptors in the brain of PTSD patients, trauma-exposed and non-traumatized healthy control subjects. We also studied changes in electrodermal skin activity and neurochemistry following infusion with the ?2-antagonist yohimbine in PTSD subjects relative to healthy controls. We found evidence for a role of the 5-HT1B receptor but not the 5-HT1A receptor in PTSD suggesting the 5-HT1B receptor as a potential target for drug development. We further substantiated the important role of noradrenergic mechanisms in PTSD. Altogether, our studies provide evidence for the involvement of monoaminergic mechanisms in the pathophysiology of PTSD and identify novel targets for drug development.



7F_04_S

The psychobiology of coping with PTSD

Miranda Olff

Center for Psychological Trauma, Academic Medical Center University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, The Netherlands, m.olff@amc.uva.nl

Although many people are exposed to trauma, only part develop post traumatic stress disorder (PTSD) or other posttrauma psychopathology. It is possible that humans differ in the degree to which trauma induces neurobiological perturbations of their threat response systems, which may result in a differential degree of psychopathology. Posttraumatic stress disorder (PTSD) has been associated with dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis as well as of the hypothalamus-pituitary-thyroid (HPT) axis. Findings have not been consistent and may depend on methodological issues like controlling for relevant variables. Results of a meta-analysis will be shown. In this paper we also present data on six HPA and HPT-axis related hormones in civilian chronic PTSD patients. Comparing chronic PTSD patients to healthy volunteers we found that patients had significantly lower plasma cortisol, prolactin and TSH levels. When studying the effects of psychotherapy in chronic PTSD patients we found that after Brief Eclectic Psychotherapy (BEP) significant changes occurred in levels of cortisol and DHEA. Responders showed an increase of cortisol and DHEA levels, while in non-responders both hormone levels decreased. Differences were only found after controlling for depressive symptoms. In conclusion, learning to cope with trauma through psychotherapy for PTSD may alter dysregulations in the HPA-axis, but comorbid depressive symptoms should be taken into account. Continued study of the psychobiology of trauma and PTSD will enhance our understanding of adaptation to psychosocial stressors and support efforts to treat associated psychological and biological sequelae.



7F_05_S

The influence of preclinical analgesia and sedation on the onset, severity and course of posttraumatic stress symptoms in accident victims

Michael Schönenberg, Ursula Reichwald, Kathrin Wilk, Heike Jacob, Gregor Domes, Andreas Badke & Martin Hautzinger

Department of Clinical and Developmental Psychology, University of Tübingen, Germany
Corresponding author: michael.schoenenberg@uni-tuebingen.de

We have previously demonstrated a strong association between the application of a single or fractionated dose of the N-methyl-D-aspartate antagonist ketamine and symptoms of acute (Schönenberg et al., 2007) and posttraumatic stress disorder (Schönenberg et al., 2005) in moderately injured accident victims. Ketamine has analgesic and sedative properties and for that reason it is widely administered in emergency care. Based on our previous data there is evidence to suggest that ketamine might profoundly augment early stress symptoms, probably via the enhancement of glutamatergic neurotransmission, resulting in worsened long-term posttraumatic sequelae. The objective of the study to be portrayed at the conference is to extend prior findings by prospectively examining ketamines’ effects on psychological, endocrinological and neuro-cognitive variables. Moderately injured accident victims were consecutively recruited in two urban trauma centres. Based on their preclinical analgosedation, patients were divided into groups (ketamine vs. opioids vs. no medication). Initial assessments of posttraumatic psychopathology were carried out within 48 hrs post-event during hospital-stay and were repeated two months, six months and one year post-event. Further, neuropsychological assessments and a diurnal profile of the biological stress markers cortisol and dehydroepiandrosterone (DHEA) were determined at each time point. First results of the ongoing study will be presented at the conference.



7F_06_S

Risk and Protective Factors in Relation to PTSD Symptoms

Beth Spenciner Rosenthal and W. Cody Wilson

York College-City Univ of NY, 94-20 Guy R. Brewer Blvd., Jamaica, NY 11451, rosenthal@york.cuny.edu

The issues of risk and protective factors in relationship to manifesting PTSD symptoms have begun to be raised in the literature. A cross-sectional correlational study of 848 adolescents recently graduated from high school in New York City tested three hypotheses: 1) witnessing the physical assault of another (independently of being a victim) is traumatic and is associated with PTSD symptoms; 2) having a sympathetic adult confidant available is a protective factor with regard to PTSD symptoms for older adolescents; and 3) having a sense of personal self efficacy is a protective factor with regard to PTSD symptoms. Theoretical analysis indicates that a “protective factor” may operate at three levels: 1) by reducing exposure to the “trauma event”; 2) by reducing levels of PTSD symptoms; and 3) by buffering or moderating the impact of the traumatic event on PTSD symptoms. The results of the empirical study indicate: first, that witnessing the physical assault of others produces PTSD symptoms (medium effect size); and second, that both “availability of an adult confidant” and “feeling of self efficacy” reduce the likelihood of an adolescent being exposed to physical assault (small effect size), reduce the level of PTSD symptoms (medium effect size), but do not significantly moderate the impact of exposure to physical assault on PTSD. Thus, both “having available an adult confidant” and “feeling of self efficacy” act as protective factors for older adolescents with respect to manifesting PTSD symptoms. The principal protective mechanism of both “availability of an adult confidant” and “feeling of self efficacy” appears to be through a general reduction of the level of PTSD symptoms.



7G_01_S

Stress-Triggered Reproductive Supression: an Evolved Adaptation?

Pablo Nepomnaschy

It is estimated that only about 23% of women trying to conceive will begin a successful pregnancy during the first menstrual cycle of their attempt. This low rate of reproductive success has led some health scientists to describe human reproduction as inefficient and, therefore, an evolutionary paradox. In contrast to this pathological vision of women's reproduction, evolutionary theorists propose that reproductive suppression may have originated as an adaptation that, in dire circumstances, helps prevent pregnancy. As practitioners’ positions on this issue can affect both diagnoses and treatments, the debate of these opposing paradigms is of critical importance.

This talk contributes to the aforementioned debate through an examination of the physiologic effects of stress on women's reproductive function. Stress is commonly reported to lead to reproductive suppression. Most of the available evidence to support this claim, however, has been derived from animal and clinical or retrospective studies. Here I present data from a population-based, longitudinal study I conducted among Kaqchikel Maya in the southwestern highlands of Guatemala. The relationship between stress axis (hypothalmic-pituitary-adrenal) activation and ovarian function, implantation and early pregnancy fate is discussed. Evolutionary and pathologic aspects of the effects of stress on reproductive function are evaluated.



7G_02_S

The relationship between psychological stress and female fertility

Sheiner Eyal, M.D

Department of Obstetrics and Gynecology, Faculty of Health Sciences & Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Fertility treatments carry emotional burdens on women and their partners. Although the psychosocial aspects of infertility have not been adequately addressed in clinical practice, there is consensus in the literature that attention to the psychological aspects of infertility is strongly advisable. Psychological factors such as depression, state-anxiety, and stress-induced changes in heart rate might be predictive of a decreased probability of achieving a viable pregnancy in various types of infertility and fertility treatments. Previous intervention trials did not include screening for psychological nor physiological stress markers known to predict pregnancy in women experiencing difficulties achieving pregnancy. It is not clear whether the psychological stress is a part of the infertility etiology as a causative factor (psychogenic hypothesis), or rather represents a development of the infertility problem (psychological consequences hypothesis). Nevertheless, it is more likely that there is an interactive causal association between infertility and psychosocial distress.



7G_03_S

THE HYPOTHALAMIC-PITUITARY-ADRENAL AND THE HYPOTHALAMIC-PITUITARY-GONADAL AXES INTERPLAY IN REPRODUCTION

George Mastorakos

Endocrine Unit, Second Department of Obstretics and Gynecology, Aretaieion Hospital, Athens University Medical School, Athens; mastorak@mail.kapatel.gr

Vertebrates respond to stress with activation of the HPA axis, the adrenergic and the autonomic nervous systems. The principal central nervous system regulators of the HPA axis are corticotropin releasing hormone (CRH) and antidiuretic hormone (AVP). Apart central nervous system, CRH has been found in the adrenal medulla, ovaries, myometrium, endometrium, placenta, testis and elsewhere. The activation of the HPA axis during stress affects all body systems. The reproductive axis is inhibited by HPA axis, for the sake of saving energy. The changes of the HPG axis during stress are species-specific, and depend on type and duration of the stimulus. Several conditions may be associated with altered regulation of the HPA axis. Polycystic ovary syndrome, anorexia nervosa and pregnancy in the third trimester are all characterized by HPA axis activation. In contrast, during postpartum period, HPA axis suppression is implicated in the “postpartum blues”. The actions of CRH are also essential in fetal development and neonatal survival.



7G_04_S

Stress during pregnancy: consequences for mother and child

PC Arck 1, M Ruecke 1, K Nakamura 2, H Fliege 1, M Rose 3, S Blois 1, M Pincus 1, BF Klapp 1

1 Charité, University Medicine Berlin, Germany

2 University of Vancouver, Canada

3 Qualitymetric, USA

Maternal stress perception has long been suspected as a possible cause of infertility, implantation failure, late pregnancy complications and impaired fetal development, notions that exist since ancient times and across all cultures. In view of the enormous complexity of the regulatory nervous, endocrine and immune mechanisms involved in pregnancy maintenance, it is evident that pregnancy failure is not a single entity condition, but most likely the result of complex dysregulation. This dysregulation can be initiated or aggravated by stress. While there are still more open questions than answers, the neuro-endocrine-immune circuitry of the stress response during pregnancy is becoming increasingly defined, e.g. due to the development of particularly instructive rodent models and prospectively designed human cohort trials. Subsequently, clinicians are becoming far more attentive to the effect of psychological stress on pregnancy complications. As a reseult of emerging basic science research endeavours elucidating hierarchical, temporal and spatial interactions of key parameters during central and peripheral responses to psychological stress, a list of candidate molecular targets for clinically useful therapeutic intervention has become available by and should be tested in interdisciplinary research approaches.



7G_05_S

Reproduction of southern muriquis in captivity (Brachyteles arachnoides): endocrinological assessment of reproductive function by measurement of fecal steroid metabolites

LIMA, A.B.F.1; VIAU, P. 1; PISSINATI, A.2; CHELINI, M.O.M. 1; OLIVEIRA, C.A. 1*

1. Laboratory of Hormone Measurements of the Department of Animal Reproduction of the Faculty of Veterinary Medicine of the University of Sao Paulo, Brazil; 2. Primate Center of Rio de Janeiro, Brazil

cadolive@usp.br

The southern muriqui (Brachyteles. arachnoides), the largest Neotropical primate species, is on the verge of extinction with critically endangered status (IUCN 2000). We validated noninvasive endocrine monitoring techniques for this species by quantifying fecal estrogens and progestins in 4 adult females as well as fecal metabolites of testosterone and glucocorticoids in 4 adult males and 1 sub-adult male. The study was conducted over a period of 11 months under two different environmental conditions: a) Two adult males, two adult females and a young male living on an island of 600 m2, with natural vegetation, at Curitiba Zoo (PPC) and b) two adult couples housed in a large cage of 15.40X5.85X4.70m at Rio de Janeiro Primate Center (CPRJ). Fecal samples were collected at least every other day over four continuous periods of 20 to 24 days with 45-day intervals between to subsequent sampling periods. Reproductive behavior was observed on the same schedule. Fecal steroids were extracted by dilution in ethanol. We used radioimmunoassay (RIA) in solid phase to quantify fecal estradiol, progesterone, testosterone, and glucocorticoid metabolites. Estrogen and progestin concentrations in female feces varied individually over a wide range (0.03 to 145.56µg/g of dried feces for progestins and 0.002 to 71.57µg/g of dried feces for estrogens). Three females did not show any ovarian activity over specific periods of the study, while ovarian cyclicity was observed over all sample periods in one female from CPRJ. Despite of their low levels of fecal reproductive steroids, all females displayed proceptive behavior and copulations. Surprisingly, despite of their semi-free ranging condition, the PPC males showed significantly higher concentrations of fecal glucocorticoids and lower concentration of fecal testosterone than the caged CPRJ males (p<0.05). As expected, the lowest concentration of testosterone metabolites (p<0.05) was found in the feces of the sub-adult male. For all males, copulations occurred when testosterone levels were the highest and peaks of glucocorticoid concentration were related to stressful situations such as copulation or fight. Therefore, this study shown that the quantification of fecal steroid metabolites was effective for reproductive monitoring as well as for assessing the physiological response to stressful events.

Key words: Endocrinology. Steroids. Metabolites. Primates. Stress.



7G_06_S

The impact of secondary sex characteristics (SSC) and social behavior to cortisol and sexual hormones in female primates

B. Wallner1, J. Dittami2 and I. H. Machatschke2

1Dept. of Anthropology, 2 Dept. of Behavioural Biology, University of Vienna, Austria

Primates living in multi male–female associations can develop SSC during sexual active periods. Size of SSC is dependent on fluctuating sex-steroids. Males intensify socio-sexual contact with females showing exaggerated SSC.

We investigated the socio-endocrine impact of SSC in three different species: Facial and anogenital redness in Japanese macaques (JM) during the breeding and non-breeding season, perineal swellings in Barbary macaques (BM) treated with the contraceptive levonorgestrel during non-sexual periods, and perineal swellings in chimpanzees (Ch) during intact cycle periods. Data from JM and BM were collected under semi-natural, from Ch under caged conditions. Fecal samples were used for analyses of sex steroid and cortisol (CORT) metabolites.

In BM, multiple regressions showed a negative relationship between SSC size and CORT and a positive one between swelling size and intersexual socio-positive contact. Females with enlarged SSC had lower progesterone levels and increased estradiol-progesterone ratios.

Ch females housed with males showed decreased CORT during late and decreasing tumescence of the SSC. In single housed individuals, increased CORT was related to decreased plasma FSH. Paired females had shorter cycle length.

In JM, a light and a dark group could be discerned with regard to redness. In the dark group, intensity of redness increased during the breeding season and correlated with the amount of socio-sexual behavior. These females had significantly elevated CORT and sex steroid titers.

In conclusion, reduced HPA activity in females is associated with exaggerated SSC and intensified male contact when male mating competition for females is diminished (e.g., BM, Ch).



Module 7 – Poster lectures:

 

7A_02_P

COGNITIVE DEFICITS CAUSED BY CHRONIC STRESS CAN BE PREVENTED BY THE GINKGO BILOBA AND HYPERICUM PERFORATUM ADMINISTRATION

Jan J. Braszko, Anna Walesiuk, Emil Trofimiuk

Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 15A, 15-274 Bia³ystok, Poland

Exposure to chronic restraint stress in rats as well as the psychosocial stress in humans has been shown to alter cognitive functions such as learning and memory and has been linked to the pathophysiology of mood and anxiety disorders. Anxiolytic/sedative/antidepressant agents used in the management of the stress-related disorders have several side effects and are not cost-effective.

Therefore, in this study we investigated efficacy of the orally given two natural medicines: extract of Ginkgo biloba (EGB 761, 100 mg/kg) and dried, standardized confection of crude Hypericum perforatum (350 mg/kg), in the prevention of the post-stress memory dysfunctions.

Male Wistar rats (150-160 g) were stressed for 21 days by placing them for 2 h daily in a tight restraint tubes. There were separate sets of experiments testing effects of EGB 761 and H. perforatum. To define specific role of the rat stress hormone (cortisol in humans) we ran also groups injected daily with corticosterone (5 mg/kg subcutaneously).

Each experimental set consisted of 6 groups of animals: CONTROL, STRESS, corticosterone (CORT), EXTRACT (EGB 761 or H. perforatum), EXTRACT + STRESS, EXTRACT + CORT.

Both, STRESS and CORT groups displayed considerable and statistically significant deficits in memory: spatial [measured in the Morris Water Maze (MWM) (p<0.05) and the Barnes Maze (BM) (p<0.05)], visuo-spatial [measured in the Object Recognition (OR) (p<0.01) Test] and non-spatial associative [measured in an inhibitory avoidance (IA) (p<0.01) Test].

Both, EGB 761 and H. perforatum administered daily during the stress procedure or chronic corticosterone treatment totally abolished most of these deficits. Interestingly, in naive rats EGB 761 improved memory of the positively (curiosity - OR) reinforced behaviour more than that of the negatively (water immersion – MWM, exposure – BM, electric current – IA) reinforced ones. The latter, however, were better remembered by the animals receiving H. perforatum. There were only minor differences between the beneficial actions of EGB 761 and H. perforatum on the deficits caused by stress- and corticosterone.

In conclusion, G. biloba and H. perforatum appear to contain agents able to effectively counteract increasingly important stress-induced cognitive deficits.


7A_04_P

Upregulation of synaptotagmin and TrkB is involved in chronic exercise-enhanced learning and memory behavior in mice

Hsiun-ing Chen1*, Yu-Fan Liu2, and Chauying J. Jen1

Department of Physiology1 and Institute of Basic Medical Sciences2, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan. *E-mail: hichen@mail.ncku.edu.tw

Acute severe exercise elevates stress hormone levels and impairs cognitive function in rodents. In contrast, chronic exercise improves cognitive function without affecting resting stress hormone levels. It is known that synaptotagmin, a Ca2+-dependent synaptic vesicle protein, brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) play important roles in hippocampus-dependent learning and memory behavior. However, whether chronic exercise can improve learning and memory by upregulating these molecules remains unraveled. To answer this question, male BALB/c mice were used as the animal model. After 4 weeks of treadmill exercise training, the ability of learning and memory was evaluated by one-trial passive avoidance test (PA), an aversive learning task. Hippocampal synaptotagmin and TrkB protein expressions were determined by Western blotting, and BDNF was measured by ELISA. Our results showed that after chronic treadmill exercise, 1) the retention latency of PA was increased; 2) protein levels of hippocampal TrkB and synaptotagmin were elevated; 3) TrkB or synaptotagmin protein expression was positively correlated with PA performance. These data suggest that the upregulation of synaptotagmin and TrkB may contribute to the chronic exercise-facilitated hippocampus-dependent cognitive function.


7A_05_P

Towards the Genetic Dissection of Anxiety

Czibere L, Bunck M, Frank E, Keßler MS, Kohli M, Bettecken T and Landgraf R

To investigate the genetic background of anxiety-related and depression-like behaviour in mice, two lines, selectively inbred for high (“HAB”) and low anxiety-related behaviour (“LAB”), starting out from outbred CD1 mice. As mutations in the genome are assumed to make up for the majority of genetic differences, we plan to pinpoint them with a linkage analysis approach. For this, the ‘Mouse Medium Density Linkage Panel’ by Illumina, was used to genotype 1449 single nucleotide polymorphisms (SNPs) in HAB and LAB mice, as well as in F1 progeny (HABxLAB).

The animals tested were derived from generation 20 or higher, providing a solid basis for genetically homogenous lines.

In a first analysis, out of the 1449 loci tested, for 225 autosomal loci HAB and LAB mice both displayed homozygosity, but for different alleles. Cross-mated animals (F1, HABxLAB) were all heterozygous for these loci.

Compared to an inter-strain analysis approach using two standard inbred mouse strains (e.g. BALB/c and C57BL6), where animals do not only differ in their anxiety-related behaviour, our intra-strain analysis considerably reduces the number of informative SNPs. Therefore, in our mouse lines, the number of informative false positive SNPs, relevant to the behavioural phenotype, will be much lower.

Interestingly, about 1/3 of the opposite homozygous SNPs are concentrated on only 5 chromosomes, whereas two chromosomes contained just 3 and 6 of these SNPs.

Altogether, the Illumina Mouse Medium Density Linkage Panel seems to provide a sufficient number of informative SNPs as to allow the identification of a linkage region, causative for the development of the anxiety trait. We are planning to genotype a larger number of freely segregating F2 generation animals (F1xF1). From this we expect being able to identify true candidate regions for anxiety-related behaviour.


7A_06_P

A reward-seeking model for distinguishing adaptation and stress

Seamus Decker

Department of Anthropology, University of Massachusetts, 215 Machmer Hall, Amherst, MA 01003 USA

sdecker@anthro.umass.edu

Lack of a unifying concept for distinguishing adaptation from stress with research on psychoneuroendocrine (PNE) processes such as hypothalamic-pituitary-adrenal axis (HPA) response to psychosocial conditions has led to at least four distinct types of errors: (i) failure to distinguish adaptive PNE activation, i.e., “arousal,” from maladaptive PNE activation, i.e., “stress;” (ii) failure to distinguish response from conditions that provoked the response, i.e., either stressors or a vulnerability of some sort; (iii) assumption that subjective distress and psychobiological activation are equivalent and interchangeable; and (iv) failure to distinguish differences in the causes and consequences of response which is episodic, ephemeral and moderated compared to response which is repetitious, prolonged, or exaggerated. Distinguishing adaptive from maladaptive response depends on a clear understanding of the adaptive purposes of PNE processes such as HPA response to psychosocial conditions, and attention to the context and consequences of any specific pattern of response. This paper presents a novel and unifying model in which episodic cortisol response to psychosocial factors is conceived as an adaptation to perceived loss of reward. Reward is conceived broadly as being the myriad of social or behavioral factors that may lead to specific psychobiological states of “reward” (e.g., increased activity in specific dopaminergic regions of the pre-frontal cortex). By testing this conceptual model, researchers stand to make substantial contributions to understanding of how the HPA works in everyday life, and effects on human health and well-being.


7A_07_P

Responsiveness of the OK-list: a new rating scale for clinical diagnosis and treatment evaluation of psychological symptoms of chronic stress

E Dorant MD PhD, AJM Schmidt PhD, GM van der Molen PhD

Maastricht University, Health Organization, Policy and Economics, PO Box 616, 6200 MD Maastricht, Netherlands; E.Dorant@beoz.unimaas.nl

Objective. A new rating scale for clinical diagnosis and treatment evaluation of complaints of chronic stress was developed in The Netherlands. This OK-list consists of 22 universally applicable complaint-like items, scorable on a 5-point Likert scale. Psychometric evaluation showed high validity, reliability and unidimensionality. In this study we evaluate the responsiveness of the OK-list in patients suffering from chronic stress syndrome, equivalent to the clinical end state of severe burnout.

Methods. A single group repeated measurements design was used. Intake and end-of-treatment information on level of chronic stress complaints was collected with the OK-list. Responsiveness was assessed using paired T-test, SRM and a graphical illustration presenting means for each chronic stress complaint. For parallel comparison SCL-90R data were used. Results were calculated for two subgroups defined by concurrent depression using data collected with the Beck Depression Inventory.

Results. Comparison with SCL-90R revealed parallel lowering of OK-scores between intake and end-of-treatment in both subgroups. All paired T-tests were statistically significant (p-values <0.001) and SRMs were close to 1.5, well above the cut-off score for high responsiveness. Differences between intake and end-of-treatment mean item scores were nearly all greater than 1 point on the Likert scale.

Conclusion. The OK-list proved to be highly responsive to change in patients treated for chronic stress syndrome and thus provides an excellent alternative to questionnaires on chronic stress complaints or burnout when evaluation of natural course or treatment effect is important.


7A_08_P

Work stress and Coping resources: Study of the mediating roles of Causal Attributions

Sayyed M Haybatollahi

haybatolahi@yahoo.com
University of Helsinki: Unioninkatu 37, PL 54, 00014, Helsinki, Finland

The literature of psychological stress contains a number of studies, investigating the mediating effects of dispositional factors such as type A behavior pattern, Negative affectivity, and Locus of Control over the stress-strain, stress-coping and stress-live events relationships (Cooper et al, 2001). Hence, In order to investigate the mediating roles of causal attributions over the association between coping resources and work stressors as well as verify a number of path models of the relationships between the concerned variables, 564 full-time stuffs, working at the Universities’ administrative office in the Helsinki capital area, participated the study. In this study work stressors were comprised of five role conflicts i.e., Overload, Insufficiency, Ambiguity, Boundary, and responsibility. Whereas, coping resources consisted of Recreation, Self-Care, Social Support, and Cognitive Coping. Study of mediation, however, were basically concerned with four dimensions of causal attributions (i.e., Locus of control, Stability, Globality, and Controllability) for negative and positive events. To measure occupational stress and personal resources, using Lazarus’ transactional model of stress (Lazarus & Folkman; 1984), 72 items were derived from Occupational Stress Inventory Revised Edition (Osipow, 1998). The employees’ attributional style was also measured by Occupational Attributional Style Questionnaire (Furnham, 2004). The primary analysis of the hypotheses indicated the existence of such mediation by causal attribution for personal resources and different levels of occupational stressors; as such the general path model was supported. However, the result of further analysis using hierarchical regression analysis and structural equation modeling identified more details of testing the hypotheses. For instance, Responsibility did not appear to be a significant predictor for the variances of personal resources. Hence, the results of this study were mostly in line with the results of the same studies in the field of causal attribution (Weiner, 1986).


7A_09_P

The effects of sex, age and population on baseline glucocorticoid levels in spiny mice (Acomys cahirinus)

Nováková M.1, Kutalová H.1, Palme R.2 Frynta D.1 & Janský L.3

1Dept.of Zoology, Faculty of Science, Charles Univ., Prague, Czech Republic
2Institute of Biochemistry, Dept. of Natural Sciences, Univ. of Veterinary Medicine, Vienna, Austria

3Dept. of Animal Physiology, Faculty of Biological Sciences, Univ. of South Bohemia, Èeské Budìjovice, Czech Republic

Corresponding author: frynta@centrum.cz

Baseline glucocortiocoid (GC) levels may be related to the social status in small animal species. Here we examined GC levels in a moderately social rodent the Egyptian spiny mouse (Acomys cahirinus). Studied animals originated from 2 populations, differing considerably in their ecology: the population from Abu Simbel (S Egypt) is a desert-dweller, while that from Cairo is commensal. To assess baseline GC levels we collected faecal samples from 68 individuals belonging to 10 social groups. Each social group consisted of animals of both sexes and two age grades (directly corresponding to dominance ranks). Levels of GC metabolites were assessed by a 5?-pregnane-3ß,11ß,21-triol-20-one enzyme immunoassays (EIA). The results showed no effect of rank and only a small effect of sex (higher levels in females) on GC metabolites levels. Thus, the hypothesis that dominant males are more stressed than other functional groups may be rejected. Surprisingly, there was a considerable difference among groups. This may be interpreted as a substantial effect of social relationships within each particular group. The commensal population exhibited much higher levels of GC metabolites than the desert one. This is consistent with behavioural differences of studied populations - commensals are more active, but simultaneously also more anxious. Evolutionary adaptation to living in buildings is suggested as the ultimate cause of these physiological and behavioural differences.


7A_10_P

Effects of stress applied at the late stage of pregnancy on the feeding behavior in the rat

Mari Kimoto1*, Rie Amano1, Reiko Ishikawa1,Yuki Ooe1, Mie Shimura1,Tami Niinuma1, Hiromi Hirakawa1, Yasuhiro Kumei2, Kazuo Toda1,3

Physiological Lab., Japan Women's University, Mejirodai, Bunkyo-ku, Tokyo 112-86811, Biochemistry, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo113-8549, Japan2, Integrative Sensory Physiology, Nagasaki University, Nagasaki 852-8588, Japan3.

* kimoto@fc.jwu.ac.jp

The purpose of the present study is to examine how stress that is imposed at the fetal stage could influence the same Wistar rat at the adult stage. The pregnant rats were exposed to either gravitational stress (1.5 and 2.0G) or wire-net restraint during the 15th through 21st day of pregnancy for 10 min daily. The male offspring of the wire-net restraint mother rat showed significant decrease of slope in growth curve at the 15th through 66th day. The 1.5G gravitational stress on mother rats did not influence the body weight of the male offspring, while 2.0G gravitational stress on mother rats increased the slope of growth curve of 6 to 10 day-old male offspring rats. By contrast, 1.5G gravitational stress and wire-net restraint did not influence the feeding behavior in the adult stage of the female offspring rats. However, 2.0G stress increased the slope of the growth curve. The somatostatin level in the blood was decreased in gravitational stress group in the male, but not in the female offspring rats. Data showed that the stress imposed at the fetal stage modified the growth pattern even at the adult stage and that the gender difference was observed in the anti-stress response. In addition, type of stress may be an important factor for producing emotional changes, such as, feeding behavior.

Supported by JSPS grants (No.18500630 and No.18613011, 2006-2007).


7A_11_P

The role of corticosterone in exercise-induced hippocampal neurogenesis

Yu-Min Kuo, Ya-Ting Chang, Yi-Chieh Chen, Chih-Wei Wu

Department of Cell Biology and Anatomy, Medical College, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan, Taiwan. kuoym@mail.ncku.edu.tw

Neurogenesis has been suggested to correlate with certain aspects of brain cognitive function. Several extrinsic stimuli, including physical exercise is known to have advantageous effects on neurogenesis and brain function. However, why exercise promotes neurogenesis remains unknown. Previously, stress-induced high level of corticosterone was shown to inhibit neurogenesis, while adrenalectomy enhance neurogenesis. As exercise modulates the level of serum corticosterone, we hypothesize that corticosterone signaling pathway is involved in the exercise-induced neurogenesis. In this study, hippocampal neurogenesis is estimated by double-labeling of mitotic marker (BrdU) and neuronal progenitor marker (DCX) in the subgranule zone. Our results showed that treadmill running exercise (TRE) significantly enhanced neurogenesis. The levels of serum corticosterone were elevated immediately and decreased 4 h after TRE. Five-week TRE down-regulated the protein levels of mineralocoticoid receptor (MR), while glucocorticoid receptor (GR) remained unaltered. To mimic the exercise-elicited corticosterone response, mice were injected with low dose of corticosterone (4mg/kg/day) for three weeks. Our results showed that mice received corticosterone injection had slightly more BrdU/DCX positive cells than those of vehicle controls with no changes in the MR and GR levels. Alternatively, mice received MR antagonist, spironolactone, treatment 90 min before TRE exhibited more neurogenesis than that of TRE. Spironolactone alone also expressed significant effect on neurogenesis. Taken together, our results suggest that reduced corticosterone signaling pathway is involved in the TRE-induced hippocampal neurogenesis.


7A_12_P

Adolescents Coping with Personal Security Stress: Strategies and Adjustment

Dr. Hanna Laufer

The Academic College of Emek Yezreel, Dept. of Human Services

Address correspondence to: Hanna Laufer, P.O. box 277, Timrat, 23840, ISRAEL (E-mail: hlaufer@research.haifa.ac.il )

living in areas of intensive combat and conflict zones, may be accompanied by psychological stress among adolescents.

The present study makes an attempt to explore the influence of the combat zone geographical proximity on the stress assessment, and to detect and define the specific resulting responses of adolescents.

A comparison was done between adolescents living in communities along the seam-zone, and adolescents living in communities remote from Israel’s borders, in the purpose to investigate whether a difference exists between the adaptation levels of adolescents exposed to military stress - to those who are not.

The test sample included 279 males and females, ages 14 to 18.

It was found that adolescents living in the seam-zone vicinity reported a primary stress evaluation level higher than that of adolescents from the comparison group. In spite of this finding - no significant differences on the secondary stress evaluation (control estimation level) was observed between the two groups. It was found that adolescents, who revealed the lowest adaptation level, were those who reported the highest level of uncontrollability.

Another finding indicates that stress situations, evaluated as uncontrollable, lead to an intense use of the secondary control engagement strategies (e.g. distraction, positive thinking, cognitive restructuring and acceptance) and the disengagement coping strategies (e.g. avoidance, denial, wishful thinking). It was also found that for both groups - coping strategies of the primary control types (problem solving; emotional regulation and emotional expression) predict a higher level of adaptation.

Based on these findings it was concluded that the stress type (controlled or uncontrolled) has an important effect on the prediction of selected coping strategies and adaptive results. Gender differences were observed: the males, living in the vicinity of the seam-zone, revealed the highest, while the females - the lowest level of adaptation.

It will be possible to utilize the present study findings in their adaptation to the treatment and the education policy for the more vulnerable part of the population of adolescents: the females.

Keywords: psychological stress; adolescents; coping; adaptation


7A_13_P

Effects of a Psychosocial Stressor on Self-Injurious Behavior and Hypothalamic-Pituitary-Adrenocortical Function in Rhesus Monkeys

J.S. Meyer, M.D. Davenport, C.K. Lutz, S. Tiefenbacher, and M.A. Novak

Univ. of Massachusetts, Amherst, MA 01003 USA; New England Primate Research Center, Southborough, MA 01772 USA; jmeyer@psych.umass.edu

Self-injurious behavior (SIB) is a disorder that occurs in both clinical and non-clinical populations. Although a role for stress in the etiology and/or maintenance of SIB has been proposed, there is little empirical evidence for this hypothesis. Our laboratory has been studying the pathophysiology of spontaneously occurring SIB (manifested as self-biting and occasional self-wounding) in singly housed male rhesus monkeys at the New England Primate Research Center. In the present study, we examined the short- and long-term effects of an administratively mandated relocation of our monkeys (both SIB and controls) on the animals’ behavior and hypothalamic-pituitary-adrenocortical (HPA) function. The relocation involved movement of the subjects to different cages in a new colony room with unfamiliar animals. Daytime and nighttime behaviors were recorded, as well as time-dependent changes in salivary, serum, and hair cortisol concentrations, and serum corticosteroid binding globulin (CBG). Relocation stress induced long-lasting behavioral abnormalities in the SIB group, including an increase in self-biting and a disruption in sleep. Both groups exhibited rapid increases in salivary and serum cortisol following the move. Hair cortisol, which we have validated as an index of long-term HPA system activity (Davenport et al., 2006), was elevated over baseline at 4 months post-move but not at 1 year. In contrast, serum cortisol remained increased over baseline at 1 year, a point at which we also observed a compensatory rise in serum CBG. These results may have relevance for humans exposed to major life stressors. Supported by RR11122 and RR00168.


7A_14_P

Association of Stage of Stress Management Behavior with Perceived Stress and Coping in Japanese College Students

MURAYAMA, Hiroyoshi1) , TANAKA , Yoshiyuki2) , ITO Sakurako1), YAJIMA, Junpei3) TSUADA, Akira1), TSUDA, Shigeko4)

1) Kurume University, Kurume, Japan

2) Tokyo University of Social Welfare, Isezaki, Japan

3) Beppu University, Beppu, Japan

4) Fukuoka Jogakuin University, Fukuoka, Japan

hiro-murayama@umin.net

Background Transtheoretical model (TTM) is a theory of behavior change that can be applied to single, multiple, and complex behavior targets (Prochaska & DiClemente, 1986). The TTM is best known for its applications to smoking, high-fat diet, and drinking. TTM assumes five stages of change, which are named as Pre-contemplation (PC), Contemplation (C), Preparation (P), Action (A), and Maintenance (M) stage. There are thus far few attempts that apply TTM to change in effective stress management behavior in Japan. To understand change in stress management behavior by TTM, this study is to examine association of stage of stress management behavior with perceived stress and coping in Japanese college students. Method Participants were 699 (243 male and 456 female) college students in Fukuoka. The mean ages were 19.7 and 19.3 years, respectively. The measures were 1) Stage of change algorithm, 2) a Japanese version of Rode Island Stress and Coping Inventory, and 3) a Japanese version of Stress Management Behaviors Inventory consisting of four subscales such as setting a limit, planning, reframing, and unhealthy behaviors. Result and Discussion Portions of students were 35 % in PC, 15 % in C, 16 % in P, 11 % in A, and 23 % in M stage, respectively. Degree of perceived stress declined as stage proceeds, whereas perceived frequency of effective coping increased across proceeding of stages. Subjects in A and M stage showed lower frequency of unhealthy behaviors, and higher planning and reframing behaviors. These results replicate previous findings using American sample that effective stress management behaviors are associated with lower levels of stress and higher levels of appropriate coping, and provided support for usefulness of applying TTM to stress management behavior in Japan.


7A_15_P

Reliability and Validity of Layered Voice Analysis technology in the detection of mental stress

Nemoto K1, Tachikawa H1, Takao T1, Sato H1, Ashizawa Y1, Endo G1, Tanaka K1, Ishii R1, Ishii N1, Hashimoto K1, Iguchi T1, Hada S2, Hori M3 and Asada T3

1Psycholosoft, 1-1-1 Tennodai, Tsukuba, Japan; 2Alegria Co., Ltd., Tokyo, Japan; 3Dept. of Psychiatry, Univ. of Tsukuba, Tsukuba, Japan. kiyotaka@nemotos.net

It is known that speech signal contains features which provide information about a human speaker. Although several technologies to detect stress using human voice are available, reports on the reliability and validity of these technologies are controversial. In this study, we investigated the reliability and validity of the Layered Voice Analysis (LVA) technology. Methods: One-hundred and six healthy subjects participated this study. First, stress was assessed by using Speilberger State-Trait Anxiety Inventory (STAI). Blood pressure (BP) was also measured. Then, subjects were randomly assigned to the anagram task group and control group. Before task begins, all of the subjects were asked to answer 10 questions vocally, and they were all recorded. After answering questions, task group underwent anagram task whereas control group just read aloud series of words. After the task, STAI-S and BP were measured again. Answers to each question were analyzed using LVA and 22 parameters were computed. The internal consistency was assessed for each parameter using answers before task. Two-sample t-test was performed to see if parameters change significantly due to anagram task. Results: Of 22 parameters, Cronbach’s alpha of 18 parameters was more than 0.6. Two-sample t-test showed that 10 of 18 parameters along with STAI-S and systolic BP changed significantly during the anagram task. Conclusion: Most of the parameters LVA computed are reliable and the value of these parameters changed significantly under stressful conditions. LVA might be useful in the detection of mental stress.


7A_16_P

Widowhood Increases Risk for Subsequent Dementia, Especially for Women: the Cache County Study

Norton MC 1, Tschanz JT 1, Ostbye T 2, Corcoran C 1, Zandi PP 3, Breitner JCS 4, Welsh-Bohmer KA 2

1 Utah State University, 2 Duke University, 3 The Johns Hopkins University, 4 University of Washington

A host of life stressors increase risk for depression in late life, most notably widowhood. Although depression, in turn, increases risk for dementia, few studies have examined the direct association between late-life stressors and subsequent dementia onset. Even more rare are large, population-based longitudinal studies addressing this research question, with their ability to minimize the selection bias inherent in clinic based samples. In Cache County, Utah (USA) elderly (aged 65+) residents were assessed for dementia (90% of entire county participated) with a multistage case ascertainment protocol in 1995-6 (baseline) and those without dementia at baseline were again assessed in 1998-9 and 2002-3. The longitudinal sample with at least two evaluations included 3,117 persons and of these, 2,231 were married, 789 were widowed, and 97 were separated or divorced at baseline. Cox proportional hazards regression was employed to model effect of marital status, on dementia-free survival (years) before and after adjustment for gender, age, and presence of APOE e4 allele. Before adjustment for covariates, widowhood (at baseline) was associated with significantly higher incident dementia compared to being married (HR=2.37, 95%CI: 1.96-2.87). A trend for the marital status*gender interaction was observed (p=.140) after covariate adjustments. Compared to being married, widowhood was associated with increased hazard for dementia in women only (HR=1.77, 95%CI: 1.00-3.12). Future studies will examine factors that may mitigate increased risk, and the effects of more recent widowhood and multiple marital transitions.


7A_17_P

Stress and memory interaction : declarative memory impairment following a 5-day military commando operation.

C. Piérard1, M. Péres1, J.C. Jouanin1, P. Liscia1, C.Y. Guézennec and D. Béracochéa2

1 : IMASSA - BP 73 - F-91223 Brétigny-sur-Orge Cedex

2 : LNC - Université Bordeaux 1 - F-33405 Talence Cedex

A commando operation is composed of multiple routines and skills that require alertness, attention to external environment, memory performance and reactivity to events. As the declarative memory system is very sensitive to environmental interactions and stress-generating situations, we decided to specifically study the effects of a 5-day commando operation on this system.

Cognitive and memory performance of 21 male cadets was examined 3 weeks before and at the end of the operation, using an original computerized cognitive test battery allowing field investigation. In a first step, the battery evaluated psychomotor and cognitive performance with : a subjective vigilance and mood testing, a visuomotor coordination test, a selective attention test, and finally a planning test. In a second step, more specific memory tests were administered to investigate short-term components on the one hand, and long-term components on the other hand. For each item, the battery measured the reaction time and calculated the percentages of good and wrong responses, as well as the percentage of omissions.

Our results evidenced that a 5-day commando operation significantly increased reaction times. In accordance with the relative but significant hypovigilance of the subjects, selective attention and short-term memory were affected (memory span, visual memory and audiovisual association). More surprisingly, long-term memory (semantic memory) was also impaired. On the contrary, spatial work