Effects Of Chronic Psychosocial Stress Research Articles

Effects of Ovarian Stimulation with Gonadotropins in the Conditions of Chronic Psychosocial Stress on the Quality of Murine Oocyte

Chronic psychosocial stress may negatively affect the female reproductive system. Meanwhile, the effect of ovarian stimulation with gonadotropins during stress on the quality of oocytes remains poorly studied. The purpose of this work was to investigate the effects of chronic psychosocial stress on the quality of murine cumulus-oocyte complexes during natural estrus cycle, as well as during ovarian stimulation with exogenous gonadotropins; the latter is an important part of modern assisted reproductive technologies. The results of the study demonstrate that psychosocial stress does not affect the number of ovulating oocytes, but worsens their quality, i. e. reduces the percentage of mature oocytes. In addition, stressed mice exhibited the increased accumulation of reactive oxygen species in oocytes, which is accompanied by the enhanced rate of apoptosis in cumulus cells. Hormonal stimulation of the ovaries with gonadotropins alleviates the negative changes associated with the psychosocial stress, normalizing the level of reactive oxygen species in oocytes and reducing the rate of apoptosis in cumulus cells.

Chronic psychosocial stress reveals Alzheimer’s disease in a novel at-risk rat model

Extensive individual variations in the time of onset and severity of the sporadic type of Alzheimer’s disease (AD), may be due to some patient-related external factors. Stress is increasingly recognized as an external factor in the development of AD. Several labs, including mine, have demonstrated that chronic stress or corticosterone administration aggravates the disease in both transgenic and non-transgenic animal models. We have developed a novel rat model that simulates seemingly normal individuals who are predisposed to develop AD. This review summarizes the findings we have reported on the effect of chronic psychosocial stress in this at-risk model of AD. Behavioral (learning and memory tests), electrophysiological (evoked long-term potentiation) and molecular (protein levels of memory-related signaling molecules a well as AD-related molecules. Our findings suggest that even mild psychosocial stress noticeably transforms this seemingly normal rat model to a full-fledge AD phenotype.

Effects of chronic psychosocial stress on ‘binge-like’ sucrose intake in mice

Binge eating episodes are persistent and are essential features of numerous eating disorders (EDs). Susceptibility to EDs is largely presumed to be associated with early life stress. In fact, converging evidence from preclinical animal studies have implicated stress as a driver of binge eating. Still, literature examination indicates that vulnerability to EDs may depend on factors such as severity, time, and the type of stressor. Therefore, we aimed at exploring the link between chronic psychosocial stress and ‘binge-like’ sucrose intake in adolescent mice. To this aim, intruders' experimental mice were exposed to the chronic subordinate colony (CSC) housing, in the presence of a resident aggressive mouse for 2 weeks. At the end of the stress period, mice were tested for anxiety-like behavior then assessed for ‘binge-like’ intake of sucrose using a long-term drinking in the dark (DID) method that successfully replicates binge eating in humans. As expected, and compared to single housed colony controls (SHC), CSC exposure elicited an anxiogenic-like response in the open field (OF) and elevated-plus maze (EPM) tests and reduced weight gain. Most importantly, we report here for the first time, that mice exposed to chronic psychosocial stress displayed a ‘binge-like’ consumption of sucrose. However, neither quinine (bitter) nor saccharin (sweet) intakes were affected by CSC exposure. Finally, using Pearson's correlation, results showed a strong correlation between anxiety-like behavior parameters and sucrose intake. Overall these findings support the validity of our chronic psychosocial stress to model binge EDs and establish the long-term consequences of stress on ‘binge-like’ eating in male mice. These data suggest that chronic psychosocial stress is a risk factor for developing anxiety-associated EDs.

Psychosocial stress increases risk for type 2 diabetes in female cynomolgus macaques consuming a western diet

Chronic psychosocial stress is associated with increased risk of many chronic diseases including type 2 diabetes mellitus. However, it is difficult to establish a causal relationship between stress and diabetes in human studies because stressors often are self-reported and may be distant in time from metabolic consequences. Macaques are useful models of the effects of chronic psychosocial stress on health and may develop obesity and diabetes similar to human beings. Thus, we studied the relationships between social subordination stress – a well-validated psychological stressor in macaques – and body composition and carbohydrate metabolism in socially housed, middle-aged female cynomolgus monkeys (Macaca fascicularis; n = 42). Following an 8-week baseline phase, the monkeys were fed a Western diet for 36 months (about equivalent to 10 human years). Social status was determined based on the outcomes of agonistic interactions (X¯= 33.3 observation hours/monkey). Phenotypes collected included plasma cortisol, body composition, circulating markers of glucose metabolism, activity levels, and heart rate variability measured as RMSSD (root of mean square of successive differences) and SDDN (standard deviation of beat to beat interval) after 1.5- and 3-years on diet. Mixed model analyses of variance revealed that aggression received, submissions sent, and cortisol were higher, and RMSSD and SDNN were lower in subordinates than dominants (social status: p < 0.05). After 3 years of Western diet consumption, fasting triglyceride, glucose and insulin concentrations, calculated insulin resistance (HOMA-IR), body weight and body fat mass increased in all animals (time: all p’s < 0.05); however, the increase in fasting glucose and HOMA-IR was significantly greater in subordinates than dominants (time x social status: p’s < 0.05). Impaired glucose metabolism, (glucose > 100 mg/dl) incidence was significantly higher in subordinates (23%) than dominants (0%) (Fisher’s exact test, p < 0.05). These findings suggest that chronic psychosocial stress, on a Western diet background, significantly increases type 2 diabetes risk in middle-aged female primates.

Behavioral and hormonal effects of prolonged Sildenafil treatment in a mouse model of chronic social stress

Chronic social defeat can inhibit the reproductive system of subordinate males and causes behavioral deficits. Sildenafil treatment increases mice testosterone levels through its effects on Leydig cells of mice and it has been found to work as an antidepressant drug both in humans and in animal models. Since previous findings showed that sildenafil can counteract the inhibitory effects of chronic social defeat on agonistic, reproductive and anxiety-like behaviors of subordinate male mice, we investigated whether these behavioral outcomes can be explained by Sildenafil stimulation of testosterone. CD1 mice underwent an intruder-resident paradigm. After the fifth day of test, subordinate mice were injected with either a 10 mg/kg Sildenafil or a saline solution for 4 weeks. The results of the present study showed that Sildenafil treatment increased counterattacking behaviors and sexual motivation of subordinate males in addition to limiting the increase in body weight often observed in subordinate mice following chronic psychosocial stress. Moreover, sildenafil treated mice showed a pattern of behaviors reflecting lower anxiety. In agreement with previous studies, Sildenafil also increased testosterone levels. These data demonstrate that sildenafil can counteract the effects of chronic stress, possibly through its stimulatory effects on Leydig cells. These data demonstrate that sildenafil might counteract the effects of chronic psychosocial stress through centrally and peripherally mediated mechanisms.

Effects of Psychosocial Stress on Subsequent Hemorrhagic Shock and Resuscitation in Male Mice.

Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multi-organ failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. To induce chronic psychosocial stress linked to mild immune activation and reduced GC signaling in male mice, the chronic subordinate colony housing (CSC) paradigm was employed. Single-housed (SHC) mice were used as controls. Subsequently, CSC and SHC mice were exposed to hemorrhagic shock following resuscitation to investigate the effects of prior psychosocial stress load on survival, organ function, metabolism, oxidative/nitrosative stress, and inflammatory readouts. An increased adrenal weight in CSC mice indicates that the stress paradigm reliably worked. However, no effect of prior psychosocial stress on outcome after subsequent hemorrhage and resuscitation could be detected. Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.

SUN-021 Chronic Psychosocial Stress during Pregnancy Affects Maternal Behavior and Neuroendocrine Function and Modulates Hypothalamic CRH Signaling Pathway and Nuclear Steroid Hormone Receptor Expression

Postpartum depression (PPD) affects up to 20% of women and exerts adverse consequences on mother and child. Gestational stress and abnormalities in neuroendocrine function have been implicated in the development of PPD. Here, we measured effects of chronic psychosocial stress during pregnancy on maternal behavior as well as hypothalamic-pituitary-adrenal (HPA) axis function and regulation in the early postpartum period. From gestational day 6.5 to 17.5, pregnant C57Bl/6 female mice were exposed to a novel chronic stress paradigm consisting of variable psychosocial stressors such as foreign object exposure, rat odor exposure, bedding removal and were assessed from postpartum day 2 to 7 for behavioral alterations in maternal care, depression, and anxiety as well as circadian and brief restraint-stress associated corticosterone response. mRNA changes in molecular regulators of the HPA axis were measured in 1mm micropunches of the hypothalamic paraventricular nucleus (PVN) via qPCR. Mice exhibited deficits in maternal care after undergoing chronic psychosocial stress during pregnancy displayed as increased latency to retrieve pups during pup retrieval task (p<0.01, n=17). Furthermore, they displayed a depressive-like phenotype as measured by increased time spent immobile in forced swim test (p<0.01, n=17) and increased anxiety as measured by increased time spent in dark zone in light/dark transition test (p<0.05, n=7-11). Abnormalities in the activity of the maternal HPA axis were also displayed as seen by a flattening of the circadian rhythm of CORT secretion (p<0.05, n=10-12), increased CORT release following 20 minutes of restraint stress (p<0.05, n=5-8), and increased adrenal gland weights (p<0.05, n=15-20). These changes were associated with increased PVN CRH mRNA (gestational day 17.5 (G17.5): 0.880+0.18 vs. 0.485+0.03, postpartum day 2 (PP2): 1.012+0.05 vs. 0.794+0.05, PP7: 0.775+0.04 vs. 0.487+0.05, p<0.05, n=6-7) and downregulation of CRH receptor 1 (G17.5: 0.821+0.07 vs. 1.03+0.05, PP2: 1.007+0.05 vs. 1.184+0.06, p<0.05, n=6-7) compared to non-stressed control dams, while vasopressin and oxytocin levels remained undisturbed. Furthermore, PVN glucocorticoid receptor (G17.5: 0.844+0.01 vs. 0.938+0.02, p<0.01, n=6-7) and progesterone receptor mRNA were downregulated (PP2: 1.008+0.03 vs. 1.196+0.047, p<0.01, n=6-7), and FK506 binding protein 5 mRNA, a co-chaperone known to negatively orchestrate GR/PR transcriptional activity, was upregulated (G17.5: 2.322+0.37 vs. 1.315+0.05, p<0.05, n=6-7). These results suggest hypothalamic changes in GR/PR signaling pathway as putative regulators of postpartum changes in CRH after stress exposure and postpartum maternal affective dysregulation. The mechanistic role GR/PR play in mediating these changes is further being investigated by selective spatiotemporal GR/PR modulation using Cre-loxP technology.

Chronic Psychosocial Stress in Mice Is Associated With Increased Acid Sphingomyelinase Activity in Liver and Serum and With Hepatic C16:0-Ceramide Accumulation.

Chronic psychosocial stress adversely affects human morbidity and is a risk factor for inflammatory disorders, liver diseases, obesity, metabolic syndrome, and major depressive disorder (MDD). In recent studies, we found an association of MDD with an increase of acid sphingomyelinase (ASM) activity. Thus, we asked whether chronic psychosocial stress as a detrimental factor contributing to the emergence of MDD would also affect ASM activity and sphingolipid (SL) metabolism. To induce chronic psychosocial stress in male mice we employed the chronic subordinate colony housing (CSC) paradigm and compared them to non-stressed single housed control (SHC) mice. We determined Asm activity in liver and serum, hepatic SL concentrations as well as hepatic mRNA expression of genes involved in SL metabolism. We found that hepatic Asm activity was increased by 28% (P = 0.006) and secretory Asm activity by 47% (P = 0.002) in stressed mice. C16:0-Cer was increased by 40% (P = 0.008). Gene expression analysis further revealed an increased expression of tumor necrosis factor (TNF)-α (P = 0.009) and of several genes involved in SL metabolism (Cers5, P = 0.028; Cers6, P = 0.045; Gba, P = 0.049; Gba2, P = 0.030; Ormdl2, P = 0.034; Smpdl3B; P = 0.013). Our data thus provides first evidence that chronic psychosocial stress, at least in mice, induces alterations in SL metabolism, which in turn might be involved in mediating the adverse health effects of chronic psychosocial stress and peripheral changes occurring in mood disorders.

Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations.

Chronic (psychosocial) stress changes gut microbiota composition, as well as inducing behavioural and physiological deficits. The microbial metabolites short-chain fatty acids (SCFAs) have been implicated in gastrointestinal functional, (neuro)immune regulation and host metabolism, but their role in stress-induced behavioural and physiological alterations is poorly understood. Administration of SCFAs to mice undergoing psychosocial stress alleviates enduring alterations in anhedonia and heightened stress-responsiveness, as well as stress-induced increases in intestinal permeability. In contrast, chronic stress-induced alterations in body weight gain, faecal SCFAs and the gene expression of the SCFA receptors FFAR2 and FFAR3 remained unaffected by SCFA supplementation. These results present novel insights into mechanisms underpinning the influence of the gut microbiota on brain homeostasis, behaviour and host metabolism, informing the development of microbiota-targeted therapies for stress-related disorders. There is a growing recognition of the involvement of the gastrointestinal microbiota in the regulation of physiology and behaviour. Microbiota-derived metabolites play a central role in the communication between microbes and their host, with short-chain fatty acids (SCFAs) being perhaps the most studied. SCFAs are primarily derived from fermentation of dietary fibres and play a pivotal role in host gut, metabolic and immune function. All these factors have previously been demonstrated to be adversely affected by stress. Therefore, we sought to assess whether SCFA supplementation could counteract the enduring effects of chronic psychosocial stress. C57BL/6J male mice received oral supplementation of a mixture of the three principle SCFAs (acetate, propionate and butyrate). One week later, mice underwent 3weeks of repeated psychosocial stress, followed by a comprehensive behavioural analysis. Finally, plasma corticosterone, faecal SCFAs and caecal microbiota composition were assessed. SCFA treatment alleviated psychosocial stress-induced alterations in reward-seeking behaviour, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addition, SCFAs exhibited behavioural test-specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress. Stress-induced increases in body weight gain, faecal SCFAs and the colonic gene expression of the SCFA receptors free fatty acid receptors 2 and 3 remained unaffected by SCFA supplementation. Moreover, there were no collateral effects on caecal microbiota composition. Taken together, these data show that SCFA supplementation alleviates selective and enduring alterations induced by repeated psychosocial stress and these data may inform future research into microbiota-targeted therapies for stress-related disorders.

Long-term effects of chronic psychosocial stress on social and general anxiety depending on the sensory contact to the stressor

Long-term effects of chronic psychosocial stress on social and general anxiety depending on the sensory contact to the stressor

Mouse psychosocial stress reduces motivation and cognitive function in operant reward tests: A model for reward pathology with effects of agomelatine

A major domain of depression is decreased motivation for reward. Translational automated tests can be applied in humans and animals to study operant reward behaviour, aetio-pathophysiology underlying deficits therein, and effects of antidepressant treatment. Three inter-related experiments were conducted to investigate depression-relevant effects of chronic psychosocial stress on operant behaviour in mice. (A) Non-manipulated mice were trained on a complex reversal learning (CRL) test with sucrose reinforcement; relative to vehicle (VEH), acute antidepressant agomelatine (AGO, 25mg/kg p.o.) increased reversals. (B) Mice underwent chronic social defeat (CSD) or control handling (CON) on days 1–15, and were administered AGO or VEH on days 10–22. In a progressive ratio schedule motivation test for sucrose on day 15, CSD mice made fewer responses; AGO tended to reverse this effect. In a CRL test on day 22, CSD mice completed fewer reversals; AGO tended to increase reversals in CSD mice associated with an adaptive increase in perseveration. (C) Mice with continuous operant access to water and saccharin solution in the home cage were exposed to CSD or CON; CSD mice made fewer responses for saccharin and water and drank less saccharin in the active period, and drank more water in the inactive period. In a separate CSD cohort, repeated AGO was without effect on these home cage operant and consummatory changes. Overall, this study demonstrates that psychosocial stress in mice leads to depression-relevant decreases in motivation and cognition in operant reward tests; partial reversal of these deficits by AGO provides evidence for predictive validity.

Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice

Prolonged and sustained stimulation of the hypothalamo–pituitary–adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum.After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene.The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.

Chronic psychosocial stress impairs early LTP but not late LTP in the dentate gyrus of at-risk rat model of Alzheimer׳s disease

The CA1 and dentate gyrus regions of the hippocampus are physically and functionally closely related but they react differently to insults. This study examined the effect of chronic psychosocial stress on the dentate gyrus of an at-risk (preclinical) rat model of Alzheimer׳s disease (subAβ rats). Chronic psychosocial stress was produced using a rat intruder model. The at-risk rat model of Alzheimer׳s disease was created by osmotic pump infusion of sub-pathological dose of Aβ (160pmol Aβ1–42/day i.c.v) for 14 days. Electrophysiological methods were used to evoke and record early and late phase LTP in the dentate gyrus of anesthetized rats, and immunoblotting was used to measure levels of memory-related signaling molecules in the same region. Electrophysiological and molecular tests in the dentate gyrus showed that subAβ rats or stressed rats were not different from control rats. However, when the subAβ rats were chronically stressed, the combined treatments severely suppressed early phase LTP without affecting the late phase LTP of dentate gyrus. Additionally, in the chronically stressed subAβ rats the expected elevation of levels of phosphorylated CaMKII did not materialize after expression of early phase LTP suggesting impaired phosphorylation, which may explain the severely blocked early phase LTP.

Chronic Stress Decreases Basal Levels of Memory-Related Signaling Molecules in Area CA1 of At-Risk (Subclinical) Model of Alzheimer's Disease.

An important factor that may affect the severity and time of onset of Alzheimer's disease (AD) is chronic stress. Epidemiological studies report that chronically stressed individuals are at an increased risk for developing AD. The purpose of this study was to reveal whether chronic psychosocial stress could hasten the appearance of AD symptoms including changes in basal levels of cognition-related signaling molecules in subjects who are at risk for the disease. We investigated the effect of chronic psychosocial stress on basal levels of memory-related signaling molecules in area CA1 of subclinical rat model of AD. The subclinical symptomless rat model of AD was induced by osmotic pump continuous intracerebroventricular (ICV) infusion of 160 pmol/day Aβ1-42 for 14 days. Rats were chronically stressed using the psychosocial stress intruder model. Western blot analysis of basal protein levels of important signaling molecules in hippocampal area CA1 showed no significant difference between the subclinical AD rat model and control rat. Following six weeks of psychosocial stress, molecular analysis showed that subclinical animals subjected to stress have significantly reduced basal levels of p-CaMKII and decreased p-CaMKII/t-CaMKII ratio as well as decreased basal levels of p-CREB, total CREB, and BDNF. The present results suggest that these changes in basal levels of signaling molecules may be responsible for impaired learning, memory, and LTP in this rat model, which support the proposition that chronic stress may accelerate the emergence of AD in susceptible individuals.

Effects of Chronic Psychosocial Stress on Reduction of Basal Glucocorticoid Levels and Suppression of Glucocorticoid Levels Following Dexamethasone Administration in Animal Model of PTSD

Aim: To further examine the neurobiological mechanisms and their outcomes responsible for the PTSD sequelae induced by laboratory animal model and to explore the effects of chronic psychosocial paradigm. We tested the hypothesis that our animal model of PTSD would display abnormalities in glucocorticoid levels that are manifest in people with PTSD and that psychosocially stressed rats exhibit a significantly greater suppression of corticosterone levels than control rats following the administration of dexamethasone.Methods: Animals were divided into two groups. The experimental group was scheduled to exposure to two types of stressors: double exposure to acute immobilization stress, and combined predator-threat stress and daily social stress. There was also administration of dexamethasone in combination with stress exposure.Results: There was a statistical difference between masses of thymus in the stress group and stress group with dexamethasone appliance (p=0.024). We found statistical significance between baseline cortisol and stress induced levels of cortisol and between stress induced group and return to baseline group.Conclusion: Significant changes in HPA activity, reductions in basal glucocorticoid levels and enhanced dexamethasone induced inhibition of glucocorticoid levels have been manifested. All of this is manifested in PTSD patients also as many other stress induces changes.

Effects of Chronic Psychosocial Stress on Reduction of Basal Glucocorticoid Levels and Suppression of Glucocorticoid Levels Following Dexamethasone Administration in Animal Model of PTSD

Aim: To further examine the neurobiological mechanisms and their outcomes responsible for the PTSD sequelae induced by laboratory animal model and to explore the effects of chronic psychosocial paradigm. We tested the hypothesis that our animal model of PTSD would display abnormalities in glucocorticoid levels that are manifest in people with PTSD and that psychosocially stressed rats exhibit a significantly greater suppression of corticosterone levels than control rats following the administration of dexamethasone.Methods: Animals were divided into two groups. The experimental group was scheduled to exposure to two types of stressors: double exposure to acute immobilization stress, and combined predator-threat stress and daily social stress. There was also administration of dexamethasone in combination with stress exposure.Results: There was a statistical difference between masses of thymus in the stress group and stress group with dexamethasone appliance (p=0.024). We found statistical significance between baseline cortisol and stress induced levels of cortisol and between stress induced group and return to baseline group.Conclusion: Significant changes in HPA activity, reductions in basal glucocorticoid levels and enhanced dexamethasone induced inhibition of glucocorticoid levels have been manifested. All of this is manifested in PTSD patients also as many other stress induces changes.

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7days of extinction trials before the 19days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

Children’s Body composition and Stress – the ChiBS study: aims, design, methods, population and participation characteristics

BackgroundThe last decades, the prevalence of childhood obesity has increased. Apart from other lifestyle factors, the effect of chronic psychosocial stress on the development of obesity has been recognized. However, more research is needed into the influence of chronic stress on appetite regulation, energy balance and body composition, as well as on the interaction with physical activity/sedentary behavior, diet and sleep in children. In this regard, the ChiBS study (Children’s Body composition and Stress) was designed at the Ghent University. Within this paper, we describe the aims, design, methods, participation and population characteristics of the ChiBS study.MethodsThe influence of chronic stress on changes in body composition is investigated over a two-year follow-up period (February-June 2010, 2011 and 2012) in primary-school children between 6 and 12 years old in the city Aalter (Flanders, Belgium).Stress is measured by child- and parent-reported stress-questionnaires, as well as by objective stress biomarkers (serum, salivary and hair cortisol) and heart rate variability. Body composition is evaluated using basic anthropometric measurements and air displacement plethysmography. Additional information on socio-economic status, medical history, physical activity, dietary intake and sleep are obtained by questionnaires, and physical activity by accelerometers.ResultsThe participation percentage was 68.7% (N = 523/761), with 71.3% of the children willing to participate in the first follow-up survey. Drop-out proportions were highest for serum sampling (12.1%), salivary sampling (8.3%) and heart rate variability measurements (7.4%).DiscussionThe ChiBS project is unique in its setting: its standardized and longitudinal approach provides valuable data and new insights into the relationship between stress and changes in body composition in a large cohort of young children. In addition, this study allows an in-depth investigation of the validity of the different methods that were used to assess stress levels in children.

Social stress interacts with diet history to promote emotional feeding in females

Stress-induced eating disorders cause significant health problems and are often co-morbid with mood disorders. Emotional feeding, particularly in women, may be important for the development of obesity and failed attempts to lose weight. However, prospective studies assessing the effect of chronic psychosocial stress on appetite in different dietary environments in females are lacking. The present study tested the hypothesis that chronic psychosocial stress would increase consumption of high caloric diet and this emotional feeding would persist even when a healthier diet was available. Socially housed female rhesus monkeys were studied to address whether subordination increases caloric intake when a high fat and sugar diet (HFSD) was available concurrently with a low fat, high fiber diet (LCD). Cortisol responsivity and food intake were quantified during this choice phase and when only the LCD was available. The order of diet condition was counterbalanced to assess whether a history of HFSD would affect appetite. All females preferred the HFSD but subordinates consumed significantly more calories during the choice phase. The increased calorie intake was maintained in subordinate monkeys even after withdrawal of the HFSD. Subordinate females demonstrated reduced glucocorticoid negative feedback, with post dexamethasone serum cortisol levels significantly predicting intake of the HFSD but not the LCD during the choice condition. The cortisol response to an acute stressor significantly predicted subsequent intake of a HFSD in all females. Continual exposure to the psychosocial stress of subordination in female monkeys results in excess caloric intake of foods that mimic a western dietary environment. In addition, this social stressor interacts with a history of HFSD intake to promote increased feeding even in a healthy dietary environment.

Effects of Chronic Social Stress on Obesity

The prevalence of overweight and obesity has markedly increased during the past few decades. Stress has been suggested as one environmental factor that may contribute to the development of obesity. In this review, we discuss the role that exposure to chronic stress may play in the development of obesity, with particular attention to the effects of chronic psychosocial stress. Of particular importance is the effect that social stress has on dietary preference, food consumption, and regional distribution of adipose tissue. We present evidence from human and animal studies that links sympathetic nervous system and hypothalamic-pituitary-adrenal axis hyperactivity with visceral obesity, and that stress tends to alter the pattern of food consumption, and promotes craving of nutrient-dense "comfort foods." Lastly, we discuss the visible burrow system, a model of chronic social stress used in our laboratory to assess the effects of social subordination on behavioral and metabolic profile.