Metaplasticity of amygdalar responses to the stress hormone corticosterone

High levels of corticosteroids (as circulate after stress) quickly and reversibly enhance hippocampal glutamatergic transmission via nongenomic actions requiring mineralocorticoid receptors. Subsequently, the hormone slowly and long-lastingly normalizes hippocampal cell function, through nuclear glucocorticoid receptors. Here we describe a rapid mineralocorticoid receptor-dependent enhancement of glutamatergic transmission in basolateral amygdala neurons. Contrary to the hippocampus, this rapid enhancement is long-lasting, potentially allowing an extended window for encoding of emotional aspects during stressful events. Importantly, the long-lasting change in state of amygdala neurons greatly affects the responsiveness to subsequent surges of corticosterone, revealing a quick suppression of glutamatergic transmission, which requires the glucocorticoid receptor. Responses of basolateral amygdala neurons to the stress hormone corticosterone can thus switch from excitatory to inhibitory, depending on the recent stress history of the organism.     

A Common Mineralocorticoid Receptor Polymorphism (I180V) Interacts with Life Events in Relation to Perfectionism in Eating Disorders: A Pilot Study

The stress response is regulated by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). When the balance between GR and MR signalling is disturbed, one's capacity to cope with a stressful event is diminished. In this pilot study, we tested the hypothesis that an interaction between common variants in the MR (rs5522) or GR gene (rs41423247) and stressful life events influences perfectionism levels in a group of patients with an eating disorder (ED; n = 113). Patients carrying the minor G allele of rs5522 had a higher perfectionism score if more stressful life events were experienced [β = 0.95, t(109) = 3.75, p < 0.01]. This effect was not found for patients carrying the AA genotype. These results suggest that rs5522 G allele carriers might be vulnerable to stressful life events. When patients with an ED are carriers and experience multiple life events, this might fuel their insecurity, which in turn may engender higher levels of perfectionism. Further studies are necessary to replicate and expand our findings. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.     

Corticosteroids,the Aging Brain and Cognition

The hippocampal region of the brain is a useful model system for understanding the plasticity and resilience of brain cells to stress hormone action and aging. Hippocampal neurons show both structural and functional plasticity, and individual differences in hippocampal function are shaped by early life experiences. For human brain aging, there are new non-invasive imaging tools to relate to the animal models, and these can help to assess the vulnerability of the aging hippocampus in relation to stress and Alzheimer's disease.     

Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects

Although neurotrophins have been postulated to have antidepressant properties, their effect on anxiety is not clear. We find that transgenic overexpression of the neurotrophin BDNF has an unexpected facilitatory effect on anxiety-like behavior, concomitant with increased spinogenesis in the basolateral amygdala. Moreover, anxiogenesis and amygdalar spinogenesis are also triggered by chronic stress in control mice but are occluded by BDNF overexpression, thereby suggesting a role for BDNF signaling in stress-induced plasticity in the amygdala. BDNF overexpression also causes antidepressant effects, because transgenic mice exhibit improved performance on the Porsolt forced-swim test and an absence of chronic stress-induced hippocampal atrophy. Thus, structural changes in the amygdala and hippocampus, caused by genetic manipulation of the same molecule BDNF, give rise to contrasting effects on anxiety and depressive symptoms, both of which are major behavioral correlates of stress disorders.     

A role for life events in the pathogenesis of Cushing's disease

OBJECTIVE We have previously reported on 30 patients with Cushing's syndrome suggesting an aetiological role for stressful life events. The investigation about life events in the year before the first signs of disease onset was extended to a larger population of patients with Cushing's syndrome, allowing us to differentiate patients with pituitary-dependent and pituitary-independent forms. DESIGN Case-control study. PATIENTS Sixty-six consecutive patients with Cushing's syndrome of various aetiologies (46 with pituitary-dependent forms and 20 with primary adrenal hyperfunction or ectopic ACTH production) and a control group of 66 healthy subjects, matched for sociodemographic variables, were studied. MEASUREMENTS Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered after the acute phase of illness while in remission. RESULTS Patients with Cushing's syndrome reported significantly more stressful life events (P < 0.001), both events that had an objective negative impact (P < 0.001) and independent events (P < 0.001), than controls, confirming previous findings. Patients with pituitary-dependent Cushing's disease were compared with their matched controls and reported significantly more total events, events with an objective negative impact and independent events (all at P < 0.001). There were no significant differences between patients with pituitary-independent forms and their matched controls. CONCLUSIONS These findings indicate a causal role for stressful life events exclusively in pituitary-dependent Cushing's disease, and suggest a limbic-hypothalamic involvement in the pathogenesis of this condition. The results are similar to those obtained in major depression, and add to other analogies between the two disorders.     

Interlocking trajectories of loss-related events and depressive symptoms among elders

OBJECTIVES: As people age, their peers (who are also aging) become increasingly susceptible to health decline and death, implying potential growth in stressful loss-related events over time for the individual. Yet little research has examined trajectories of stress and their relationship to trajectories of depression among elders. The purpose of this research was to determine whether growth in loss-related events occurs for elders and whether stress growth is related to the well-known growth in depressive symptomatology in later life. METHODS: Three waves of National Institute on Aging Established Populations for Epidemiologic Studies of the Elderly (Duke University site) data were used in the analyses. Latent growth curve models were estimated for stress, for depressive symptoms, and for stress predicting depression net of several covariates. RESULTS: Findings include that (a) loss-events evidence clear growth across age at the aggregate level, but with much variation within the sample, and (b) variation in growth in stress is strongly related to variation in growth in depressive symptoms. DISCUSSION: The results suggest that stress in later life may be conceived of as a growth process, with strong consequences for trajectories of mental health.     

Stressful life events and depressive symptoms among the elderly. Evidence from a prospective community study

We examined the effect of a series of common stressful life events on change in depressive symptoms among the elderly. The subjects were 1,962 noninstitutionalized people 65 years of age or older from the New Haven EPESE project. Multivariate regression models revealed that 8 of 11 stressful life events examined predicted change in depressive symptoms at follow-up (1985) after controlling for baseline depressive symptoms age, socioeconomic factors, functional status, and chronic conditions. In addition, the total number of stressful life events was significantly associated with higher CES-D depression scores. A dose-response relationship between cumulative life event stress and change in depressive symptoms was also shown. These results suggest that certain common life event stressors may have an impact on mental health, both singly and in combination.     

Emotional stress and the development of multiple sclerosis: Case-control evidence of a relationship

One hundred multiple sclerosis (MS) patients were compared to hospital controls, for life stress prior to onset age in the MS patients. The MS patients and controls did not differ on: the happiness of their childhood environment; their pre-onset age reaction to life's problems (relaxed and taking things in stride/tense or easily upset); or on their tendency to seek professional help with an emotional problem. However significantly more MS patients than controls reported that they were under unusual stress in the 2yr period prior to onset age; and the MS patients described a greater number of stressful life situations, or single events, than the controls.     

Life events, daily stresses and coping in patients with Graves' disease

OBJECTIVE The contribution of stress to the aetiology of Graves' disease (GD) remains controversial. We have therefore examined life events, dally stress and coping in patients with this disease. We wished to determine whether the clinical presentation of Graves' hyperthyroidism is associated with preceding stressful events. DESIGN A prospective controlled study. Ninety-five patients with newly diagnosed GD were compared to matched controls. METHOD A self-reporting questionnaire recalling life events, dally stress and coping In the twelve months preceding the diagnosis. RESULT More Graves' disease patients than controls reported negative events (P<0·0005), whereas the number of subjects reporting positive events and neutral events were similar in both groups. Graves' disease patients also experienced more negative events (P<0·0001) and perceived them with higher ratings (P<0·0001). Each group had similar coping ability In terms of the number of coping methods and magnitude of utilization of these methods. Similarly, Graves' disease patients reported more dally hassle (P<0·0001) and had higher hassle scores (P<0·0001). CONCLUSION Patients with Graves' disease experienced greater psychological stress and adverse events prior to the onset of the disease. As stress may alter the immune system, it could play an important role in precipitating the disease in subjects predisposed to auto-immune thyroid disorders.     

Social support, stress, and well-being among older adults

The purpose of this study was to examine whether social support buffers the deleterious effects of stressful life events on depressive symptoms among a random community sample of older adults. Previous research has provided contradictory conclusions regarding the stress buffering capacity of supportive social relations. The reason for these inconclusive findings may be traced in part to the failure of researchers to disaggregate their social support and stressful life event inventories. The findings from the present study reveal that, although social support fails to modify the effects of a global stressful life events indicator, specific types of social support buffer the impact of specific types of stressors (bereavement, crime, and social network crises).     

Behavioral stress modifies hippocampal plasticity through N-methyl-D-aspartate receptor activation.

Behavioral stress has detrimental effects on subsequent cognitive performance in many species, including humans. For example, humans exposed to stressful situations typically exhibit marked deficits in various learning and memory tasks. However, the underlying neural mechanisms by which stress exerts its effects on learning and memory are unknown. We now report that in adult male rats, stress (i.e., restraint plus tailshock) impairs long-term potentiation (LTP) but enhances long-term depression (LTD) in the CA1 area of the hippocampus, a structure implicated in learning and memory processes. These effects on LTP and LTD are prevented when the animals were given CGP39551 (the carboxyethylester of CGP 37849; DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, before experiencing stress. In contrast, the anxiolytic drug diazepam did not block the stress effects on hippocampal plasticity. Thus, the effects of stress on subsequent LTP and LTD appear to be mediated through the activation of the NMDA subtype of glutamate receptors. Such modifications in hippocampal plasticity may contribute to learning and memory impairments associated with stress.     

Stressful life events, acid hypersecretion, and ulcer disease

We have evaluated 2 patients with symptomatic gastric disease who dated the onset of their illnesses to stressful events in their lives. In 1 patient, six family members had recently died and our patient feared that he too would die. The other patient was accused of grand theft, was under police surveillance, and had lost his job. Both patients had markedly increased gastric acid secretion rates that decreased to normal after hospitalization and reassurance in the first case and acquittal in the second case. Ulcer symptoms subsided at the same time as the decrease in acid secretion. Although we cannot prove that severe emotional stress in our patients led to acid hypersecretion and ulcer disease, their courses suggest that stressful life events caused increased acid secretion which, in turn, led to ulceration and symptoms.     

Psychosomatic aspects of Cushing’s syndrome

There has been growing interest in the psychosocial aspects of Cushing’s syndrome, such as the role of life stress as a pathogenetic factor, the association with affective disorders, and the presence of residual symptoms after treatment. Interestingly, a temporal relationship between stressful life events and disease onset is relevant only to pituitary-dependent Cushing’s disease, and not to the pituitary-independent forms. A number of psychiatric and psychological disturbances may be associated with the active hypercortisolemic state, regardless of its etiology. Within the high frequency of mood disorders (about 60%), major depression is the most common complication. Other psychopathological aspects include mania, anxiety disorders, psychological symptoms (demoralization, irritable mood, somatization) and cognitive impairment. Cognitive symptoms are associated with brain abnormalities (mainly loss of brain volume). Quality of life may be seriously compromised during both active and post-treatment phases. Long-standing hypercortisolism may imply a degree of irreversibility of the pathological process. Recovery, thus, may be delayed and be influenced by highly individualized affective responses. Outcomes of Cushing’s syndrome treatment are not fully satisfactory. Within its great complexity, a conceptual shift from a merely biomedical care to a psychosomatic consideration of the person and his/her quality of life appears to be necessary to improve effectiveness. It is time to translate the research evidence that has accumulated into clinical practice initiatives. To patients who show persistence or even worsening of psychological distress upon adequate endocrine treatment psychiatric/psychological interventions should be readily available. Applying interdisciplinary expertise and addressing the needs for rehabilitation would markedly improve final outcome.     

Amygdala stimulation modulates hippocampal synaptic plasticity

Experience-dependent synaptic plasticity is a fundamental feature of neural networks involved in the encoding of information, and the capability of synapses to express plasticity is itself activity-dependent. Here, we introduce a "low-frequency burst stimulation" protocol, which can readily induce both long-term potentiation (LTP) and long-term depression (LTD) at in vivo medial perforant path-dentate gyrus synapses. By varying stimulation parameters, we were able to build a stimulus-response map of synaptic plasticity as a LTP-LTD continuum. The response curve displayed a bidirectional shift toward LTP and LTD, depending on the degree and timing of neural activity of the basolateral amygdala. The range of this plastic modulation was also modified by past activity of the basolateral amygdala, suggesting that the amygdala can arrange its ability to regulate the dentate plastic responses. The effects of the BLA activation were replicated by stimulation of the lateral perforant path and, hence, BLA stimulation may recruit the lateral entorhinal cortex. These results represent a high-order dimension of heterosynaptic modulations of hippocampal synaptic plasticity.     

Graded bidirectional synaptic plasticity is composed of switch-like unitary events

Biological information storage events are often rapid transitions between discrete states. In neural systems, the initiation of bidirectional plasticity by all-or-none events may help confer robustness on memory storage. Here, we report that at CA3-CA1 hippocampal synapses, individual potentiation and depression plasticity events are discrete and heterogeneous in nature. Individual synapses began from extreme high and low strength states. Unitary plasticity events were all-or-none and drove synaptic strength between extremes in <1 min. Under na?ve conditions, approximately three-fourths of synapses began in a low-strength state. The timing of these unitary events can account for the time course of macroscopic synaptic plasticity.     

Stressful Life Events and Psychological Well-being in a Brazilian Sample of Older Persons: The Role of Resilience

The study aimed to identify the most frequent stressful life events that older persons experience while identifying the most stressful ones. It also aimed to test the hypothesis that resilience moderates the impact of stressful events on older persons’ well-being. The sample included 111 participants, ranging from 56 to 85 years, living independently in the community. Participants answered a demographic questionnaire, the Elders Life Stress Inventory, the shortened Psychological Well-Being Scales, and the Resilience Scale. Stressful events were analyzed according to their frequency and intensity. A mean of five events were reported by participants regarding their experiences over the last year. The most frequent events were memory deterioration, deterioration in health/behavior of a family member, death of a friend/family member, decrease in recreational activities, and personal injury/illness. The most stressful events were divorce/marital separation, parent institutionalization, and child, spouse or parent death. A main effect of resilience was found, high resilience being associated with higher well-being. A main effect of stressful events was also found, high stress being associated with less well-being. However, the interaction between resilience and stressful events did not yield a significant result. Interpersonal variations regarding psychological well-being in response to stressful life events may reveal that older people manifest different degrees of resilience, which in turn could help to reduce the impact of stress. This is an important aspect for successful aging which requires further research in order to find out factors which may enhance resilience in adversity, to promote positive outcomes through the life span.     

Life events, personality, and physical risk factors in recent-onset duodenal ulcer. A preliminary study.

To clarify the interactions between stressful life events and other risk factors in the development of duodenal ulcer disease, we studied 33 patients with active ulcer, symptomatic for less than or equal to 6 months and untreated during the previous year, using the Paykel Interview for stressful life events, the Minnesota Multiphasic Personality Inventory (MMPI), and Zung's Anxiety and Depression scales. MMPIs were abnormal in 64% of the patients, and 61% showed some degree of depression. The 16 patients whose symptoms had been preceded by severe stress and more pathological MMPIs, especially on paranoia and dependency scales; were more depressed; and had used less nonsteroidal anti-inflammatory drugs than those without (p less than 0.05). They were somewhat more likely to be single, to be of low social class, and to have recently increased use of cigarettes, alcohol, or coffee (though their absolute level of alcohol consumption was low). Anxiety levels did not differ between stress and nonstress groups. Correspondence analysis yielded four clusters of patients, characterized by (a) alcohol/cigarette use, personality disorder, chronicity; (b) early onset, neurosis; (c) depression, life events; (d) late onset, psychosocial stability. The analysis changed little according to whether life events were or were not considered in cluster formation. We conclude that ulcer patients who become ill under stress from a distinct subgroup, that depressed mood and stress-related increases in use of alcohol and cigarettes may mediate between stress and ulcer formation, and that life events are a quantitatively minor factor in ulcerogenesis.     

Inflammatory bowel disease versus irritable bowel syndrome: a hospital‐based,case‐control study of disease impact on quality of life

Background: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are intestinal diseases perceived differently by patients and doctors: the former is considered essentially as an ‘organic’ disease (i.e. an illness in which the role of stress or psychological factors is at best secondary to the disease itself), whereas the latter is acknowledged as a ‘functional’ disorder (i.e. illness thought to be more in the ‘mind’ than in the body of the patient). Accordingly, the respective impact of the two diseases on patients' health‐related quality of life (HRQOL) is perceived to be very different. We aimed to compare the relative impact of the disease on HRQOL, psychological profile and perceived burden of stressful life events in two groups of outpatients suffering from IBS and IBD and attending our outpatient department at an Italian university hospital. Eighty patients with IBD (26 with ulcerative colitis and 54 with Crohn disease) and 85 controls with IBS formed the patient samples of the study. Methods: Three questionnaires were given to the patients while they were attending the outpatient department because of their previously diagnosed disease, namely the SF‐36 (a generic well‐validated tool for measuring HRQOL), the SCL‐90 (for assessing the psychological profile of patients), and the Holmes &; Rahe schedule (for the assessment of stressful life experiences). The results were then compared by means of analysis of variance (ANOVA) and Bonferroni‐adjusted t test, when appropriate. Results: HRQOL appeared to be similarly reduced in both disease groups (SF‐36 overall mean value: 58.2?±?16.1 in IBS patients versus 56.4?±?22.3 in IBD patients; P?>?0.05) in comparison with normative Italian data. Furthermore, the overall severity of psychological symptoms was not statistically different between patients suffering from IBD versus IBS, as shown by SCL‐90 mean scores of 0.89?±?0.45 versus 0.83?±?0.48, respectively (P?>?0.05). On the contrary, the severity of recent stressful life experiences was perceived to be higher by IBS than by IBD patients (mean SRE score: 110.8?±?110.2 versus 61.6?±?78.8; P?Conclusion: Our study supports the notion that, at least in referral centres, patients with IBS show health‐related quality of life, psychological distress and recent occurrence of stressful life events of severity at least comparable with age‐matched IBD patients.     

Stressful life events among community-living older persons

OBJECTIVES: To identify the life events that older persons experience as most stressful, to evaluate older persons' perceptions of the consequences of these stressful events for their lives, and to evaluate the relationship of demographic factors and measures of health and functional status to these perceptions. DESIGN: Cross-sectional study. PARTICIPANTS: Seven hundred fifty-four community-living persons aged 70 years or older. MEASURES: During a comprehensive assessment, participants identified the most stressful event that they had experienced in the past 5 years and, subsequently, rated its stressfulness and perceived consequences. RESULTS: Six hundred three participants (80%) identified a stressful life event. Of these, 18% identified a personal illness, 42% the death of a family member or friend, 23% the illness of a family member or friend, and 17% a nonmedical event. Although participants consistently rated their events as highly stressful, they reported widely varied consequences of these events for their lives. While 27% to 59% of participants across the 4 event types reported considerable negative consequences, 17% to 36% reported positive consequences such as starting new activities that have become important to them and changing for the better how they feel about their lives. Dependence in instrumental activities of daily living and depressive symptoms were independently associated with several negative perceived consequences. CONCLUSIONS: Older persons experience a wide array of stressful life events, with only a small minority reporting personal illnesses as the most stressful. Similar stressful events can have either negative or positive consequences for older persons' lives. This variation in response to stressful events among older persons may indicate different degrees of resilience, a potentially important factor underlying successful aging that deserves further investigation.