Stress Reactivity Systems Research Articles

Mediterranean diet, stress resilience, and aging in nonhuman primates

Persistent psychological stress increases the risk of many chronic diseases of aging. Little progress has been made to effectively reduce stress responses or mitigate stress effects suggesting a need for better understanding of factors that influence stress responses. Limited evidence suggests that diet may be a factor in modifying the effects of stress. However, long-term studies of diet effects on stress reactive systems are not available, and controlled randomized clinical trials are difficult and costly. Here we report the outcomes of a controlled, randomized preclinical trial of the effects of long-term consumption (31 months, ~ equivalent to 9 human years) of Western versus Mediterranean - like diets on behavioral and physiological responses to acute (brief social separation) and chronic (social subordination) psychosocial stress in 38 adult, socially-housed, female cynomolgus macaques. Compared to animals fed a Western diet, those fed the Mediterranean diet exhibited enhanced stress resilience as indicated by lower sympathetic activity, brisker and more overt heart rate responses to acute stress, more rapid recovery, and lower cortisol responses to acute psychological stress and adrenocorticotropin (ACTH) challenge. Furthermore, age-related increases in sympathetic activity and cortisol responses to stress were delayed by the Mediterranean diet. Population level diet modification in humans has been shown to be feasible. Our findings suggest that population-wide adoption of a Mediterranean-like diet pattern may provide a cost-effective intervention on psychological stress and promote healthy aging with the potential for widespread efficacy.

Genome-wide association studies in suicidology — analysis of main results

Studies of suicide genetics can be divided into 3 periods: 1) period of classical methods of behavioral genetics; 2) candidate genes association studies, and 3) genome-wide association studies. The majority of studies using candidate genes strategy has been dedicated to main neurotransmitter systems (serotonine, catecholamines, GABA, excitatory aminoacids system, etc.) and in the last decade — to genes of the stress-reactivity system and neurotrophins. On the other hand among main GWAS findings are genes that are involved in neurodevelopment, neuroplasticity, cell adhesion and migration, proliferation and intracellular signaling, as well as immune system functions. We consider it a confirmation of the relevance of the stressvulnerability models that imply key role of the early development and involvement of the neuroplasticity, as well as models that focus on stress as a systemic reaction of the organism in pathogenesis of suicidal behavior. It should be noted that findings of different GWAS studies most often do not coincide and in general produce rather heterogeneous picture. It may be due to differing bioinformatics approaches, phenotypes description differences and study design peculiarities. We consider that more research is needed in all three directions with involvement of NGS approaches, in particular whole-exome sequencing.

Involuntary Engagement Stress Responses and Family Dynamics: Time-Lagged Models of Negative Mood

Low-income Latino youth display disproportionate rates of mood problems compared with peers in other ethnic groups. Dysregulation of the stress reactivity system, reflected by involuntary engagement stress responses (IESRs), contributes to mood problems. However, two important family constructs—parent-child conflict and familism—may moderate the association between IESRs and negative mood. Parent-child conflict might exacerbate the link between IESRs and negative mood. Fortunately, low-income Latino youth may benefit from the cultural value of familism. Familism might weaken the tie between IESRs and negative mood and the tie between parent-child conflict and negative mood. The present study used a daily diary methodology and time-lagged models to examine these processes among low-income Latino adolescents. Hierarchical linear modeling (HLM) was used to test the moderating effects of parent-child conflict and familism on the association between daily IESRs and negative mood. In addition, the moderating effect of familism was tested on the association between parent-child conflict and negative mood. Findings indicated that parent-child conflict exacerbated the relation between IESRs and negative mood on the same day, but not on the following day. Familism weakened the relation between IESRs and negative mood on the same day, but not on the following day. Familism fully buffered the link between parent-child conflict and negative moods, on the same day and on the following day. Thus, for low-income Latino youth, involuntary stress responses may have a significant impact on mood problems, though family-level factors are also important.

Examination stress at unified state examination: student destabilization or success factor?

The aim of the research is to clear up the influence of examination stress on the results of completing examination papers by students in the situation of trial General and Unified State Examinations, imitating the real-life environment of unified state certification of schoolchildren. The tasks of the research included determining the dynamics of psychophysiological stress indices at different examination stages, and evaluating additional factors (the subject in which the examination is held, the strategy of solving the variant, success of solving the task etc.), influencing the quantity and quality of stress reactions at the examination. The novelty of the research is in the attempt to overcome the problem of confusing the notions of examination stress and examination anxiety, caused by metering the students’ state either before or after the examination. The technology of online monitoring the students’ psychophysiological state is used in the work, which makes it possible to eliminate a number of restrictions occurring during subjective evaluation of the state by the students themselves. Telemetric cardiorhythmography was chosen as the basic method. The method is based on a three-component model of extreme states with consequent domination of one of the three stress-reactive systems. A cardiointervalogramm was being registered in the research process in the online mode and underwent spectral analysis. The following indices of heart rate variability were recorded in order to determine stress reactions: the total power of the spectrum (TP), the spectrum power in low-frequency (LF) and high-frequency (HF) regions, and a vegetative balance index (relation of the spectrum powers in low-frequency and high-frequency regions (LF/HF)). When the total power of the heart rate fell and, at the same time, the vegetative balance index rose, a conclusion was made of there being a stress reaction. Twenty-five students of an illustrious school were examined. Stress reactions were already recorded when the students read the instructions, and their number increased in the process of the examination, reaching the maximum by the end of completing the work. The analysis of subjective evaluation of the state by the students themselves reveals that they often evaluate it inadequately. Significant statistical differences were found between the levels of stress at examinations in different subjects. The highest stress level was recorded at the examination in Russian. It was revealed, that the students who chose a free strategy of completing the tasks and followed it, had fewer stress reactions than those who completed the tasks one by one. The differences in the stress levels were registered between students who got different grades: the students who were graded “good”, had the most stress reactions, those who were graded “satisfactory”, had the fewest stress reactions. The results of the study show that the General and Unified State Examinations are highly stressful events: in average, the students were under stress about one third of the time of completing the exam tasks. The given events have a significant impact on school leavers’ psychophysiological state. Additional factors were determined that cause stress reactions at the examination.

Effects of Activation of κ-Opioid Receptors on Behavior during Postnatal Formation of the Stress Reactivity Systems

Stress at any age, including at the early stages of postnatal development, leads to changes in the state and reactivity of the stress-related humoral systems, particularly the hypothalamo-hypophyseal-adrenal system (HHAS) and the dynorphin- κ-opioid system (DKOS). These changes are suggested to underlie a number of diseases. Stress-induced changes in the HHAS have been well studied. However, the role of the DKOS is unclear. Further studies of this system require generalization of existing published data on the physiological mechanisms and ethological characteristics of DKOS activation seen at different stages of the body’s development. The generalization provided here leads to the conclusion that the mode of the animal’s response to stimulation of the DKOS during early ontogeny differs from that in adults and changes depending on the stage of development of the stress reactivity system, at any particular period depending on whether the stress system had previously been activated.

Differential associations between infant affective and cortisol responses during the Still Face paradigm among infants born very low birth weight versus full-term

Psychological stress responses may have both emotional and cortisol reactivity correlates, but there are limited data addressing the association between generalized negative and positive emotional states and cortisol reactivity to a psychological stressor among infants born very low birth weight (VLBW; <1250g) compared to infants born full-term. Examining this relationship between behavioral (affect) and physiological (cortisol) responses may provide insight into the nature of regulation difficulties identified in infants born VLBW. The purpose of this study was to assess the association between infant affective and cortisol responses to the Still Face paradigm (SF) in a cohort of six- to eight-month old infants born VLBW compared with infants born full-term (N=53 total; N=29 and N=24, respectively). Infant affect was coded in 1-s intervals while mother–infant dyads participated in the SF paradigm, and percent positive affect and percent negative affect were calculated separately for each SF episode. We had hypothesized that because infants born VLBW are at increased risk for dysregulation, they would show, compared to full-term controls, greater dysregulation in the form of less synchrony (i.e., less correlated affective and cortisol responses) across the two SF stressors (episodes 2 and 4). This hypothesis was largely supported: the associations between affective and cortisol responses were different for the two groups across the two stressors for percent positive affect (both stressor episodes 2 and 4) and percent negative affect (episode 4 only). For the full-term group, follow up correlations revealed significant negative associations between percent positive affective and cortisol responses for both stressors. Mothers’ responsiveness did not explain the term group association differences between infant affective and cortisol responses across stressors. The (lack of) association of stress reactivity systems may index dysregulation or dysregulation correlates in preterm children. Understanding how this lack of coordination among stress systems relates to greater dysregulation, learning, and attentional difficulties may be important in recognizing early precursors to such problems in preterm children, and in this way, aid in early intervention efforts. Future research is warranted to determine how these findings relate to infants’ stress reactions in naturalistic settings, and the directionality and temporal relationship between cortisol and infant affective stress responses.

Effortful control and parenting: Associations with HPA axis reactivity in early childhood

While activation of the hypothalamic-pituitary-adrenal (HPA) axis is an adaptive response to stress, excessive HPA axis reactivity may be an important marker of childhood vulnerability to psychopathology. Parenting, including parent affect during parent-child interactions, may play an important role in shaping the developing HPA system; however, the association of parent affect may be moderated by child factors, especially children's emerging self-regulatory skills. We therefore tested the relationship between parent affectivity and 160 preschoolers' cortisol reactivity during a laboratory visit, examining children's effortful control (EC) as a moderator. Greater parent negative affectivity was related to greater initial and increasing cortisol over time, but only when children were low in EC. Higher parent positive affectivity was related to a higher baseline cortisol for children with low EC and lower baseline cortisol for children with high EC. Results indicate that children's EC moderates the extent to which parent affect shapes stress reactive systems in early childhood.

Early-life stress and recurrent psychological distress over the lifecourse predict divergent cortisol reactivity patterns in adulthood

Early-life stress (ELS) is associated with substantially increased lifetime risk for recurrent psychological problems, with evidence indicating that dysregulation of the physiological stress reactivity system may be partly responsible. However, some ELS-exposed people remain psychologically resilient. Although two distinct patterns of hypothalamic-pituitary-adrenal axis (HPA) stress reactivity have been observed in ELS-exposed samples (hyper- and hypo-reactive), the hypothesis that these patterns may be associated with long-term history of psychological problems has not been explored. We used healthy Whitehall II study subjects (n=543) who participated in the 2008 Heart Scan Study (HSS) to assess salivary cortisol responses to a cognitive stressor, ELS exposure, and other psychosocial factors. Mean age of the sample at the HSS was 63 years. HSS data were linked to nearly 20 years of participants' Whitehall data, including repeated measures of psychological distress (GHQ-28). Piecewise growth curve analyses revealed that ELS-exposed persons with a history of recurrent psychological distress in adulthood had significantly blunted cortisol reactivity compared to non-ELS-exposed participants, while ELS-exposed persons with little or no history of distress had significantly elevated baseline cortisol, prolonged responses, and greater total cortisol production. Our findings indicate that for ELS-exposed individuals, different trajectories in psychological health over their adult lifetimes predict different cortisol reactivity patterns. These findings have important implications for our understanding of ELS-related mental health risk and treatment of these disorders.

The maternal-neonatal neuro-immune interface: are there long-term implications for inflammatory or stress-related disease?

Inflammatory stimuli reliably elicit hypothalamic-pituitary-adrenal (HPA) activation, and it is now established that the immune and HPA systems are mutually regulatory and that their interactions partly determine stress effects on immune function. What has not been extensively investigated, however, is the interactive nature of the development of the endocrine and immune systems and whether this might alter predisposition to inflammatory disease or stress-related pathologies. Increasing attention is now being focused on the role of early life environments determining long-term predisposition to disease, and a role for the HPA axis in disease predisposition is emerging. Stress generally refers to the condition where coping with actual or perceived stimuli alters the homeostatic state of the organism. The classic stress response involves the activation of central and peripheral catecholamine systems and HPA responses. Increased glucocorticoid levels are thought to protect the organism, both by providing energy substrates to deal with immediate environmental demands and by blocking potentially harmful overreaction by the immune system and other stress-reactive systems (1). However, to avoid immunosuppression and degenerative pathologies associated with increased glucocorticoid levels, the HPA stress response must terminate efficiently once the environmental demands are removed (2). Consequently, disturbances in endocrine-immune interactions upset the normal regulatory homeostatic balance and alter susceptibility to a variety of disease states associated with immune dysregulation (3). The physiological impact of stress is variable across individuals, and susceptibility to stress apparently depends on attributes of the organism, such as genetic endowment and age, and experiential factors, such as previous stress experiences, and early life events (4, 5). Indeed, the endocrine and immune systems and the CNS all respond to environmental pressures during development, and the interactive nature of these systems suggests that alterations in one system could have developmental consequences for the others and potential long-term implications for disease vulnerability. Plasticity in most developing physiological systems is thought to be of adaptive importance, enabling an organism to better meet the demands of the environment in which it matures and will most likely reside. However, the short-term reorganization or re-setting of regulatory systems to deal with immediate demands may also have long-term consequences for normal physiological function, thereby predisposing an organism to pathology. This may particularly be the case when the environmental pressures differ between development and adulthood. A number of epidemiological studies have indicated that nutritional factors early in life have long-term implications for cardiovascular and metabolic disease in adulthood. Most data suggest that maternal nutrition and limited intrauterine growth are responsible for reorganizing metabolic regulation and results in metabolic and cardiovascular pathologies in adult life (6). The concept of “perinatal programming” is not new and has long been investigated in neuroendocrine development of both the adrenal and the gonadal axes (see review, ref. 7). Immune responses, too, are influenced by early life experiences, and it has been suggested that pathogen exposure during development is important for the developing immune repertoire and that too little activation may be associated with the development of allergy (8). Available data also indicate that there are long-term consequences following endocrine-immune interactions during the first week of life. Thus, the administration of steroids during antigen exposure alters the development of immune tolerance (9), and immune challenge during the first week of life is associated with altered endocrine development (10, 11). These data demonstrate the interactive nature of both the immune and the neuroendocrine systems during development and show that these interactions can alter both immune and endocrine function in the long term. Maternal factors represent some of the most salient environmental influences altering endocrine development (12–14). Indeed, there is an extensive literature detailing both prenatal and postnatal influences on the development of the HPA axis. It is also well established that immune factors passed in utero and also to the neonate via milk have a direct impact on the its immunocompetence (15, 16). However, evidence examining the neuro-immune interface and maternal factors is limited.