Eduardo Fano

Effects of chronic mild stress (CMS) and imipramine administration, on spleen mononuclear cell proliferative response, serum corticosterone level and brain norepinephrine content in male mice

There is increasing evidence that stress and emotional reactions produce changes in various immune processes. These changes may be due to alterations of the stress responses endocrine and for autonomic mediating mechanisms. In order to study such effects, the impact of chronic mild stress (CMS) application, and of subsequent imipramine administration were studied on the spleen mononuclear cell proliferative response period. OFI strain male mice were subjected to 4 or 7 weeks of CMS. The effects of these treatments on serum corticosterone levels and hypothalamic and hippocampal norepinephrine (NE) contents were also assessed. Subjects submitted to CMS had a higher spleen mononuclear cell proliferative response after either treatment duration. Imipramine treatment diminished this response enhancement in CMS exposed animals, but did not alter the proliferative responses of control subjects. Serum corticosterone levels, as well as hypothalamic and hippocampal nonrepinephrine contents did not significantly vary between groups. Taken together, these results suggest that CMSs effects on immune reactivity are not related to serum glucocorticoids or NE changes in these locations associated with the hypothalamic-pituitary- adrenocortical (HPA) axis.

Social stress paradigms in male mice: Variations in behavior, stress and immunology

Male OF1 strain mice were allocated, after 2 weeks of individual housing, to cohabitating (6 or 16 days), fixed dyadic interaction pairs (6 or 16 daily encounters) or control groups (6 or 16 days). These different social stress situations were assessed for their effects on splenic contents of NE, IL-1 and IL-2 and serum levels of corticosterone. Spleen NE contents showed no significant variations, but serum corticosterone titers were generally higher in interacting pairs and subordinates. Splenic IL-2 did not respond in the same way to the treatments as IL-1. The differences in splenic interleukin contents could not be simply related to observed changes in serum corticosterone levels. Different mechanisms appear to regulate changes in glucocorticoids and the measured cytokines. These physiological phenomena do not simply reflect in the animals social status (dominant or submissive). The intensity and duration of the agonistic behavior displayed as well as the interaction experience accumulated may account for the observed differences between the paradigms.

Endocrine and lymphoproliferative response changes produced by social stress in mice

Daily dyadic resident-intruder encounters and uninterrupted cohabitation in pairs were used to assess the impact of different durations (5 and 15 days) of dominance and subordination experiences on splenic lymphoproliferative responses in male OF1 strain mice. HPA axis activity was assessed by measuring serum corticosterone levels, whereas splenic norepinephrine (NE) content provided a sympathetic activity index. Corticosterone levels in subordinate subjects were generally higher than in their control or dominant counterparts in both treatment paradigms. Corticosterone levels in dominant subjects were lower than in their control counterparts in both. Increasing the duration of treatments generally decreased such titers, especially so in subordinate subjects. No differences were detected in splenic NE content. Animals subjected to social interaction generally showed greater proliferation than their control counterparts. This effect was more pronounced in subordinates than dominants and after longer- rather than short-duration treatments. There was no inverse relation between proliferative responses and the subjects corticosterone levels. While corticosterone may have a general immunomodulating effect, other mediators apparently account for the effects produced by these social stress paradigms on splenic proliferative response.

Social behavior, cortisol, and sIgA levels in preschool children

OBJECTIVE This study aims to explore the possible existence of behavioral states in early stages of development, which are associated with specific cortisol production profiles and consequently with changes in the immune response [secreted immunoglobulin A (sIgA)]. METHODS The subjects were 27 boys and 21 girls of preschool age whose behavior was videotaped in free play interactions. Their behavior was then evaluated using an ethogram of the social behavior of the child. Cortisol levels were measured using a radioimmunoassay in saliva samples, and sIgA levels were measured by means of an ELISA, also in saliva samples. RESULTS No correlation between cortisol and sIgA levels was found. Variance analysis revealed that the only behavioral pattern, which showed significant differences with regard to cortisol levels, was isolation. CONCLUSIONS There seems to be a connection between cortisol levels and isolation behavior; we found no relation between high cortisol levels and a lower sIgA secretion.

Relations between aggressive behavior, immune activity, and disease susceptibility

Psychoneuroimmunology has sought to analyze the effects of stress on the immune function and the way in which emotional states and other psychological processes influence the immune response. Agonistic interactions may be considered a special form of psychological stress: social stress, thereby constituting a natural stress model that may be useful for studying the effects of this phenomenon on the immune system. The majority of studies in this area were carried out with mammals, mainly rodents. In general, results have shown a reduction in diverse humoral response measurements in submissive subjects and indicated that stress produced by agonistic interaction also results in the decrease of diverse cellular immune parameters, although this inhibitory effect is not global. In short, despite the diversity of paradigms used and the existence of some contradictory results, it may be concluded that low social ranking, submissive social status, or subjection to threat or attack behavior is linked to a state of immunodepression. As regards the influence of this type of social stress on disease susceptibility, some studies indicate that submissive subjects have a lower resistance to tumoral development and viral infections, although not all studies have obtained consistent results in this area.

Exposure to fine particle matter, nitrogen dioxide and benzene during pregnancy and cognitive and psychomotor developments in children at 15 months of age.

BACKGROUND Prenatal exposure to air pollutants has recently been identified as a potential risk factor for neuropsychological impairment. OBJECTIVES To assess whether prenatal exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and benzene were associated with impaired development in infants during their second year of life. METHODS Regression analyses, based on 438 mother-child pairs, were performed to estimate the association between mother exposure to air pollutants during pregnancy and neurodevelopment of the child. The average exposure to PM2.5, NO2 and benzene over the whole pregnancy was calculated for each woman. During the second year of life, infant neuropsychological development was assessed using the Bayley Scales of Infant Development. Regression analyses were performed to estimate the association between exposure and outcomes, accounting for potential confounders. RESULTS We estimated that a 1 μg/m(3) increase during pregnancy in the average levels of PM2.5 was associated with a -1.14 point decrease in motor score (90% CI: -1.75; -0.53) and that a 1 μg/m(3) increase of NO2 exposure was associated with a -0.29 point decrease in mental score (90% CI: -0.47; -0.11). Benzene did not show any significant association with development. Considering women living closer (≤ 100 m) to metal processing activities, we found that motor scores decreased by -3.20 (90% CI: -5.18; -1.21) for PM2.5 and -0.51 (-0.89; -0.13) for NO2, while mental score decreased by -2.71 (90% CI: -4.69; -0.74) for PM2.5, and -0.41 (9% CI: -0.76; -0.06) for NO2. CONCLUSIONS Our findings suggest that prenatal residential exposure to PM2.5 and NO2 adversely affects infant motor and cognitive developments. This negative effect could be higher in the proximity of metal processing plants.

Family context assessment in a public health study

OBJECTIVES To analyze the factorial structure of a new instrument to assess the quality of the family context (Etxadi-Gangoiti Scale) in a sample from the Gipuzkoa cohort of the Environment and Childhood (Infancia y Medio Ambiente [INMA]) study. METHODS Families in a sample of 433 two-year-old children were assessed in a home visit with subsequent analysis of the factorial structure and psychometric properties of the data. RESULTS An exploratory factorial analysis (principal axis factoring and varimax rotation) and a confirmatory factorial analysis were carried out; partial confirmation of the original factorial structure of the instrument was obtained, which revealed the following factorial structures. Subscale (1): promotion of cognitive and linguistic development, social skills, psychomotor skills, and pretend play and imitation; subscale (2): promotion of independence and self-esteem, provision of optimal frustration, social and emotional quality of the relationship, and absence of physical punishment; subscale (3): paternal involvement, low exposure to family conflict, low frequency of family conflict, relationship with the extended family, social support, diversity of experiences, low frequency of stressful events, and low parental perception of stress. DISCUSSION The structure of the original instrument structure was partially confirmed, which was attributed to the characteristics of the sample. We stress the importance of the variability obtained in the evaluation of the families, as well as of adequate indicators of reliability in such evaluation. The new instrument could be used in public health to identify deficient family contexts and to design preventive interventions focused on parenting skills.

Association between Child Cortisol Levels in Saliva and Neuropsychological Development during the Second Year of Life

Exposure to highly elevated levels of cortisol has been linked with impairments in cognitive capacities in both children and adults. By contrast, moderate levels of cortisol may engender beneficial effects. The main aim of this study was to assess the association between child cortisol levels and neuropsychological development during the second year of life. A population-based birth cohort was established in the city of Sabadell (Catalonia, Spain) as part of the INMA (Environment and Childhood) Project. We assessed the cognitive and psychomotor development at the age of 14 months using the Bayley Scales of Infant Development (BSID). We included 302 children assessed during their second year of life for whom we had information on neuropsychological assessment and measurements of cortisol in saliva. Higher levels of cortisol were associated with better scores in BSIDs mental scale. There was no association between cortisol levels and psychomotor test scores. We found a small positive association between duration of breastfeeding and child cortisol levels. This association was only found in boys. The results of this study suggest that moderate levels of cortisol in children could have small beneficial effects on their early neuropsychological development.

The INMA—INfancia y Medio Ambiente—(Environment and Childhood) project: More than 10 years contributing to environmental and neuropsychological research

BACKGROUND In 2003 the INMA-INfancia y Medio Ambiente (Environment and Childhood) project, a Spanish national network of birth cohorts including more than 3500 participants, was set up with the aim to assess the health impacts of pre- and postnatal environmental exposures on children. The project has published more than 60 papers on maternal and environmental factors related to neuropsychological development in children, one of the main research interests within the project. With the present review, we evaluate the evidence provided by the INMA project on this topic and discuss how the data can contribute to cover the challenges that childrens environmental health research will face in the coming years. RESULTS The INMA project has contributed to provide increasing evidence of the association between prenatal exposure to persistent organic pollutants (POPs) and child neuropsychological development, but it has also shown, using innovative methodologies, that postnatal exposure to these compounds does not play a role in this association. The project has also contributed to show the detrimental influence of certain air pollutants on child neuropsychological development, as well as how a balanced maternal fish intake can protect from the potential adverse effects of prenatal exposure to mercury. Also, the project has contributed to the understanding of impacts of nutritional factors including supplement intake and vitamin D levels during pregnancy and the role of breastfeeding on the neuropsychological benefits. CONCLUSIONS INMA findings underscore the importance of continued research on the delineation of the sensitive windows of exposure both during pregnancy and postnatally and on the combined effects of environmental exposures, denoted the exposome. In terms of health policy, INMA findings have important implications for the development of public health policies to advance the health and development of children.

Testosterone and aggression in male and female preschool children

Testosterone titers in adults and adolescents are positively correlated with chronic aggressive behavior1,2. Current data (e.g. Miczek et al.3) supports a bi-directional model with androgens both influencing and being influenced by aggressive behavior. Brain4 also maintains that it is unlikely that androgens have a simple causal effect on human aggression and violence. Patterns of sex steroid secretion appear to alter several features (e.g. ‘aggressive feelings’, self-image and social signaling), predisposing individuals to carry out actions that can be labeled ‘aggression’. The links between endocrine secretion and human violence are clearly very complex5,6.