Possible associations between prenatal exposure to environmental pollutants and neurodevelopmental outcome in children.

This study aimed to evaluate associations between prenatal and childhood exposure to phthalates and prenatal exposure to polychlorinated biphenyls (PCBs) and the development of 4-year-old children. Urinary metabolites of five phthalates were measured in women upon delivery, as well as serum concentrations of four PCB congeners. Postnatal phthalate metabolites were measured from children's urine obtained at the time of developmental assessment. The primary outcome was cognitive function as evaluated by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) administered at 4 years. Secondary outcomes were motor function and response to sensory stimuli as evaluated by the Developmental Coordination Disorder Questionnaire (DCDQ) and Short Sensory Profile (SSP) that the mothers filled out, respectively. The study included 57 mother-child pairs. Higher maternal phthalate metabolite concentrations were inversely associated with WPPSI-III scores among boys and not among girls. After using linear regression models and controlling for confounding variables, we found that higher levels of monobenzyl phthalate (MBzP) were the ones associated with lower WPPSI-III scores (p=0.004, 95%CI [-14.18; -3.16]), lower DCDQ scores (p=0.007, 95%CI [-6.08; -1.17] and lower SSP scores (p=0.004, 95%CI [-7.47; -1.79]). No association was found between child urinary phthalate metabolite concentrations or maternal PCB blood concentrations and developmental function. These findings indicate that higher prenatal phthalate metabolite levels may be associated with deficits in neurologic development of young boys.

Psychological Distress in Women with Fibromyalgia: The Roles of Body Appreciation, Self-Compassion, and Self-Criticism.

BACKGROUND: While past research detected a direct link between symptoms of fibromyalgia (FM) and psychological distress, body appreciation was suggested as a viable mediator of this link. The aim of the present study was to further develop an explanatory model for the effect of FM on women's psychological distress and identify possible protective and risk factors. Specifically, it was hypothesized that self-compassion would moderate the indirect effect of body appreciation and self-criticism on psychological distress in women with FM. METHOD: This study comprised a total of 293 women, aged 20-68 (M = 34.8, SD = 12.3), of whom 146 were women with FM and 147 were heathy controls. All the women completed questionnaires regarding demographic characteristics, depression (PHQ-9), anxiety (GAD-7), self-criticism (DEQ-SC), body appreciation (BAS2), and the self-compassion scale (SCS). RESULTS: A moderated serial mediation model demonstrated lower body appreciation in participants with FM compared to controls. These lower levels of body appreciation, together with lower levels of self-compassion, were associated with greater self-criticism and, consequently, higher levels of psychological distress. CONCLUSIONS: The results emphasize the role of self-compassion as a protective mechanism against psychological distress among women with FM. Future studies should further investigate the effect of self-compassion-focused interventions on patients with FM.

Psychological distress in individuals with irritable bowel syndrome: the roles of body image and self-criticism.

Objective: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder associated with reduced quality of life and psychological distress (PD) including anxiety and depression. The mechanisms linking IBS to PD are unclear. Previous studies showed that body image and self-criticism may be contributory factors. Thus, the objective of this study was to test the potential mediating roles of these factors in the relationship between IBS and PD. Method: 507 adults participated, including 142 with IBS (Mean age = 31.9, SD = 11.7), and 365 healthy peers (Mean age = 26.2, SD = 6.4), ranging in age from 18 to 75. The majority of participants were women (78%). Self-report measures assessed IBS status, body appreciation, body dissatisfaction, self-criticism, sociodemographic status, depression, and anxiety. Path analysis tested the hypothesized mediation model. Results: IBS participants reported greater PD, lower body appreciation, higher body dissatisfaction, and higher self-criticism than controls. Body appreciation and self-criticism sequentially mediated the link between IBS status and both depression and anxiety. IBS was associated with reduced body appreciation, which in turn was linked to heightened self-criticism, thereby leading to elevated psychological distress. Conclusion: Results suggest IBS negatively impacts body image appreciation, fostering self-critical judgments that exacerbate psychological symptoms. This study is the first to demonstrate a significant association between body appreciation and IBS, specifically highlighting this relationship. Findings clarify the psychosocial pathways at play in the comorbidity of mental health issues in IBS. Physicians and other health professionals are advised to detect women with IBS who are distressed, and to offer them appropriate intervention to prevent downstream consequences.

Body appreciation as a protective factor in women with fibromyalgia: an examination of associations between pain perception, social comparison and psychological distress.

OBJECTIVES: While symptoms of fibromyalgia (FM) and psychological distress are directly linked, indirect effects are also apparent. The aim of the present study was to develop an explanatory model for the effect of FM on women's psychological distress and identify possible protective and risk factors. METHODS: This study comprised of total of 293 women aged 20-68 (M= 34.3, SD = 12.1), of which 141 were women with FM and 152 healthy peers (HP), who completed questionnaires regarding demographic characteristics, anxiety (GAD-7), depression (PHQ-9), body appreciation (BAS-2), social comparison strategies, and pain assessment (SF-MPQ). RESULTS: FM patients demonstrated higher psychological distress, i.e., depression and anxiety and lower body appreciation. Body appreciation significantly correlated with social comparison coping strategies. Body appreciation and social comparison strategies mediated the link between FM and psychological distress. Among FM patients, body appreciation moderated the links between pain intensity and aspects of social comparison strategies, thus explaining the link between pain intensity and psychological distress. CONCLUSIONS: Women with FM demonstrated higher levels of anxiety and depression symptoms and lower body appreciation compared to HP. The unique role of body appreciation in moderating the indirect link between pain and psychological distress appears to be protective.

Predictors of Psychological Distress in Women with Endometriosis: The Role of Multimorbidity, Body Image, and Self-Criticism.

While large numbers of women report high levels of psychological distress associated with endometriosis, others report levels of distress that are comparable to those of healthy women. Thus, the aim of the current study was to develop an explanatory model for the effect of endometriosis on women's psychological distress. Furthermore, it sought to further investigate the role of body image, self-criticism, and pain intensity on the psychological distress associated with endometriosis and establish the effect of chronic illness load on the development of this distress. This study comprised a total of 247 women aged 20-49 (M = 31.3, SD = 6.4)-73 suffering from endometriosis only, 62 suffering from endometriosis and an additional chronical illness (ACI), and 112 healthy peers (HP)-who completed the Patient Health Questionnaire, the Generalized Anxiety Disorder-Item Scale, the Body Appreciation Scale-2, and the Self-Criticism Sub-Scale. When comparing each endometriosis group to their HP's, we found that the differences between HP and endometriosis ACI in depression and anxiety were mediated by body image (Betas = 0.17 and 0.09, respectively, p's < 0.05) and self-criticism (Betas = 0.23 and 0.26, respectively, p's < 0.05). When comparing endometriosis participants to endometriosis ACI participants, differences in depression were mediated by body image, self-criticism, and pain intensity (Betas = 0.12, 0.13, 0.13 respectively, p's < 0.05), and the differences in anxiety were mediated by self-criticism and pain intensity (Betas = 0.19, 0.08, respectively, p's < 0.05). Physicians and other health professionals are advised to detect women with endometriosis ACI who are distressed, and to offer them appropriate intervention.

Health-related quality of life after injury: examining the roles of perceived daily-life stress and injury perceptions.

PURPOSE: The present study aimed to examine the effects of injury perceptions and perceived daily stress on health-related quality of life (HRQL) of individuals affected by a physical injury. METHODS: Two hundred and forty injured individuals completed questionnaires assessing HRQL (Medical Outcome Health Survey short-form 36), perceived daily-life stress (Perceived Stress Scale), and injury perceptions (Brief-InjPQ). RESULTS: The direct effects of stress on HRQL scores were not moderated by gender. Emotional representation of the injury significantly mediated the links between PSS and all HRQL subscales only among women, but not among men. However, the mediation of the HRQL total score by emotional representations was significant for both genders. In addition, treatment control perceptions of the injury mediated the link between PSS and self-assessed health among men but not women, and injury-self perceptions mediated the link between PSS and physical functioning among men but not women. CONCLUSION: These findings underscore the importance of perceived daily stress, gender, and injury perceptions as key factors for explaining variance in HRQL following injury. In addition to their conceptual contributions, the findings have clinical implications for treating injured populations.

Physical injury, stress, and health: Protective role of dispositional optimism.

Physical injuries are common occurrences that can have substantial implications for personal, emotional, and social functioning. A recent study reported higher prevalence of common illnesses and reduced health-related quality of life (HRQL) in injury victims. Based on these findings, the present study examined the role of the antibody immunoglobulin A (IgA) and the stress hormone cortisol in the association between injury and health. Additionally, the role of daily life stress and dispositional optimism in this association was examined. Thirty-seven victims of injury (e.g., fractures and burns) and 41 noninjured participants were assessed for cortisol and IgA levels and completed a battery of questionnaires assessing illness prevalence, HRQL, perceived stress, and optimism. Injured participants reported higher prevalence of illness and poorer HRQL compared with noninjured participants; however, changes in cortisol or IgA levels did not explain this increase in illness. Correlations between perceived stress and HRQL were stronger in injured participants compared with noninjured controls, indicating that injured individuals are more affected by stress. Dispositional optimism was lower in injured participants, and optimism buffered the negative effect of stress on HRQL. Accordingly, it is suggested that optimism played a protective role against the negative consequences of stress in injured individuals, thus improving HRQL.

The role of centrality to self-concept in moderating the associations between injury perceptions and outcomes.

OBJECTIVES: To test the centrality of injury to self-concept as a moderator of the associations between injury perceptions and outcomes. METHODS: Two concurrent studies on samples of injured individuals. MEASURES: The centrality of injury to one's self concept was measured by the degree of self-injury separation (PRISM); injury perceptions were measured by the injury perception questionnaire; and outcomes by standard scales of self-assessed health, physical, emotional and social functioning, vitality, depression, anxiety and somatisation. Regression analyses examined the significance of adding the interactions between injury centrality and injury perceptions to explained outcome variance, beyond their separate contributions. RESULTS: Both injury centrality and injury perceptions significantly explained variance in patients' functioning and well-being. Injury centrality moderated the associations between various injury perceptions and outcomes, especially pronounced for emotional representations of the injury. As hypothesised, the effects of injury perceptions on outcomes were stronger among patients for whom the injury was central to their self-concept compared to patients who perceived the injury as peripheral to their self-concept. CONCLUSIONS: 'Centrality to the self' is a moderator of the impact of perceptions on outcomes of injuries. The findings suggest ways to tailor interventions to sub-groups of injured patients based on injury centrality to their self-concept.

Physical injury, health, and well-being: Role of stress perception.

OBJECTIVE: Physical injuries are common occurrences that can have substantial implications for mental health and well-being. Ample studies indicated that increased levels of perceived stress is associated with increased prevalence of general health problems, as well as reduced health-related quality of life. Thus, the goal of the present study was to examine the long-lasting association between bodily injuries and general health. In addition, the role of stress perception in moderating the association between injury and general health was assessed. METHODS: Two-hundred and forty victims of past injury and 251 non-injured participants completed a self-report health inventory questionnaire assessing illness prevalence during the six-month period prior to the study. In addition, they completed the short-form Medical Outcomes Survey (MOS SF-36) questionnaire and the Perceived Stress Scale. RESULTS: Victims of past injuries reported higher incidences of illness, mainly upper respiratory infections and fever, compared to non-injured participants. In addition, injured participants reported poorer perceived health status, including reduced general health, physical functioning, and health beliefs. Perceived stress levels were similar in injured and non-injured participants, however, correlations between perceived stress and self-reported medical outcomes were stronger in injured participants compared to non-injured controls. CONCLUSIONS: Past physical injuries are associated with increased incidence of general health concerns and poorer health-related well-being. Moreover, injured individuals do not report increased stress perception; however, when stressed, injured individuals are more affected and health-related quality of life is reduced. Promoting well-being in individuals who have suffered a significant injury is, thus, a clinical necessity and a pressing social priority. This study highlights the role of stress perception in the association between physical injury and health, and may assist in providing better multi-disciplinary care for the injured.

Development of the Injury Perceptions Questionnaire (InjPQ).

OBJECTIVES: Injuries are major causes of morbidity and mortality in the population. Given the central role of perceptions in self-regulation of health conditions, it is important to investigate how they are perceived. This article describes the development of the Injury Perceptions Questionnaire (InjPQ). METHODS: A concurrent study in a diverse sample of injured individuals (n = 333). The internal structure and the reliability (Cronbach's α) of InjPQ sub-scales were explored by factor analyses. Relationships between injury perception dimensions and equivalent illness perception scales and outcome measures (self-assessed health; physical, emotional and social functioning; depression, anxiety and somatisation; satisfaction with life) were investigated. RESULTS: The InjPQ was found to represent the following perception scales: injury identity composed of social and body part components, PTSD symptoms, Injury event, Injury specific emotions, Injured self-image, Positive consequences, Responsibility/guilt, Coping, Time distance, Dependency, Healthy self, External attributions and Injury risk factors. The reliability and construct validity of the scales were found adequate. CONCLUSIONS: Injury perceptions can be reliably measured. While partly overlapping with equivalent illness perception scales, the InjPQ depicts cognitive dimensions unique to injury that add significantly to explaining variance in outcomes. The InjPQ is recommended for research and clinical use as a measure of injury perceptions.

Escitalopram or novel herbal treatments differentially alter cytokine and behavioral responses to immune challenge.

Studies suggest that inflammation is involved in the pathophysiology of depression. The present study examined the effects of the commonly used antidepressant escitalopram, in comparison with a novel herbal treatment (NHT) consisted of Crataegus pinnatifida, Triticum aestivum, Lilium brownii and Fructus Ziziphus jujuba, on cytokine and behavioral responses to an immune challenge. Escitalopram augmented lipopolysaccharide-induced tumor necrosis factor (TNF)-α peripheral secretion and induced a faster kinetics of interleukin-1ß secretion, while marginally reducing sickness behavior. NHT, on the other hand, completely abolished lipopolysaccharide-induced interleukin-1ß and TNFα peripheral secretion and diminished sickness behavior. These findings may have implications for the treatment of depressive symptoms associated with immune activation.

Prenatal fluoxetine modifies the behavioral and hormonal responses to stress in male mice: role for glucocorticoid insensitivity.

Women with major depressive disorder during pregnancy often use selective serotonin reuptake inhibitors (SSRIs) antidepressants. These drugs readily cross the placental barrier and impact the developing fetal brain. Recently, we reported that prenatal fluoxetine (FLX), an SSRI antidepressant drug, altered corticosterone and behavioral responses to stress in female mouse offspring. The present study assessed the effects of prenatal FLX on these responses in males. The results showed that prenatal FLX significantly augmented the corticosterone response to acute stress in young prepubescent mice. The corticosterone response to continuous stress was not affected by prenatal FLX irrespective of age. In addition, continuous stress reduced general activity, and anxiety-like and depressive-like behaviors in adult animals prenatally exposed to FLX, but not in controls. The dexamethasone suppression test showed that prenatal FLX induced a state of glucocorticoid insensitivity in adult males, indicating that the negative feedback control of the hypothalamic-pituitary-adrenal axis response to stress was disrupted. Together, these findings indicate that prenatal FLX altered hormonal and behavioral responses to stress and suggest a role for the development of glucocorticoid insensitivity in these effects. These findings may aid understanding of the limitations and precautions that should be taken in the use of SSRIs by pregnant women.

Increased symptoms of illness following prenatal stress: Can it be prevented by fluoxetine?

Stress during pregnancy is associated with lifetime negative consequences for the offspring. The present study examined the effects of prenatal stress on symptoms of illness following an immune challenge in mice. Additionally, this study examined whether pretreatment with fluoxetine (FLX) could prevent the effects of maternal stress on illness symptoms. Mice prenatally exposed to stress, with or without FLX were administered with saline or endotoxin. In males, prenatal stress significantly augmented endotoxin-induced body-weight loss and reduced food consumption; prenatal FLX did not prevent these responses, and, in many cases, augmented them. In females, prenatal stress worsened endotoxin-induced suppression of sucrose intake, and prenatal FLX reversed this effect. These findings provide the first indication of altered response to an immune challenge following prenatal stress and selective serotonin reuptake inhibitor (SSRI) treatment. These results may have implications for health and well-being of offspring exposed to stress during pregnancy.

Prenatal SSRI alters the hormonal and behavioral responses to stress in female mice: Possible role for glucocorticoid resistance.

Life time prevalence of major depression disorder (MDD) is higher in women compared to men especially during the period surrounding childbirth. Women suffering from MDD during pregnancy use antidepressant medications, particularly Selective Serotonin Reuptake Inhibitors (SSRI). These drugs readily cross the placental barrier and impact the developing fetal brain. The present study assessed the effects of prenatal exposure to fluoxetine (FLX), an SSRI antidepressant drug, on corticosterone and behavioral responses to stress in female mice. In young females, prenatal FLX significantly elevated corticosterone response to continuous stress. In adults, prenatal FLX augmented corticosterone response to acute stress and suppressed the response to continuous stress. Additionally, prenatal FLX significantly augmented stress-induced increase in locomotion and reduced anxiety- and depressive-like behaviors in adult, but not young mice. The dexamethasone suppression test revealed that prenatal FLX induced a state of glucocorticoid resistance in adult females, indicating that the negative feedback control of the hypothalamic-pituitary-adrenal axis response to stress was disrupted. These findings provide the first indication of altered hormonal and behavioral responses to continuous stress and suggest a role for the development of glucocorticoid resistance in these effects. According to these findings, prenatal environment may have implications for stress sensitivity and responsiveness to life challenges. Furthermore, this study may assist in understanding the limitations and precautions that should be taken in the use of SSRIs during pregnancy.

Affiliation, reward, and immune biomarkers coalesce to support social synchrony during periods of bond formation in humans.

Social bonds are critical for survival and adaptation and periods of bond formation involve reorganization of neurobiological systems as mediated by social behavior. Theoretical accounts and animal studies suggest similarity between parent-infant and pair bonding, a hypothesis not yet directly tested in humans. In this study, we recruited three groups of human adults (N=189); parents who had their firstborn child in the last 4-6months, new lovers who began a romantic relationship within the past 4months, and non-attached singles. We measured plasma oxytocin (OT), beta endorphin (ß-End), and interlukin-6 (IL-6), biomarkers of the affiliation, reward, and stress-response systems, and micro-coded gaze and affect synchrony between parents and infants and among new lovers during social interaction. OT significantly increased during periods of parental and romantic bonding and was highest in new lovers. In contrast, IL-6 and ß-End were highest in new parents and lowest in singles. Biomarkers became more tightly coupled during periods of bond formation and inter-correlation among hormones was highest during romantic bonding. Structural equation modeling indicated that the effects of IL-6 and ß-End on behavioral synchrony were mediated by their impact on OT, highlighting the integrative role of the oxytocinergic system in supporting human social affiliation. Findings suggest that periods of bond formation are accompanied by increased activity, as well as tighter cross-talk among systems underpinning affiliation, reward, and stress management and that research on the multidimensional process of bonding may shed further light on the effects of attachment on health.

Prenatal exposure to selective serotonin reuptake inhibitors (SSRI) increases aggression and modulates maternal behavior in offspring mice.

Selective serotonin reuptake inhibitors (SSRI) are commonly prescribed antidepressant drugs in pregnant women. SSRIs cross the placental barrier and affect serotonergic neurotransmission in the fetus. Although no gross SSRI-related teratogenic effects were reported, infants born following prenatal exposure to SSRIs are at higher risk for various developmental abnormalities. The aim of this study was to examine the effects of prenatal SSRI on social and maternal behavior in mice. To this end, pregnant female dams were exposed to saline or fluoxetine (FLX) throughout pregnancy, and the behavior of the offspring was examined. The results indicate that in utero FLX increased aggression in adult males and delayed emergence of maternal behavior in adult females. Social exploration and recognition memory were not affected by prenatal FLX exposure. These findings support the notion that alterations in the development of serotonergic pathways following prenatal exposure to SSRIs are associated with changes in social and maternal behavior throughout life.

Prenatal fluoxetine exposure affects cytokine and behavioral response to an immune challenge.

Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) is a commonly prescribed antidepressant drug in pregnant women. FLX readily crosses the placenta, consequently altering serotonergic neurotransmission in the fetus and causing physiological and behavioral disturbances in the newborn. Studies have shown that serotonin plays a role in modulating immune signaling. Thus, the goal of this study was to assess the effects of prenatal exposure to FLX on the response to an immune challenge in offspring mice. Male and female mice were prenatally exposed to FLX and later injected with lipopolysaccharide (LPS) at different stages of development. Results indicated that prenatal FLX modulated aspects of the response to the endotoxin challenge. Prenatal FLX diminished the secretion of interleukin (IL)-6 in adult male and female mice. Prenatal exposure to FLX further suppressed TNFα and augmented IL-1ß secretion in adult males. Early effects of LPS (within 24h of administration) on body weight and food consumption were diminished by prenatal exposure to FLX in adult mice. Delayed effects of LPS (within 60h of administration) were modulated by prenatal FLX in young animals. These results provide an indication that prenatal modulations of the serotonergic system had lasting implications for host response to an immune challenge. These findings may contribute to the understanding of the effects of prenatal environment on the development of physiological systems that are important to coping with infectious challenges, and assist in understanding the limitations and precautions that should be taken in the use of SSRIs during pregnancy.

Early adversity, immunity and infectious disease.

Complex interactions between biological, behavioral and environmental factors are involved in mediating individual differences in health and disease. In this review, we present evidence suggesting that increased vulnerability to infectious disease may be at least, in part, due to long-lasting effects of early life psychosocial adversities. Studies have shown that maternal psychosocial stress during pregnancy is associated with long lasting changes in immune function and disease resistance in the offspring. Studies further indicated that harsh environmental conditions during the neonatal period may also cause lasting changes in host response to infectious disease. Although the mechanisms involved in these effects have not been fully examined, several potential mediators have been described, including changes in the development of the offspring hypothalamic-pituitary-adrenal axis, alterations in epigenetic pathways, stress-related maternal health risk behavior and infection during pregnancy. Although there are ample literature indicating that perinatal psychosocial stress increases vulnerability to disease, other reports suggest that mild predictable stressors may benefit the organism and allow better coping with future stressors. Thus, understanding the possible consequences of perinatal adversities and the mechanisms that are involved in immune regulation is important for increasing awareness to the potential outcomes of early negative life events and providing insight into potential therapies to combat infection in vulnerable individuals.

Neonatal stress modulates sickness behavior: role for proinflammatory cytokines.

Neonatal stress increased the duration and augmented symptoms of sickness behavior induced by influenza virus infection or endotoxin challenge in mice. Since proinflammatory cytokines were implicated in sickness behavior, the present study sought to determine the effect of neonatal stress on cytokines-induced sickness behavior and on proinflammatory cytokine secretion. Data indicate that separation of mouse pups from the dams at an early age (maternal separation, MSP) increased the duration and augmented some of the symptoms of sickness behavior induced by proinflammatory cytokines. In addition, MSP partially suppressed cytokine and corticosterone secretion in response to endotoxin administration. These data may suggest that MSP increased sensitivity to the effects of proinflammatory cytokines on sickness behavior following an immune challenge.

Sex differences in the response to influenza virus infection: modulation by stress.

Influenza virus infection is a significant public health problem; however factors affecting the incidence and severity of disease have not been fully elucidated. The present study sought to examine the role of sex and stress in mediating susceptibility to an influenza viral infection in mice. Male and female mice underwent repeated cycles of restraint (RST) stress, followed by an influenza A/PR8 virus infection. Following these manipulations, levels of circulating corticosterone, lung proinflammatory cytokine gene expression and sickness behavior were examined. The data indicate sex differences in several aspects of the response to the A/PR8 virus infection. The kinetics of lung interleukin-1ß mRNA expression were faster in infected males compared to females, while circulating corticosterone levels were elevated in infected females, but not in males. Anorexia and reduced saccharin consumption began earlier and symptoms were more pronounced in infected males than in females. In addition, RST modulated the response to the A/PR8 virus infection. Proinflammatory cytokine gene expression in response to infection was enhanced and sickness behavior was modulated by RST in both males and females. These data suggest that males mount more vigorous immune and behavioral responses to influenza viral infection compared to females, and stress exacerbates the response in both males and females. In conclusion, complex interactions between biological and behavioral factors are involved in mediating individual differences in health and disease. Additional studies may help uncover some of the factors contributing to the individual differences in susceptibility to influenza infection.