Pregnancy: a final frontier in mental health research

International audienc

Serotonin and motherhood: From molecules to mood

Emerging research points to a valuable role of the monoamine neurotransmitter, serotonin, in the display of maternal behaviors and reproduction-associated plasticity in the maternal brain. Serotonin is also implicated in the pathophysiology of numerous affective disorders and likely plays an important role in the pathophysiology of maternal mental illness. Therefore, the main goals of this review are to detail: 1) how the serotonin system of the female brain changes across pregnancy and postpartum; 2) the role of the central serotonergic system in maternal caregiving and maternal aggression; and 3) how the serotonin system and selective serotonin reuptake inhibitor medications (SSRIs) are involved in the treatment of maternal mental illness. Although there is much work to be done, studying the central serotonin system’s multifaceted role in the maternal brain is vital to our understanding of the processes governing matrescence and the maintenance of motherhood

O uso das novas tecnologias nas aulas de Geografia para a melhoria do ensino e aprendizagem em escolas de ensino básico

Este trabalho tem como objetivo apresentar a importância do uso das novas tecnologias como instrumento para a melhoria do ensino e aprendizagem em Geografia. A atividade foi realizada em duas escolas do ensino básico na cidade de Fortaleza no ano 2014, onde se desenvolveram práticas com o uso de recursos tecnológicos, tais como a plataforma Moodle, criação e reprodução de slides, além de vídeos, havendo uma maior socialização e produção de conhecimentos e uma nova forma de conduzir as aulas de Geografia. Podemos perceber a importância e os desafios quanto ao uso das novas tecnologias

Altered emotionality, hippocampus-dependent performance and expression of NMDA receptor subunit mRNAs in chronically stressed mice.

N-Methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission in the hippocampus is implicated in cognitive and emotional disturbances during stress-related disorders. Here, using quantitative RT-PCR, we investigated the hippocampal expression of NR2A, NR2B and NR1 subunit mRNAs in a mouse stress paradigm that mimics clinically relevant conditions of simultaneously affected emotionality and hippocampus-dependent functions. A 2-week stress procedure, which comprised ethologically valid stressors, exposure to a rat and social defeat, was applied to male C57BL/6J mice. For predation stress, mice were introduced into transparent containers that were placed in a rat home cage during the night; social defeat was applied during the daytime using aggressive CD1 mice. This treatment impaired hippocampus-dependent performance during contextual fear conditioning. A correlation between this behavior and food displacement performance was demonstrated, suggesting that burrowing behavior is affected by the stress procedure and is hippocampus-dependent. Stressed mice (n = 22) showed behavioral invigoration and anomalous anxiolytic-like profiles in the O-maze and brightly illuminated open field, unaltered short-term memory in the step-down avoidance task and enhanced aggressive traits, as compared to non-stressed mice (n = 10). Stressed mice showed increased basal serum corticosterone concentrations, hippocampal mRNA expression for the NR2A subunit of the NMDAR and in the NR2A/NR2B ratio; mRNA expression of NR2B and NR1 was unchanged. Thus, stress-induced aberrations in both hippocampal-dependent performance and emotional abnormalities are associated with alterations in hippocampal mRNA NR2A levels and the NR2A/NR2B ratio and not with mRNA expression of NR2B or NR1

Perinatal fluoxetine increases hippocampal neurogenesis and reverses the lasting effects of pre-gestational stress on serum corticosterone, but not on maternal behavior, in the rat dam

There is increasing evidence that mental health concerns, stress-related mental illnesses, and parental stress prior to conception have long-term effects on offspring outcomes. However, more work is needed to understand how pre-gestational stress might affect neurobehavioral outcomes in the mother. We investigated how chronic stress prior to gestation affects maternal behavior and related physiology, and aimed to determine the role that perinatal SSRIs have in altering these stress effects. To do this, female Sprague-Dawley rats were subject to chronic unpredictable stress (CUS) prior to breeding. During the perinatal period they were administered fluoxetine (10 mg/kg/day). Four groups of dams were studied: Control + Vehicle, Pre-gestational Stress + Vehicle, Control + Fluoxetine and Pre-gestational Stress + Fluoxetine. Maternal weight, breeding success, and maternal caregiving behaviors were recorded. Measures of serum corticosterone and corticosteroid-binging globulin (CBG) and the number of immature neurons in the dorsal hippocampus were also assessed in the late postpartum. Main findings show pre-gestational stress resulted in poor reproductive success and maintenance of pregnancy. Pre-gestationally stressed dams also showed higher levels of nursing and fewer bouts of licking/grooming offspring in the first week postpartum – behaviors that were not reversed by perinatal fluoxetine treatment. In the dam, perinatal fluoxetine treatment reversed the effect of pre-gestational maternal stress on serum corticosterone levels and increased serum CBG levels as well as neurogenesis in the dorsal hippocampus. Maternal corticosterone levels significantly correlated with blanket and passive nursing. This work provides evidence for a long-term impact of stress prior to gestation in the mother, and shows that perinatal SSRI medications can prevent some of these effects. © 2017 Elsevier B.V

Developmental Fluoxetine Exposure Normalizes the Long-Term Effects of Maternal Stress on Post-Operative Pain in Sprague-Dawley Rat Offspring

Early life events can significantly alter the development of the nociceptive circuit. In fact, clinical work has shown that maternal adversity, in the form of depression, and concomitant selective serotonin reuptake inhibitor (SSRI) treatment influence nociception in infants. The combined effects of maternal adversity and SSRI exposure on offspring nociception may be due to their effects on the developing hypothalamic-pituitary-adrenal (HPA) system. Therefore, the present study investigated long-term effects of maternal adversity and/or SSRI medication use on nociception of adult Sprague-Dawley rat offspring, taking into account involvement of the HPA system. Dams were subject to stress during gestation and were treated with fluoxetine (2×/5 mg/kg/day) prior to parturition and throughout lactation. Four groups of adult male offspring were used: 1. Control+Vehicle, 2. Control+Fluoxetine, 3. Prenatal Stress+Vehicle, 4. Prenatal Stress+Fluoxetine. Results show that post-operative pain, measured as hypersensitivity to mechanical stimuli after hind paw incision, was decreased in adult offspring subject to prenatal stress alone and increased in offspring developmentally exposed to fluoxetine alone. Moreover, post-operative pain was normalized in prenatally stressed offspring exposed to fluoxetine. This was paralleled by a decrease in corticosteroid binding globulin (CBG) levels in prenatally stressed offspring and a normalization of serum CBG levels in prenatally stressed offspring developmentally exposed to fluoxetine. Thus, developmental fluoxetine exposure normalizes the long-term effects of maternal adversity on post-operative pain in offspring and these effects may be due, in part, to the involvement of the HPA system

Fluoxetine during Development Reverses the Effects of Prenatal Stress on Depressive-Like Behavior and Hippocampal Neurogenesis in Adolescence

Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

The specific role of relationship life events in the onset of depression during pregnancy and the postpartum

Background The precipitating role of life events in the onset of depression is well-established. The present study sought to examine whether life events hypothesised to be personally salient would be more strongly associated with depression than other life events. In a sample of women making the first transition to parenthood, we hypothesised that negative events related to the partner relationship would be particularly salient and thus more strongly predictive of depression than other events. Methods A community-based sample of 316 first-time mothers stratified by psychosocial risk completed interviews at 32 weeks gestation and 29 weeks postpartum to assess dated occurrence of life events and depression onsets from conception to 29 weeks postpartum. Complete data was available from 273 (86.4%). Cox proportional hazards regression was used to examine risk for onset of depression in the 6 months following a relationship event versus other events, after accounting for past history of depression and other potential confounders. Results 52 women (19.0%) experienced an onset of depression between conception and 6 months postpartum. Both relationship events (Hazard Ratio = 2.1, p = .001) and other life events (Hazard Ratio = 1.3, p = .020) were associated with increased risk for depression onset; however, relationship events showed a significantly greater risk for depression than did other life events (p = .044). Conclusions The results are consistent with the hypothesis that personally salient events are more predictive of depression onset than other events. Further, they indicate the clinical significance of events related to the partner relationship during pregnancy and the postpartum

The Power of an Infant\u27s Smile: Maternal Physiological Responses to Infant Emotional Expressions

Infant emotional expressions, such as distress cries, evoke maternal physiological reactions. Most of which involve accelerated sympathetic nervous activity. Comparatively little is known about effects of positive infant expressions, such as happy smiles, on maternal physiological responses. This study investigated how physiological and psychological maternal states change in response to infants\u27 emotional expressions. Thirty first-time mothers viewed films of their own 6- to 7-month-old infants\u27 affective behavior. Each observed a video of a distress cry followed by a video showing one of two expressions (randomly assigned): a happy smiling face (smile condition) or a calm neutral face (neutral condition). Both before and after the session, participants completed a self-report inventory assessing their emotional states. The results of the self-report inventory revealed no effects of exposure to the infant videos. However, the mothers in the smile condition, but not in the neutral condition, showed deceleration of skin conductance. These findings demonstrate that the mothers who observed their infants smiling showed decreased sympathetic activity. We propose that an infant\u27s positive emotional expression may affect the branch of the maternal stress-response system that modulates the homeostatic balance of the sympathetic and parasympathetic nervous systems