Environmental Disruption of the Developmental System During Early Life

Early experiences are fundamental for social, cognitive, and behavioral development. Caregivers, particularly mothers, play an essential role in this development. The mother-infant relationship is characterized by reciprocal, regulatory, and dynamic processes which determine developmental trajectory of the young. The predictable nature in onset and progression of some behaviors in development ensures offspring survival while permitting a degree of modification to more precisely determine developmental trajectory. Modifiers of early experiences include individual and intergenerational life history of the mother, peers, paternal effects, and environmental contributions. This dissertation explores the effects of some of these modifiers on offspring development. The first study identifies multiple sources of individual variation in hypothalamic-pituitary-adrenal (HPA) axis response to stress in human participants and highlights HPA dysregulation that can result from historical and concurrent toxic stress. Next, the effects of early experience on development of central oxytocin systems related to HPA regulation (paraventricular nucleus of the hypothalamus, amygdala, hippocampus) were investigated in Long-Evans rats using an environmental manipulation, limited bedding and nesting material (LBN), to change early life experience. Effects on central oxytocin were age, sex, and region specific, and generally increased the number of oxytocin and oxytocin receptor cells in females and decreased the number in males. These changes were accompanied by changes in social interaction and behavioral social buffering in LBN females. A separate analysis assessed lineage and LBN effects on maternal behavior in dams from three lineages. This data provides evidence of inter-lineage variability that is greater than inter-condition variability for some maternal behaviors which demonstrates limitations in maternal behavior plasticity within a single generation. Finally, LBN effects on pup behavioral and physiological indices of thermal regulation were assessed to determine if LBN presents a thermal challenge to pups. LBN pups had disrupted huddling and changes in physiological markers of thermogenesis: brown adipose tissue activation and mitochondria biogenesis. There were also sex differences between control males and females and between LBN males and females. Together, these data emphasize the importance of multiple inputs in determining developmental trajectory during early life and raises new questions about resilience and vulnerability to stress within and between generations

Seeing a Face in a Crowd of Emotional Voices: Changes in Perception and Cortisol in Response to Emotional Information across the Senses

One source of information we glean from everyday experience, which guides social interaction, is assessing the emotional state of others. Emotional state can be expressed through several modalities: body posture or movements, body odor, touch, facial expression, or the intonation in a voice. Much research has examined emotional processing within one sensory modality or the transfer of emotional processing from one modality to another. Yet, less is known regarding interactions across different modalities when perceiving emotions, despite our common experience of seeing emotion in a face while hearing the corresponding emotion in a voice. Our study examined if visual and auditory emotions of matched valence (congruent) conferred stronger perceptual and physiological effects compared to visual and auditory emotions of unmatched valence (incongruent). We quantified how exposure to emotional faces and/or voices altered perception using psychophysics and how it altered a physiological proxy for stress or arousal using salivary cortisol. While we found no significant advantage of congruent over incongruent emotions, we found that changes in cortisol were associated with perceptual changes. Following exposure to negative emotional content, larger decreases in cortisol, indicative of less stress, correlated with more positive perceptual after-effects, indicative of stronger biases to see neutral faces as happier

Postnatal maternal care moderates the effects of prenatal bisphenol exposure on offspring neurodevelopmental, behavioral, and transcriptomic outcomes.

Bisphenols (BP), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and in rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal bisphenol exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal bisphenol exposure and postnatal maternal care on neurodevelopment and behavior in rats. Our findings suggest that the effects of prenatal bisphenol exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal bisphenol exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal bisphenol exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal bisphenol exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal bisphenol exposure and improve health and well-being in human populations

Psychiatric risk and resilience: Plasticity genes and positive mental health

Abstract Objective The at‐risk mental state (ARMS) for psychosis has long played a key role in diathesis‐stress models of schizophrenia. More recent studies, however, have called for extending the boundaries of the ARMS construct beyond attenuated psychosis in nonhelp‐seeking samples to include not only other vulnerability indicators but also protective factors related to genotype, mental health, personality, and cognition. Method Accordingly, we assessed in a sample of 100 college students, the ARMS construct with the Brief Prodromal Questionnaire (PQ‐B) for psychosis, in conjunction with measures of positive mental health, childhood adversity, psychiatric symptoms, personality traits, social cognition, and genetic variables derived from assays of the serotonin transporter (5‐HTTLPR) and the brain‐derived neurotrophic factor (BDNF). Results Higher PQ‐B scores correlated positively with vulnerability indicators of childhood adversity and heightened levels of a wide variety of psychiatric symptoms but correlated negatively with protective factors of better overall mental health, social cognition as well as with a distinct NEO profile marked by reduced neuroticism and elevated agreeableness and conscientiousness. Multivariate analyses indicated that a composite ARMS measure comprised of PQ‐B scores plus anxiety and depression symptoms revealed significant genotype differences, with lowest risk and highest resilience for allelic carriers of 5‐HTTLPR‐short and BDNF Met polymorphisms. Conclusions Results provided support for extending the ARMS construct, pointing to important contributions of personality, social cognition, and genes that support neural plasticity in mitigating vulnerability and enhancing resilience and well‐being