Clinical and preclinical research both indicate that early life adversities alter sensitivity to stress well into adulthood. Although clinical research identifies infancy, childhood, and adolescence as periods of heightened vulnerability, the majority of preclinical research experiments have examined the enduring impact of stressors delivered either prenatally or prior to weaning. It was recently shown that exposing rats to intermittent stressors across the childhood/ adolescent period (PD 21-51) increased their behavioural and endocrine sensitivity to stress in adulthood. The purpose of the current project was to determine whether specific developmental periods are differentially sensitive to the lasting effects of intermittent stress. Male and female Long-Evans rats were exposed to three stressors (foot shock, elevated platform exposure, and cold water emersion) two times each, randomly over a twelve day period (childhood: PD 22-33 vs. adolescence: PD 35-46). Age-matched controls were briefly handled on each of the stressor application days. After completion of the stress exposure period, rats were left undisturbed for 27 days and behavioural testing commenced in adulthood. Intermittent physical stress exposure during the childhood period increased anxiety-like behaviours in adulthood, as indexed by the Elevated-Plus Maze (EPM) and Shock Probe Burying Test (SPBT). This also increased depression-like behaviour in adult male rats and decreased depression-like behaviour in adult female rats, as indexed by the Forced Swim Test (FST). Intermittent physical stress exposure in the adolescent period increased open-arm activity, increased burying behaviour and increased immobility in the forced swim test, in both male and female rats. Stress during either developmental period, failed to alter corticosterone (CORT) reactivity to restraint stress in adulthood. Thus, it appears that the long lasting behavioural impact of early-life adversity can vary, according to the developmental period the stressors are experienced in, but this is further modified by sex and the type of test used to evaluate adult behaviour. / Thesis (Master, Psychology) -- Queen's University, 2010-08-25 18:53:24.136

Mood and cognition, along with numerous other physiological processes, are under circadian regulation. The synthesis and secretion rhythm of the pineal hormone melatonin is under the direct regulation of the central circadian pacemaker and the secretion rhythm of melatonin can be used to assess circadian alterations. In this thesis, it was demonstrated that low levels of endogenous nocturnal melatonin was associated with subsyndromal depression and alterations in sleep architecture. Studies in individuals with endogenous circadian rhythm disorder, with and without comorbid depressive symptoms, revealed that individuals with depressive symptoms had a greater phase delay in melatonin profiles as compared to individuals without depressive symptoms. Furthermore, in the same study, exogenous melatonin administered to induce phase advances significantly improved depression scores and sleep initiation. In addition to endogenous circadian disruption, circadian rhythms can also be disrupted by repeated atypical alterations in environmental time cues. In mammals, light is the strongest environmental cue that can modulate circadian rhythms. Recent studies suggest that circadian response to photic stimuli is preferentially sensitive to short wavelengths in the range of 450-480 nm. Using an animal model it was demonstrated that filtering a 10 nm bandwidth between 470-480 nm from polychromatic white light prevents nocturnal light exposure induced disruptions in melatonin and corticosterone secretion as well as central and peripheral clock gene expression. These findings were further investigated in humans and revealed that filtering short wavelengths below 480 nm attenuates 12 h nocturnal light exposure induced suppression of melatonin secretion, increased cortisol secretion and disrupted peripheral clock gene expression. Furthermore, attenuation of these changes was associated with improvements in mood, alertness and vigilance at a time close to the endogenous circadian wake drive. However, filtering short wavelengths below 460 nm or reducing the optical transmission by up to 30% below 480 nm did not attenuate the disruptive effects of nocturnal light exposure on physiological and behavioural variables. Overall, the results presented in this thesis support the role of circadian dysfunction in neuropsychometric impairment and presents evidence supporting spectral modulation as a promising approach to attenuate light-mediated chronodisruption.

Thesis (M.S.)--University of Delaware, 2008. / Principal faculty advisor: Robert A. Sikes, Dept. of Biological Sciences. Includes bibliographical references.

Since the time of the introduction of the spontaneously hypertensive rat (SHR) into medical research, several neuropharmacological studies have been performed on these animals which have been unrelated to their cardiovascular systems. A few of these studies have indicated possible abnormalities in the dopaminergic systems of SHR. Therefore the present study was undertaken to examine more closely the sensitivity of SHR to stimulation of their dopamine (DA) receptors.

This dissertation develops a feminist materialist interpretation of the role the neuroendocrine system plays in the development of gender/sex differences in religion. Data emerging from psychology, sociology, and cognitive science have continually indicated that women are more religious than men, in various senses of those contested terms, but the factors contributing to these findings are little understood and disciplinary perspectives are often unhelpfully siloed. Previous scholarship has tended to highlight socio-cultural factors while ignoring biological factors or to focus on biological factors while relying on problematic and unsubstantiated gender stereotypes. Addressing gender/sex difference is vital for understanding religion and how we study it. This dissertation interprets this difference by means of a multidisciplinary theoretical and methodological approach. This approach builds upon insights from the cognitive and evolutionary science of religion, affect theory and affective neuroscience, and social neuroendocrinology, and it is rooted in the foundational insights of feminist materialism, including that cultural and micro-sociological forces are inseparable from biological materiality. The dissertation shows how a better way of understanding gender/sex differences in religion emerges through focusing on the co-construction of biological materiality and cultural meanings. This includes deploying a gene-culture co-evolutionary explanation of ultrasociality and an understanding of the biology of performativity to argue that religious behavior and temperaments emerge from the enactment and hormonal underpinnings of six affective adaptive desires: the desires for (1) bonding and attachment, (2) communal mythos, (3) deliverance from suffering, (4) purpose, (5) understanding, and (6) reliable leadership. By hypothesizing the patterns of hormonal release and activation associated with ritualized affects—primarily considering oxytocin, testosterone, vasopressin, estrogen, dopamine, and serotonin—the dissertation theorizes four dimensions of religious temperament: (1) nurturant religiosity, (2) ecstatic religiosity, (3) protective/hierarchical religiosity, and (4) antagonistic religiosity. This dissertation conceptualizes hormones as chemical messengers that enable the diversity emerging from the imbrication of physical materiality and socio-cultural forces. In doing so, it demonstrates how hormonal aspects of gender/sex and culturally constructed aspects of gender/sex are always already intertwined in their influence on religiosity. This theoretical framework sheds light on both the diversity and the noticeable patterns observed in gender/sex differences in religious behaviors and affects. This problematizes the terms of the “women are more religious than men” while putting in place a more adequate framework for interpreting the variety of ways it appears in human lives.

Despite the extraordinary diversity of behavior across the animal kingdom, the genes and molecules that contribute to such natural diversity are largely unknown. In this thesis, I leverage the dramatic divergence in behavior between two closely related species of deer mice (genus Peromyscus) to investigate the genetic, cellular, and neuroendocrine basis of behavior. In chapter 2, I show that the monogamous oldfield mouse (Peromyscus polionotus subgriseus) has evolved a novel cell type in the adrenal gland that expresses the enzyme AKR1C18, which converts progesterone into 20α-hydroxyprogesterone (20α-OHP). I then demonstrate that 20α-OHP is more abundant in oldfield mice than in the closely-related promiscuous prairie deer mouse (P. maniculatus bairdii) and that it increases monogamous-typical parental behaviors when administered to both monogamous fathers. Using quantitative trait locus mapping in a cross between these species, I discover interspecific genetic variation that drives expression of the glycoprotein tenascin N and ultimately contributes to gain of adrenal AKR1C18 expression in oldfield mice. In chapter 3, I investigate the genetic architecture underlying the striking difference in exploratory behavior between prairie deer mice and oldfield mice. Through congenic fine-mapping, I identify a 15-Mb locus that strongly contributes to species differences in exploratory behavior. I then investigate the potential contributions of one of the 18 genes in the locus, Olfm4, which harbors cis-regulatory variants that drives its expression in the oldfield hypothalamus. Taken together, my research advances our understanding of the genetic and molecular causes that drive rapid behavioral divergence between species.

Prader-Willi Syndrome (PWS) is a genetic disease that results in abnormal hormone levels, developmental delay, intellectual disability, hypogonadism, and excessive appetite. The disease is caused by a de novo genetic deletion in chromosome 15. While many of the deleted genes have been identified, there is little known about their molecular function. There is evidence that a cluster of non-coding RNA genes in the deleted region known as the SNORD116 genes may be the most critical genes deleted in Prader-Willi Syndrome. It is unknown what the SNORD116 genes do at the molecular level, but recent evidence suggests they regulate the expression of other genes involved in the neuroendocrine system. Specifically, the SNORD116 gene is implicated in regulation of NHLH2, a transcription factor gene which plays a key role in development, hormonal regulation, and body weight. In this study we identify phylogenetically conserved regions of SNORD116 and predict interactions with its potential downstream RNA targets. We show that mouse Snord116 post-transcriptionally increases Nhlh2 RNA levels dependent on its 3'UTR and protects it from degradation within 45 minutes of its transcription. Additionally, a single nucleotide variant within Nhlh2 at the predicted Snord116 interaction site may disrupt Snord116's protective effect. This is the first observation of a molecular mechanism for Snord116, identifying its role in RNA stability, and leads us closer to understanding Prader-Willi Syndrome and finding a possible treatment. However, Snord116 in vitro knockdown or paternally inherited in vivo deletion fail to detect differential expression of Nhlh2, likely due to missing the key timepoint of Snord116 regulatory effects on Nhlh2 RNA soon after its transcriptional stimulation, and dependent on leptin signals. Furthermore, the hypothalamic mRNA expression profile of PWS mouse models fed a nutraceutical dietary supplement of conjugated linoleic acid reveals minimal overall changes, while the effect of diet may be stronger than genotype and potentially changes gene expression of metabolic molecular pathways. / Doctor of Philosophy / Prader-Willi Syndrome is a genetic disease that results in abnormal hormone levels, slow development, intellectual disability, gonad deficiency, and excessive appetite. The disease is caused by a genetic deletion in chromosome 15 that is almost always a spontaneous mutation not inherited from the parents. While many of the deleted genes have been identified, there is little known about what their molecular function is. There is evidence that a cluster of genes in the deleted region known as the SNORD116 genes may be the most critical genes deleted in Prader-Willi Syndrome. It is unknown what the SNORD116 genes do at the molecular level, but recent evidence suggests that it regulates other genes involved in the hormone system. Specifically, the SNORD116 gene is implicated to regulate the levels of NHLH2, a gene which plays a key role in development, hormonal regulation, and body weight. In this study we identify key regions of SNORD116 and predict interactions with its potential downstream targets. We show that SNORD116 increases NHLH2 levels and slows its degradation at the RNA transcript level. This is the first observation of a molecular mechanism for SNORD116 and leads us closer to understanding Prader-Willi Syndrome and finding a possible treatment. However, other mouse models of Snord116 deletion fail to find differences in Nhlh2. This is likely due to missing a brief key timepoint and hormonal signal when Nhlh2 is most subject to Snord116's effects. Furthermore, PWS mouse models fed a supplement intended for weight loss leads to mild overall gene expression changes in the hypothalamus, a brain region that regulates many hormonal signals including appetite and energy balance. The effect of diet may be stronger than genotype in this brain region, with diet potentially changing the activity of metabolic molecular pathways.

<p dir="ltr">The Pekin duck, a major poultry product, is an important livestock species that requires further study to understand their physiological needs and welfare. Welfare improvements can be obtainable by measuring a duck’s response to its environment and developing management practices that allow ducks to explore positive natural behaviors and minimize negative affective states. Assessing welfare includes measuring physical and mental states of an animal and how it copes with its environment. This thesis sets out to use established indicators for mental state, such as serotonin (5-HT) and dopamine (DA), to validate methods of measuring duck affective state applied to environment changes. Affective states can be assessed using neurotransmitter concentrations inserted into turnover equations to understand serotonergic and dopaminergic activity within the synapse. Similarly, gene expression can be linked to affective state by investigating the rate-limiting enzyme in 5-HT and DA synthesis. Developing neuroendocrine profiles for the Pekin duck can elucidate how environmental changes affect physiology and welfare. </p><p dir="ltr">Preening cups are a semi open water source placed within duck barns to improve welfare and allow for positive natural behaviors. Since ducks are waterfowl, many believe these birds need access to open water to develop naturally and have positive welfare. Our lab designed an experiment, referenced in Chapter 3, to compare ducks raised with preening cups to ducks raised with only water nipple lines. At Purdue Animal Science Research and Education Center (ASREC), 260 grow-out Pekin ducks were raised to the industry standard. There were 2 pens that had access to preening cups on day 18 and 2 pens had access to only nipple lines. We collected duck brains on day 18 before preening cup placement (PRE, n = 6). On day 43, we collected duck brains from pens with preening cups (PC, n = 6) and from pens without preening cups (CON, n = 6). Then, brains were hemisected and further dissected into caudal mesencephalon (CM), rostral mesencephalon (RM), diencephalon (DI), and forebrain (FB). The right portions of each brain were used to investigate neurotransmitter concentrations and turnover using mass spectrometry. While the left portions were used to investigate gene expression of tryptophan hydroxylase (TPH1, TPH2) and tyrosine hydroxylase (TH). Our results found no significant differences in 5-HT turnover or 5-HT static levels associated with preening cups across collection days. In the CM, we found a decrease in DA turnovers for PC and CON (p = 0.0067) when compared to PRE. Also, we found a decrease in DA turnover for PC when compared to PRE and CON (p = 0.003) in the RM. In the CM, we found increases in TPH1 expression (p = 0.022) for PC and CON when compared to PRE and in TH expression (p = 0.022) for CON when compared to PRE. There were no significant differences found in the RM and DI brain areas for gene expression. In the FB, we found a decrease in TH gene expression (p = 0.031). Overall, our data highlights an increase in dopaminergic activity within the midbrain. This increase in DA can be correlated with aggressive behavior witnessed from ducks housed with preening cups. Elevated DA is associated with addiction and resource guarding. In this experimental study, we concluded that preening cups placed with a small number of ducks (n = 65 ducks per preening cup) may elicit aggressive behavior and decrease welfare. </p><p dir="ltr">The results of this initial study led us to the question of how a duck affective state is altered by preening cups in a large commercial setting. A commercial Pekin duck barn will place one preening cup for approximately 1,000-1,500 ducks, which means a barn will carry about 3-5 preening cups. Similar methodology was used in Chapter 4 to investigate the ducks affective state using mass spectrometry and qRT-PCR to assess 5-HT and DA activity within the brain. We visited four commercial duck barns with an average of 7,500 ducks on day (d)21 prior to preening cup placement, d28 one week after preening cup placement, and d35 one day prior to processing. We collected litter samples to test moisture content (n = 3/barn/day) and found no differences before or after preening cup placement. We performed a transect walk by moving systematically through each barn and recording the frequency of welfare concerns. All barns showed low percentages of welfare concerns while differences were likely due to natural aging of ducks in a production system. Brains were collected from two locations in the barn including ducks actively using the preening cup (PC) and ducks across the barn not actively performing any behaviors other than standing or sitting (CON). Brains were divided into CM, RM, and DI brain areas and each half was assessed with 5-HT and DA turnover along with TPH1, TPH2, and TH gene expression. No differences were found for 5-HT turnover or static levels. This suggests that preening cups are not altering affective state. DA turnover was decreased in the CM (p < 0.05) and DI (p < 0.001) due to age, but no differences were found between collection location (PC vs CON). We link this increase in dopaminergic activity to natural aging and preparation for puberty as no aggressive behavior was witnessed in commercial barns. Aggression and resource guarding of commercial preening cups is unlikely due to the increased number of ducks per water source and the large space the ducks can access. There was increased TPH1 expression within the RM brain area for d35 ducks when compared to d28 and d21. We conclude that affective state is not variable within the barn based on collection locations. Overall, 5-HT was not affected by preening cups and DA was affected by age. This means that preening cups may not improve affective state and welfare, but they also do not cause determinantal effects either. </p><p dir="ltr">Another major welfare concern associated with environment is transportation for Pekin ducks. To assess how affective state is altered by crating and transportation of hens and drakes, Chapter 5 used similar methodology as the previous studies. Transportation may cause an acutely stressful event while activating a physiological stress response. Chapter 5 measured several central and peripheral physiological parameters to assess responses to transportation. Thirty-six, 23-week-old breeder ducks from a commercial facility were randomly assigned to one of three treatment groups. The control group (CON) was caught and immediate euthanized in the pen, the crate group (CRA) was caught and crated for 90 minutes before euthanasia, and the transport group (TRA) was caught, crated, and loaded into the back of a truck to be driven on country roads at 55 mph for 90 minutes before immediate euthanasia. Blood was collected for corticosterone ELISA analysis and blood smear heterophil to lymphocyte ratio (HLR) analysis. We found that hens showed an increase in HLR (p = 0.035) and serum corticosterone (p = 0.01) due to CRA. Drakes and hens showed an increase in HLR (p = 0.035) and serum corticosterone (p = 0.0084) for TRA. These results suggest that transportation is a stressor that elicits a sex dependent response where hens increase corticosterone and HLR under CRA unlike drakes who only showed a stress response under TRA. Likewise, a sex difference was shown for 5-HT turnover where hens show a stepwise increase from CON to CRA (p = 0.01) and from CRA to TRA (p = 0.016) in the CM and RM. There were no differences for DA turnover while TPH1 gene expression was decreased (p = 0.03) for TRA hens when compared to CON and CRA hens. Our results suggest that transportation negatively shifts affective state by increasing stress responses in ducks and reducing serotonergic activity in hens. In the future, care should be taken to evaluate stress between sexes and minimize transportation time. </p><p dir="ltr">In conclusion, preening cups and transportation are important aspects of a Pekin ducks’ life that alter affective state and physiology. We recommend proper management of preening cups to ensure positive welfare by placing water sources over open pits to prevent excess accumulation of water in the barn. We recommend that while evaluating stressors, researchers need to assess different sexes and collection time from the onset of the stressor. Future studies can include determining affective state for other enrichments such as environmental enrichment devices or investigating commercial barns without preening cups during the production cycle. Continued research could measure affective state following shorter transportation stress or chronic stress to resolve what timeframes alter 5-HT and DA turnover. Transportation may be minimized by installing on-site processing facilities to stun and process animals without transportation to reduce negative affective states. In an academic setting, pharmaceutical intervention may be interesting to investigate to improve affective state during stressful events.</p>

The purpose of the project was to determine if testosterone reactivity and neural changes could be observed in response to a reward-seeking competitive task, respectively, and whether testosterone was related to neural activation. Forty nine undergraduate students were recruited playing the Monetary Incentive Delay (MID). We found that a subset of participants (N=20) showed testosterone reactivity to the task (ps < .05). During the EEG analyses, cue had a main effect on FRN amplitude in a trend level (p = .084): The large incentive cue triggered smaller (less negative) FRN amplitude than the small incentive cue did (p < .05), especially during the second reward seeking block (A’) (p = .065) and especially within males (p < .05). Testosterone level and reactivity were not further associated with FRN amplitude (ps > .1). Taken together, results show both testosterone and FRN amplitude may be sensitive to a complex reward-seeking and competition.

Diversos procedimentos são capazes de induzir a recuperação de memórias traumáticas (RecMem). Técnicas de psicoterapia têm sido usadas para reduzir a resposta emocional às memórias traumáticas, através de processos de re-estruturação e re-significação das vivências, baseados na resiliência dos sujeitos. Durante a RecMem podem ocorrer sinais clínicos de ativação autonômica que não são reações devidas a estressores externos. Pelo contrário, constituem o resultado de estímulos de natureza psíquica gerados internamente. Assim, é possível se especular se eles podem funcionar como estressores puramente psicológicos e, como tais, induzir respostas autonômicas e neuroendócrinas. O objetivo deste trabalho é o de se determinar se estas respostas ocorrem, assim como o de identificar suas características qualitativas e quantitativas. Seis voluntários de ambos os sexos, previamente selecionados e avaliados por testes psicológicos (SICD, Hamilton e BDI) e de cronotipagem, foram submetidos a duas condições: 1. condição controle (CC), e 2. condição de recuperação (CR). Em ambas as condições, os sujeitos foram colocados em ambiente controlado, com coleta de material destinado a dosagens de ACTH, adrenalina, cortisol, prolactina, TSH e GH (hormônios envolvidos com as respostas ao estresse), a cada 15 minutos, por 2 horas, com a primeira coleta 30 minutos antes do início dos procedimentos. Em ambas as condições, os sujeitos repousaram durante estes 30 minutos. Na CC os sujeitos permaneceram em repouso e na CR foram submetidos aos processos de RecMem, com seguimento psicoterapêutico subseqüente. Os dados obtidos foram avaliados quanto ao perfil das curvas tempo e resposta para cada hormônio e submetidos a testes estatísticos de comparação da secreção hormonal em ambas as condições. Concluímos que existiram respostas autonômicas e neuroendócrinas compatíveis com estresse psicológico que não são constantes em todos os sujeitos, onde se ressalta a variabilidade das respostas individuais obtidas. / Several procedures are capable to induce retrieval of traumatic memories (RecMem). Psychotherapy techniques have been used to reduce the traumatic memories emotional response through rebuilding and re-meaning of the traumatic memories based on the subject´s resilience. Clinical signs of autonomic activation may be seen during RecMem, not representing reactions to external stressors. On the contrary, they are the result of psychic inputs internally generated. Therefore, it is possible to speculate that they can act as pure psychological stressors and, as such, able to induce autonomic and neuroendocrine responses. The aim of the present report is to determine whether these responses actually happen, as well as to determine their qualitative and quantitative characteristics. Six volunteers of both sexes, previously selected, and submitted to psychological testing (SCID, Hamilton and BDI) as well as chronotype determination, were submitted to two conditions: 1. Control condition (CC) and 2. Retrieval condition (CR). The subjects were placed in a controlled environment in both conditions, with ACTH, cortisol, adrenalin, prolactin, TSH and GH (stress related hormones) blood testing at every 15 minutes, for 2 hours; the first sample was obtained 30 minutes before the beginning of the procedures. In both conditions the subjects rested during these 30 minutes. In the CC the subjects remained resting, and in the CR were submitted to RecMem procedures followed by psychotherapeutic support. The resulting data were analyzed in their time-response curve profiles as well as were submitted to hormonal secretion statistical evaluation in both conditions. We conclude for autonomic and neuroendocrine responses compatible with psychological stress, that are not the same in all subjects, high lightening the variability of individual obtained responses.