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Emotion Regulation refers to the process of controlling our emotions. However, the brain regions which are involved in emotional processes, such as the prefrontal cortices, are the last regions to be developed throughout the human brain. Those who are most affected by this slow development are adolescents especially since they undergo hormonal and neural changes. Previous research has shown mindfulness meditation improves emotional stability and inhibitory control. Since our brain is not fully developed until the age of 25, it is particularly interesting to get knowledge of the effect of mindfulness on emotion regulation in adolescents, which is the aim of this thesis. A total of three studies met the inclusion criteria and were included in this systematic review. The results showed a larger reaction in the amplitude of P2, N2, and late positive potentials on both negative and positive stimuli but not neutral stimuli. Differences were observed in the high vs low mindfulness adolescents in frontal EEG asymmetry during emotion regulation tasks. These findings suggest that even brief mindfulness can have a positive effect on emotion regulation processes by enhancing prefrontal cortices. These findings contribute to the understanding of whether mindfulness affects emotional regulation in a developing brain. However, future research is needed to clarify the effects of mindfulness on emotion regulation in adolescents.

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In recent years, screening approaches known as two-step methods have been proposed to detect gene-environment interactions for genome-wide association studies (GWAS). Genetic and environmental factors are believed to affect disease outcome as well as various quantitative traits such as height and blood pressure. The performance of the two-step methods has not been demonstrated in the quantitative trait setting. This thesis examines the method proposed by Wang and Abbott (2008) for generating genotyped markers in linkage disequilibrium (LD) and takes this approach in simulating data pertaining to a quantitative trait. The simulation results demonstrate that the two-step methods maintain type I error and have power to detect the quantitative trait locus. In this setting, the EG method (Murcray et al., 2009) is influenced by the strength and structure of the gene-environment dependency, the sample type, and the disease model. As such, the power of the EG method can fluctuate depending on the type of data while the DG method (Kooperberg and LeBlanc, 2008) remains fairly robust across a wide range of scenarios. The performance of the combined two-step approaches (EDGE (Gauderman et al., 2013) and H2 (Murcray et al., 2011) methods) tends to favour the more powerful underlying method. The power of the EDGE method can be improved if DG and EG demonstrates similar power while the H2 method can be made more powerful by choosing the appropriate parameters. / Thesis / Master of Science (MSc)

La survie d'un individu repose essentiellement sur sa capacité d’adaptation à des conditions de vie en constante évolution. Il existe une grande variabilité entre les individus concernant leur réponse au stress chronique, définissant le concept de résilience. Il s’agit d’un mécanisme d'adaptation actif correspondant à la capacité d'un individu à éviter les conséquences négatives sociales, psychologiques et biologiques d'un stress extrême, qui compromettraient son bien-être psychologique ou physique. Le phénomène est complexe et fait intervenir de nombreuses structures cérébrales et de nombreux neurotransmetteurs. Parmi les systèmes neuropeptidergiques, les opioïdes endogènes, comme les enképhalines (ENKs), seraient des cibles potentiellement impliquées dans ces variations naturelles et pourraient ainsi, être un élément déterminant de la capacité d'adaptation individuelle, au cours de l'exposition au stress chronique. Dans une précédente étude de l’équipe du Dr Guy Drolet, il avait été démontré que les niveaux d'expression de l'ARNm des ENKs étaient diminués dans le noyau basolatéral de l’amygdale (BLA) chez les rats vulnérables après un stress chronique de défaite sociale (SCDS). De plus, l’inhibition des ENKs dans la BLA permettait de reproduire un phénotype de vulnérabilité chez le rat, démontrant ainsi le rôle prépondérant de la circuiterie des ENKs dans le développement de la résilience. Cette thèse a pour objectif principal de comprendre la contribution dans la résilience au stress chronique du circuit des ENKs via les récepteurs opioïdergiques Delta (DOPr), tant au niveau neuroanatomique que fonctionnel. Nous avons, tout d’abord, examiné par hybridation in situ, les niveaux d’expression des ENKs dans la BLA chez la souris après un SCDS : comme chez le rat, les souris vulnérables présentaient une diminution de l’ARNm des ENKs dans la BLA par rapport aux animaux résilients et contrôles. Ce résultat confirme une conservation entre les rongeurs concernant l’implication des ENKs dans la résilience. Par la suite, nous avons évalué les niveaux d’expression de DOPr dans les structures cibles de la BLA. Nous avons spécifiquement ciblé l’hippocampe qui entretient un dialogue privilégié avec l’amygdale dans la réponse au stress et dans lequel, DOPr est fortement exprimé. L’expression de l’ARNm de DOPr était réduite dans la région CA1 de l'hippocampe ventral (CA1-vHPC) chez les souris vulnérables tandis que le niveau était maintenu chez les animaux résilients comme chez les témoins. Afin de disséquer l’importance de la signalisation DOPr dans le développement de la résilience, une activation pharmacologique a été effectuée : l’administration d’un agoniste de DOPr, le SNC80, dans la circulation systémique, a augmenté la proportion de souris résilientes après le SCDS. Dans un second temps, nous avons fait l’hypothèse que le maintien du niveau d’expression de DOPr au niveau du CA1-vHPC permettait de maintenir un statut oxydatif contrôlé dans les neurones, conduisant au phénotype de résilience. En effet, le rôle neuroprotecteur de l’activation de DOPr contre les dommages oxydatifs cellulaires (i.e. stress oxydatif, SO) a été démontré dans différents contextes, notamment chez le rat ischémique. Nous avons ainsi observé des marqueurs du SO - comme les neurones « sombres » ou la dilatation du réticulum endoplasmique - par microscopie électronique à transmission (MET) après un SCDS, avec ou sans traitement au SNC80. Nous avons spécifiquement ciblé les neurones excitateurs et inhibiteurs du CA1-vHPC. Nous avons pu mettre en évidence que le SNC80 diminuait la proportion de certains marqueurs du SO, autant chez les animaux résilients que vulnérables, tandis que pour d’autres marqueurs, il restaurait les dommages oxydatifs induits par le SCDS, uniquement chez les vulnérables. Enfin, une étude ultrastructurelle des mitochondries - comme leur nombre et leur taille - par MET, a confirmé ces résultats où le SNC80 restaure les effets délétères du stress uniquement chez les souris vulnérables. Ces résultats ont permis de démontrer que l’activation de la signalisation DOPr est responsable de la résilience en maintenant un statut oxydatif contrôlé dans les neurones excitateurs et inhibiteurs du CA1-vHPC. Pour finir, une étude moléculaire a été effectuée par western blot, dans l’hippocampe total, afin de déterminer la cible moléculaire de DOPr impliquée dans le SO permettant la résilience. Les complexes de la chaîne respiratoire mitochondriale et des enzymes antioxydantes ont été ciblés. L’activation de DOPr a résulté en une diminution de l’expression de certains complexes sans dévoiler la cible moléculaire exacte de DOPr permettant la résilience au stress chronique. Collectivement, ces études proposent un nouveau mécanisme par lequel la signalisation ENK-DOPr permettrait le développement de la résilience au stress chronique en favorisant un état oxydatif contrôlé dans les neurones de l'hippocampe. / The survival of an individual is essentially based on his ability to adapt to ever-changing living conditions. There is a great variability among individuals regarding their response to chronic stress, defining the concept of resilience. Resilience is an active coping mechanism corresponding to an individual's ability to avoid the negative social, psychological and biological consequences of extreme stress that would compromise their psychological or physical well-being. The phenomenon is complex and recruits many brain structures and several neurotransmitters. Among the neuropeptidergic systems, endogenous opioids, such as enkephalins (ENKs), could be potential targets involved in the occurrence of these natural variations and could thus be a crucial determinant of an individual’s capacity to adapt to chronic stress. In a previous study by Dr Guy Drolet's team, ENK mRNA expression levels were shown to be decreased in the nucleus of basolateral amygdala (BLA) in vulnerable rats after chronic social defeat stress (CSDS). In addition, the inhibition of ENKs in the BLA reproduced this vulnerability phenotype in rats, thus demonstrating the preponderant role of the ENK circuitry in the development of resilience. The main objective of this thesis was to investigate the contribution of the ENKs circuit via the Delta opioid receptors (DOPr) in the chronic stress resilience, both at the neuroanatomical and functional levels. We first examined, by in situ hybridization, the expression levels of ENKs in BLA in mice after CSDS: as in rats, susceptible mice showed a decrease in ENK mRNA in BLA compared to resilient and controls animals. This result confirmed the implication of the ENKs in resilience in rodents. Subsequently, we evaluated the expression levels of DOPr in the target structures of the BLA. We specifically targeted the hippocampus, which maintains a privileged dialogue with the amygdala in the response to stress and in which DOPr is strongly expressed. DOPr mRNA expression was reduced in the ventral hippocampal CA1 region (CA1-vHPC) in vulnerable mice while the level was preserved in both resilient and control animals. In order to dissect the importance of DOPr signaling in the development of resilience, pharmacological activation was performed: the administration of a DOPr agonist, SNC80, into the systemic circulation, increased the proportion of resilient mice after the CSDS. In a second step, we hypothesized that the maintenance of DOPr mRNA expression in CA1-vHPC allowed the preservation of a controlled oxidative status in neurons, leading to the phenotype of resilience. Indeed, the neuroprotective role of DOPr activation against cellular oxidative damages (i.e. oxidative stress, OS) was demonstrated in different contexts, particularly in ischemic rats. Thus, we observed markers of OS - such as dark neurons and endoplasmic reticulum dilation - by transmission electron microscopy (TEM) after CSDS, with or without SNC80 treatment. We specifically targeted excitatory and inhibitory neurons of CA1-vHPC. We were able to demonstrate that the SNC80 decreased the proportion of some OS markers in both resilient and vulnerable animals, while for other markers, it restored CSDS-induced oxidative damages only in vulnerable mice. Finally, an ultrastructural study of mitochondria by TEM, confirmed these results where the SNC80 restored the deleterious effects of stress only in vulnerable mice. These results demonstrated that activation of DOPr signaling is responsible for resilience by the preservation of a controlled oxidative status in excitatory and inhibitory neurons of CA1- vHPC. Finally, a molecular study was performed by western blot, in the total hippocampus, to determine the molecular target of DOPr involved in OS, allowing stress resilience. Complexes of the mitochondrial respiratory chain and antioxidant enzymes were measured. The activation of DOPr showed a decrease in the expression of certain complexes without revealing the exact molecular target of DOPr allowing resilience to chronic stress. Overall, these studies propose a novel mechanism by which ENK-DOPr signaling promotes resilience to chronic stress by enhancing a controlled oxidative status in hippocampal neurons.

Unipolar depression is a leading cause of disability and overall burden of disease for millions of individuals across the world. Depressive symptoms (e.g., depressed mood, anhedonia, fatigue, feelings of worthlessness, difficulties concentrating, etc.) can drastically affect an individual's life leading to occupational, social, and personal impairment. Past research shows significant ethnic and racial differences in depression rates and treatment. Moreover, previous literature has also begun to explore the multidimensional nature of depression, investigating its occasion-like (or episodic) and trait-like (or stable) factors. However, prior studies have not explored differences in occasion and trait depression by race or ethnicity, nor have they explored these questions in nurses, a group that faces substantial workplace stressors. To redress these gaps, the current study investigated trait and occasion depression in a large sample of nurses (N = 390) tracked across 12 months and aimed to understand whether trait versus occasion rates of depression differed by racial and ethnic minority status. Findings indicated substantially more trait depression (65.93%) than occasion depression (34.11%) across the year in nurses. However, there were no significant differences based on racial and ethnic minority status. Results highlight the importance of understanding depression as a much more stable aspect of an individual's personality, instead of merely viewing it as a direct response to changes in an individual's external environment. Additionally, findings suggest that focusing on adaptation of more long-term skills to target trait-like depression may be more helpful for nurses experiencing depression.

AN ABSTRACT OF THE DISSERTATION OFKaleigh C. Best, for the Doctor of Philosophy degree in Anthropology, presented on May 12, 2023, at Southern Illinois University Carbondale. TITLE: AN INVESTIGATION INTO INTRAINDIVIDUAL VARIATION IN HUMAN SKELETAL SEXUAL TRAIT MORPHOLOGYMAJOR PROFESSOR: Dr. Izumi ShimadaSex estimation is the most vital component of the biological profile assessment as several other subsequent analyses across biological anthropology rely on the correct identification of biological sex. This is especially important in times of commingling, fragmentary and partial remains, in inconsistent sex estimation, or in studies of sex estimation variation. While a multitude of studies have contributed to the documentation of similarities and differences in the morphological expression of a specific trait and how well this trait can be used to classify the sex of an unknown individual, how the expression of these morphological traits relate to each other within the individual has been poorly studied. Further, although several intrinsic and extrinsic factors are known to contribute to sexual trait expression, how they interact to produce morphology, and how that morphology may change in response to different biological conditions is not well understood. This dissertation utilizes 3D scans of 235 individuals collected from the University of Tennessee Donated Skeletal Collection (UTK) and the Robert J. Terry Osteological Collection (Terry) to examine sexual trait expression across the cranium, mandible, os coxae, sacrum and scapula. Specifically, it evaluates: 1) if sexual trait expression is correlated between skeletal regions including localized anatomical regions, through matrix correlation and Pearson correlation tests, 2) if age affects morphological sexual trait expression through M/ANOVA and if so, how and when these changes occur using ANOVA and Tukey post-hoc tests, 3) if the magnitude and pattern of sexual trait expression varies between populations through M/ANOVA and matrix correlations, 4) using discriminate function analyses, how well geometric morphometric analyses capture sexual trait expression compared to published rates, and 5) through M/ANOVA and discriminant function analyses, which intraindividual skeletal regions are the most accurate in sex classification analyses compared to others. For each skeletal element, landmarks were placed on each scan and sexual trait expression and an intra observer placement study was conducted. The landmark configurations were then subjected to a generalized Procrustes analysis, variance- covariance matrices were generated, and a principal component (PC) analyses in MorphoJ for combined sex data, derived male and females from combined sex data, and for independently input males and females. PCs were visually interpreted and subjected to M/ANOVA for three age groups: 18-29, 30-45, and 45 and older. PCs were then subjected to stepwise linear discriminant function analyses with leave- one-out cross validation. The first five PCs for each element were then utilized for a matrix correlation test and evaluated using a strength of correlation test (Chan et al 2003) and for significance using a Pearson’s correlation test. Results indicate that for intraobserver error is low, with scores being mostly considered excellent in reliability. For UTK data, shape changes associated with sexual trait classification were found for each of the five elements. Within these tests, many influential regions were known to sex estimation analyses, but other, such as the basicranium are currently underutilized. M/ANOVA revealed that sex was significant for all five skeletal elements, with some contributions from age and ancestry impacting sexual trait expression, however these interactions were not within a consistent pattern. Through the results of the discriminant function analyses, it appears some skeletal elements, such as the os coxae, scored higher correct classification rates than those reported in the literature, while others were on par or below reported rates. The os coxae and regions around it, were the best elements for correct sex classification accuracy, with the scapula rated as the worst. In the Terry data, sexual trait related shape changes are presented for each of the skeletal elements studied. Known morphological regions, as well as some more subtle ones, were found to be influential. M/ANOVA revealed that all elements, but the scapula had statistically significant shape changes present for sex estimation. Age and ancestry appear to contribute minimally to sexual trait morphology, but again, not in a way that is consistent, either within the collection or similarly to UTK. By examining the discriminant function analyses, some correct sex-estimation rates were on higher or on par with those reported in the literature, but others, such as the scapula were lower. This may be due the size being a larger contributor for sex estimation than shape, and the geometric morphometric analyses minimizing its effects in these analyses. Also using these tests, the os coxae was selected as the best element for high levels of sex classification accuracy, but which element was next best was different than the UTK results. This likely indicates biocultural influences are affecting sexual trait morphology and should be considered in future analyses. Significant inter-element correlations were detected in both skeletal collections, with UTK having more pairings than Terry. The most common and most statistically significant inter-element correlation across collections was between the cranium-mandible, which may be reflective of the integrated nature of these two elements. Different element correlations existed between each collection, with no clear pattern in pairings present in both collections, which may suggest that biocultural influences are impacting sexual trait expression. However, in both collections, females had more overall correlations, and more statistically significant correlations than males, although there was less of a difference between sexes in Terry than in UTK. This result may be due to circulating hormones present during puberty, which may be contributing to more correlation between elements in females and not males. It also suggests that once again, biocultural differences between the Terry and UTK collections may be impacting the magnitude and patterns of correlation. This research highlights the complex dynamic nature of sexual trait expression in bone in relation to several intrinsic and extrinsic factors. It supports the idea that sexual trait expression is not concordant between skeletal regions among the same individual and that these inter-element correlations appear to be different between skeletal collections. Likewise, it suggests that age and ancestry may minimally be affecting sexual trait expression, but not in a consistent way across skeletal elements or between collections. It also suggests that while geometric morphometrics may help in capturing shape variation, it does not always translate to higher correct classification rates. This research also supports previous literature that the os coxae is the best element for sex estimation, although is not clear on what element is next best. Future studies in sexual trait expression should account for biocultural influences, as this research suggests that sexual trait expression is influenced by poorly understood intrinsic and extrinsic factors.

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