Immediate and enduring effects of corticosterone administration during adolescence and adulthood on anxiety and depressive behavior in male rats

Previous research has shown that the stress hormone corticosterone can increase depressive and anxiety-like behavior in rats as well as dampen the HPA response to a novel stressor (Kalynchuk et aI., 2004; Johnson et aI., 2006). Several studies have also shown that adolescence is a period of increased sensitivity to the negative effects of stressors (reviewed in McCormick et aI., 2010), which are often the result of exposure to corticosterone, and yet there is no research to date examining the effects of corticosterone administration during adolescence. The purpose of these experiments is to determine both the immediate and enduring effects of prolonged exposure to corticosterone in adolescence and adulthood on anxiety-like behavior, depressive behavior, and the HPA response. In Experiment 1 adolescent and adult rats were administered an injection of 40 mg/kg of corticosterone or vehicle daily for 16 days. Ha l f of the rats were then tested on the elevated plus maze (EPM) one day after their last injection, and the following day were tested on the forced swim test (FST). After the FST, which is a stressor, blood samples were collected at three time points, and the plasma concentrations of corticosterone were determined using a radioimmunoassay. The remaining rats were left undisturbed for three weeks, and then underwent the same testing as the first group. Corticosterone treatment had little effect on anxiety-like and depressive behavior, but it did alter the HPA response to the FST. In those rats tested soon after the period of injections, corticosterone dampened the HPA response as compared to vehicle treated rats in both adolescent and adult treated rats. For the adolescent treated rats that were tested several weeks later, corticosterone treatment increased HPA response as compared to the vehicle treated rats, but the same was not true for the adult treated rats. I t was hypothesized that the lack of behavioral effects of the corticosterone treatment may be the result of the vehicle injections inducing a stress response and thereby both groups would have similarly altered behavior. In Experiment 2 rats were administered corticosterone dissolved in their drinking water with 2.5% ethanol, or jus t the 2.5% ethanol or plain water, to determine the effects of corticosterone treatment without a stressor present. The regular drinking water was replaced with treated water for 16 days either during adulthood or adolescence, and as before, rats were either tested in the FST one day after the water was removed or three weeks later. Again there was no effect of treatment on depressive behavior. Similar to what was observed in Experiment 1, corticosterone treatment dampened the HPA response to a stressor for the rats tested soon after the treatment period. However, in Experiment 2 there was no effect of treatment on HPA response in those rats tested several weeks after they were treated. These results indicate that corticosterone can have a lasting effect on the HPA when administered in adolescence by injections but not in drinking water, which is likely because of the different schedules of exposure and rates of absorption between the two administration methods.

Physical Activity and Fitness in Children with Developmental Disorder

Introduction: Developmental coordination disorder (DCD) is a prevalent condition characterized by poor motor proficiency that interferes with a child‟s activities of daily living. Children with DCD often experience compromised health-related fitness components such as cardiorespiratory fitness (CRF). Purpose: To better understand the physical activity and fitness characteristics of children with probable DCD (pDCD), with a particular focus on CRF. Specifically: (1) to present a synopsis of current literature; (2) to determine the longitudinal trajectories of CRF; (3) to compare the submaximal CRF of children with and without pDCD. Methods: A comprehensive, systematic literature review was conducted of the recent available data on fitness and physical activity and pDCD (Chapter 2). This review provided the background for the other two studies included in this thesis. In Chapter 3, a prospective cohort design was used to assess how CRF in children with pDCD changes over time (56 months) relative to a group of typically developing controls. Using a nested-case control design, 63 subjects with pDCD and 63 matched controls from the larger sample were recruited to participate in the lab-based component of the study (Chapter 4). In this investigation CRF was examined using the oxygen cost of work (VO2) during an incremental test on a cycle ergometer. Results: The literature review showed that fitness parameters, including CRF and physical activity levels, were consistently reduced in children with pDCD. Chapter 3 demonstrated that the difference in CRF between children with pDCD and typically developing children is substantial, and that it tends to increase over time. Results from VO2 assessments showed that children with pDCD utilized more oxygen to sustain the same submaximal workloads compared to typically developing children. Conclusions: Findings from this thesis have made several important contributions to our understanding of children with pDCD. Since differences in CRF between children with and without pDCD tend to worsen over time, this adds to the argument that interventions intended to improve CRF may be appropriate for children with motor difficulties. This thesis also presented the first evidence suggesting that DCD involves higher energy expenditure, and could help explain why children with pDCD perform poorly on tasks requiring CRF.

Dynamic Upper Leg Strength and Neuromuscular Function in Children, Adolescents and Adults

This study examined muscle strength, muscle performance, and neuromuscular function during contractions at different velocities across maturation stages and between sexes. Participants included pre-pubertal, late-pubertal and adult males and females. All completed 8 isometric and 8 isokinetic leg extensions at two different velocities. Peak torque (PT), rate of torque development (PrTD), electromechanical-day (EMD), rate of muscle activation (Q30), muscle activation efficiency and coactivation were determined. Sex, maturity, and velocity main effects were found in PT and PrTD, reflecting greater values in men, adults, and isometric contractions respectively. When values were normalized to quadriceps cross-sectional area (qCSA), there was still an increase with maturity. EMD decreased with maturity. Adults had greater activation efficiency than children. Overall, differences in muscle size and neuromuscular function failed to explain group differences in PT or PrTD. More research is needed to investigate why adults may be affected to a greater extent by increasing movement velocity.

Deconstructing Evidence-Based Practice and Its Application in Children to with Mental Health Disorders

This is a mixed methodology study that uses an autoethnographic approach to combine both an autobiography and a survey of practitioners who work in children’s mental health. It is largely about the implementation of Evidence-Based Practice (EBP), and the questions, concerns, experiences that I have had, and compared them with those of my fellow practitioners. In addition, it is about my journey as a mental health professional, and how I have come to recognize that in order to achieve the goals I wanted to achieve, I needed to return to university to pursue a Master’s degree. Within the research, I identify and discuss different definitions of EBP and identify several themes. I deconstruct the implementation of EBPs through the lens of Foucault and his notions of governmentality. I offer policy and practice recommendations to improve the implementation of EBP and the services received by children facing mental health issues.

The Effects of a Psychosocial Behavioural Intervention on Arterial Health in Children

This study evaluated the effects of a Leisure and Well-Being Model (LWM) psychosocial intervention on arterial health, measured by arterial stiffness and thickness, in 82 children aged 10-13 (n=41; intervention, n=41; control) over one year. The intervention was to provide children with the awareness, skill development, and application of positive emotion, personal strengths, coping, and free-time vitality. Results showed no change in arterial health for children exposed to the intervention compared to controls. However, a significant systolic blood pressure decrease was found in children exposed to the intervention and increased in those of the control group (F (1, 73) = 4.085, p = 0.047). This is the first study to show that a psychosocial intervention has a positive effect on childhood cardiovascular health within one year. Hence, if exposed for-or followed for- a longer period of time, it may be possible to see further improvements in arterial health.

The electromyographic threshold in children: Differences in neuromuscular activation during progressive exercise between boys and men

The electromyographic threshold (EMGTh), defined as an upward inflexion in the rising EMG signal during progressive exercise, is thought to reflect the onset of increased type-II MU recruitment. The study’s objective was to compare the relative exercise intensity at which the EMGTh occurs in boys vs. men. Participants included 21 men (23.4±4.1 yrs) and 23 boys (11.1±1.1 yrs). Ramped cycle-ergometry was conducted to volitional exhaustion with surface EMG recorded from the vastus lateralis muscles. The EMGTh was mathematically determined using a composite of both legs. EMGTh was detected in 95.2% of the men and in 78.3% of the boys (χ2(1, n=44) =2.69, p =.10). The boys’ EMGTh was significantly higher than the men’s (86.4±9.6 vs. 79.7±10.0% of peak power-output at exhaustion; p <.05). These findings suggest that boys activate their type-II MUs to a lesser extent than men during progressive exercise and support the hypothesis of differential child–adult MU activation.

In danger of jammed minds: A deconstructive discourse analysis of the criteria for early onset schizophrenia and imagination in children's literature

The purpose of this research is to expose and complicate those discourses of childhood imagination as demonstrated in the diagnostic criteria for early onset schizophrenia by using an antipsychiatry perspective. This will be done by evaluating those discourses alongside those found in popular children’s literature, specifically, Harry Potter and The Philosopher’s Stone, Bridge to Terabithia, and A Wrinkle in Time. Once uncovered, the underlying power discourses were then exposed. This research will then employ a minor reading as provided by Deleuze and Guattari’s (1987) approach to minor literature to demonstrate the ways in which the child can subvert those dominant discourses. The potential of literature is evaluated for its ability to provide alternative modes of experience and lines of flight for the child subjected to the diagnostic criteria of schizophrenia.

ARTERIAL STIFFNESS IN CHILDREN WITH AND WITHOUT DEVELOPMENTAL COORDINATION DISORDER

The purpose of this study was to determine whether children with potential developmental coordination disorder (p-DCD) demonstrate increased arterial stiffness and thickness compared to age and school matched controls (mean age 14.7 yrs). We also assessed whether these measures differed by sex. Compliance, distensibility, and intima-media thickness (IMT) were measured at the common carotid artery for 28 children with p-DCD and 47 controls. ECG-R-wave-toe pulse wave velocity (PWV) was also measured for 29 children with p-DCD and 45 controls. We found that compared to controls males with p-DCD had significantly higher PWV (3.8±0.2 vs. 4.1±0.3, p=0.001) and lower distensibility (0.82± 0.19 vs. 0.70± 0.17, p=0.034) while females showed no significant differences (p=0.523 and p=0.123 respectively). As a result, it is apparent that sex differences exist with respect to arterial health within this population and that children with p-DCD may be more likely to develop cardiovascular disease later in life.

The Association of Energy Intake with Body Mass in Children With and Without Probable Developmental Coordination Disorder

Objective To determine if there is an association between energy intake (EI) and overweight or obesity status (OWOB) in children with and without probable developmental coordination disorder (p-DCD). Methods 1905 children were included. The Bruininks-Oseretsky Test of Motor Proficiency was used to assess p-DCD, body mass index for OWOB, and the Harvard Food Frequency Questionnaire for EI. Comparative tests and logistic regressions were performed. Results Reported EI was similar between p-DCD and non-DCD children among boys (2291 vs. 2281 kcal/day, p=0.917), but much lower in p-DCD compared to non-DCD girls (1745 vs.. 2068 kcal/day, p=0.007). EI was negatively associated with OWOB in girls only (OR: 0.82 (0.68, 0.98)). Conclusions Girls with p-DCD have a lower reported EI compared to their non-DCD peers. EI is negatively associated with OWOB in girls with p-DCD. Future research is needed to assess longitudinally the potential impact of EI on OWOB in this population.

Autonomic Cardiovascular Control in Children and Adolescents

This thesis investigated the impact of pubertal maturation and sex on cardiovagal baroreflex sensitivity (BRS) and arterial properties of the common carotid artery (CCA), and the relationship between CCA arterial properties and BRS. This thesis also investigated the effect of orthostatic stress on arterial properties of the CCA and carotid sinus (CS), as well as their impact on BRS in response to orthostatic stress. Children and adolescents between the ages of 8-18 years were examined. To assess pubertal maturation participants were organized into five pubertal groups based on the criteria of Tanner. BRS was assessed by transfer function analysis in the low frequency range (0.05 – 0.15Hz). Pulse pressure (PP) was measured at the CCA (PPCCA) and CS (PPCS) using applanation tonometry, and at the finger (PPFinger) using photoplethysmography. Ultrasound sonography and applanation tonometry were used to determine the distensibility coefficient (DC) at the CCA (DCCCA) and CS (DCCS). A moderate posture stimulus was implemented by passively moving participants into a 50° seated-recumbent (SR) position. The results demonstrated a sex-by-maturation interaction on BRS (p= 0.019). BRS decreased from early- to post-puberty in males (p<0.01), and remained unchanged in females. Females demonstrated greater BRS compared to males post-puberty (p<0.05). CCA distensibility was not affected by sex or maturation and was not related to BRS. PPCS was greater than PPCCA (p<0.001), while PPFinger was greater than both PPCCA (p<0.001) and PPCS (p<0.001). In response to SR, the relative change in PPFinger was significantly different than the relative change in PPCCA (p<0.001) and PPCS (p<0.001), while the relative change between PPCCA and PPCS were not different. Finally, in response to SR there was a significant decrease in DCCS (p=0.001), but not DCCCA. The relative change in BRS in response to SR was significantly correlated to the relative change in DCCS (p=0.004), but not DCCCA. The findings demonstrated an important sex-dependent maturation effect on BRS in children and adolescents that was not explained by CCA distensibility. Also, the CS and CCA responded differently to orthostatic stress. The CS was more suitable to evaluate the effect of arterial distensibility on BRS in response to posture change.

Acute endocrine responses to plyometrics versus resistance exercise in children

The purpose of this study was to examine the acute hormonal responses to a bout of resistance versus plyometric exercise in young male athletes. Specifically, changes in salivary cortisol, testosterone and testosterone-to-cortisol ratio from pre- to post-exercise between the two different exercise protocols were examined. Twenty-six peri-pubertal active boys participated in this cross-over study, completing two exercise sessions. During each session, participants first completed a 30 min control period, which did not include any exercise, and then was randomly assigned to perform a 45 min of either a resistance exercise or a plyometric exercise protocol. All participants crossed over to perform the other exercise protocol during their second exercise session, a week later. Four saliva samples during each protocol were taken at: baseline, pre-exercise, 5 min post-exercise and 30 min post-exercise. Significant increases in testosterone values were reported 5 min post-exercise following the resistance protocol, but not the plyometric protocol. Both exercise protocols resulted in significant cortisol decreases overtime, as well as significant testosterone-to-cortisol ratio increases. The post-exercise increases in salivary testosterone and testosterone-to-cortisol ratio followed the typical exercise induced anabolic response seen in adults. However, the post-exercise decrease in salivary cortisol was different than the typical adult response indicating an insufficient stimulus for this age group maybe due to their stage of the biological development. Thus, in the adolescent boys, exercise appears to change the anabolic to catabolic balance in favor of anabolism.

Canadian Society for Exercise Physiology Position Paper: Resistance Training in Children and Adolescents

Many position stands and review papers have refuted the myths associated with resistance training (RT) in children and adolescents. With proper training methods, RT for children and adolescents can be relatively safe and improve overall health. The objective of this position paper and review is to highlight research and provide recommendations in aspects of RT that have not been extensively reported in the pediatric literature. In addition to the well-documented increases in muscular strength and endurance, RT has been used to improve function in pediatric patients with cystic fibrosis, cerebral palsy and burn victims. Increases in children’s muscular strength have been attributed primarily to neurological adaptations due to the disproportionately higher increase in muscle strength than in muscle size. Although most studies using anthropometric measures have not shown significant muscle hypertrophy in children, more sensitive measures such as magnetic resonance imaging and ultrasound have suggested hypertrophy may occur. There is no minimum age for RT for children. However the training and instruction must be appropriate for children and adolescents involving a proper warm-up, cool-down and an appropriate choice of exercises. It is recommended that low-to-moderate intensity resistance should be utilized 2-3 times per week on non-consecutive days, with 1-2 sets initially, progressing to 4 sets of 8-15 repetitions for 8-12 exercises. These exercises can include more advanced movements such as Olympic style lifting, plyometrics and balance training, which can enhance strength, power, co-ordination and balance. However specific guidelines for these more advanced techniques need to be established for youth. In conclusion, a RT program that is within a child’s or adolescent’s capacity, involves gradual progression under qualified instruction and supervision with appropriately sized equipment can involve more advanced or intense RT exercises which can lead to functional (i.e. muscular strength, endurance, power, balance and co-ordination) and health benefits.

Prediction of the clinical response to psychostimulant by the basal and reactive salivary cortisol in children with ADHD.

Le trouble du déficit de l’attention/hyperactivité (TDA/H) est un des troubles comportementaux le plus commun chez les enfants. TDAH a une étiologie complexe et des traitements efficaces. Le médicament le plus prescrit est le méthylphénidate, un psychostimulant qui bloque le transporteur de la dopamine et augmente la disponibilité de la dopamine dans la fente synaptique. Des études précliniques et cliniques suggèrent que le cortisol peut potentialiser les effets de la dopamine. Un dysfonctionnement du système hypothalamo-hypophyso-surrénalien (HHS) est associé avec plusieurs maladies psychiatriques comme la dépression, le trouble bipolaire, et l’anxiété. Nous avons fait l’hypothèse que le cortisol influence l’efficacité du traitement des symptômes du TDAH par le méthylphénidate. L’objectif de cette étude est de mesurer les niveaux de cortisol le matin au réveil et en réponse à une prise de sang dans un échantillon d’enfants diagnostiqué avec TDAH âgé de 8 ans. Le groupe était randomisé dans un protocole en chassé croisé et en double aveugle avec trois doses de méthylphénidate et un placebo pour une période de quatre semaines. Les enseignants et les parents ont répondu aux questionnaires SWAN et à une échelle d’évaluation des effets secondaires. Les résultats ont démontrés qu’un niveau de cortisol élevé au réveil prédit les sujets qui ne répondent pas au traitement du TDAH, si on se fie aux rapports des parents. En plus, la réactivité au stress élevé suggère un bénéfice additionnel d’une dose élevée de méthylphénidate selon les enseignants. Aussi, les parents rapportent une association entre la présence de troubles anxieux co-morbide avec le TDAH et une meilleure réponse à une dose élevée. Cette étude suggère qu’une forte réactivité de l’axe HHS améliore la réponse clinique à des doses élevées, mais qu’une élévation chronique du niveau de cortisol pourrait être un marqueur pour les non répondeurs. Les résultats de cette étude doivent être considérés comme préliminaires et nécessitent des tests plus approfondis des interactions possibles entre les médicaments utilisés pour traiter le TDAH et l’axe HHS.

Genes involved in the metabolism of fatty acids and risk for Crohn's disease in children: a candidate gene study

Contexte - La prévalence de la maladie de Crohn (MC), une maladie inflammatoire chronique du tube digestif, chez les enfants canadiens se situe parmi les plus élevées au monde. Les interactions entre les réponses immunes innées et acquises aux microbes de l'hôte pourraient être à la base de la transition de l’inflammation physiologique à une inflammation pathologique. Le leucotriène B4 (LTB4) est un modulateur clé de l'inflammation et a été associé à la MC. Nous avons postulé que les principaux gènes impliqués dans la voie métabolique du LTB4 pourrait conférer une susceptibilité accrue à l'apparition précoce de la MC. Dans cette étude, nous avons exploré les associations potentielles entre les variantes de l'ADN des gènes ALOX5 et CYP4F2 et la survenue précoce de la MC. Nous avons également examiné si les gènes sélectionnés montraient des effets parent-d'origine, influençaient les phénotypes cliniques de la MC et s'il existait des interactions gène-gène qui modifieraient la susceptibilité à développer la MC chez l’enfant. Méthodes – Dans le cadre d’une étude de cas-parents et de cas-témoins, des cas confirmés, leurs parents et des contrôles ont été recrutés à partir de trois cliniques de gastro-entérologie à travers le Canada. Les associations entre les polymorphismes de remplacement d'un nucléotide simple (SNP) dans les gènes CYP4F2 et ALOX5 ont été examinées. Les associations allélique et génotypiques ont été examinées à partir d’une analyse du génotype conditionnel à la parenté (CPG) pour le résultats cas-parents et à l’aide de table de contingence et de régression logistique pour les données de cas-contrôles. Les interactions gène-gène ont été explorées à l'aide de méthodes de réduction multi-factorielles de dimensionnalité (MDR). Résultats – L’étude de cas-parents a été menée sur 160 trios. L’analyse CPG pour 14 tag-SNP (10 dans la CYP4F2 et 4 dans le gène ALOX5) a révélé la présence d’associations alléliques ou génotypique significatives entre 3 tag-SNP dans le gène CYP4F2 (rs1272, p = 0,04, rs3093158, p = 0.00003, et rs3093145, p = 0,02). Aucune association avec les SNPs de ALOX5 n’a pu être démontrée. L’analyse de l’haplotype de CYP4F2 a montré d'importantes associations avec la MC (test omnibus p = 0,035). Deux haplotypes (GAGTTCGTAA, p = 0,05; GGCCTCGTCG, p = 0,001) montraient des signes d'association avec la MC. Aucun effet parent-d'origine n’a été observé. Les tentatives de réplication pour trois SNPs du gene CYP4F2 dans l'étude cas-témoins comportant 225 cas de MC et 330 contrôles suggèrent l’association dans un de ceux-ci (rs3093158, valeur non-corrigée de p du test unilatéral = 0,03 ; valeur corrigée de p = 0.09). La combinaison des ces deux études a révélé des interactions significatives entre les gènes CYP4F2, ALOX et NOD2. Nous n’avons pu mettre en évidence aucune interaction gène-sexe, de même qu’aucun gène associé aux phénotypes cliniques de la MC n’a pu être identifié. Conclusions - Notre étude suggère que la CYP4F2, un membre clé de la voie métabolique LTB4 est un gène candidat potentiel pour MC. Nous avons également pu mettre en évidence que les interactions entre les gènes de l'immunité adaptative (CYP4F2 et ALOX5) et les gènes de l'immunité innée (NOD2) modifient les risques de MC chez les enfants. D'autres études sur des cohortes plus importantes sont nécessaires pour confirmer ces conclusions.

Sleep spindle activity in children with ADHD

Le trouble du déficit de l’attention/hyperactivité (TDA/H) est le désordre du comportement le plus commun chez les enfants. Les études suggèrent qu'un pourcentage élevé d'enfants atteints de TDA/H souffre de problèmes de sommeil et de somnolence diurne. Le mécanisme sous-jacent à ces difficultés demeure inconnu. Plusieurs études ont suggéré que les fuseaux de sommeil jouent un rôle dans les mécanismes de protection du sommeil. L'objectif de cette étude est de comparer les fuseaux lents (11-13 Hz) et rapides (14-15 Hz) chez des enfants atteints du TDA/H et des sujets contrôles. Nous prévoyons que comparativement aux enfants contrôles, les enfants atteints du TDA/H montreront une plus faible densité des fuseaux lents et rapides, et auront des fuseaux plus courts (sec), moins amples (uV) et plus rapides (cycle/sec). Enfin, nous prévoyons que ces effets seront plus prononcés dans les dérivations cérébrales antérieures que dans les dérivations plus postérieures du cerveau. Les enregistrements polysomnographiques (PSG) du sommeil de nuit ont été menés chez 18 enfants diagnostiqués avec le TDA/H et chez 26 sujets témoins âgés entre 7 et 11 ans. Un algorithme automatique a permis de détecter les fuseaux lents et rapides sur les dérivations frontales, centrales, pariétales et occipitales. Les résultats ont montré que, les caractéristiques PSG du sommeil ne différaient pas significativement entre les deux groupes. On ne note aucune différence significative entre les groupes sur nombre/densité des fuseaux lents et rapides ainsi que sur leurs caractéristiques respectives. Cette étude suggère que les mécanismes de synchronisation du l'EEG en sommeil lent, tel que mesuré par la densité et les caractéristiques des fuseaux lents et rapides en sommeil lent ne différent pas chez les enfants atteints du TDA/H.