Goal: To determine whether the Cortisol Awakening Response (CAR) associates with treatment response and course in hospital for inpatients with major depressive disorder (MDD). Methods: The CAR was measured at admission and discharge in patients completing a four-week inpatient program for MDD. Self-report questionnaires were used to assess changes in depression, anxiety, and perceived stress. Results: Over the four week hospital stay measures of CAR reactivity (Delta, AUCi) decreased, but there was no significant correlation between the change in CAR reactivity and change in clinical symptoms. Cross-sectional measurements of the CAR reactivity at both admission and discharge were strongly correlated with the drop in depression scores in hospital. Furthermore, poor treatment responders had a significantly lower CAR reactivity at both admission and discharge than did good responders. Conclusion: Individuals with higher CAR reactivity at admission and discharge had the greatest reduction in depression over the course of treatment.

Goal: To determine whether the Cortisol Awakening Response (CAR) associates with treatment response and course in hospital for inpatients with major depressive disorder (MDD). Methods: The CAR was measured at admission and discharge in patients completing a four-week inpatient program for MDD. Self-report questionnaires were used to assess changes in depression, anxiety, and perceived stress. Results: Over the four week hospital stay measures of CAR reactivity (Delta, AUCi) decreased, but there was no significant correlation between the change in CAR reactivity and change in clinical symptoms. Cross-sectional measurements of the CAR reactivity at both admission and discharge were strongly correlated with the drop in depression scores in hospital. Furthermore, poor treatment responders had a significantly lower CAR reactivity at both admission and discharge than did good responders. Conclusion: Individuals with higher CAR reactivity at admission and discharge had the greatest reduction in depression over the course of treatment.

In dieser Arbeit wurde bei 137 Probanden im Alter zwischen 8 und 14 Jahren untersucht, inwiefern sich die Basalcortisolsekretion sowie die Cortisol Awakening Response bei Kindern und Jugendlichen mit internalisierenden oder externalisierenden Störungsbildern von gesunden Kindern und Jugendlichen unterscheiden. Außerdem wurde der Einfluss schlafbezogener Faktoren wie Schlafdauer, Zeitpunkt des Erwachens, Grad der Erholung und Schlafqualität auf die beiden Parameter untersucht. Diagnosegruppe, Schlafqualität und Grad der Erholung zeigten dabei keinen Einfluss auf die Cortisolparameter. Eine kurze Schlafdauer, frühes Erwachen, weibliches Geschlecht und höheres Alter der Probanden, zeigten eine signifikante Assoziation mit höheren Cortisolparametern. Die Interpretation einer HPA- Achsen- Dysregulation als diagnostischer Marker für psychiatrische Störungsbilder im Kindes- und Jugendalter sollte daher kritisch betrachtet werden. Co- Faktoren wie Geschlecht, Alter des Probanden, Schlafdauer und Zeitpunkt des Erwachens scheinen sowohl die basale Cortisolsekretion, als auch die CAR in signifikantem Maße zu beeinflussen und sollten in zukünftigen Studien zur Rolle der HPA- Achsen- Funktion im Rahmen psychiatrischer Störungsbilder sorgfältig kontrolliert werden.

abstract: Built upon Control Value Theory, this dissertation consists of two studies that examine university students’ future-oriented motivation, socio-emotional regulation, and diurnal cortisol patterns in understanding students’ well-being in the academic-context. Study 1 examined the roles that Learning-related Hopelessness and Future Time Perspective Connectedness play in predicting students’ diurnal cortisol patterns, diurnal cortisol slope (DS) and cortisol awakening response (CAR). Self-reported surveys were collected (N = 60), and diurnal cortisol samples were provided over two waves, the week before a mid-term examination (n = 46), and the week during students’ mid-term (n = 40). Using multi-nomial logistic regression, results showed that Learning-related Hopelessness was not predictive of diurnal cortisol pattern change after adjusting for key covariates; and that Future Time Perspective Connectedness predicted higher likelihood for students to have low CAR across both waves of data collection. Study 2 examined students’ future-oriented motivation (Future Time Perspective Value) and socio-emotional regulation (Effortful Control and Social Support) in predicting diurnal cortisol patterns over the course of a semester. Self-reported surveys were collected (N = 67), and diurnal cortisol samples were provided over three waves of data collection, at the beginning of the semester (n = 63), during a stressful academic period (n = 47), and during a relaxation phase near the end of the semester (n = 43). Results from RM ANCOVA showed that Non-academic Social Support was negatively associated with CAR at the beginning of the semester. Multi-nomial logistics regression results indicated that Future Time Perspective Value and Academic Social Support jointly predicted CAR pattern change. Specifically, the interaction term marginally predicted a higher likelihood of students switching from having high CAR at the beginning or stressful times in the semester to having low CAR at the end the semester, compared to those who had low CAR over all three waves. The two studies have major limits in sample size, which restricted the full inclusion of all hypothesized covariates in statistical models, and compromised interpretability of the data. However, the methodology and theoretical implications are unique, providing contributions to educational research, specifically with regard to post-secondary students’ academic experience and well-being. / Dissertation/Thesis / Doctoral Dissertation Family and Human Development 2017

Posttraumatic stress disorder (PTSD) is a trauma-related disorder that may develop in response to traumatic or stressful events. Dysfunction of the Hypothalamic-Pituitary-Adrenal (HPA) axis has been implicated in the disorder. Studies support such dysfunction as being a consequence of PTSD, rather than a precursor. However, most studies of the HPA are either cross-sectional or have been carried out in adults. The aim of the present study was to identify whether HPA dysregulation interacts with stressful experiences to increase the likelihood of developing PTSD symptoms in a community-recruited sample of healthy adolescent girls. Adolescent girls (N = 550) and one of their parents participated. Adolescents’ clinical symptoms were assessed at baseline and at a nine month follow-up. Saliva samples were collected from all adolescent participants at waking, 30 minutes after waking, and 8 pm on 3 consecutive days. Flattened diurnal slope of cortisol at baseline was associated with increased PTSD symptoms nine months later. Baseline cortisol awakening response (CAR) per se was not prospectively related to developing PTSD symptoms, but its interactions with stressful experience was associated with elevated PTSD symptoms at follow-up. Effects were small and need to be replicated in samples with more severe stressors, as well as more clinical levels of PTSD. Nevertheless, findings suggest that dysregulated basal HPA functioning may be involved in the development of PTSD symptoms.

Ce mémoire débute avec deux chapitres portant sur les problèmes des conduites et la régulation du stress, notamment sur l’axe hypothalamique-pituitaire-surrénal (HPS). Ensuite, la littérature est résumée et nous voyons que les études qui cherchent à établir un lien entre les problèmes des conduites et l’axe HPS ont trouvé des résultats différents et parfois contradictoires. Le chapitre suivant illustre les problèmes méthodologiques qui pourraient expliquer ces résultats différents. Vient ensuite l’étude présentée dans ce mémoire qui cherche à établir un lien entre la réponse cortisolaire à l’éveil (RCE), considérée comme un bon indice du fonctionnent de l’axe HPS, et les problèmes de conduites chez l’enfant. De plus, les émotions négatives ont été associées avec les problèmes des conduites ainsi qu’aux dysfonctions de l’axe HPS, notamment le RCE. L’étude présentée dans ce mémoire cherche aussi à établir si les émotions négatives pourrait être une variable médiatrice dans la relation potentielle entre la RCE et les problèmes des conduites. L’étude révèle que pour les garçons mais pas pour les filles, une RCE réduite est associée avec les émotions négatives, ce qui est successivement associé avec les problèmes des conduites. Le dernier chapitre du mémoire examine les implications théoriques de cette médiatisation et propose également des pistes psychobiologiques pour expliquer les différences sexuelles observées. / This thesis begins with two chapters which discuss conduct problems and stress regulation, with a focus on the hypothalamic-pituitary-adrenal (HPA) axis. Subsequently, the literature is reviewed and we see that with regards to the relationship between conduct problems and HPA axis activity, the findings are inconsistent. It is possible that methodological considerations underlie the inconsistency found in the literature and the following chapter is concerned with methodology. This is followed by the featured study presented in this thesis which examines the link between the cortisol awakening response (CAR), which is considered a good indicator of HPA axis functioning, and conduct problems in children. Further, negative affect has been linked to both conduct problems and the Cortisol Awakening Response (CAR). Thus it was hypothesized that negative affect acts as a mediator in the cortisol-conduct problems relationship. The featured study found that a reduced CAR was associated with both negative affect and conduct problems, however only in boys and not in girls. Further, the mediation hypothesis was supported in boys. The last chapter in this thesis discusses the implications of this mediation finding for theories of conduct problems as well as proposing some psychobiological mechanisms to explain the sex differences found.

A depressão pós-parto (DPP) tem sido associada com alterações no funcionamento do eixo hipotálamo-hipófise-adrenal (HHA), mas pouco se sabe do envolvimento de estruturas cerebrais, ou outros mecanismos subjacentes a estas alterações. Uma hipótese fundamental é que o estresse inerente ao período puerperal, vulnerabilidade individual e, principalmente, as alterações hormonais decorrentes do final da gravidez desempenham um importante papel causal nas alterações do eixo HHA e na incidência da DPP. Estudos sobre o transtorno depressivo maior mostram que alterações funcionais em áreas cerebrais como o giro do cíngulo anterior (GCA) estão relacionadas com humor deprimido, e outros pesquisadores investigaram a relação entre a neuroquímica do GCA e a atividade do eixo HHA. Pesquisas sobre genes de interesse do eixo HHA também têm reportado associações entre polimorfismos nestes genes e alterações nos níveis de cortisol. O presente trabalho testou a hipótese de que mulheres deprimidas no puerpério remoto apresentariam atenuação no funcionamento do eixo HHA, medido pelos níveis de cortisol em 30 minutos após o despertar (CAR) e ao longo da variação diurna (VD); e também que polimorfismos em um gene do eixo HHA, o gene promotor do receptor do tipo 1 do hormônio liberador de corticotrofina (CRHR1), estariam associados com sintomas depressivos no puerpério para prever os níveis de cortisol; e finalmente que as alterações verificadas no funcionamento do eixo HHA de puérperas deprimidas teriam relação com a neuroquímica do GCA. Os resultados indicaram que (1) ao redor do sexto mês após o parto, o CAR e a VD estavam atenuados em puérperas deprimidas comparadas com puérperas eutímicas, e com controles saudáveis não-puérperas; (2) os metabólitos presentes no GCA tinham correlação com as medidas do eixo HHA nas puérperas deprimidas; e (3) a presença de sintomas depressivos em associação com polimorfismos do CRHR1 previram alterações nos níveis de cortisol. No geral, estes resultados sugerem que as alterações do eixo HHA de puérperas deprimidas no puerpério tardio estão associadas com fatores genéticos e com a neuroquímica funcional do GCA / Postpartum depression (PPD) has been associated with changes in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but little is known about the involvement of brain structures, or other mechanisms underlying these changes. A key assumption is that stress inherent to the puerperal period, individual vulnerability, and especially the hormonal changes resulting from the end of pregnancy play an important causal role in the alterations of the HPA axis and in the incidence of PPD. Studies on major depressive disorder show that functional changes in brain areas, such as the anterior cingulate gyrus (ACG), are related to depressed mood, and other researchers investigated the relation between the neurochemistry of the ACG and the activity of the HPA axis. Research on the HPA axis genes of interest have also reported associations between polymorphisms in these genes and changes in cortisol levels. The present study tested the hypothesis that depressed women in the remote postpartum period would show attenuation in the functioning of the HPA axis, measured by cortisol levels 30 minutes after awakening (cortisol awakening response, CAR) and by diurnal variation (DV) throughout the day; and also that polymorphisms in a gene of the HPA axis, the promoter gene of the corticotropin releasing hormone receptor type 1 (CRH-R1), would present association with depressive symptoms in the postpartum period to predict the levels of cortisol; and finally that the changes in the functioning of the HPA axis of postpartum depressed women have a relationship with the neurochemistry of the ACG. Results indicated that (1) around the sixth month after delivery, CAR and DV were attenuated in depressed postpartum women compared with euthymic postpartum women and with non-postpartum healthy control women; (2) metabolites present in the ACG showed correlation with measures of the HPA axis in depressed postpartum women; and (3) the presence of depressive symptoms in association with CRHR1 polymorphisms predicted changes in cortisol levels. Overall, these results suggest that changes in the functioning of the HPA axis of depressed postpartum women in the remote postpartum period are associated with genetic factors and with the functional neurochemistry of the ACG

A depressão pós-parto (DPP) tem sido associada com alterações no funcionamento do eixo hipotálamo-hipófise-adrenal (HHA), mas pouco se sabe do envolvimento de estruturas cerebrais, ou outros mecanismos subjacentes a estas alterações. Uma hipótese fundamental é que o estresse inerente ao período puerperal, vulnerabilidade individual e, principalmente, as alterações hormonais decorrentes do final da gravidez desempenham um importante papel causal nas alterações do eixo HHA e na incidência da DPP. Estudos sobre o transtorno depressivo maior mostram que alterações funcionais em áreas cerebrais como o giro do cíngulo anterior (GCA) estão relacionadas com humor deprimido, e outros pesquisadores investigaram a relação entre a neuroquímica do GCA e a atividade do eixo HHA. Pesquisas sobre genes de interesse do eixo HHA também têm reportado associações entre polimorfismos nestes genes e alterações nos níveis de cortisol. O presente trabalho testou a hipótese de que mulheres deprimidas no puerpério remoto apresentariam atenuação no funcionamento do eixo HHA, medido pelos níveis de cortisol em 30 minutos após o despertar (CAR) e ao longo da variação diurna (VD); e também que polimorfismos em um gene do eixo HHA, o gene promotor do receptor do tipo 1 do hormônio liberador de corticotrofina (CRHR1), estariam associados com sintomas depressivos no puerpério para prever os níveis de cortisol; e finalmente que as alterações verificadas no funcionamento do eixo HHA de puérperas deprimidas teriam relação com a neuroquímica do GCA. Os resultados indicaram que (1) ao redor do sexto mês após o parto, o CAR e a VD estavam atenuados em puérperas deprimidas comparadas com puérperas eutímicas, e com controles saudáveis não-puérperas; (2) os metabólitos presentes no GCA tinham correlação com as medidas do eixo HHA nas puérperas deprimidas; e (3) a presença de sintomas depressivos em associação com polimorfismos do CRHR1 previram alterações nos níveis de cortisol. No geral, estes resultados sugerem que as alterações do eixo HHA de puérperas deprimidas no puerpério tardio estão associadas com fatores genéticos e com a neuroquímica funcional do GCA / Postpartum depression (PPD) has been associated with changes in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but little is known about the involvement of brain structures, or other mechanisms underlying these changes. A key assumption is that stress inherent to the puerperal period, individual vulnerability, and especially the hormonal changes resulting from the end of pregnancy play an important causal role in the alterations of the HPA axis and in the incidence of PPD. Studies on major depressive disorder show that functional changes in brain areas, such as the anterior cingulate gyrus (ACG), are related to depressed mood, and other researchers investigated the relation between the neurochemistry of the ACG and the activity of the HPA axis. Research on the HPA axis genes of interest have also reported associations between polymorphisms in these genes and changes in cortisol levels. The present study tested the hypothesis that depressed women in the remote postpartum period would show attenuation in the functioning of the HPA axis, measured by cortisol levels 30 minutes after awakening (cortisol awakening response, CAR) and by diurnal variation (DV) throughout the day; and also that polymorphisms in a gene of the HPA axis, the promoter gene of the corticotropin releasing hormone receptor type 1 (CRH-R1), would present association with depressive symptoms in the postpartum period to predict the levels of cortisol; and finally that the changes in the functioning of the HPA axis of postpartum depressed women have a relationship with the neurochemistry of the ACG. Results indicated that (1) around the sixth month after delivery, CAR and DV were attenuated in depressed postpartum women compared with euthymic postpartum women and with non-postpartum healthy control women; (2) metabolites present in the ACG showed correlation with measures of the HPA axis in depressed postpartum women; and (3) the presence of depressive symptoms in association with CRHR1 polymorphisms predicted changes in cortisol levels. Overall, these results suggest that changes in the functioning of the HPA axis of depressed postpartum women in the remote postpartum period are associated with genetic factors and with the functional neurochemistry of the ACG

During pregnancy, the basal activity is increased in both of our major stress response systems: the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. At the same time, the reactivity towards stressors is reduced. These alterations sustain maternal and fetal homeostasis, and are involved in the regulation of gestational length. Although the feto-placental hormone synthesis produces the main endocrinological changes, also the central nervous system undergoes adaptation. Together, these profound adjustments have been suggested to make women’s mental health more vulnerable during pregnancy and postpartum period. The aim of this thesis was to examine factors connected to physiological stress responses during the late pregnancy in relation to pain, labour onset, emotional reactivity, and mental health. The first study examined the pain and sympathetic response during cold stress, in relation to time to delivery. Women with fewer days to spontaneous delivery had lower sympathetic reactivity, while no pain measure was associated with time to delivery. In the second study, acoustic startle response modulation was employed to study emotional reactivity during late gestation, and at four to six weeks postpartum. The startle response was measured by eye-blink electromyography, while the participants watched pleasant and unpleasant pictures, and positive and negative anticipation stimuli. A significant reduction in startle modulation by anticipation was found during the postpartum assessment. However, no startle modulation by pleasant, or unpleasant, pictures was detected at either time-point. The serum level of allopregnanolone, a neurosteroid implied in pregnancy-induced hyporeactivity, was analysed in relation to self-reported symptoms of anxiety and depression. Although the participants reported low levels of depression, the women with the highest depression scores had significantly lower levels of serum allopregnanolone. There was no correlation between allopregnanolone and anxiety scores. In the fourth study, the cortisol awakening response was compared between women with depression during pregnancy, women with depression prior to pregnancy, and women who had never suffered from depression. No group differences in cortisol awakening response during late pregnancy were found. The results are in line with the previously described pregnancy-induced hyporesponsiveness, and add to the knowledge on maternal stress hyporeactivity, gestational length, and maternal mental health.

Ce mémoire débute avec deux chapitres portant sur les problèmes des conduites et la régulation du stress, notamment sur l’axe hypothalamique-pituitaire-surrénal (HPS). Ensuite, la littérature est résumée et nous voyons que les études qui cherchent à établir un lien entre les problèmes des conduites et l’axe HPS ont trouvé des résultats différents et parfois contradictoires. Le chapitre suivant illustre les problèmes méthodologiques qui pourraient expliquer ces résultats différents. Vient ensuite l’étude présentée dans ce mémoire qui cherche à établir un lien entre la réponse cortisolaire à l’éveil (RCE), considérée comme un bon indice du fonctionnent de l’axe HPS, et les problèmes de conduites chez l’enfant. De plus, les émotions négatives ont été associées avec les problèmes des conduites ainsi qu’aux dysfonctions de l’axe HPS, notamment le RCE. L’étude présentée dans ce mémoire cherche aussi à établir si les émotions négatives pourrait être une variable médiatrice dans la relation potentielle entre la RCE et les problèmes des conduites. L’étude révèle que pour les garçons mais pas pour les filles, une RCE réduite est associée avec les émotions négatives, ce qui est successivement associé avec les problèmes des conduites. Le dernier chapitre du mémoire examine les implications théoriques de cette médiatisation et propose également des pistes psychobiologiques pour expliquer les différences sexuelles observées. / This thesis begins with two chapters which discuss conduct problems and stress regulation, with a focus on the hypothalamic-pituitary-adrenal (HPA) axis. Subsequently, the literature is reviewed and we see that with regards to the relationship between conduct problems and HPA axis activity, the findings are inconsistent. It is possible that methodological considerations underlie the inconsistency found in the literature and the following chapter is concerned with methodology. This is followed by the featured study presented in this thesis which examines the link between the cortisol awakening response (CAR), which is considered a good indicator of HPA axis functioning, and conduct problems in children. Further, negative affect has been linked to both conduct problems and the Cortisol Awakening Response (CAR). Thus it was hypothesized that negative affect acts as a mediator in the cortisol-conduct problems relationship. The featured study found that a reduced CAR was associated with both negative affect and conduct problems, however only in boys and not in girls. Further, the mediation hypothesis was supported in boys. The last chapter in this thesis discusses the implications of this mediation finding for theories of conduct problems as well as proposing some psychobiological mechanisms to explain the sex differences found.