La lectine de Helix pomatia (HPA), extraite de la glande à albumine de l'escargot de Bourgogne et spécifique du résidu GalNAc, appartient à une nouvelle famille de lectine dite de type H. Elle est utilisée depuis plus de vingt ans comme marqueur d'adénocarcinomes (notamment du sein, du colon, du poumon) à fort pouvoir métastatique et donc faible pronostic vital. Son utilisation comme outil de routine en oncologie est, cependant, fortement limitée par son impossibilité à la produire sous forme recombinante. Afin de contourner ces difficultés, des protéines homologues ont été recherchées chez d'autres invertébrés. Deux lectines de type H ont été identifiées chez l'amibe Dictyostelium discoideum (discoidines) et une chez le corail Sinularia lochmodes (SLL-2). Les discoidines sont composées de deux domaines distincts, un domaine C-terminal, spécifique des résidus galactosylés et homologue à HPA et un domaine N-terminal, dit domaine discoidine, de fonction inconnue. Ces travaux de thèse portent, dans un premier temps, sur la poursuite de la caractérisation structurale de la discoidine 1 puis sur la production du domaine N-terminal de la discoidine 2 afin de confirmer la fonction lectine supposée. Dans un second temps, des expériences de microscopie confocale ont montrés que les discoidines ne possédaient pas la capacité d'HPA dans la discrimination des cellules métastatiques par rapport aux non métastatiques. La construction, par mutagenèse, d'une protéine chimérique entre la discoidine 2, très facilement produite dans E. coli, et HPA a alors été entreprise, le but étant de lui apporter la même spécificité qu'HPA. Enfin, la protéine SSL-2 a été clonée et de nombreux essais d'expression sous forme soluble et de purification ont été réalisés en vue de sa caractérisation biochimique et structurale pour sa possibilité d'utilisation comme marqueurs en histopathologie / The lectin of Helix pomatia (HPA), extracted from the albumin gland of the Roman snail and specific for the residue GalNAc, belongs to a new H type lectin family. It is used for twenty years as marker for metastatic adenocarcinoma (in particular breast, colon, lung) associated with poor life prognostic. Nevertheless, its use as routine tool in oncology is highly limited because of its incapability to produce it in a recombinant form. To avoid these difficulties, homologous proteins were searched in others invertebrates. Two H type lectins have been identified in the amiboe Dictyostelium discoideum (discoidins) and one in the coral Sinularia lochmodes (SLL-2). Discoidins are composed of two distinct domains, a C-terminal domain, specific for galactosylated residues and homologuous to HPA and an N-terminal domain, called discoidin domain, with unknown function. This thesis is focused, in a first time, on the continuation of structural characterization of discoidin 1 and on the production of the N-terminal domain of discoidin 2 to confirm the supposed lectin function. In a second time, confocal microscopy experiments showed that discoidins was not able to discriminate metastatic cancer cells to non metastatic ones, as HPA does. The construction, by mutagenesis, of a chimeric protein between discoidin 2, easily produced in E. coli, and HPA, began. The purpose was to give the same specificity as HPA. Last, SLL-2 was cloned and numerous expression assays, in a soluble form, and purification was tried to characterize the protein biochemistrycally and structurally. The aim was to test it as marker in histopathology.

As interações entre o sistema nervoso central e os sistemas imune e endócrino são o objeto de estudo da psiconeuroimunologia. Protocolos de indução de estresse têm sido amplamente utilizados como métodos confiáveis de investigação da relação entre transtornos psiquiátricos, aspectos psicológicos, traços de personalidade, ansiedade e a resposta imune. O procedimento de simulação de falar em público (SFP) é um protocolo experimental validado que reconhecidamente é capaz de ativar o eixo hipotálamo-hipófise-adrenal (HPA) e produzir respostas de estresse em sujeitos humanos. Esse método foi utilizado para: 1) Comparar a reatividade imunológica de indivíduos com diagnóstico de fobia social com a de indivíduos sem qualquer diagnóstico psiquiátrico; 2) Investigar se ocorrem alterações imunes subseqüentes à exposição a um estressor agudo induzido em laboratório e 3) identificar e correlacionar parâmetros imunológicos com traços de personalidade, humor, níveis de ansiedade e medidas fisiológicas. Os traços de personalidade foram investigados por meio dos seguintes instrumentos: Inventário de Temperamento e Caráter (TCI), Escala de Afeto Positivo e Negativo (PANAS), Inventário de Ansiedade Traço (IDATE-T), Inventário de Depressão de Beck (BDI), Inventário de Estratégias de ?Coping? de Folkman e Lazarus e Adaptação da Escala de Percepção de Estresse (PSS). Os sintomas de ansiedade foram avaliados por meio da Escala Analógica Visual de Humor (VAMS), da Escala de Sintomas Somáticos (ESS) e do IDATE-Estado. As variáveis psicofisiológicas avaliadas foram pressão arterial sistólica (PAS), diastólica (PAD), batimentos cardíacos (BPM), resposta galvânica da pele (GSR) e temperatura. Os níveis plasmáticos de catecolaminas (adrenalina, noradrenalina e dopamina) e hormônios do eixo HPA (cortisol e ACTH) também foram dosados. Realizou-se a contagem de células imunes polimorfonucleares e mononucleares no sangue periférico e mediu-se a atividade citotóxica de células NK e neutrófilos. Dosou-se proteínas de fase aguda e imunoglobulinas (A, D, G, M e E) a produção de citocinas no sangue por ELISA e RT-PCR. Os dados foram submetidos a análises de variância para dados com medidas repetidas testando efeitos de grupo, sexo, momento experimental e interações. As correlações entre as variáveis foram testadas por regressões múltiplas e coeficientes de correlação de Pearson. Os resultados apontam que o SFP foi eficiente para induzir estresse e produzir alterações detectáveis em diversos dos parâmetros investigados. As diferenças entre fóbicos sociais e controles são significativas para traços de personalidade e atuam ao longo do tempo para as medidas psicofisiológicas. Alterações imunes e hormonais estiveram mais frequentemente associadas ao gênero do que ao grupo experimental, e afetaram mais homens. Além disso, as alterações imunes foram de pequena magnitude afetando componentes inespecíficos da resposta imune. Conjuntamente, os resultados apontam uma relativa ativação do eixo HPA em fóbicos mas que não corresponde a alterações imunes de mesma magnitude. Mais estudos com uma amostra maior e a investigação de outros parâmetros são necessários para compreender melhor como a fobia social afeta o sistema imune de homens e mulheres e investigar se as alterações podem aumentar a susceptibilidade a doenças nesse grupo de sujeitos. Uma vez que essa interação seja melhor compreendida poderá subsidiar estratégias mais adequadas para abordar e elaborar estratégias de prevenção e intervenção capazes de promover comportamentos saudáveis. / Interactions among the nervous, immune and endocrine systems are the object of study of Psychoneuroimmunology. Stress protocols have been broadly used as reliable means to investigate the relationship among psychiatric disorders, psychological aspects, personality traits, anxiety and immune response has been studied using these interactions. The Simulated Public Speaking (SPS) is a validated experimental procedure known to activate the Hypothalamus-Pituitary-Adrenal (HPA) axis and produce stress responses in human subjects. This method was used to: 1) compare the immune reactions of individuals with a diagnosis of social phobia to that of individuals without any psychiatric diagnosis; 2) investigate if immune alterations occur subsequent to the exposure to an acute laboratory induced stressor; 3) identify and correlate immune parameters with personality traits, mood, anxiety levels and physiologic measures. Personality traits were investigated with Cloninger?s Temperament and Character?s Inventory (TCI), Positive and Negative Affects Scale (PANAS), State-Trait Anxiety Scale (STAI?T), Beck?s Depression Inventory (BDI), Lazarus?s Coping Strategies Inventory, Perceived Stress Scale (PSS). Anxiety symptoms were investigated along the procedure with the Bodily Symptoms Scale (ESS), STAI-E and the Visual Analogue Mood Scale (VAMS). Psychophysiologic variables assessed were Systolic (PAS) and Diastolic (PAD) Blood Pressure, Heart Rate (BPM), Galvanic Skin Response (GSR) and temperature. Plasmatic circulating levels of cathecolamines (Adrenaline, Noradrenaline and Dopamine) and HPA axis hormones (Cortisol, ACTH) were assessed. Peripheral blood cell population counts were obtained for polymorphonuclear (PMN) and mononuclear cells. Cytotoxic activity of neutrophils and NK cells was assessed, as well as cytokine production by ELISA and RT-PCR. Acute phase proteins and immunoglobulins (A, D, G, M, and E) were dosed on peripheral blood. Data was submitted to variance analysis for data with repeated measures testing effects of group, sex, experimental moment and interactions on variables. Correlations among variables were tested by multiple regressions and Pearson?s correlation deltas. The results show SPS was efficient in inducing stress and produce detectable alterations in several of the parameters investigated. Differences between social phobics and controls are significant for personality traits and, along time for psychophysiologic measures. Hormonal and immune alterations were more often associated to gender rather than to the group subjects belonged to, with men being more susceptible to the procedure. Also, immune changes were of small magnitude, usually affecting inespecific components of the response. Together, the results point to a relatively higher activation of the HPA-axis in social phobics, but one that does not correspond to immune responses of the same magnitude. Further studies with a larger sample and investigation of other parameters are necessary to better understand how social phobia affects the immune system of men and women and to investigate if the alterations can increase susceptibility to diseases in this group of individuals. Once this interaction is better understood it may provide the basis for an improved design to approach and elaborate prevention/intervention strategies and promote healthy behaviours.

An association between inflammation and mood deterioration has been proposed as a potential explanatory mechanism underlying many pathologies. Previous research attributes this consistently reoccurring connection between inflammation and psychopathology that is often reported within the literature, to a relationship between the HPA axis, the body’s stress response system and the immune system. There is evidence of a bidirectional feedback loop between end-products of the immune system and the HPA-axis such as cytokines and cortisol. This is supported by research reporting that components of subjective well-being such as positive affect, optimism and life satisfaction can produce beneficial health outcomes by potentially targeting this feedback loop. The present longitudinal study tested if higher positive affect independently corresponds to lower levels of inflammatory markers Interleukin-6 (IL-6) and C-reactive protein (CRP) and HPA axis marker cortisol. The study further tested if higher subjective well-being decreases levels of IL-6 and CRP as well as cortisol. The study employed a subsample of participants from the Midlife in Japan (MIDJA) Biomarker project (n=174) that underwent testing at two separate time points across a period of 4 years. The data included subjective well-being, positive affect, IL-6, CRP, cortisol, perceived stress, neuroticism and demographic variables. Positive affect was not associated with any inflammatory marker or cortisol. Subjective well-being had no effect on CRP but reduced IL-6 and cortisol even when controlling for all control and demographic variables. It is concluded that subjective well-being may be linked to lower inflammation and HPA axis activity. / Ett samband mellan inflammation och sjukdomsbeteende har föreslagits som en förklaringsmekanism bakom förekomsten av många patologier. Den konsekventa anknytningen mellan inflammation och psykopatologi som många tidigare studier demonstrerat innebär ett samband mellan immunsystemet och HPA-axeln som är den struktur som utgör kroppens svar på stressorer. Det finns tecken på en återkopplingsslinga mellan slutprodukter av det immunologiska systemet och HPA-axeln såsom cytokiner och kortisol. Detta har stöd i tidigare forskning som rapporterat att komponenter av subjektivt välbefinnande så som positiv affekt, optimism och livstillfredställelse kan medföra positiva hälsoutfall genom att potentiellt influera denna återkopplingsslinga. Förevarande longitudinella studie testar om högre positiv affekt leder till lägre nivåer av de inflammatoriska markörerna interleukin-6 (IL-6) och C-reaktivt protein (CRP) samt HPA-axel markören kortisol. Studien testar vidare även om högre subjektivt välbefinnande leder till lägre nivåer av IL-6, CRP och kortisol. Deltagarna är ett subsampel från Biomarkerprojektet (n = 174) inom Midlife in Japan (MIDJA) som genomgick testning vid två separata tidpunkter över en period av 4 år. Data består av subjektivt välbefinnande, positiv affekt, IL-6, CRP, kortisol, upplevd stress, neuroticism samt demografiska variabler. Positiv affekt hade ingen signifikant effekt på någon av de inflammatoriska markörerna eller kortisol. Subjektivt välbefinnande hade inte någon signifikant effekt på CRP men reducerade signifikant IL-6 och kortisol och dessa effekter förblev signifikanta efter kontroll för samtliga kontroll och demografiska variabler. Följaktligen dras slutsatsen att subjektivt välbefinnande kan leda till lägre inflammation och HPA-axel aktivitet.

Recent research shows, that gut microbiome can influence various functions of the organism and is able to communicate with the brain. The data also show that changes in the composition of gut microbiome can influence behavior and stress reactions and vice versa, psychological state of the organism can cause changes in gut microbiome. The aim of this master's thesis was to examine changes of HPA activation and local metabolism of glucocorticoids caused by stress in the presence or absence of gut microbiome. We therefore used germ-free mice and studied the effect of stress in pituitary, adrenal gland, colon and spleen. We found that, stress has different impact on gene expression in adrenal gland, colon and spleen in the presence or absence of gut microbiome. In contrast, there wasn't any significant effect of stress on pituitary in germ free mice and their conventionaly colonized counterparts.

Accumulating data indicate a common occurrence of tic exacerbations and periods of psychosocial stress. Patients with Tourette’s syndrome (TS) also exhibit aberrant markers of hypothalamic-pituitary-adrenal (HPA) axis activation. Based on these findings, a functional relationship between stress and tic disorders has been suggested, but the underlying mechanism of how stress may affect tic pathology remains to be elucidated. We suggest that dopaminergic and noradrenergic neurotransmission as well as immunology play a crucial role in mediating this relationship. Two possibilities of causal direction might be assumed: (a) psychosocial stress might lead to an exacerbation of tics via activation of HPA axis and subsequent changes in neurotransmission or immunology and (b) TS-related abnormalities in neurotransmission or immunology result in a higher vulnerability of affected

Background: Effective interventions for maltreated children are impeded by gaps in our knowledge of the etiopathogenic mechanisms leading from maltreatment to mental disorders. Although some studies have already identified individual risk factors, there is a lack of large-scale multilevel research on how psychosocial, neurobiological, and genetic factors act in concert to modulate risk of internalizing psychopathology in childhood following maltreatment. To help close this gap, we aim to delineate gender-specific pathways from maltreatment to psychological disorder/resilience. To this end, we examine the interplay of specific maltreatment characteristics and psychological, endocrine, metabolomic, and (epi-)genomic stress response patterns as well as cognitive-emotional/social processes as determinants of developmental outcome. Specifically, we will explore endocrine, metabolomic, and epigenetic mechanisms leading from maltreatment to a higher risk of depression and anxiety disorders.

Decades of research in quantitative genetics have found substantial heritability for personality traits as well as for mental disorders which formed the basis of the ongoing molecular genetic studies that aim to identify genetic variations that actually contribute to the manifestation of complex traits. With regard to psychological traits, genetic variation impacting neurotransmitter function have been of particular interest. Additionally, the role of environmental factors including gene × environment interactions has been further investigated and the impor-tance of developmental aspects has been stressed. Furthermore, endophenotypes which link complex traits with their respective biological underpinnings and thus bridge the gap between gene and behaviour have begun to be included in research efforts. In accordance with this approach, this thesis aims to further examine the influence of genetic variation impacting serotonergic and dopaminergic functioning on endophenotypes of anxiety-related behaviour. To this end, two well established paradigms – the acoustic startle reflex and the cortisol stress response – were employed. Both show considerable interindividual variation which has been found in quantitative genetic studies to be at least partly based on genetic factors. In addition, the neural circuits underlying these endophenotypes are relatively well understood and thus reveal references for the detection of associated genetic influences. The results of this thesis associate the overall startle magnitude in two independent samples of young adults with a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene (5-HTTLPR): Carriers of the short (S) allele which results in a reduced gene ex-pression showed a stronger startle magnitude which is in line with numerous findings linking the S allele to increased measures of negative emotionality. In addition to 5-HTTLPR, the effects of past stressful life events on the startle response were investigated: Participants who had recently experienced at least one stressful life event exhibited stronger startle responses and reduced habituation of the startle reflex although there was no 5-HTTLPR × environment inter-action effect. A third study revealed independent and joint effects of 5-HTTLPR and a poly-morphism in the dopamine receptor 4 gene (DRD4) in the same sample of young adults with regard to the cortisol stress response with carriers of the DRD4 7R allele which has been associ-ated with higher scores in sensation seeking, showing reduced cortisol responses. In addition, a 5-HTTLPR × DRD4 interaction effect emerged: 5-HTTLPR long (L) allele carriers showed the lowest cortisol response but only when they possessed at least one copy of the DRD4 7R allele. Moreover, in a fourth study a life span approach was taken and the influence of a further important serotonergic polymorphism which impacts the functioning of tryptophan hydroxylase 2 (TPH2), the rate limiting enzyme in the biosynthesis of serotonin, on interindividual differences in the startle response was investigated in three different age samples: children, young adults and older adults. There was a sex × TPH2 genotype interaction effect in a sample of young adults on the overall startle response while there was no effect of TPH2 in children or older adults. The last study of this thesis presents findings regarding the influence of two dopaminergic polymorphisms in genes encoding the enzyme catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT), respectively, which both terminate dopamine signalling and are thus important regulators of dopaminergic neurotransmission, on the startle reflex in older adults. COMT met/met homozygotes showed the strongest and val/val homozygotes displayed the smallest startle magnitude which is in line with findings linking the COMT met allele to increased scores of anxiety related traits and disorders. Regarding DAT, participants homozygous for the 10R allele, which had previously associated with attention-deficit hyperactivity disorder, showed a stronger overall startle response. In sum, this thesis comprises data on interindividual differences in an electrophysiological and a hormonal endophenotype across the life span and their association with serotonergic and dopaminergic function based on genetic variation. One major finding is the clear evidence for the influence of serotonergic polymorphisms on the startle response in young adults while in contrast in older adults genetic variation in the dopaminergic system exerted considerable influence. These differences might be due to developmental processes in the different stages of life although cohort effects and effects of different recruitment strategies can also not be ruled out. Furthermore, there were significant differences regarding the genetic influence on the acoustic startle reflex and cortisol stress response in one and the same sample which might be due to methodological differences of the two paradigms as well as differences in their underlying neuronal circuits. In conclusion, this thesis supports the acoustic startle reflex and the cortisol stress response as valuable endophenotypes and thus indicators for underlying neurobiological circuits although some methodological issues remain. It also highlights the importance of taking developmental factors and changes over the course of life into account. Finally, this thesis emphasizes the necessity to include reliably and validly assessed past experienced events in molecular genetic studies in order to understand the interplay between genetic and environmental factors in shaping (endo)-phenotypes.

Familial risk and environmental stress promote the development of alcohol dependence. We investigated whether a positive family history of alcoholism affects the neuroendocrine response to a standardized laboratory stress test in healthy subjects without alcohol use disorders. Twenty-four high-risk subjects with a paternal history of alcoholism (PHA) and 16 family history negative (FHN) controls were evaluated. Psychosocial stress was induced by having subjects deliver a 5-min speech and mental arithmetics in front of an audience on separate days, after drinking either placebo or ethanol (0.6 g/kg) in a randomized sequence. Adrenocorticotropin (ACTH) was measured in 10 plasma samples covering up to 75 min after the stress test. Plasma arginine vasopressin (AVP) was determined before the stressor, at the time of maximum ACTH secretion, and at 75 min after stress onset. The stress test induced a phasic increase in ACTH secretion. At the time of maximum ACTH, AVP was significantly increased in relation to baseline. Compared to placebo, alcohol administration significantly attenuated maximum ACTH concentration in PHA but not FHN subjects, and decreased AVP measured in the same samples in PHA but not FHN subjects. We conclude that activation of the hypothalamic–pituitary–adrenal system by psychosocial stress is accompanied by an increase in peripheral plasma AVP levels. Secretion of both ACTH and AVP suggest that alcohol attenuates the stress response selectively in PHA but not FHN subjects. This might imply some short-term positive alcohol effect in sons of alcoholics, but also constitute a mechanism by which their risk to develop alcohol use disorders is increased.

This thesis focuses on addressing the challenges of resource management in cloud environments, specifically in the context of running resource-optimized applications on Kubernetes. The scale and growth of cloud services, coupled with the dynamic nature of workloads, make it difficult to efficiently manage resources and control costs. The objective of this thesis is to explore the proactive autoscaling of virtual resources based on traffic demand, aiming to improve the current reactive approach, the Horizontal Pod Autoscaler (HPA), that relies on predefined rules and threshold values. By enabling proactive autoscaling, resource allocation can be optimized proactively, leading to improved resource utilization and cost savings. The aim is to strike a balance between resource utilization and the risk of Service Level Agreement (SLA) violations while optimizing resource usage for microservices. The study involves generating predictions and assessing resource utilization for both the current HPA implementation and the proposed solution. By comparing resource utilization and cost implications, the economic feasibility and benefits of adopting the new approach can be determined. The analysis aims to provide valuable insights into resource utilization patterns and optimization opportunities. The analysis shows significant improvements in CPU utilization and resource consumption using the proposed approach compared to the current HPA implementation. The proactive strategy allows for handling the same number of requests with fewer replicas, resulting in improved efficiency. The proposed solution has the potential to be applied to any type of service running on Kubernetes, with low computational costs. In conclusion, the analysis demonstrates the potential for resource optimization and cost savings through the proposed approach. By adopting proactive strategies and accurately predicting resource needs, organizations can achieve efficient resource utilization, system robustness, and compliance with SLA. Further research and enhancements can be explored based on the findings of this analysis. / Denna avhandling fokuserar på att adressera utmaningarna med resurshantering i molnmiljöer, specifikt i kontexten att köra resursoptimerade applikationer på Kubernetes. Skalan och tillväxten av molntjänster, tillsammans med arbetsbelastningarnas dynamiska natur, gör det svårt att effektivt hantera resurser och kontrollera kostnader. Syftet med denna avhandling är att utforska proaktiv autoskalning av virtuella resurser baserat på trafikbehov, med målet att förbättra den nuvarande reaktiva metoden, Horizontal Pod Autoscaler (HPA), som förlitar sig på fördefinierade regler och tröskelvärden. Genom att möjliggöra proaktiv autoskalning kan resurstilldelningen optimeras i förväg, vilket leder till förbättrad resursanvändning och kostnadsbesparingar. Målet är att hitta en balans mellan resursanvändning och risken för överträdelser av Service Level Agreements (SLA) samtidigt som resursanvändningen för mikrotjänster optimeras. Studien innefattar att generera förutsägelser och bedöma resursanvändning för både den nuvarande HPA-implementeringen och den föreslagna lösningen. Genom att jämföra resursanvändning och kostnadsimplikationer kan den ekonomiska genomförbarheten och fördelarna med att anta det nya tillvägagångssättet bestämmas. Analysen syftar till att ge värdefulla insikter i mönster för resursanvändning och möjligheter till optimering. Analysen visar betydande förbättringar i CPU-användning och resursförbrukning med den föreslagna metoden jämfört med den nuvarande HPA-implementeringen. Den proaktiva strategin möjliggör hantering av samma antal förfrågningar med färre replikor, vilket resulterar i förbättrad effektivitet. Den föreslagna lösningen har potential att tillämpas på alla typer av tjänster som körs på Kubernetes, med låga beräkningskostnader. Sammanfattningsvis visar analysen potentialen för resursoptimering och kostnadsbesparingar genom det föreslagna tillvägagångssättet. Genom att anta proaktiva strategier och noggrant förutsäga resursbehov kan organisationer uppnå effektiv resursanvändning, systemets robusthet och uppfyllnad av SLA:er. Vidare forskning och förbättringar kan utforskas baserat på resultaten av denna analys.

Postpartum depression is a psychiatric disorder affecting a substantial proportion of newly delivered women, and remains a significant cause of childbirth-related morbidity. The aim of the present thesis was to examine psychological, endocrine and genetic aspects of postpartum depression in a large, population-based sample of women in Uppsala, Sweden. All included studies were undertaken as parts of the BASIC-project, a longitudinal study on psychological wellbeing during pregnancy and the postpartum period. Study participants were screened for depressive symptoms in pregnancy week 17 and 32 as well as at six weeks and six months postpartum, mainly by use of the Swedish version of the Edinburgh Postnatal Depression Scale (EPDS). Furthermore, personality was assessed with the Swedish universities Scale of Personality (SSP) in pregnancy week 32. Evening cortisol levels in saliva were measured in pregnancy week 36 and at six weeks postpartum. Blood samples were obtained to measure corticotropin-releasing hormone levels (CRH) and to perform genetic analyses. The results of this thesis demonstrate that neuroticism is a strong and independent predictive factor of depressive symptoms at six weeks and six months postpartum, and has a significant mediatory role in the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene (HSD11B1) and postpartum depression. Furthermore, women with postpartum depressive symptoms present with a dysregulated hypothalamic-pituitary-adrenal axis activity in terms of elevated cortisol levels postpartum, as well as elevated CRH levels in mid-gestation. In conclusion, this thesis develops current knowledge on several attributes of postpartum depression. Further studies are required to replicate and expand on these results, which would further contribute to early identification of women at risk of postpartum depression and adoption of proper interventions that may moderate the short- and long-term consequences of the disorder.