FKBP51 in a dynamic environment

Mental health disorders are a pressing global health-threat, affecting millions of people world-wide, which has already cost the world economy over 2.5 trillion dollars, making it a critical burden to society. These psychiatric disorders, including major depressive disorders, anxiety disorders and posttraumatic stress disorders, commonly arise as a combination of genetic and environmental factors. In the past decades, these gene by environment interactions (GxE) have increasingly been studied in both clinical and pre-clinical settings. Exposure to early life adversity has often been associated with negative outcomes on brain and behaviour and it has frequently been described as a risk factor for developing psychiatric disease. Nevertheless, there is also cumulative evidence that exposure to early life stress (ELS) in a milder form can result in adaptive responses that prepare an individual to cope with future life challenges. One gene that has repeatedly been implicated in the risk for psychiatric disease development is the FK506-binding protein 5 (FKBP5) gene, that encodes the glucocorticoid receptor (GR) co-chaperone FKBP51. FKBP51 plays an important role in regulating the sensitivity of the GR to the stress-hormone cortisol in humans or corticosterone in rodents. Interestingly, polymorphisms in the FKBP5 gene were found to interact with traumatic early life events to increase the risk for developing psychiatric disorders. In recent years, FKBP51 has extensively been studied in relation to stress resilience and vulnerability, however the mechanisms by which it contributes to these processes, particularly in combination with ELS, are not yet fully understood. Apart from genetic factors and early life events, there are a number of additional environmental factors that can be of great influence on mental health, such as age or sex. In fact, research from the past decades has shed an increasing light on the pivotal role that sex plays in the resilience to (early life) stress. Nevertheless, since many studies historically only included males, there is unfortunately still a large gap in information on the female sex when it comes to stress resilience and vulnerability mechanisms. In this thesis, the importance of including both sexes in rodent stress research study designs is emphasized, by demonstrating sex-differential phenotypes of chronic social defeat stress using a recently developed hands-on protocol for chronic social defeat in females. Moreover, using genetic mouse models, this thesis demonstrates not only clear sex-dependent, but also cell-type specific functionality of FKBP51, either under baseline conditions in an older aged sample or in interaction with ELS stress exposure. Furthermore, it underlines the FKBP51-mediated beneficial effects of ELS exposure in female mice and proposes novel underlying pathways in this process. Ultimately, this thesis corroborates the notion that FKBP5 is not per se a psychiatric risk factor, but rather a highly dynamic stress-responsive gene that interacts with the environment in shaping stress resilience

Examining adolescents’ well-being: How do the orientations to happiness relate to their leisure time activities?

Three ways of achieving happiness—life of pleasure, life of engagement, and life of meaning (Seligman, 2002)—have been examined among adult samples. However, very few studies have investigated these orientations to happiness in non-adult populations. Numerous studies have found that different ways of spending leisure time affect the psychological well-being of adolescents. Bringing these two perspectives together, the aim of the present study is to identify the extent to which orientations to happiness are related to well-being and choice of leisure time activities in a sample of adolescents from eight European countries

Metabolic effects of early life stress and pre-pregnancy obesity are long lasting and sex specific in mice

Early life stress (ELS) is associated with metabolic, cognitive, and psychiatric diseases and has a very high prevalence, highlighting the urgent need for a better understanding of the versatile physiological changes and identification of predictive biomarkers. In addition to programming the hypothalamic-pituitary-adrenal (HPA) axis, ELS may also affect the gut microbiota and metabolome, opening up a promising research direction for identifying early biomarkers of ELS-induced (mal)adaptation. Other factors affecting these parameters include maternal metabolic status and diet, with maternal obesity shown to predispose offspring to later metabolic disease. The aim of the present study was to investigate the long-term effects of ELS and maternal obesity on the metabolic and stress phenotype of rodent offspring. To this end, offspring of both sexes were subjected to an adverse early-life experience, and their metabolic and stress phenotypes were examined. In addition, we assessed whether a prenatal maternal and an adult high-fat diet (HFD) stressor further shape observed ELS-induced phenotypes. We show that ELS has long-term effects on male body weight (BW) across the lifespan, whereas females more successfully counteract ELS-induced weight loss, possibly by adapting their microbiota, thereby stabilizing a balanced metabolome. Furthermore, the metabolic effects of a maternal HFD on BW are exclusively triggered by a dietary challenge in adult offspring and are more pronounced in males than in females. Overall, our study suggests that the female microbiota protects against an ELS challenge, rendering them more resilient to additional maternal- and adult nutritional stressors than males.This work was supported by the “GUTMOM” grant of the ERA-Net Cofund HDHL-INTIMIC (INtesTInal MIcrobiomics) under the JPI HDHL (Joint Programming Initiative – A healthy diet for a healthy life) umbrella (01EA1805; MVS), the SCHM2360-5-1 grant (MVS) from the German Research Foundation (DFG), the ZonMw grant from the Netherlands Organisation for Health Research and Development (project number 529051019), the DIM-ELI-2 grant of La Fundación La Marató-TV3 (ref. 2018-27/30-31), the PID2019-108973RB-C22 and PCIN2017-117 grants from the Ministerio de Ciencia e Innovación of Spain and the grants GV/2020/048 and IDIFEDER/2021/072 from the Generalitat Valenciana of Spain. Open Access funding enabled and organized by Projekt DEAL.Peer reviewe

Personal narratives as a predictor of trait change and state fluctuations in self-esteem and life satisfaction during the transition from education to work

Narrative identities are not only a product of lived experiences, but also predict new experiences and developmental outcomes over time. In this study, we examined whether the characteristics of students' narratives about a previous turning point in their lives predicted self-esteem and life satisfaction during their education-to-work transition. We examined predictions of trait change and of stability in state self-esteem and life satisfaction in daily life. Students (aged 24 years on average) in diverse master's programs in the Netherlands who expected to graduate before the end of the study took part in an 8-month longitudinal (n = 216) and 14-day diary (n = 192) part of the study. Our findings show that more agentic and redemptive turning point narratives did not predict significant change in trait self-esteem and life satisfaction during the next 8 months of the transition. Narrative agency and redemption were no consistent significant predictors of higher day-to-day stability in state self-esteem and life satisfaction. Yet, higher levels in narrative agency tended to be associated with higher stability in daily self-esteem. Our findings show promising possibilities to further examine how and when the characteristics of people's narratives relate to the development and stability of psychological adjustment.</p

A Review and Integration of Three Key Components of Identity Development: Distinctiveness, Coherence, and Continuity

Abstract. Studies on identity formation focus on various components of identity. However, these components have mainly been studied separately, and researchers in different fields are not always aware of each other’s work. Therefore, this systematic review provides an overview of theories and empirical studies on three key components of identity: distinctiveness (seeing the self as unique and distinct from others), coherence (perceiving the self as similar across life domains), and continuity (perceiving the self as the same person over time). This systematic review focused on the development of these components and linkages with psychosocial functioning. Findings suggest important differences between the three identity components. Therefore, we propose an integrative developmental framework of identity, including all three identity components and their linkages

A Review and Integration of Three Key Components of Identity Development: Distinctiveness, Coherence, and Continuity

Studies on identity formation focus on various components of identity. However, these components have mainly been studied separately, and researchers in different fields are not always aware of each other’s work. Therefore, this systematic review provides an overview of theories and empirical studies on three key components of identity: distinctiveness (seeing the self as unique and distinct from others), coherence (perceiving the self as similar across life domains), and continuity (perceiving the self as the same person over time). This systematic review focused on the development of these components and linkages with psychosocial functioning. Findings suggest important differences between the three identity components. Therefore, we propose an integrative developmental framework of identity, including all three identity components and their linkages

A Review and Integration of Three Key Components of Identity Development: Distinctiveness, Coherence, and Continuity

Abstract. Studies on identity formation focus on various components of identity. However, these components have mainly been studied separately, and researchers in different fields are not always aware of each other’s work. Therefore, this systematic review provides an overview of theories and empirical studies on three key components of identity: distinctiveness (seeing the self as unique and distinct from others), coherence (perceiving the self as similar across life domains), and continuity (perceiving the self as the same person over time). This systematic review focused on the development of these components and linkages with psychosocial functioning. Findings suggest important differences between the three identity components. Therefore, we propose an integrative developmental framework of identity, including all three identity components and their linkages

A Review and Integration of Three Key Components of Identity Development: Distinctiveness, Coherence, and Continuity

Abstract. Studies on identity formation focus on various components of identity. However, these components have mainly been studied separately, and researchers in different fields are not always aware of each other’s work. Therefore, this systematic review provides an overview of theories and empirical studies on three key components of identity: distinctiveness (seeing the self as unique and distinct from others), coherence (perceiving the self as similar across life domains), and continuity (perceiving the self as the same person over time). This systematic review focused on the development of these components and linkages with psychosocial functioning. Findings suggest important differences between the three identity components. Therefore, we propose an integrative developmental framework of identity, including all three identity components and their linkages