The Affective Amygdala : towards a better understanding of adolescent depressive and anxiety disorders

This thesis aimed to investigate the neurobiological mechanisms of adolescent onset depression and anxiety disorders. A longitudinal fMRI study design was used that included both task related brain activation and resting state functional connectivity. All participants were scanned three times in a six-month period. In between scan sessions the adolescents from the clinical group received treatment as usual. Adolescents from the control group were scanned within the same time interval but did not receive treatment. During a scan session several MRI parameters were collected including task based fMRI (emotional face processing task) and resting state fMRI. We also administered several questionnaires about derpession and anxiety symptomatology. It was demonstrated that adolescents with depressive and anxiety disorders show differentiating patterns of amygdala reactivity and connectivity compared to a healthy control group. Furthermore, using a dimensional approach and taking individual differences in self-reported depression and anxiety symptoms into account highlighted the role of self-reported anxiety symptoms in amygdala reactivity during emotional faces processing. These findings indicate that the amygdala indeed is an important region involved in emotional face processing and that focusing on this region can provide further insights in the development and persistence of depressive and anxiety disorders in adolescents.Pathways through Adolescenc

Human Metapneumovirus: Discovery, Characterisation and Associated Disease

__Abstract__ Acute respiratory tract infections are responsible for considerable morbidity and mortality and costs attributable to acute respiratory tract illnesses (ARI) are an important burden on national health care budgets. A variety of viruses, bacteria and fungi are associated with ARI. This thesis only focuses on viral causes of ARI Diagnosis of respiratory tract infections is important for adequate treatment of patients and community surveillance studying the spread of respiratory viruses forms the basis for preventive strategies. Despite the use of a variety of diagnostic assays, 15-50% of the samples obtained from persons suffering from ARI do not yield positive diagnoses, which is at least in part due to limitations of diagnostic procedures. However, a proportion of ARI may be caused by still unknown pathogens, providing an additional explanation for the relatively high proportion of negative laboratory diagnoses. This thesis describes the identification and characterisation of a hitherto unknown virus as the causative agent of ARI, wh

Great successes and great failures: The impact of project leader status on project performance and performance extremeness

Research supporting the Matthew Effect demonstrates that high-status actors experience performance benefits due to increased recognition of their work and greater opportunities and resources, but recent research also indicates that high-status actors face a greater risk of negative performance evaluations. In this paper, we seek to contribute to the status literature by reconciling these findings and ask: To what extent does status influence heterogeneity in performance evaluations? We explore how project leader status affects the performance of innovation projects in the video game industry. We hypothesize that there is an inverted U-shaped relationship between project leader status and project performance, and a positive relationship between project leader status and performance extremeness (i.e., performance variation). In order to test our hypotheses, we analyzed the performance of video game projects and computed the status of project leaders by applying a project affiliation social network analysis. We find that an intermediate level of status—neither too much nor too little—is positively associated with average project performance. We also reveal more extreme performance effects for high-status leaders: While some achieve superior project performance, others experience significant project failures. We therefore provide important theoretical and practical insights regarding how status affects the implementation of innovations. We also discuss the implications of these findings for the literature on middle-status conformity

The Prosocial Cyberball Game: Compensating for social exclusion and its associations with empathic concern and bullying in adolescents

In this study we examined prosocial compensating behavior towards socially excluded ingroup and outgroup members by using a ‘Prosocial Cyberball Game’ in 9–17 year old Dutch adolescents (N = 133). Results showed that adolescents compensated for the social exclusion of an unknown peer in a virtual ball tossing game, by tossing the ball more often to that player in compensation conditions compared to the fair play condition. The proportion of tosses towards the excluded player did not significantly differ as a function of the group status of that player. Although compensating behavior towards ingroup versus outgroup members did not differ, the underlying motivation for this behavior may vary. More empathic concern was associated with more prosocial tosses towards an ingroup member, while more self-reported bullying behavior was associated with less compensating behavior in the outgroup condition. These findings may have practical implications for programs intending to change bystander behavior in bullying situations

Armed oncolytic viruses: A kick-start for anti-tumor immunity

Oncolytic viruses (OVs), viruses that specifically result in killing tumor cells, represent a promising class of cancer therapy. Recently, the focus in the OV therapy field has shifted from their direct oncolytic effect to their immune stimulatory effect. OV therapy can function as a “kick start” for the antitumor immune response by releasing tumor associated antigens and release of inflammatory signals. Combining OVs with immune modulators could enhance the efficacy of both immune and OV therapies. Additionally, genetic engineering of OVs allows local expression of immune therapeutics, thereby reducing related toxicities. Different options to modify the tumor microenvironment in combination with OV therapy have been explored. The possibilities and obstacles of these combinations will be discussed in this review

ADAR1: "Editor-in-Chief" of Cytoplasmic Innate Immunity

Specialized receptors that recognize molecular patterns such as double stranded RNA duplexes—indicative of viral replication—are potent triggers of the innate immune system. Although their activation is beneficial during viral infection, RNA transcribed from endogenous mobile genetic elements may also act as ligands potentially causing autoimmunity. Recent advances indicate that the adenosine deaminase ADAR1 through RNA editing is involved in dampening the canonical antiviral RIG-I-like receptor-, PKR-, and OAS-RNAse L pathways to prevent autoimmunity. However, this inhibitory effect must be overcome during viral infections. In this review we discuss ADAR1’s critical role in balancing immune activation and self-tolerance

Social judgments, frontal asymmetry, and aggressive behavior in young children: A replication study using EEG

Development Psychopathology in context: famil

Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients

During a 17-month period, we performed retrospective analyses of the prevalence of and clinical symptoms associated with human metapneumovirus (hMPV) infection, among patients in a university hospital in The Netherlands. All available nasal-aspirate, throat-swab, sputum, and bronchoalveolar-lavage samples (N=1515) were tested for hMPV RNA by reverse-transcriptase polymerase chain reaction. hMPV RNA was detected in 7% of samples from patients with respiratory tract illnesses (RTIs) and was the second-most-detected viral pathogen in these patients during the last 2 winter seasons. hMPV was detected primarily in very young children and in immunocompromised individuals. In young children, clinical symptoms associated with hMPV infection were similar to those associated with human respiratory syncytial virus (hRSV) infection, but dyspnea, feeding difficulties, and hypoxemia were reported more frequently in hRSV-infected children. Treatment with antibiotics and corticosteroids was reported more frequently in hMPV-infected children. From these data, we conclude that hMPV is an important pathogen associated with RTI

Effects of the Video-feedback intervention to promote positive parenting and sensitive discipline on mothers' neural responses to child faces: A randomized controlled ERP study including pre- and post-intervention measures

Parenting interventions have proven to be effective in enhancing positive parenting behavior and child outcomes. However, the neurocognitive mechanisms explaining the efficacy remain largely unknown. We tested effects of the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) on mothers' neural processing of child faces. Our primary focus was on the N170 and the secondary focus on the LPP. We expected the intervention to enhance the amplitudes of both ERP components in response to emotional compared to neutral faces. A total of 66 mothers visited the lab for two identical sessions separated by 4.28 months (SD = 0.86) during which a random 33% of the mothers received the VIPP-SD. During both pre- and post-intervention sessions, mothers' electroencephalographic (EEG) activity in response to photographs of children's neutral, happy and angry facial expressions were acquired. In contrast to our expectations, we found smaller (less negative) N170 amplitudes at post-test in the intervention group. There was no intervention effect on the LPP, although overall LPP amplitudes were more positive for neutral and angry compared to happy faces. Our study shows that the N170 is affected by the VIPP-SD, suggesting that the intervention promotes efficient, less effortful face processing. Trial registration: Dutch Trial Register: NTR5312; Date registered: 3 January 2017.Education and Child Studie