Social anxiety disorder (SAD) runs in families. Parents with SAD may contribute to SAD development in their children in two ways: First, temperamental dispositions for anxiety can be inherited from SAD parents. Second, parents can transmit anxiety environmentally, by (non-verbally) modelling anxious behaviour, or by (verbally) communicating threat/anxiety in social situations. Not all children, however, are equally sensitive to this environmental transmission. Child temperamental dispositions not only increase the risk for SAD, but also enhance sensitivity to environmental transmission. Theoretical accounts highlight the joint influence of parents’ anxious behaviour and child temperamental dispositions on the emergence of SAD. However, the effect of verbal anxiety expressions by SAD parents, and the moderating role of child temperament in the acquisition of social anxiety is currently unknown. This 12-month project, for the first time, examines the causal effects of parents’ verbal anxiety expressions, and its interplay with child temperament on the acquisition of social anxiety. The project is the first one to incorporate child physiology, cognition and behavior to investigate child reactions to strangers in a single multi-method experimental design, in the period preceding the onset of SAD in children (5-6 years). The project has direct implications for prevention of intergenerational SAD transmission.

When people have to perform some cognitively difficult task, they can get nervous about the level of their performance and others? judgment. Mild arousal might improve performance, but often this anxiety gets so bad that it is really harmful to actual performance. For example, we all know people who fail their drivers? license exam because of performance anxiety and it is estimated that 10-52% of schoolchildren experiences significant hinder from test anxiety. This reduces the predictive value of their scholastic aptitude tests which threatens the economic output potential of our educational system. These are just two examples, but cognitive performance anxiety (CPA) occurs in many situations and human and societal costs that arise from CPA are considerable. Clinical and cognitive psychological theories assume that worries and cues of threat in the environment (e.g., an unfriendly expression on the face of the examiner) are automatically processed more strongly in anxious than in non-anxious people. This then reduces availability of executive cognitive resources for the task at hand, resulting in bad performance. I offer an elaborated theoretical model which also incorporates the most recent insights in the direct neurochemical effects of stress on parts of the brain that are responsible for the relevant cognitive processes, focusing on the role of nor-adrenaline and the hormone cortisol. In the proposed innovative research, I will test vital assumptions of this theoretical model. I will also critically re-evaluate a current harmacotherapeutic treatment. Lastly I will test effectiveness of several innovative interventions. One intervention will apply neurofeedback training to target a promising neuro-biomarker for vulnerability to CPA (an EEG spectrum parameter). I also propose to test and compare effects of several pharmacotherapeutic interventions. Among others, a novel test for the effectiveness of cortisol and groundbreaking theory-driven off-label use of an existing nor-adrenergic drug.

Childhood Emotional Maltreatment (CEM) consists of any act of omissive (emotional neglect), or comissive (emotional abuse) behavior that is potentially harmful to a child?s emotional and psychological development. CEM is the most prevalent type of abuse, and is strongly associated with adult psychopathology. CEM increases risk for subsequent psychopathology through altering neurobiology (brain structure and brain functioning). In order to reduce CEM related psychopathology rates, it is crucial that factors that increase resilience to prior CEM effects in affected individuals are understood. During adolescence, when the brain goes through major developmental changes, adolescents are very receptive to their social environment (i.e. peers). In animals, the effects of early life stress on neurobiology can be reduced by positive environmental changes during adolescence. The intriguing question is whether adolescent friendships similarly reduce the neurobiological impact of CEM (thereby increasing individual?s resilience). With a Rubicon grant, I would be poised to examine this at the Department of Psychiatry (UCDP), University of Cambridge. My expertise in CEM and developmental neuroscience, together with the UCDP?s world leading expertise in computational neuroscience in adolescent psychiatry, allows me to examine the importance of adolescent friendship in the aftermath of CEM, using the latest multivariate computational (brain) analyses.

Suicide is notoriously difficult to predict and suicidal thoughts greatly fluctuate in daily life. Using real time assessments, we can capture the factors that lead to increased suicidal ideation or reduced risk. In our study we aim to assess day and night variability in suicidal ideation and its risk factors (mood, cognitions, stressful events, social interactions, coping), by using real time ecological momentary assessments and sleep/activity monitoring, in order to establish high and low risk conditions. This will greatly assist both patients and clinicians in developing personalized safety plans and treatments.

Posttraumatic stress disorder (PTSD) is a common and very debilitating disorder. Current treatment strategies for PTSD yield suboptimal effects: irrespective of treatment strategy, fifty percent of PTSD patients remain symptomatic after treatment. Knowledge of the processes that account for therapeutic change is imperative to improve treatment efficacy. One of the first-line treatments for PTSD is exposure therapy, the clinical counterpart of extinction. The crucial insight is that extinction of fear is not based on the weakening of threat associations, but on the learning of non-threat associations that compete with the threat associations. This is referred to as inhibitory learning. For exposure therapy to be long-term successful, non-threat associations need to be learned and remembered across time and contexts. Studies in animals, healthy-human samples and simple phobias have provided new ideas on how inhibitory learning can be enhanced. These ideas have not yet been tested in PTSD. The central question of this project is: Can exposure therapy for PTSD be optimized by maximizing inhibitory learning? The enhancement strategies that yield most promise to augment exposure effects are 1) enhancing expectancy violation, and 2) maximizing variability. Building on my expertise on exposure therapy for PTSD, I propose to investigate these enhancement strategies in a clinical PTSD sample. In three studies, I will test the effects of expectancy violation, stimulus and fear variability, and context variability on exposure outcome. By using an innovative design, the effects of these augmentation strategies on a brief exposure intervention (clinical assay) will be assessed using psychophysiological, behavioural, and verbal outcome measures. This project will directly test the effect of manipulating inhibitory learning on exposure success. Findings will impact the delivery of exposure therapy for PTSD and contribute to improved treatment efficacy for those suffering from PTSD.