PEERWISE: Susceptibilidade ao Feedback dos Pares na Depressão na Adolescência – Mecanismos Neurocognitivos e Implicações Psicofarmacológicas

Drawing from advances in computational modelling, our knowledge of social cognition in adolescence and the interdisciplinarity demonstrated by our international team leaders in the areas covered here, we will pioneer the field by employing a novel paradigm recently developed by us. This paradigm will characterise the neurocognitive mechanism that may lead to increased risk vs resilience to develop depression in response to negative social experiences in adolescence and test if these mechanisms can be modified using antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs). This project addresses important challenges in the literature of adolescent depression. Because current paradigms may not be sufficiently sensitive to capture real-time cognitions and behaviours that change rapidly in response to social feedback, we have used our expertise in computational modelling to propose a sophisticated novel paradigm that can elucidate individual differences as to how exactly different types of feedback are represented and processed in the adolescent brain. In addition, there is a scarcity of research looking into the neurocognitive mechanisms of peer susceptibility to peer feedback in adolescence, and how this knowledge could be used to increase resilience and reduce risk to develop depression following negative social experiences in this age group. Lastly, it is of high interest to test if antidepressants influence susceptibility to peer feedback, specifically by increasing resilience to negative feedback. This proposal includes two studies (fig. 3). In the first study in a community sample, we aim to employ this novel paradigm to quantify individual differences in adolescents’ ability to determine the accuracy of different types of peer feedback (i.e., malicious, ambiguous and overly-positive) and how these various types of feedback impact the adolescent’s self-views. We will then test whether a lower ability to identify and discount negative feedback is associated with an increased risk to develop depression, and, conversely, whether a higher ability to identify and discount negatively biased feedback is associated with increased resilience to depression following negative social experiences in a community adolescent sample. The second study will include depressed adolescents who have not yet started antidepressant treatment, and healthy controls, who will be assessed twice. At baseline, we will characterise their ability to determine the accuracy of different types of peer feedback (i.e., malicious, ambiguous and overly-positive) and how these various types of feedback impact the adolescent’s self-views and depressive symptoms. We expect that depressed adolescents will show a reduced ability to discount malicious feedback (compared to controls), as well as increased activity in neural areas such as the subgenual ACC in response to negative feedback. Subsequently, depressed adolescents will receive an 8-week treatment with SSRIs. At the end of treatment, we will differentiate between responders and non-responders. We expect those demonstrating a better response to treatment will show an increased ability to discount malicious feedback, as well as reduced neural activity in areas such as the sgACC in response to this negative feedback, given recent evidence from our team showing that, in adolescents, SSRIs shift both the behavioural and neural processing of social cues so that they are perceived as less negative [11-13].