Periodic Reporting for period 1 - AnxNPS (Anxiety across childhood and adolescence: Neural, psychological, and social factors)
Berichtszeitraum: 2020-01-01 bis 2021-12-31
Anxiety disorders are one of the most prevalent forms of psychiatric disorder, and have an extremely negative impact on quality of life. These disorders currently rank in the top ten contributors to global disability, and thus also represent a huge economic burden for society. Critically, anxiety disorders often have an early onset and are chronic, with childhood and adolescence having been identified as the core period of developmental risk. If left untreated, anxiety in this period can lead to academic, social, and emotional difficulties, as well as substance abuse and long-term mental health problems. Therefore, to help design more effective treatments and early interventions for children and adolescents, expanding our knowledge and understanding of how and why anxiety disorders may develop early on in life, and why certain individuals are more at risk than others, is crucial.
Accordingly, the aim of this project is to investigate the cognitive mechanisms through which anxiety may emerge and be maintained during childhood and adolescence, as well as the neural bases of this and how early social experience may increase the risk for anxiety. More specifically, the main objectives are to address the following questions using a macaque model of early social adversity: 1) how do differences in early social experience influence the development of an attention bias to threat (ABT), hypothesized to play an important role in the early emergence of anxiety, across childhood and adolescence; 2) how does ABT relate to anxiety across this period; and 3) how might development of the amygdala, a brain region implicated in fear learning and anxiety, and its connectivity with prefrontal cortex modulate this development? This requires a multimodal approach (neuroimaging, behavioural, and observational techniques), and incorporating interdisciplinary insights from developmental and clinical psychology, and developmental cognitive neuroscience.
Results from the project so far have shown that exposure to early social adversity is related to greater ABT during the childhood period, which in turn, is related to more anxiety. Findings have also shown that early social adversity is related to differences in both structural and functional connectivity of the amygdala across childhood and adolescence.
Accordingly, the aim of this project is to investigate the cognitive mechanisms through which anxiety may emerge and be maintained during childhood and adolescence, as well as the neural bases of this and how early social experience may increase the risk for anxiety. More specifically, the main objectives are to address the following questions using a macaque model of early social adversity: 1) how do differences in early social experience influence the development of an attention bias to threat (ABT), hypothesized to play an important role in the early emergence of anxiety, across childhood and adolescence; 2) how does ABT relate to anxiety across this period; and 3) how might development of the amygdala, a brain region implicated in fear learning and anxiety, and its connectivity with prefrontal cortex modulate this development? This requires a multimodal approach (neuroimaging, behavioural, and observational techniques), and incorporating interdisciplinary insights from developmental and clinical psychology, and developmental cognitive neuroscience.
Results from the project so far have shown that exposure to early social adversity is related to greater ABT during the childhood period, which in turn, is related to more anxiety. Findings have also shown that early social adversity is related to differences in both structural and functional connectivity of the amygdala across childhood and adolescence.
The time covered by the entire reporting period involved the piloting of tasks and preparation of materials for data collection, followed by behavioural and MRI data collection from two groups of macaque monkeys differing in terms of early social experience. Data collection was performed at two time-points (corresponding approximately to childhood and adolescence), including assessment of attention bias to threat (ABT), observation of anxious behaviour in the everyday environment, and collection of anatomical, structural, and resting-state functional MRI. This was followed by coding and analysis of all behavioural data at time-point one, coding and analysis of anxiety data at time-point two, and pre-processing and analysis of amygdala-connectivity at time-points one and two.
The analysis of the behavioural data at time-point one revealed that early social adversity is related to greater ABT, and only in those exposed to early adversity is this linked to more anxiety. Results from analysis of the MRI data have also revealed effects of early adversity on amygdala connectivity at both childhood and adolescent time-points. More specifically, differences have been revealed between early adversity-exposed versus non-exposed groups in terms of amygdala-prefrontal cortex structural connectivity (i.e. white matter integrity of the uncinate fasciculus), and resting-state functional connectivity between the amygdala and various brain regions, including areas of prefrontal cortex. Findings from this project have been presented at two conferences (International Society for Developmental Psychobiology Conference, 2020; National Congress of the Italian Society for Neuroscience, 2021), behavioural results from time-point one have been written-up and published (Rayson et al., Scientific Reports, 2021), project information and the related publication have been made available on a personal website created by the fellowship recipient, and scripts used to analyse data in this publication have been made freely accessible via github by the recipient.
The analysis of the behavioural data at time-point one revealed that early social adversity is related to greater ABT, and only in those exposed to early adversity is this linked to more anxiety. Results from analysis of the MRI data have also revealed effects of early adversity on amygdala connectivity at both childhood and adolescent time-points. More specifically, differences have been revealed between early adversity-exposed versus non-exposed groups in terms of amygdala-prefrontal cortex structural connectivity (i.e. white matter integrity of the uncinate fasciculus), and resting-state functional connectivity between the amygdala and various brain regions, including areas of prefrontal cortex. Findings from this project have been presented at two conferences (International Society for Developmental Psychobiology Conference, 2020; National Congress of the Italian Society for Neuroscience, 2021), behavioural results from time-point one have been written-up and published (Rayson et al., Scientific Reports, 2021), project information and the related publication have been made available on a personal website created by the fellowship recipient, and scripts used to analyse data in this publication have been made freely accessible via github by the recipient.
The project has already provided a number of important insights into the mechanisms underlying the emergence of an attention bias to threat (ABT) and its links to anxiety during early development, as well as the effects of early social experience on this and brain networks (amygdala-centred) implicated in anxiety disorders. In the near future, completion of ongoing analyses will also provide other unique insights into how early social experience effects on ABT and amygdala development may link to anxiety risk across childhood and adolescence.
In order to design the most effective early treatments and preventative interventions targeting younger populations, it is crucial to identify the predictive and maintaining factors of anxiety across development, especially in populations already at increased risk for anxiety disorders (e.g. those with atypical early social experience). Such measures are essential for improving the outcomes for young people diagnosed with anxiety disorders, for early identification of those most at risk, and thus for reducing the prevalence and persistence of these conditions. By guiding future research with humans (i.e. revealing the most worthwhile avenues of investigation and aiding the interpretation of human findings), the more complex and nuanced understanding afforded by this project in terms of how brain development and attention biases contribute to early anxiety, as well as the effects of early social experience on this, will contribute significantly towards the achievement of this goal.
In order to design the most effective early treatments and preventative interventions targeting younger populations, it is crucial to identify the predictive and maintaining factors of anxiety across development, especially in populations already at increased risk for anxiety disorders (e.g. those with atypical early social experience). Such measures are essential for improving the outcomes for young people diagnosed with anxiety disorders, for early identification of those most at risk, and thus for reducing the prevalence and persistence of these conditions. By guiding future research with humans (i.e. revealing the most worthwhile avenues of investigation and aiding the interpretation of human findings), the more complex and nuanced understanding afforded by this project in terms of how brain development and attention biases contribute to early anxiety, as well as the effects of early social experience on this, will contribute significantly towards the achievement of this goal.