Brain mechanisms and psychological determinants of mental health resilience. Learning from the COVID-19 pandemic

Abstract

[eng] When confronted with a stressful situation, our reactions can vary greatly. In general, the population comes across to be resilient, being able to resist or adapt to disturbances. However, this is not the case for everyone or every situation, and therefore understanding what lies behind a resilient response becomes very valuable knowledge when promoting emotional, social, and psychological well-being. The study of these phenomena shows that resilience is the result of numerous and complex interactions, among biological, psychological, and environmental factors that evolve throughout life. From the appraisal of the stressful event to coping with it, processes involving the activity of multiple body systems (for example, the hormonal response promoted by the hypothalamic-pituitary-adrenal axis) and mental processes come into play. During these processes, the central nervous system plays a major role, in triggering and modulating this response. Areas such as the hippocampus, the amygdala, and the anterior insula, anterior cingulate, and prefrontal cortices, as well as brain networks partially coinciding with them (Default Mode Network, Salience Network, and Frontoparietal Network), are involved. Much of these findings have been derived from the study of magnetic resonance imaging. However, these studies have serious limitations at various levels, such as the use of small populations or the lack of data prior to exposure to stressful or traumatic events. Within this gap in the literature, the COVID-19 pandemic presents a unique opportunity to study the stress response in large populations, in some cases with data available before the pandemic outbreak. This is possible since the COVID-19 pandemic has been widely regarded as a threat to mental health due to the many stressful situations it has led to.

Particularly, in this doctoral thesis, it was hypothesized that, despite this level of threat, the general population would remain resilient, and if affected, it would do so differently for

different dimensions of mental health (emotional, social, and psychological). Furthermore, associations were expected to be found between this response to the pandemic and basal brain characteristics in terms of functional connectivity balance in certain brain networks, as well as psychological factors, and interactions between them. As a result, the present doctoral thesis aimed to study the emotional, social, and psychological changes in a healthy middle-aged population, with a special focus on understanding the characteristics of the most resilient individuals compared to the most vulnerable ones.

Three research studies were conducted to answer the questions posed. All three studies included longitudinal data before and throughout the pandemic, with a total follow-up of up to four years (two of them belonging to the basal pre-pandemic period), for approximately two thousand participants among which up to around seven hundred had magnetic resonance imaging available. The first study identified longitudinal trajectories in which the studied population mainly experienced resilient responses, although vulnerable ones were also observed. In light of the results of this study, together with those of the second study, these trajectories were associated with various protective and risk factors at the sociodemographic, psychological, lifestyle, and functional status of brain network levels. Since each dimension of mental health was affected differently and characterized by distinct factors, these results emphasize the importance of studying mental health as a set of semi-independent components. The third study focused on the emotional response at the individual level, confirming that, despite the predominantly resilient effect of the studied population, a subtle but consistent worsening of anxious-depressive symptoms could be found, which was associated with the levels of stress perceived during the pandemic. It also identified brain and psychological mechanisms that modulated the resilient or vulnerable nature of this emotional change, in line with what was described in the previous two studies. Overall, the present doctoral thesis has

identified at-risk populations (individuals living alone, women, or young adults) and factors to promote to protect them (coping strategies or healthy lifestyle habits that foster general and cognitive health). Essentially, this thesis has identified for the first time the role that the balance of connectivity (i.e., the integration-segregation balance) between networks at the level of the complete brain system plays in the resilient response to stressful situations. Specifically, it highlights the role that the Default Mode Network, the Salience Network, and the Frontoparietal Network have in psychological resilience, encouraging the development of future preventive strategies.

As a general conclusion, the work carried out reveals the imperative need to consider psychological, lifestyle, and sociodemographic factors along with brain mechanisms, with a particular emphasis on their interactions, to fully understand the phenomena of resilience and vulnerability and, thus, promote more effective interventions.