Can measures of sleep quality or white matter structural integrity predict level of worry or rumination in adolescents facing stressful situations? Lessons from the COVID-19 pandemic.

INTRODUCTION: COVID-19 has resulted in major life changes to the majority of the world population, particularly adolescents, with social-distancing measures such as home-based schooling likely to impact sleep quality. Increased worry is also likely considering the substantial financial, educational and health concerns accompanying COVID-19. White matter (WM) integrity has been shown to be associated with anxiety and depression symptoms, including worry, as well being closely associated with sleep quality. This study aimed to investigate the associations between pre-COVID sleep quality, WM structural integrity and levels of worry and rumination about COVID. METHODS: N = 30 adolescent participants from Queensland, Australia, completed diffusion tensor imaging (DTI) scanning pre-COVID, the Pittsburgh Sleep Quality Index (PSQI) pre and during COVID, and 9 items designed to measure 3 constructs, perceived impact of COVID, general worry, and COVID-specific worry and rumination. RESULTS: Sleep quality (PSQI total) was significantly poorer during COVID compared with pre-COVID. Sleep onset latency measured pre-COVID was significantly associated with COVID-specific worry and rumination. While the structural integrity of a number of WM tracts (measured pre-COVID) were found to be significantly associated with COVID-specific worry and rumination. Follow-up regression analysis using a model including pre-COVID sleep onset latency, structural integrity of the posterior limb of the internal capsule (PLIC), gender and change in PSQI explained a significant 47% of the variance in COVID-specific worry and rumination. CONCLUSIONS: These findings suggest that adolescents with poor sleep quality and perturbed WM integrity may be at risk of heightened reactivity to future stressful events and interventions should focus on improving sleep onset latency.

Why Severe COVID-19 Patients Are at Greater Risk of Developing Depression: A Molecular Perspective.

The prevailing evidence suggests that patients with severe COVID-19 seem to have an overreaction of the immune system demonstrating exacerbated levels of inflammation caused by a "cytokine storm." At this early stage, the mechanisms underpinning COVID-19 are still subject to intense scrutiny and the long-term mental health consequences as a result of the disease are unknown. Here we discuss the hypothesis that patients who survive severe COVID-19 and who experience significant activation of the immune system, are at greater risk of developing depression. We posit that a phenomenon known as cytokine storm dramatically activates the enzyme indoleamine 2,3-dioxygenase (IDO-1), resulting in the increase in kynurenine metabolites. Kynurenine is metabolized by IDO-1 in the brain, producing chemokines, in which a prolonged exposure may result long-term brain impairment. In this article, we also propose the possibility that a SARS-CoV-2 neuroinvasion increases the local levels of angiotensin II by angiotensin-converting enzyme 2 down-regulation. Thereby, angiotensin II could increase kynurenine metabolites producing pro-oxidative and pro-inflammatory effects, resulting in impairment of cognitive function, enhanced oxidative stress and decreased brain-derived neurotrophic factor. It is our premise that patients who experience such a cytokine storm may be at increased risk of long-term mental illness, such as depression.