Anxiety And Depression Are Associated With Limbic Atrophy And Severe Disruption Of Brain Functional Connectivity After Mild COVID-19 Infection (S21.007)

Objective:

To investigate gray matter atrophy (GMA) and alterations of functional connectivity (FC) associated with anxiety and depression after mild COVID-19 infection.

Background:

Although anxiety and depression are frequently observed in long-COVID syndrome, little is known about correlated structural and functional brain changes.

Design/Methods:

We evaluated 254 individuals after mild COVID-19 (177women, median age of 41 years, median interval of 82 days from RT-PCR test) with 3T-MRI, BDI (Beck Depression Inventory), and BAI (Beck anxiety inventory). Patients were separated into asymptomatic (152, ASYMPT-group) and simultaneous groups (if presented with anxiety and depression symptoms simultaneously) (102subjects, SIMULT-group, BAI>10 and BDI>13). GMA was assessed with voxel-based morphometry (VBM, CAT12-TOOLBOX/MATLAB2019/SPM12), comparing the two groups of patients with 148 healthy controls. We reported results with p<0.05 after Bonferroni adjustments. The FC analysis included the ASYMPT-group (84 subjects), SIMULT-group (70 subjects), and 90 controls. We used UF2C/SPM12/MATLAB2019b to analyze 12 large-scale brain networks (NW; with 70 ROIs, regions-of-interest) with resting-state fMRI. We reported results with p<0.05 after FDR adjustments.

Results:

SIMULT groups exhibited functional and structural abnormalities, but the ASYMPT-group showed fewer functional alterations and no GMA. SIMULT-group presented a widespread, bilateral pattern of hyperconnectivity involving the 12 networks and GMA in the left cingulum (86 voxels) and the inferior frontal lobe (91 voxels). The ASYMPT-group showed hyperconnectivity involving only five networks (posterior salience, ventral and dorsal Default Mode Networks, and right and left executive control) and nine ROIs.

Conclusions:

These findings indicate structural and functional alterations may occur even after mild infection. The combination of anxiety and depression is associated with atrophy of the limbic system and a severe pattern of abnormal cerebral functional connectivity. The magnitude of these changes suggests an association with cognitive dysfunction. Further analyses are necessary to yield specific treatment targets to prevent persistent deficits and improve quality of life. Disclosure: Miss Costa has nothing to disclose. Lucas Silva has nothing to disclose. Maria Mendes has nothing to disclose. Dr. Karmann Aventurato has received research support from Coordenadoria de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES). The institution of Brunno de Campos has received research support from São Paulo Research Fundation. Mateus Nogueira has nothing to disclose. Prof. João has received research support from FAPESP. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Biopharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for United Medical – Brazil. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zodiac Pharma . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eurofarma – Brazil . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Epilepsia. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology - Epilepsy. The institution of Dr. Cendes has received research support from São Paulo Research Foundation - FAPESP. The institution of Dr. Cendes has received research support from Conselho Nacional de Desenvolvimento Científico e Tecnológico - Brazil . The institution of Dr. Cendes has received research support from NIH. Clarissa Yasuda has nothing to disclose.