Work

Reduced Adenosine Triphosphate-to-Phosphocreatine Ratios in Neuropsychiatric Post-COVID Condition: Evidence From 31P Magnetic Resonance Spectroscopy

Year: 2026

Type: article

Abstract: BACKGROUND: Post-COVID condition (PCCo) affects 5% to 10% of individuals following SARS-CoV-2 infection, with cognitive disturbances being a major feature. Central hypotheses regarding its pathophysiology include disturbed cell energy metabolism and oxidative stress pointing to mitochondrial dysfunction. However, brain energy metabolism remains unexplored. METHODS: P-magnetic resonance spectroscopic imaging at 3T. Adenosine triphosphate/phosphocreatine (ATP/PCr) ratios were quantified throughout the brain and analyzed with voxel-based and regional statistics including correlations with neuropsychological performance (Montreal Cognitive Assessment and Trail Making Test Part B). Statistical analysis used voxelwise comparisons with age as covariate, followed by region-of-interest analysis of cingulate cortex subdivisions. RESULTS: Patients with PCCo showed a significant cluster of reduced ATP/PCr ratios centered on the cingulate cortex. Regional analysis revealed consistent reductions across the anterior cingulate cortex (ACC), midcingulate cortex (MCC), and posterior cingulate cortex. Lower ATP/PCr ratios in the ACC specifically correlated with poorer cognitive performance. Exploratory analyses revealed a trend toward higher intracellular pH in the MCC, with significant negative correlation between pH and ATP/PCr observed only in patients, suggesting disease-specific alterations in pH regulation and bioenergetic homeostasis. Subgroup analysis showed similar metabolic alterations in patients with PCCo who met criteria for myalgic encephalomyelitis/chronic fatigue syndrome. CONCLUSIONS: Our study provides the first in vivo evidence of impaired brain energy metabolism in PCCo, with anterior cingulate dysfunction directly linked to cognitive impairment. The observed pH-ATP/PCr relationship suggests broader disruption of cellular bioenergetic regulation. These findings support mitochondrial dysfunction as a key pathophysiological mechanism and may inform targeted therapeutic strategies.

Source: Biological Psychiatry

DOI: 10.1016/j.biopsych.2026.01.004