IMPACT OF CHRONIC STRESS AND LONG-TERM CORTISOL OUTPUT ON STRUCTURAL CONNECTIVITY BETWEEN AMYGDALA AND PREFRONTAL CORTEX

The regulatory relationship between prefrontal cortex (PFC) and the amygdala has been of particular interest in understanding brain response to stress. Prefrontal white matter may be particularly vulnerable to effects of stress since oligodendrocytes and myelination are negatively affected by glucocorticoids. The main goal of our study was to investigate changes in amygdala-PFC structural connectivity in participants without history of psychiatric disorders who experience different levels of chronic stress. We examined associations between chronic stress, perceived stress, hair cortisol concentration (HCC) and microstructural properties of amygdala-PFC white matter connections in healthy adults (n=40). Chronic stressors (last 3 month) were rated on the Trier Inventory for Chronic Stress. Structural Magnetic Resonance Imaging and Diffusion Tensor Imaging datasets were acquired on 3T Siemens Prisma scanner. HCC was analyzed using the high-resolution liquid chromatography–mass spectrometry method. Probabilistic tractography was implemented using the FSL FDT toolbox. Tractography was run between amygdala manual segmentations as seed and six ipsilateral/contralateral PFC segmentations as target. Increased chronic stress levels were associated with lower fractional anisotropy (FA) and higher radial diffusivity in amygdala pathways to medial orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC). Higher levels of perceived stress were also linked to lower FA and higher radial diffusivity in projections between amygdala and medial OFC. Increased HCC was associated with lower axial diffusivity and smaller tract volumes of amygdala pathways to DLPFC, lateral and medial OFC. Our results provide first evidence for negative effects of chronic stress and increased long-term cortisol output on amygdala-PFC structural connectivity.