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This project investigates how depression may affect the regulation of the brain’s glucose metabolism and blood flow. By studying these processes, we aim to uncover previously unknown biological mechanisms that may underlie depression. We hypothesise that depression disrupts how the brain produces and uses energy, possibly driven by imbalances in stress hormones, particularly cortisol. This dysfunction may contribute to cognitive problems such as difficulties with learning and memory, as well as the changes in brain structures often observed in people with depression. 

To investigate the regulation of the brain energy metabolism, we propose a novel brain imaging experiment setup that combines positron emission tomography (PET) and MRI scanning along with a hypoxic-stress physiological challenge in the scanner. During the scan, participants will breathe air with moderately reduced oxygen levels through an adapted training device. This safely stimulates both energy use and blood flow in the brain in the short period that the participant are exposed to reduced oxygen.

We expect healthy individuals to show increased brain blood flow and glucose metabolism in response to hypoxic exposure. In contrast, people with depression will show a reduced or disrupted response, reflecting impaired energy regulation. We further anticipate that an impaired response may be linked to long term elevations in stress hormones.

The results from the study may guide future preventive strategies against cognitive decline and brain atrophy in depression. The scanning will be conducted at the Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, in collaboration with Professor Henrik B. W. Larsson, MD, DMSc. Recruitment and clinical assessment of patients will be carried out in collaboration with the Psychiatric Center Glostrup, Center for Neuropsychiatric Depression Research, headed by Professor Poul Videbech, MD, DMSc.