Research

This project is the first at evaluating mitochondrial biomarkers in the brain and peripheral blood and its response to antidepressant treatment in one patient group. We aim to include patients within depressive episodes with Major Depressive Disorder (MDD, N = 80) compared to healthy controls (N = 80). We aim to evaluate a wide age range from 18 – 80 years in order to account for the effect of normal aging on mitochondrial function.

The proposed brain biomarker is cytochrome-c-oxidase (COX), an enzyme of the electron transport chain at the inner mitochondrial membrane responsible for cell energy production. We will evaluate COX changes using near-infrared spectroscopy (NIRS), an optical neuroimaging method. Our recent pilot study showed reduced COX changes in MDD an BD patients compared to controls that correlated significantly with depression severity. Assessment of mitochondrial COX derived from NIRS goes way beyond routine neuroimaging, cannot be assessed using other methods and is specific to brain mitochondrial function.

To compare mitochondrial function in the brain with that in the periphery, we will assess biomarkers in the peripheral blood. The proposed markers are well-established models of depression including mitochondrial respiration, inflammatory markers, lipid peroxidation and as well as the more recently introduced lipid fingerprinting. The correlation between brain and peripheral mitochondrial and/or inflammatory markers aims to explain the pathophysiology of mood-regulating pathways.

The study is a first step to explore the relationship between mitochondrial and/or inflammatory dysfunction in the brain and periphery by studying these two major domains in the same patient group. A second important question is whether first-line antidepressant medication, SSRI, work to normalize both pathophysiological domains and whether the combined effects are more closely related to clinical improvement than one effect measured in isolation. The answers to these questions may provide new biomarkers to advance etiological insight into common mechanisms of unipolar and bipolar depression and may lead to novel diagnostic mitochondrial targets that directly address the biology of depression.

Keywords

Affective disorders

Major depression

Mitochondria

Near-infrared spectroscopy (NIRS)

Research Projects

Brain cytochrome-c-oxidase assessed by NIRS as mitochondrial biomarker in depressive episodes (Swiss National Science Foundation, 2020 – 2024, Nr. 320030_184755)