Unraveling the role of mitochondria in anxiety disorders

• Applicant: Michaela Filiou, Ph.D.
• Subject Area: Biological Psychiatry
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 222123460

Anxiety disorders are the most common psychiatric disorders affecting more than 20% of the general population. Due to our poor understanding of the molecular mechanisms of anxiety pathophysiology, no molecular biomarker exists for any anxiety disorder. As a result, diagnosis and treatment are solely based on the oral communication between the doctor and the patient. Biomarker discovery will substantially aid accurate diagnosis, disease classification and development of novel therapeutics. To identify biomarkers for anxiety disorders we compared the brain proteomes and metabolomes of high (HAB) and low (LAB) anxiety-related behavior mice and found alterations in mitochondrial pathways, which indicate a previously non-highlighted role of mitochondria in anxiety-related behavior. The aim of the proposed project is to pharmacologically target in vivo these altered mitochondrial pathways in HAB mice with compounds that act as pathway modulators. We will then investigate the effects of this selective mitochondrial targeting on the behavioral as well as molecular level by phenotypic, biochemical and mass spectrometry-based approaches. In addition, selected molecular alterations observed in HAB mice will be evaluated in patients with psychiatric disorders.This is the first time that a mechanism-based treatment is applied to rescue a strong predisposition to high anxiety. Achieving an anxiolytic effect through the manipulation of mitochondrial functions and characterizing the underlying molecular alterations of this anxiolytic effect provide an innovative approach to reveal new key molecular players, biomarkers and novel drug targets for anxiety disorders.

• DFG Programme: Research Grants