: Clarifying the etiology of mental disorders should lead to significant therapeutic and preventive measure improvements. Mental disorders are caused by genetic, epigenetic, and environmental factors. A valid assessment of environmental etiological factors is complicated due to a lack in methodologies. We aim to demonstrate how to optimally assess the environmental etiological factors with a special focus on stress. We searched the PubMed database up to December 2024 for relevant state-of-the-art references. The most frequently used stress assessment method involves self-reporting questionnaires. Blood or salivary cortisol, heart rate, respiratory rate, plethysmography readings, and electrodermal activity are biological markers of acute stress. Other biological markers such as hair and nail cortisol levels, telomere length, mitochondrial DNA copy number, and epigenetic markers are indicative of a history of stress. A quantitative prospective assessment of environmental etiological factors including their frequency, severity, total exposure length, timing, and possible accumulation is still needed. In addition, protective environmental factors of mental disorders should not be neglected.
