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Start of funding 01.07.2017

Microbiota-Derived Biosignatures for Major Depressive Disorder

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At present there are no biomarker-based diagnostic procedures available in psychiatry. Instead, all current diagnostics is based on imprecise rating scales, and treatment decisions are made on a trial-and-error basis. Therefore, diagnostic tests able to stratify patients and predict response to a particular antidepressant meet an obvious need in depression therapy, both for psychiatrists and patients alike. Microbiota composition and microbial-derived metabolites impact human health through signaling to distant organs including the central nervous system where they can contribute to the development of psychiatric disorders. For the identification of biomarkers that can stratify patients and monitor therapy response, we will interrogate by mass spectrometry skin microbiota-secreted molecules from patients and control subjects.

Final report:
Background. The implementation of a precision medicine approach in the clinical practice of psychiatric disorders has been unsuccessful due to a complete lack of reliable biosignatures. Diagnosis is based on rating scales and pharmacological treatment options are not tailored to the patient’s phenotype. As a consequence almost fifty percent of depressed patients do not respond to currently used antidepressants. Dynamic biomarkers that are able to stratify patients and predict a priori whether an individual patient will respond to the treatment of choice allowing an early distinction of responders and non-responders during antidepressant therapy, can have a significant impact to achieve this goal. The availability of specific and sensitive biosignatures in clinical practice would ultimately help to stratify patients and predict antidepressant treatment response and drug dosing at an early time point during therapy, allowing the psychiatrist to select the right drug for the right patient. Microbiota composition and microbial-derived metabolites impact human health through signaling to distant organs including the central nervous system where they can contribute to the development of psychiatric disorders.

Project Aim. The aim of the project was to identify biosignatures for Major Depressive Disorder using skin swabs from patients. For this purpose we analyzed metabolites present on the skin that are in part derived from microbiota. Different areas of the body were swapped with 50% ethanol and the extracted metabolites analyzed by tandem mass spectrometry. More than 400 skin swab samples were collected, processed by Prof. Turck in Prof. Dorrestein’s laboratory at UC San Diego and analyzed by mass spectrometry using an untargeted metabolomics sample infusion approach.

Results. Three m/z features (176.1032, 159.0765, 572.2703) showed statistically significant level differences (p<0.01) between Anxiety Patients/PTSD Patients/Control group. The 176.1032 feature was annotated as arginic acid or citrulline. The m/z feature 725.4628 distinguished Mood Disorder Patient from Control group.
A second set of samples is presently being collected. Skin swabs are obtained from the same patients at baseline and following four weeks of antidepressant therapy. Metabolomics data from these samples will be acquired in early 2019.

Outlook. The quantitative assessment of metabolite profiles from skin swabs can be easily adapted by psychiatry clinics and certified clinical service laboratories and will ultimately help to reduce costs by shortening hospital stays and treatment duration. The fact that skin swabs are less invasive than blood and cerebrospinal fluid collection is of particular relevance for patients suffering from psychiatric disorders who tend to be very sensitive with regard to any medical procedure inflicting pain. Before the method can be applied in the clinic we plan to carry out further tests with greater sample numbers.