Third-Party Funded Projects on Affective Disorders

Insight into personalised medicine for people with mental illness - InDepth (Individualised Depression Therapy)

Project leader: Dr. Scheiber, Biovariance; Prof. Holzgrabe and Prof. Hoegger, Institute of Pharmaceutics, Julius-Maximilians-Universität Würzburg; Prof. Dr. Deckert and Prof. Dr. Romanos, Center of Mental Health, UKWürzburg.
Project funding: Bavarian Ministry of Economics
Project duration: 2017-2019

Rationale of the investigation

Major depressive disorder (MDD) implicates a huge burden for patients and society. Although currently available antidepressants are effective treatment options, more than 50 % of the patients do not respond to the first administered antidepressant. In addition, in more than 25 % with antidepressants treated patients, adverse effects occur. Currently, the selection of treatment does not reflect objectively measurable data from neurobiological and behavioral systems. This study aims to combine clinical variables such as therapeutic drug monitoring, inflammatory and stress markers with static and variable genetic information of depressed patients to develop an algorithm that predicts treatment response, and tolerability using machine learning algorithms. Psychometric evaluation covers the Hamilton Depression Rating Scale, the Childhood Trauma Questionnaire, and adverse drug reactions. An in-depth (epi-)genetic assessment combines genome-wide gene association data with DNA methylation patterns of genes coding CYP enzymes along with a pharmacogenetic battery focusing on CYP enzymes. Using these measures to stratify depressed patients, this approach should contribute to a data-driven assessment and management of MDD, which can be referred to as precision medicine or high-definition medicine.

Work package Center of Mental Health

In the first three quarters of 2018, the structural conditions for carrying out the investigations have been optimized:
In April 2018, a Maldi-Tof device was purchased from Agena. The device will be used to determine polymorphisms in pharmacokinetically relevant genes using the iPLEX PGx74 panel and the VeriDose CYP2D6 CNV Plex with established assays for a total of 69 SNPs/INDELS and 16 CNVs from 20 pharmacogenetically relevant genes, as well as another self-developed assay with a further 33 SNPs/INDELs in 5 additional genes or for optimal coverage of genes already present in the PGx74 panel. The validation of the assays was completed in September 2018 and genotyping has been performed since then.
In 2018, the German Research Foundation (DFG) approved an application for two mass spectrometers for therapeutic drug monitoring. By now, two ABSciex MD 4500 mass spectrometers have been purchased. After the implementation of corresponding construction measures in the second quarter of 2019 and the establishment of methods, the mirror determinations are expected to be carried out from the fourth quarter of 2019 onwards using two mass spectrometers instead of the 5 Agilent HPLC instruments and thus according to the latest state of science.

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