The most common epigenetic marks on DNA include chemical changes known as "methylations". The authors of the new meta-analysis took a close look at precisely these methylations. A meta-analysis uses the data from previous studies on a specific question. This ultimately results in a larger sample, which usually enables statistically valuable analyses.

This was also the case here: the DNA methylation of more than 26,000 test subjects with and without depression was intended to provide insights into whether a certain epigenetic pattern can be identified that typically occurs more frequently in patients with the disease. And about which genes are epigenetically altered in these patients. Both provide clues to the mechanisms of depression development.

The Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy at LMU Hospital contributed extensive data on adolescents from the BioMD-Y study, which is headed by Prof. Dr. Gerd Schulte-Körne and in which Prof. Dr. Ellen Greimel, Dr. Lisa Feldmann and Dr. Aline Scherff from the Department of Child and Adolescent Psychiatry are involved. In the context of the project, there is also a long-standing cooperation between child and adolescent psychiatry and the Max Planck Institute of Psychiatry.

In total, the researchers have identified 15 specific methylation targets in the genome that are significantly associated with a diagnosis of depression. These sites include genes that are associated with autoimmune diseases (such as rheumatoid arthritis). In line with this, a methylation score calculated from the data was found to be associated not only with depression, but also with certain inflammatory characteristics. "This," explains Aline Scherff, "points to the mediating role of the immune system in the development of depression."

In addition, the methylation pattern is linked to depression-relevant characteristics such as the body mass index. The BMI is relevant to depression because it reflects the general state of health and nutrition as well as metabolic processes, which are not only associated with risk factors for physical and mental illnesses, but can also specifically promote the development of depression. Last but not least, according to Scherff, "the analysis of the data provided evidence that DNA methylation may contribute to the development of depression." However, this finding needs to be confirmed in further studies.

Regardless of the current results, depression is multifactorial according to the latest research. This means that the development of depression is always a complex interplay of stress in the form of stressful life events or persistent everyday burdens and biological/genetic or psychological predisposition. "Epigenetics allows us to explain how a genetic predisposition in interaction with environmental factors could contribute to an increased risk of depression as part of this development model," emphasizes Ellen Greimel. In the long term, the psychologist continues, "the investigation of DNA methylation could help to determine the individual risk of depression."