PSYCHIATRIC GENOMICS IN CLINICAL PRACTICE IN GERMANY: THE CENTER FOR RARE MENTAL HEALTH DISORDERS IN BONN

Background In routine clinical practice in Germany, the national genetic testing landscape for adults has changed in recent years from the testing of individual candidate genes and gene panels and stepped approaches utilizing different methodologies to a preponderance of whole exome sequencing and, most recently, efforts to establish whole genome sequencing as the gold standard. These state-of-the-art testing strategies are—in theory—also available to individuals with a mental health disorder that mandates genetic testing. Yet, they are still heavily underutilized in the mental health disorder space, highlighting an important healthcare gap. Methods 37 Centers for Rare Diseases exist across Germany, most of which are associated with university hospitals. At all Centers for Rare Diseases, subcenters specializing in different disease areas or disease entities exist, spanning pediatrics to oncology to neurodegeneration. Building upon this established and highly interdisciplinary infrastructure, in 2024, we established the first Center for Rare Mental Health Disorders in the country as a specialist subcenter of the Center for Rare Diseases Bonn. Co-headed by psychiatrists and clinical geneticists, here, we provide specialist assessment and treatment, genetic counselling, and, when indicated, genetic testing for (1) individuals with psychiatric conditions and their families and (2) individuals with known rare genetic conditions and mental health symptoms. Pre and post genetic testing, cases are presented to and discussed by an interdisciplinary board representing the entire Center for Rare Diseases in Bonn. Results Since its inception, we have evaluated and provided genetic counselling to approximately 50 individuals and their families. We have further developed standard operating procedures for diagnostic genetic testing and genomic data interpretation in adult mental health disorders. In a subset of individuals, we have identified rare pathogenic or likely pathogenic variants as well as variants of unknown significance according to ACMG criteria that we have reported back to patients and their families as well as to treating physicians/psychiatrists. On a case-by-case basis, this has had important impact on any number of the following areas: (1) end of a diagnostic odyssey and personal concept of the disorder, (2) information on prognosis and expected disease course, (3) (molecularly) tailored health screening and treatment measures, (4) estimation of family recurrence risk, and (5) access to social support and trial participation. Conclusion The Center for Rare Diseases’ and the Center for Rare Mental Health Disorders’ concept is unique in that it leverages clinical and clinical genetics expertise beyond the sphere of neuropsychiatric disorders in an approach spanning medical disciplines. Both, available interdisciplinary infrastructures and the development of the standard operating procedures for diagnostic genetic testing geared especially at the mental health disorder context, have provided invaluable opportunities to provide state-of-the-art healthcare and set the stage for the implementation of tailored treatments and preventive measures to bridge the existing clinical care gap in rare mental health disorders.