Increased BDNF methylation in saliva, but not blood, of patients with borderline personality disorder

Abstract

BackgroundThe importance of epigenetic alterations in psychiatric disorders is increasingly acknowledged and the use of DNA methylation patterns as markers of disease is a topic of ongoing investigation. Recent studies suggest that patients suffering from Borderline Personality Disorder (BPD) display differential DNA methylation of various genes relevant for neuropsychiatric conditions. For example, several studies report differential methylation in the promoter region of the brain-derived neurotrophic factor gene (BDNF) in blood. However, little is known about BDNF methylation in other tissues.ResultsIn the present study, we analyzed DNA methylation of the BDNF IV promoter in saliva and blood of 41 BPD patients and 41 matched healthy controls and found significant hypermethylation in the BPD patient’s saliva, but not blood. Further, we report that BDNF methylation in saliva of BPD patients significantly decreased after a 12-week psychotherapeutic intervention.ConclusionsProviding a direct comparison of BDNF methylation in blood and saliva of the same individuals, our results demonstrate the importance of choice of tissue for the study of DNA methylation. In addition, they indicate a better suitability of saliva for the study of differential BDNF methylation in BPD patients. Further, our data appear to indicate a reversal of disease-specific alterations in BDNF methylation in response to psychotherapy, though further experiments are necessary to validate these results and determine the specificity of the effect.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0544-6) contains supplementary material, which is available to authorized users.

DNA hypermethylation in disease: mechanisms and clinical relevance

“…• Ascertaining that the examined tissue is meaningful to the analyzed phenotype (e.g., blood, buccal samples or saliva sometimes, but not always, provide DNA methylation markers relevant to other tissues [41]); • Confirming the differential DNA methylation findings in biological replicates and by different assay methods (e.g., [42,43],) to rule out technical problems and individual-specific variation in methylation of the examined CpG sites, unless it is a population study looking at person-specific epigenetic variation [44];…”

“…Among the complex neurological diseases with evidence for the involvement of DNA methylation changes is borderline personality disorder. Bisulfite pyrosequencing of saliva DNA sequences was tested for its ability to detect borderline personality disorder-linked hypermethylation at a promoter of the brain-related BDNF gene [41]. This gene, which encodes a nerve growth factor implicated in mood disorders, showed small but significant increases in DNA methylation in patients, and these increases were dampened by psychotherapeutic treatment.…”

A preliminary study showing no association between methylation levels of C3 gene promoter and the risk of CAD

“…So, samples in most studies about DNA methylation and CAD were selected from blood cells [23]. The methylation status in different tissues from the same subjects was discrepancy [24]. The methylation level in blood cells might differ from that in vascular tissues.…”

Umwelt und Epigenetik

“…In einer longitudinalen humanen Studie konnte gezeigt werden, dass nicht nur Misshandlung in der Kindheit, sondern auch die Teilnahme an einer präventiven psychosozialen Intervention in den Monaten nach der Geburt mit epigenetischen Veränderungen bei 27-Jährigen assoziiert war [51]. Einige Studien konnten auch zeigen, dass Psychotherapie mit peripheren epigenetischen Änderungen einhergeht [52][53][54][55]. In Zukunft könnte es möglich sein, mittels Positronenemissionstomographie(PET)-Liganden, welche die Aktivität von Histon-Deacetylasen, wichtigen epigenetischen Regulatoren, erfassen können, epigenetische Veränderungen im Gehirn zu messen.…”