scholarly journals OXTR-Related Markers in Clinical Depression: a Longitudinal Case–Control Psychotherapy Study

Author(s):  
Iris C. Reiner ◽  
Gerald Gimpl ◽  
Manfred E. Beutel ◽  
Marian J. Bakermans-Kranenburg ◽  
Helge Frieling

AbstractWe investigated stability and change of plasma and urinary oxytocin as well as OXTR DNA methylation patterns through psychotherapy. Furthermore, we explore the potential impact of inpatient psychotherapy on oxytocin-related biomarkers and vice versa by differentiating patients who remitted from depression versus non-remitters. Blood and urine samples were taken from 85 premenopausal women (aged 19–52), 43 clinically depressed patients from a psychosomatic inpatient unit, and 42 healthy control subjects matched for age and education at two points of time. Serum and urine oxytocin was measured using standard ELISA, and DNA methylation of the OXTR gene was assessed using bisulfite sequencing at the time of admission (baseline) and at discharge and from controls at matched time points. Oxytocin plasma levels were not associated with depression and were influenced by neither time in healthy controls nor psychotherapy in patients. Non-remitting depressed patients had significantly lower oxytocin urine levels before and after psychotherapy treatment. We found significantly lower exon 1 OTXR methylation in depressed patients over time and these differences were driven by patients remitting due to psychotherapy. A reverse pattern — higher levels of methylation in remitters — was found for exon 2 OXTR DNA methylation. Plasma oxytocin, urinary oxytocin, and OXTR DNA methylation patterns were intrapersonally relatively stable. OXTR-related factors were seemingly unaffected by inpatient psychotherapeutic treatment, but we found significant differences between remitting and non-remitting patients in urinary oxytocin and OXTR DNA methylation. If replicated, this suggests that OXTR-related markers may predict inpatient treatment outcomes of clinically depressed patients.

2020 ◽  
Vol 21 (20) ◽  
pp. 7459
Author(s):  
María Elena González-Benito ◽  
Miguel Ángel Ibáñez ◽  
Michela Pirredda ◽  
Sara Mira ◽  
Carmen Martín

Epigenetic variation, and particularly DNA methylation, is involved in plasticity and responses to changes in the environment. Conservation biology studies have focused on the measurement of this variation to establish demographic parameters, diversity levels and population structure to design the appropriate conservation strategies. However, in ex situ conservation approaches, the main objective is to guarantee the characteristics of the conserved material (phenotype and epi-genetic). We review the use of the Methylation Sensitive Amplified Polymorphism (MSAP) technique to detect changes in the DNA methylation patterns of plant material conserved by the main ex situ plant conservation methods: seed banks, in vitro slow growth and cryopreservation. Comparison of DNA methylation patterns before and after conservation is a useful tool to check the fidelity of the regenerated plants, and, at the same time, may be related with other genetic variations that might appear during the conservation process (i.e., somaclonal variation). Analyses of MSAP profiles can be useful in the management of ex situ plant conservation but differs in the approach used in the in situ conservation. Likewise, an easy-to-use methodology is necessary for a rapid interpretation of data, in order to be readily implemented by conservation managers.


2019 ◽  
Vol 29 ◽  
pp. S793-S794
Author(s):  
Shaunna Clark ◽  
Mohammad Hattab ◽  
Andrey Shabalin ◽  
Laura Han ◽  
Robin Chan ◽  
...  

2020 ◽  
Author(s):  
Elisabeth Hummel ◽  
Magdeldin Elgizouli ◽  
Jasmin Beygo ◽  
Johanna Giuranna ◽  
Maurizio Sicorello ◽  
...  

AbstractBackgroundDNA methylation patterns can be responsive to environmental influences. This observation has sparked interest in the potential for psychological interventions to influence epigenetic processes. Recent studies have observed correlations between DNA methylation changes and therapy outcome. However, most did not control for changes in cell composition from pre- to post-therapy. Here, we addressed this limitation and analyzed DNA methylation patterns by targeted deep bisulfite sequencing (DBS) of commonly assessed candidate genes in isolated monocytes from 60 female patients with post-traumatic stress disorder (PTSD) before and after in-patient treatment. Furthermore, in two patients with PTSD and three patients with anorexia nervosa (AN), whole-genome bisulfite sequencing (WGBS) was performed before and after intervention with the aim of identifying novel genomic regions with notable pre-to-post intervention DNA methylation changes.ResultsWGBS yielded only a limited set of candidate regions with suggestive evidence of differential methylation pre- to post-therapy. These differential methylation patterns did not prove replicable when investigated in the entire cohort. Furthermore, equivalence testing and Bayesian analyses provided evidence against physiologically meaningful intervention associated DNA methylation changes in monocytes of PTSD patients in commonly investigated target genes (NR3C1, FKBP5, SLC6A4, OXTR).ConclusionsWe conclude that there is no evidence for major, recurrent intervention-associated DNA methylation changes in the investigated genes in monocytes of patients with either PTSD or anorexia nervosa.


2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)


2011 ◽  
pp. 13-19
Author(s):  
Nhu Minh Hang Tran ◽  
Huu Cat Nguyen ◽  
Dang Doanh Nguyen ◽  
Van Luong Ngo ◽  
Vu Hoang Nguyen ◽  
...  

Objectives: To determine factors impact on the relapse in depressed patients treated with Cognitive Behavioral Therapy (CBT) during one year follow-up. Materials and Methods: 80 depressed patients divided into two groups, group 1: included 40 patients treated with CBT; group 2: 40 patients on amitriptyline. Non-randomized controlled clinical trial, opened, longiditual and prospective research. Results and Conclusions: relapse rate after CBT during 1 year follow-up is 10% (compared to 25% in control group), related factors to relapse rate in depression after CBT are age and education. Shared predictors between 2 groups are severity and recurrence of depression. Key words: Depression, relapse, Cognitive Behavioral Therapy (CBT)


2020 ◽  
pp. 19-29
Author(s):  
Patricia Diaz Ortega ◽  
Manuel García Manero

Introduction: Symptomatic uterine fibroids can cause symptoms that can be disabling. There are many treatments, including ulipristal acetate, whose role in reducing symptoms and decreasing the size of the fibroid is well known. With this preliminary study, we also try to evaluate the correlation between myoma vascularization measured by ultrasound (Power Doppler 2D) and serum VEGF levels, before and after treatment with ulipristal acetate; in patients diagnosed with symptomatic uterine fibroids. Materials and Methods: A preliminary, prospective observational pilot study was designed. Twenty-four premenopausal women, diagnosed with symptomatic uterine fibroids, were included and all of them completed the study. Four cycles of ulipristal acetate were administered according to the dose and indications specified in the data sheet. In order to assess the influence of this treatment on the angiogenesis process of the fibroids, measurements of VEGF serum levels were made and their vascularization was assessed by means of 2D power doppler ultrasound; at the beginning and the end of treatment. In addition, several determinations of the same parameters were made throughout the successive visits. Endpoints were defined as the decrease in VEGF levels from previous levels, the decrease in myoma vascularization on ultrasound, and the reduction in myoma size. Result: 24 patients who met the inclusion criteria were enrolled (n=24). The average size of myomas was reduced from 45,08 ? 24,02mm to 29?16,96mm after treatment. The average VEGF serum level significantly decreased after the first treatment cycle (from 147,17 ? 153,51 pg/ml to 102,04 ? 186,08pg/ml). Vascularization of myomas after treatment with ulipristal acetate was analyzed, and a significantly decrease was achieved in 83,3% of cases. Conclusion: There is a correlation between myoma vascularization and treatment with Ulipristal acetate. SPRMs may provide effective treatment for women with symptomatic fibroids by two ways: supports selective progesterone receptor modulators and reduced angiogenesis. Keywords: Angiogenesis; Ulipristal Acetate; Uterine fibroids; VEGF


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 888
Author(s):  
Mohammed A. Ibrahim Al-Obaide ◽  
Kalkunte S. Srivenugopal

Background: The therapeutically important DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) is silenced by promoter methylation in human brain cancers. The co-players/regulators associated with this process and the subsequent progression of MGMT gene transcription beyond the non-coding exon 1 are unknown. As a follow-up to our recent finding of a predicted second promoter mapped proximal to the exon 2 [Int. J. Mol. Sci.2021, 22(5), 2492], we addressed its significance in MGMT transcription. Methods: RT-PCR, RT q-PCR, and nuclear run-on transcription assays were performed to compare and contrast the transcription rates of exon 1 and exon 2 of the MGMT gene in glioblastoma cells. Results: Bioinformatic characterization of the predicted MGMT exon 2 promoter showed several consensus TATA box and INR motifs and the absence of CpG islands in contrast to the established TATA-less, CpG-rich, and GAF-bindable exon 1 promoter. RT-PCR showed very weak MGMT-E1 expression in MGMT-proficient SF188 and T98G GBM cells, compared to active transcription of MGMT-E2. In the MGMT-deficient SNB-19 cells, the expression of both exons remained weak. The RT q-PCR revealed that MGMT-E2 and MGMT-E5 expression was about 80- to 175-fold higher than that of E1 in SF188 and T98G cells. Nuclear run-on transcription assays using bromo-uridine immunocapture followed by RT q-PCR confirmed the exceptionally lower and higher transcription rates for MGMT-E1 and MGMT-E2, respectively. Conclusions: The results provide the first evidence for transcriptional pausing at the promoter 1- and non-coding exon 1 junction of the human MGMT gene and its activation/elongation through the protein-coding exons 2 through 5, possibly mediated by a second promoter. The findings offer novel insight into the regulation of MGMT transcription in glioma and other cancer types.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Vanessa Lakis ◽  
◽  
Rita T. Lawlor ◽  
Felicity Newell ◽  
Ann-Marie Patch ◽  
...  

AbstractHere we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.


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