Abstract Background Brain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE). Methods The BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study’s main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression Rating Scale (HDRS-24), and the occurrence of AE. Ethics and dissemination The trial protocol has received approval from the Institutional Review Boards at the five participating universities. This trial holds significance in generating valuable data on a predictive biomarker for antidepressant treatment in patients with MDD. The findings will be shared with study participants, disseminated through professional society meetings, and published in peer-reviewed journals. Trial registration German Clinical Trial Register DRKS00032503. Registered on 17 August 2023.
Background Chronic kidney disease (CKD) has emerged as a risk factor for cognitive impairment. Living kidney donation results in reduction of the donors' renal function. This is considered acceptable in general but possible associations with cognitive function have not yet been studied. Methods Sixty living kidney donors (LKD), who had donated between 2003 and 2012 at Hannover Medical School, underwent neurocognitive testing including attentional and memory testing. In a cross-sectional design results were compared with data of healthy controls (n = 40) and with norm data given in the respective test manuals adjusted for age, sex, and education. Results The median age of the LKD was 58 (range 39-70) years and the median time since donation was 7 (range 4-14) years. The LKD did not differ from controls in most of the cognitive test results and a composite attention test sum score. However, LKD did worse than controls in tests of working memory, parallel processing of stimuli, and sustained attention. No differences were found regarding quality of life. In LKD cognitive test results correlated significantly only with educational level but not with time since transplantation, eGFR, somatic comorbidity, quality of life and levels of fatigue, distress, depression, and anxiety. Conclusions Our data show a fairly normal performance of LKD in most attentional and memory tests. However, our pilot study also suggests some cognitive impairment in attention tests in LKD which would need to be confirmed in longitudinal prospective studies.
The northern white rhinoceros (NWR; Ceratotherium simum cottoni ) is functionally extinct, with only two females remaining alive. Efforts to rescue the NWR have inspired the exploration of unconventional conservation methods, including the generation of artificial gametes from induced pluripotent stem cells and somatic cell nuclear transfer. To enable the technologies required for these approaches, we used complementary sequencing and mapping methods to generate a NWR chromosome-level reference genome that meets or exceeds the metrics proposed by the Vertebrate Genome Project. It represents 40 autosomes, an X and a partially-resolved Y chromosome, and the mitochondrial genome. We compared the NWR reference genome to the southern white rhinoceros (SWR) population that has been physically separated from the NWR for tens of thousands of years. Using short-read data from the SWR and optical mapping, we found that the two populations are very similar on both the chromosome level and mitochondrial genome level. The results of this study are encouraging for the efforts underway to rescue the NWR.
Zusammenfassung Einleitung Die Häufigkeit negativer Effekte von Psychotherapie und die Korrelate ihrer Anzahl wurden bislang selten systematisch untersucht. Die Häufigkeit negativer Effekte variiert zwischen 3 Studien mit dem Inventar zur Erfassung negativer Effekte von Psychotherapie (INEP) mit 20, 84 und 93,8% erheblich. Ob Bias-Effekte daran beteiligt waren, bleibt ungeklärt. Diese Studie hatte daher zum Ziel, die Häufigkeit negativer Effekte mit dem INEP in einer konsekutiven Stichprobe zu erheben. Zudem sollten in Vorstudien berichtete Korrelate der Anzahl negativer Effekte überprüft und um weitere mögliche Korrelate ergänzt werden. Material und Methoden Eine klinische Stichprobe (teil)stationärer Patienten (N=200) beurteilte die letzte Psychotherapie vor der aktuellen Behandlung retrospektiv mit dem INEP, das anhand von 21 Items 6 Dimensionen negativer Effekte abbildet. Soziodemografische und klinische Daten der Patienten und Therapeuten sowie zeitliche und methodische Aspekte der Therapie wurden als mögliche Korrelate der Anzahl negativer Effekte untersucht. Ergebnisse 70,5% (n=141) der Patienten berichtete über mind. einen negativen Therapieeffekt (INEP: MW=2,11; SD=2,23) in ihrer letzten Psychotherapie. Am häufigsten wurden „längere Phasen in schlechter psychischer Verfassung“ (39,9%) und „Verletztheit durch Aussagen des Therapeuten“ (28%) angegeben. Eine höhere Symptombelastung, ein als gering eingeschätzter „allgemeiner Therapieerfolg“ und „unerfüllte Therapieerwartungen“ nicht aber die „Qualität der therapeutischen Beziehung“ waren mit einer höheren Anzahl an negativen Effekten assoziiert. Eine negative Assoziation konnte auch für weibliches Geschlecht sowohl bei Patienten als auch Therapeuten und ein jüngeres Therapeutenalter gefunden werden. Diskussion Die Häufigkeit von selbst berichteten negativen Therapieeffekten war nicht unerheblich. Am häufigsten betroffen waren übereinstimmend mit Vorstudien die INEP-Dimensionen „Symptomatik“ und „therapeutische Beziehung“. Die Studie konnte einige Korrelate für die Anzahl retrospektiv angegebener negativer Effekte bestätigen. Patienten sollten zu Beginn einer Psychotherapie über mögliche negative Effekte informiert werden.
Due to organ shortage, living kidney donation is gaining increasing importance. Medical progress enables a successful transplantation between unrelated individuals, even individuals with AB0-incompatibilities. Spouses are the largest group of living kidney donors. The aim of this study was to assess partnership status and partnership satisfaction in living kidney donors. In the cross-sectional study we investigated 361 living kidney donors. The time since donation ranged between 1 and 38 years. The partnership satisfaction was assessed with the German version of the Quality of Marriage Index. We compared the donor sample with a representative German population sample (n = 1995). In addition, we compared donors who have donated to their partner (spouse donors) to those who have donated to someone else (non-spouse donors). In comparison to the population sample significantly more kidney donors were living in a relationship (82 vs. 60%). Most donors reported an unchanged (76.6%) or improved (20.5%) relationship to the recipient since transplantation. A significantly higher partnership satisfaction could be found in the donor sample compared to the population sample which was mainly due to a higher partnership satisfaction of the spouse donors compared to the non-spouse donors. High partnership satisfaction in living kidney donors might be an indicator for a successful selection process before transplantation. Alternatively, kidney donation might have a stabilizing or even positive impact on the partnership. Due to the design of our study causative interpretations cannot be made. Therefore, prospective studies are required to assess partnership satisfaction before and after living kidney donation.
Since living kidney donors have repeatedly been shown to be mentally more healthy compared to the general population, they might also exhibit more adaptive personality characteristics. We investigated the personality traits of 315 living kidney donors (202 female and 113 male donors) on average 7.1 years after donation using the NEO-Five Factor Inventory, a frequently used personality inventory measuring the "big five" dimensions of personality (neuroticism, extraversion, openness, agreeableness, and conscientiousness). In addition, levels of depression, anxiety, and fatigue were assessed with the Patient Health Questionnaire-Depression Scale, GAD-7, and Multidimensional Fatigue Inventory. Kidney donors showed more adaptive personality traits with higher agreeableness and lower neuroticism scores compared to the German general population. This was even more pronounced in living kidney donors with a high motivation to donate again (non-regreters). Scores for depression, anxiety, and fatigue did not differ from general population values and were significantly correlated with most personality dimensions. The more adaptive personality characteristics of living kidney donors might either be a selection effect or the consequence of the experience of donation and improved health of the close relative. Regardless of the causal relationship, adaptive personality traits might positively influence both physical and psychosocial well-being of the donor. Longitudinal studies should investigate if living donation might lead to persistent adaptive changes in personality traits.