Deep phenotyping as a contribution to personalized depression therapy: the GEParD and DaCFail protocols.

Depressive patients suffer from a complex of symptoms of varying intensity compromising their mood, emotions, self-concept, neurocognition, and somatic function. Due to a mosaic of aetiologies involved in developing depression, such as somatic, neurobiological, (epi-)genetic factors, or adverse life events, patients often experience recurrent depressive episodes. About 20-30% of these patients develop difficult-to-treat depression. Here, we describe the design of the GEParD (Genetics and Epigenetics of Pharmaco- and Psychotherapy in acute and recurrent Depression) cohort and the DaCFail (Depression-associated Cardiac Failure) case-control protocol. Both protocols intended to investigate the incremental utility of multimodal biomarkers including cardiovascular and (epi-)genetic markers, functional brain and heart imaging when evaluating the response to antidepressive therapy using comprehensive psychometry. From 2012 to 2020, 346 depressed patients (mean age 45 years) were recruited to the prospective, observational GEParD cohort protocol. Between 2016 and 2020, the DaCFail case-control protocol was initiated integrating four study subgroups to focus on heart-brain interactions and stress systems in patients > 50 years with depression and heart failure, respectively. For DaCFail, 120 depressed patients (mean age 60 years, group 1 + 2), of which 115 also completed GEParD, and 95 non-depressed controls (mean age 66 years) were recruited. The latter comprised 47 patients with heart failure (group 3) and 48 healthy subjects (group 4) of a population-based control group derived from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study. Our hypothesis-driven, exploratory study design may serve as an exemplary roadmap for a standardized, reproducible investigation of personalized antidepressant therapy in an inpatient setting with focus on heart comorbidities in future multicentre studies.

Childhood trauma dependent anxious depression sensitizes HPA axis function.

Anxious depression is a common subtype of major depressive disorder (MDD) and is associated with greater severity and poorer outcome. Alterations of the hypothalamic-pituitary-adrenal (HPA) axis, especially of the glucocorticoid receptor (GR) function, are often observed in MDD, but evidence lacks for anxious depression. Childhood adversity is known to influence both the HPA axis and risk of MDD. Therefore, we investigated GR-function in anxious depression dependent on childhood adversity. We enrolled 144 depressed in-patients (49.3% females). Anxious depression was defined using the Hamilton Depression Rating Scale (HAM-D) anxiety/somatization factor score ≥7. Blood draws were performed at 6 pm before and 3 h after 1.5 mg dexamethasone ingestion for measurement of cortisol, ACTH and blood count to assess GR-function and the immune system. In a subgroup of n = 60 FKBP5 mRNA controlled for FKBP5 genotype was measured before and after dexamethasone. Childhood adversity was evaluated using the Childhood Trauma Questionnaire (CTQ). We identified 78 patients (54.2%) with anxious depression who showed a greater severity and worse outcome. These patients were more often exposed to sexual abuse (30% vs. 16%/p = 0.04) and emotional neglect (76% vs. 58%/p = 0.02) than patients with non-anxious depression. Anxious depressed patients showed an enhanced GR-induced FKBP5 mRNA expression (F = 5.128; p = 0.03) and reduced cortisol levels, partly dependent on sexual abuse (F = 7.730; p = 0.006). Additionally, the GR-induced leukocyte response was enhanced in patients with sexual abuse (F = 7.176; p = 0.008). Anxious depression in dependence of childhood trauma is associated with heightened sensitivity of the HPA axis and the immune system which should be considered for treatment algorithms and targets.

Dental problems and emergencies of trekkers--epidemiology and prevention. Results of the ADEMED Expedition 2008.

OBJECTIVE: Dental problems are rarely mentioned in the training of medical students or physicians in travel medicine, and there are little data on dental problems of travellers in the literature. We studied the epidemiology of dental problems amongst trekkers in Nepal to develop strategies for preventive care during/before travelling and propose a curriculum for dental First Aid training. MATERIAL AND METHODS: We undertook a prospective, cross-sectional questionnaire and clinical dental survey of Trekkers at Manang (3550 m, Annapurna Circuit, Nepal). The questionnaire was developed based on published literature and clinical experience (exploring: availability of dental kits, dental history, current dental problems, and nutritional behavior). Dental examination included: dental status, papillary bleeding index (PBI), and plaque index (Quigley and Hein; QH). Questionnaire and clinical findings were compared to data of the Annapurna Conservancy Authority about the number of days of trekkers in the region to estimate the incidence of dental problems of trekkers. RESULTS: None of the 309 participants carried a dental first aid kit. Dental problems, potentially treatable with a dental first aid kit, were reported by 50/309 (16.5%). Oral hygiene en route was significantly worse than home hygiene practice; overall increased plaque indices were found (Median QH: 2.25 in women; 2.36 in men). Participants who visited a dentist ≤6 months before departure had significantly fewer problems, and had lower PBI [males 0.07 (IQR 0.0 to 0.29), females 0.0 (IQR 0.0 to 0.11)]. Combining our findings with data of the park authorities on person days in the region (2007), we found a risk of dental problems as follows: any dental problem 1:23.7 trekking days; gingival bleeding 1:37.7 trekking days; dental pain 1:145.2 trekking days; lost fillings 1:339 trekking days; fractured teeth 1:509 trekking days. CONCLUSIONS: Dental problems can pose significant discomfort for anybody travelling in regions with low/missing infrastructure. Improved awareness regarding dental first aid is essential and physicians counseling travellers in preventive strategies should advise a dental checkup pre-departure. Dental first aid and emergency treatment in the field should be included in the training curricula in travel medicine for both undergraduate and postgraduate students.