An online program with individualized vs automated support for significant others of depressed individuals - study protocol of a randomized controlled trial.

BACKGROUND: Due to budget restrictions in mental health care, non-professional caregivers are increasingly burdened with the emotional and practical care for their depressed relatives. However, informal family caregiving is mostly a stressful role with negative consequences on the physical and mental health of the caretakers to the extent that they have an elevated risk of experiencing psychiatric disorders themselves. While psychoeducation for relatives of depressed individuals showed positive results both in terms of the caretakers' strain and the depressive symptoms of the affected person, there are major barriers to participate in presence in those programs. Digital programs might be a viable alternative. We found no empirically evaluated digital program available for informal caregivers of depressed patients. METHODS: An online program for relatives of depressed individuals has been developed including four interactive modules on 1) psychoeducation, 2) how to strengthen the relationship with the depressed person, 3) how to deal with the depressive symptoms of the patient, and 4) find the right balance between caring for the depressed person and self-care. We investigate if this self-help program is more effective when used with individualized versus automated e-mail support, and if both supported conditions are more effective than treatment-as-usual (TAU in form of written information material) in terms of the risk of mental diseases in caregivers. The primary outcome is the reduction of the caregiver's nonspecific mental distress as measured by the change of the Kessler Psychological Distress Scale score from baseline to four weeks after randomization. Caregivers (n = 500:500:250) will be randomized to one of the three conditions. DISCUSSION: Psychological support for caregivers of individuals with mental disorders such as depression should be offered as part of integrated services. There is a huge potential to develop and implement interactive online approaches to support informal caregivers of patients with depression to function in their multiple roles and to help them to remain healthy. TRIAL REGISTRATION: DRKS, DRKS00025241 . Registered 5 Mai 2021.

Perturbation of left posterior prefrontal cortex modulates top-down processing in sentence comprehension.

Communication is an inferential process. In particular, language comprehension constantly requires top-down efforts, as often multiple interpretations are compatible with a given sentence. To assess top-down processing in the language domain, our experiment employed ambiguous sentences that allow for multiple interpretations (e.g., The client sued the murderer with the corrupt lawyer., where the corrupt lawyer could either belong to The client or the murderer). Interpretation thus depended on whether participants chunk the words of the sentence into short or long syntactic phrases. In principle, bottom-up acoustic information (i.e., the presence or absence of an intonational phrase boundary at the offset of the murderer) indicates one of the two possible interpretations. Yet, acoustic information often indicates interpretations that require words to be chunked into overly long phrases that would overburden working memory. Processing is biased against these demands, reflected in a top-down preference to chunk words into short rather than long phrases. It is often proposed, but also hotly debated, that the ability to chunk words into short phrases is subserved by the left inferior frontal gyrus (IFG). Here, we employed focal repetitive transcranial magnetic stimulation to perturb the left IFG, which resulted in a further decrease of the aptitude to tolerate long phrases, indicating the inability of the left IFG to assist the chunking of words into phrases. In contrast, the processing of auditory information was not affected. Our findings support a causal top-down role of the left inferior frontal gyrus in the chunking of words into phrases.

Suicide rates during and after the first COVID-19 lockdown in Germany in 2020.

The impact of the COVID-19 pandemic and of measures implemented to curb the spread of the virus on suicidal behavior has been investigated in different regions of the world, but does not yet allow to draw conclusions for Germany. Especially lockdowns might have effects on suicide rates via impact on mental disorders, changes in the choice of suicide method, a decrease in help seeking behavior, or a deterioration in the quality of medical care for people with mental disorders. The following research questions were addressed: i) did suicide rates in Germany in 2020 change during lockdown and non-lockdown periods when compared to a ten-year baseline? ii) was there a change in the proportion of suicide methods during the lockdown compared to baseline? An interrupted time-series analysis based on a linear regression was used. For the comparisons of predicted and observed suicide rates, excess suicide mortality rates (ESMR) were chosen among others. Changes in the choice of method were analyzed by comparing the rates of different methods to those at baseline. Although the mean suicide rate in 2020 was not significantly different from baseline, the weekly analysis of suicide rates revealed a significant difference (χ2 = 64.16; df = 39; p = 0.007), with some weeks showing higher and others lower rates than previous years. The effects for separate weeks were attenuated to non-significance after correction for multiple testing. Suicide mortality during the first lockdown in 2020 was significantly lower than expected (ESMR = 0.933; 95% CI: 0.890; 0.985) whereas, in the post-lockdown period, the registered suicide mortality was not significantly different from the expected one (ESMR = 1.024; 95% CI: 0.997; 1.051). During lockdown, there was a significant increase of the percentage of the suicide method categories jumping and 'other methods' and a decrease of poisoning and lying in front of a moving object. Being able to determine whether the choice of more or less lethal methods during lockdown versus non-lockdown periods partly explains this finding would require a representative assessment of attempted suicides.

The German Alliance Against Depression and suicide rates: A retrospective analysis.

Supported by the German Alliance Against Depression, 82 regions in Germany launched their own community-based multi-level intervention programs targeting both depression and suicidal behavior prior to January 2016. Sixteen of these regions have implemented the full 4-level intervention program comprising 1) training of General Practitioners, 2) a public awareness campaign, 3) training of community facilitators and 4) support for depressed patients and their relatives for at least three years. The aim of the study was to examine possible suicide prevention effects in these sixteen 4-level intervention regions (comprising a population of 6,976,309) by 1) comparing the annual suicide rates during the 3-year intervention period to a 10-year baseline and 2) comparing these differences to corresponding trends in Germany after excluding all intervention regions (Germany-IR). Primary outcome was the annual rate of suicides. Analyses included negative binomial regression models. When examining differences between suicide rates during the intervention period compared to the baseline period, only a trend towards a significant reduction was found. This reduction of suicides in the sixteen 4-level intervention regions did not differ from that in Germany-IR as control. The interpretation of these findings has to take into account that the training of General Practitioners, police and other community facilitators might have improved the recognition of suicides, thus increasing detection rates. Furthermore, destigmatizing effects of the public awareness campaigns might have increased the number of suicides by lowering suicide threshold ("normalization") for those at risk and by decreasing the rate of suicides deliberately hidden by suicide victims or their relatives.

Distinct antifibrogenic effects of erlotinib, sunitinib and sorafenib on rat pancreatic stellate cells.

AIM: To study if three clinically available small molecule kinase inhibitors (SMI), erlotinib, sunitinib and sorafenib, exert antifibrogenic effects on pancreatic stellate cells (PSC) and analyze the basis of their action. METHODS: Cultured rat PSC were exposed to SMI. Cell proliferation and viability were assessed employing 5-bromo-2'-deoxyuridine incorporation assay and flow cytometry, respectively. 2-Deoxy-2-[(18)F] fluoroglucose ((18)F-FDG) uptake was measured to study metabolic activity. Exhibition of the myofibroblastic PSC phenotype was monitored by immunofluorescence analysis of α-smooth muscle actin (α-SMA) expression. Levels of mRNA were determined by real-time PCR, while protein expression and phosphorylation were analyzed by immunoblotting. Transforming growth factor-ß1 (TGF-ß1) levels in culture supernatants were quantified by ELISA. RESULTS: All three SMI inhibited cell proliferation and (18)F-FDG uptake in a dose-dependent manner and without significant cytotoxic effects. Furthermore, additive effects of the drugs were observed. Immunoblot analysis showed that sorafenib and sunitib, but not erlotinib, efficiently blocked activation of the AKT pathway, while all three drugs displayed little effect on phosphorylation of ERK1/2. Cells treated with sorafenib or sunitinib expressed less interleukin-6 mRNA as well as less collagen type 1 mRNA and protein. Sorafenib was the only drug that also upregulated the expression of matrix metalloproteinase-2 and reduced the secretion of TGF-ß1 protein. All three drugs showed insignificant or discordant effects on the mRNA and protein levels of α-SMA. CONCLUSION: The tested SMI, especially sorafenib, exert inhibitory effects on activated PSC, which should be further evaluated in preclinical studies.

Grading of infrared confocal scanning laser tomography and video displays of digitized color slides in exudative age-related macular degeneration.

PURPOSE: To detect and localize exudative lesions in exudative age-related macular degeneration and to compare images obtained from infrared scanning laser tomography and video displays of digitized color slides in detection and localization of exudation. METHODS: In a prospective study, 11 eyes of 11 patients with exudative age-related macular degeneration were studied. From 32 images with infrared scanning laser tomography, confocal images were chosen in the following focal planes: anterior to the retina, the retinal surface, and the deep retina. Using the fluorescein angiogram as a standard, three retinal specialists rank-ordered the ability to discern the lesion in these confocal images, the summary of confocal images, and video displays of digitized color slides that were adjusted to the same resolution as that of the confocal images (approximately 23 microm per pixel). RESULTS: For choroidal neovascularization, both the retinal surface image and the summary image were rated superior to video displays of digitized color slides (P < 0.004). The confocal images were ranked in the following fashion: best, retinal surface; next, deep retina; and then, anterior to the retina (P < 0.01). For pigment epithelial detachment, all three confocal images and summary images were superior to video displays of digitized color slides (P < 0.002). There were no significant differences among the confocal images (P = 0.95). CONCLUSION: Infrared confocal imaging was superior to video displays of digitized color slides for visualization of both pigment epithelial detachment and choroidal neovascularization. This technique could have an impact on epidemiologic studies.