Identification of dihydromyricetin as a natural DNA methylation inhibitor with rejuvenating activity in human skin.

Changes in DNA methylation patterning have been reported to be a key hallmark of aged human skin. The altered DNA methylation patterns are correlated with deregulated gene expression and impaired tissue functionality, leading to the well-known skin aging phenotype. Searching for small molecules, which correct the aged methylation pattern therefore represents a novel and attractive strategy for the identification of anti-aging compounds. DNMT1 maintains epigenetic information by copying methylation patterns from the parental (methylated) strand to the newly synthesized strand after DNA replication. We hypothesized that a modest inhibition of this process promotes the restoration of the ground-state epigenetic pattern, thereby inducing rejuvenating effects. In this study, we screened a library of 1800 natural substances and 640 FDA-approved drugs and identified the well-known antioxidant and anti-inflammatory molecule dihydromyricetin (DHM) as an inhibitor of the DNA methyltransferase DNMT1. DHM is the active ingredient of several plants with medicinal use and showed robust inhibition of DNMT1 in biochemical assays. We also analyzed the effect of DHM in cultivated keratinocytes by array-based methylation profiling and observed a moderate, but significant global hypomethylation effect upon treatment. To further characterize DHM-induced methylation changes, we used published DNA methylation clocks and newly established age predictors to demonstrate that the DHM-induced methylation change is associated with a reduction in the biological age of the cells. Further studies also revealed re-activation of age-dependently hypermethylated and silenced genes in vivo and a reduction in age-dependent epidermal thinning in a 3-dimensional skin model. Our findings thus establish DHM as an epigenetic inhibitor with rejuvenating effects for aged human skin.

Fat-Phobic and Non-Fat-Phobic Anorexia Nervosa: A Conjoint Analysis on the Importance of Shape and Weight.

With the introduction of new diagnostic criteria in DSM-5, fear of weight gain no longer represents a sine qua non-criterion for the diagnosis of anorexia nervosa (AN). This is of relevance as a subgroup of individuals with AN denies fear of weight gain as the reason for restrictive eating but still remain at a very low weight. As self-reports are susceptible to bias, other methods are needed to confirm the existence of the subtype in order to provide adapted treatment. Therefore, we aimed to measure fear of weight gain using a novel method in clinical psychology, the conjoint analysis (CA). Relative importance and preference scores for various life aspects, including appearance/shape and weight were assessed in women with fat-phobic AN (FP-AN, n = 30), NFP-AN (n = 7), and healthy controls (n = 29). Individuals with FP-AN showed a significant lower preference for weight gain versus weight maintenance than HC (p = 0.011, η p 2 = 0.107). Correlation between explicitly assessed drive for thinness and CA score was low. As expected, in FP-AN the explicitly endorsed fear of weight gain was confirmed by the marked preference for weight maintenance compared to HC, while for NFP-AN explicit and implicit measures diverged, indicating that against their self-report they may experience at least some fear of weight gain. The utility of CA as a tool to measure fear of weight gain - and potentially other psychopathological constructs -requires further confirmation.

Testing the specificity of interpretation biases in women with eating disorder symptoms: An online experimental assessment.

OBJECTIVE: Cognitive biases, such as memory, attention, and interpretation bias, are thought to play a central role in the development and maintenance of eating disorders (EDs). The aim of the present study was to investigate whether the interpretation bias is ED-specific or can be generalized to comorbid disorder-related threats in women with high levels of ED symptoms. METHOD: In an online study, we measured interpretation bias using the modified Sentence Word Association Paradigm (SWAP), comparing women with (n = 39) and without (sub)threshold eating disorders (n = 56). We assessed endorsement and rejection rates as well as reaction times in response to a positive/neutral or a negative ED-specific, social anxiety-specific (SAD), or generalized anxiety-specific (GAD) interpretive word following an ambiguous sentence. RESULTS: In ambiguous situations, women with high ED symptoms selected more negative (p < .001) and fewer positive/neutral ED-related interpretations (p < .001). Negative interpretations were endorsed significantly faster (p < .001), while positive interpretations were rejected faster in this group (p < .001). These women also manifested negative SAD-specific interpretation bias patterns in reaction time measures. Nevertheless, ED severity was best predicted by the endorsement of negative ED-specific stimuli, whereas ED and SAD reaction time measures seemed to have a negligible effect. DISCUSSION: The results indicate that the interpretation bias might be ED-specific. The SWAP can be a useful tool for the further investigation of the etiological relevance of the interpretation bias as well as for the development of modification training interventions.

[Metacognitive Therapy in the Treatment of Depression.] / Die Metakognitive Therapie in der Behandlung der unipolaren Depression.

Metacognitive Therapy (MCT) developed by A. Wells is one of the new developments of Behavior Therapy. It assumes that not the content of cognition is important for the treatment of psychological disorders. Instead of this from a metacognitive perspective persistent and unflexible patterns of thinking and focusing attention and therewith associated dysfunctional coping behaviors play a crucial role for their development and maintenance. These patterns are called Cog-nitive Attentional Syndrome (CAS). In depres-sion the CAS consists of excessive rumination and worry, focusing attention on potential danger (threat monitoring) and maladaptive coping strategies, e. g. avoidance of social contact or substance abuse. The reason for the use of these strategies is the existence of positive metacognitions which highlight its benefit for the patient (e. g. "Rumination helps me to find a solution for my problems!"). Over time however negative metacognitive beliefs develop about the uncontrollability and danger of these processes (e. g., "Rumination is uncontrollable!"). They account for the continued use of these strategies and of further coping behaviors that backfire. The aim of MCT is to improve the metacognitive awareness of the patients and to regain flexible control over processes of thinking and focusing attention. The CAS is reduced, the underlying metacognitive beliefs are changed and alternative plans of cognitive processing are generated. The existing data suggest that regarding treatment outcome MCT is possibly superior to Cognitive Behavior Therapy.