Digital Health Applications in the Area of Mental Health.

BACKGROUND: The introduction of digital health applications (DiGA) is a fundamental innovation in Germany. In the field of mental health, numerous applications are already available whose efficacy has been tested in clinical trials. We investigated whether, and to what extent, the use of DiGA can be recommended on the basis of the available evidence. METHODS: In this scoping review, we summarize the evidence supporting the use of DiGA in the mental health field through an examination of relevant publications that were retrieved by a systematic literature search. We provide an annotated tabular listing and discuss the current advantages of, and obstacles to, the care of mentally ill patients with the aid of DiGA. RESULTS: We identified 17 DiGA for use in depression, anxiety disorders, addiction disorders, sleep disorders, stress/burnout, vaginismus, and chronic pain. These DiGA have been evaluated to date in 3 meta-analyses, 39 randomized controlled trials (RCTs), and two single-armed intervention trials. 23 of the 36 published trials were carried out with the direct participation of the manufacturers. 29 of the 39 RCTs were not blinded or contained no information regarding blinding. Active controls were used in 6 of the 39 RCTs. The reported effect sizes, with the exclusion of pre-post analyses, ranged from 0.16 to 1.79. CONCLUSION: Most of the published studies display a high risk of bias, both because of the manufacturers' participation and because of methodological deficiencies. DiGA are an increasingly important therapeutic modality in psychiatry. The available evidence indicates that treatment effects are indeed present, but prospective comparisons with established treatments are still entirely lacking.

Adiponectin, leptin, cortisol, neuropeptide Y and profile of mood states in athletes participating in an ultramarathon during winter: An observational study.

Background: The Montane® Yukon Arctic Ultra (YAU) is one of the longest (690 km) and coldest (+10.6°C-43.9°C) ultramarathons worldwide. Taking part in an ultramarathon is associated with great physiological and psychological stress, which can affect one's mood, level of hormones, and peptides. The current study aimed to identify relationships between peptides, hormones, and mood states in participants during this ultramarathon. Methods: The study cohort consisted of 36 participants (19 men, 17 women, 38.64 ± 9.12 years) split into a finisher (n = 10), non-finisher (n = 19), and control group (n = 7). Data were collected at four time points: baseline (PRE), during (D1 after 277 km, D2 after 383 km), and after the race (POST). Questionnaires were used to assess ratings of perceived exertion (RPE), total quality of recovery (TQR), and profile of mood states (POMS-SF). Serum NPY, leptin, adiponectin, and cortisol were measured. Results: Among non-finishers, scores for confusion, anger, depression, and tension-anxiety (PRE vs. D2, p < 0.05) increased, while vigor decreased (PRE vs. D1, p < 0.05). In contrast, finishers' tension-anxiety scores decreased (PRE vs. D1, p < 0.05). Fatigue increased in finishers (PRE vs. POST, p < 0.05) and non-finishers (PRE vs. D1, p < 0.05). In non-finishers, depressive mood correlated positively with leptin, anger, and confusion at several time points (p < 0.001). In finishers, NPY correlated with TQR at PRE (p < 0.05), while leptin correlated negatively with TQR at POST (p < 0.05). Tension-anxiety correlated highly with perceived exertion in non-finishers (p < 0.001) and with cortisol in finishers (p < 0.05) and non-finishers (p < 0.001). In finishers, confusion correlated negatively with NPY (p < 0.01). Conclusion: The study reveals an essential interplay between hormones and mood states affecting performance: Leptin was associated with anger and a depressive mood state in non-finishers and worse recovery in finishers. In contrast, NPY appeared linked to a lower confusion score and heightened recovery in finishers. A simultaneous increase in depressed mood, anger, tension-anxiety, and confusion might harm performance and lead to race failure.

Influences on glycocalyx shedding during the Yukon Arctic Ultra: the longest and the coldest ultramarathon.

The endothelial glycocalyx maintains vascular structure and may be subject to shedding during inflammation and also during high-intensive exercise. There are no studies on shedding during ultra-endurance exercise. The "Yukon Arctic Ultra" (YAU) is one of the longest and coldest ultramarathons and its impact on glycocalyx shedding was investigated. Thirteen adults (38.92 ± 8.67 yr, 6 females) of YAU editions 2015-2019 completed 657.03 ± 71.65 km at a moving velocity of 4.17 ± 0.62 km/h. Mean daily temperatures ranged from -12.6°C to -30.5°C. Glycocalyx elements heparan sulfate, hyaluronan, and syndecan CD-138 were quantified from serum at start, 277 km, 383 km, and 690 km. Cortisol, C-reactive protein, creatine kinase, and N-terminal-prohormone of brain natriuretic peptide were also quantified. Seven YAU volunteers (36.14 ± 11.04 yr, 5 females) served as control. There were no time-changes among the control. Among finishers, there was a significant increase for hyaluronan and a significant decrease for syndecan CD-138. Values were greater among female finishers for heparan sulfate at start, 383 km, and 690 km, and among male finishers for hyaluronan at 277 km. Values for syndecan CD-138 were greater among older finishers at all timepoints. There were weak significant correlations (R2 < 0.215) between hyaluronan and distance, creatine kinase, and NT-Pro BNP, respectively. Shedding of glycocalyx elements is shown among participants of the YAU. Greater shedding of heparan sulfate among female, greater increases of hyaluronan among male, and greater shedding of syndecan CD-138 among older athletes indicate complex glycocalyx shedding during ultra-endurance exercise.NEW & NOTEWORTHY This is the first study to investigate changes in glycocalyx elements in an endurance footrace and first study to investigate exercise-induced shedding in both sexes. This study comprised of an athlete group who finished the ultra-long distance of up to 690 km during the Yukon Arctic Ultra as well as a control group. Results indicate relevant and different shedding of glycocalyx elements heparan sulfate, hyaluronan, and syndecan CD-138. Sex, age, BMI, and covered distance appear to have an influence on the shedding. Other serum parameters indicative of stress appear to be associated with shedding.

Reduced mitochondrial respiration in T cells of patients with major depressive disorder.

Converging evidence indicates that major depressive disorder (MDD) and metabolic disorders might be mediated by shared (patho)biological pathways. However, the converging cellular and molecular signatures remain unknown. Here, we investigated metabolic dysfunction on a systemic, cellular, and molecular level in unmedicated patients with MDD compared with matched healthy controls (HC). Despite comparable BMI scores and absence of cardiometabolic disease, patients with MDD presented with significant dyslipidemia. On a cellular level, T cells obtained from patients with MDD exhibited reduced respiratory and glycolytic capacity. Gene expression analysis revealed increased carnitine palmitoyltransferase IA (CPT1a) levels in T cells, the rate-limiting enzyme for mitochondrial long-chain fatty acid oxidation. Together, our results indicate metabolic dysfunction in unmedicated, non-overweight patients with MDD on a systemic, cellular, and molecular level. This evidence for reduced mitochondrial respiration in T cells of patients with MDD provides translation of previous animal studies regarding a putative role of altered immunometabolism in depression pathobiology.

Neural correlates of RDoC-specific cognitive processes in a high-functional autistic patient: a statistically validated case report.

The level of functioning of individuals with autism spectrum disorder (ASD) varies widely. To better understand the neurobiological mechanism associated with high-functioning ASD, we studied the rare case of a female patient with an exceptional professional career in the highly competitive academic field of Mathematics. According to the Research Domain Criteria (RDoC) approach, which proposes to describe the basic dimensions of functioning by integrating different levels of information, we conducted four fMRI experiments targeting the (1) social processes domain (Theory of mind (ToM) and face matching), (2) positive valence domain (reward processing), and (3) cognitive domain (N-back). Patient's data were compared to data of 14 healthy controls (HC). Additionally, we assessed the subjective experience of our case during the experiments. The patient showed increased response times during face matching and achieved a higher total gain in the Reward task, whereas her performance in N-back and ToM was similar to HC. Her brain function differed mainly in the positive valence and cognitive domains. During reward processing, she showed reduced activity in a left-hemispheric frontal network and cortical midline structures but increased connectivity within this network. During the working memory task patients' brain activity and connectivity in left-hemispheric temporo-frontal regions were elevated. In the ToM task, activity in posterior cingulate cortex and temporo-parietal junction was reduced. We suggest that the high level of functioning in our patient is rather related to the effects in brain connectivity than to local cortical information processing and that subjective report provides a fruitful framework for interpretation.

Associations between COVID-19 related media consumption and symptoms of anxiety, depression and COVID-19 related fear in the general population in Germany.

In context of the current COVID-19 pandemic the consumption of pandemic-related media coverage may be an important factor that is associated with anxiety and psychological distress. Aim of the study was to examine those associations in the general population in Germany. 6233 participants took part in an online-survey (March 27th-April 6th, 2020), which included demographic information and media exploitation in terms of duration, frequency and types of media. Symptoms of depression, unspecific anxiety and COVID-19 related anxiety were ascertained with standardized questionnaires. Frequency, duration and diversity of media exposure were positively associated with more symptoms of depression and unspecific and COVID-19 specific anxiety. We obtained the critical threshold of seven times per day and 2.5 h of media exposure to mark the difference between mild and moderate symptoms of (un)specific anxiety and depression. Particularly the usage of social media was associated with more pronounced psychological strain. Participants with pre-existing fears seem to be particularly vulnerable for mental distress related to more immoderate media consumption. Our findings provide some evidence for problematical associations of COVID-19 related media exposure with psychological strain and could serve as an orientation for recommendations-especially with regard to the thresholds of critical media usage.

Glutamate in the Dorsolateral Prefrontal Cortex in Patients With Schizophrenia: A Meta-analysis of 1H-Magnetic Resonance Spectroscopy Studies.

BACKGROUND: To date, there is no systematic overview of glutamate in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia. Here, we meta-analyzed case-control studies of high-field proton magnetic resonance spectroscopy (1H-MRS) investigating glutamate in DLPFC. Additionally, we estimated variance ratios to investigate homo/heterogeneity. METHODS: Preregistration of the study was performed on September 20, 2019. The predefined literature search on PubMed comprised articles with search terms (magnetic resonance spectroscopy OR MRS) AND (glutamate OR glut∗ OR GLX) AND (schizophrenia OR psychosis OR schizophren∗). Meta-analyses with a fixed- and random-effects model with inverse variance method, DerSimonian-Laird estimator for τ2, and Cohen's d were calculated. For differences in variability, we calculated a random-effects model for measures of variance ratios. The primary study outcome was the difference in glutamate in the DLPFC in cases versus controls. Secondary outcomes were differences in variability. RESULTS: The quantitative analysis comprised 429 cases and 365 controls. Overall, we found no group difference (d = 0.03 [95% confidence interval (CI), -0.20 to 0.26], z = 0.28, p = .78). Sensitivity analysis revealed an effect for medication status (Q = 8.35, p = .039), i.e., increased glutamate in antipsychotic-naïve patients (d = 0.46 [95% CI, 0.08 to 0.84], z = 2.37, p = .018). Concerning variance ratios, we found an effect of medication status (Q = 16.95, p < .001) due to lower coefficient of variation ratio (CVR) in medication-naïve patients (logCVR = -0.49 [95% CI, -0.78 to -0.20], z = -3.33, p < .001). In studies with medicated patients, we found higher CVR (logCVR = 0.22 [95% CI, 0.06 to 0.39], z = 2.67; p = .008). CONCLUSIONS: We carefully interpret the higher levels and lower variability in cortical glutamate in antipsychotic-naïve patients as a possible key factor resulting from a putative allostatic mechanism. We conclude that care has to be taken when evaluating metabolite levels in clinical samples in which medication might confound findings.

Risk, resilience, psychological distress, and anxiety at the beginning of the COVID-19 pandemic in Germany.

BACKGROUND: The current COVID-19 pandemic comes with multiple psychological stressors due to health-related, social, economic, and individual consequences and may cause psychological distress. The aim of this study was to screen the population in Germany for negative impact on mental health in the current COVID-19 pandemic and to analyze possible risk and protective factors. METHODS: A total of 6,509 people took part in an online survey in Germany from 27 March to 6 April. The questionnaire included demographic information and ascertained psychological distress, anxiety and depressive symptoms, and risk and protective factors. RESULTS: In our sample, over 50% expressed suffering from anxiety and psychological distress regarding the COVID-19 pandemic. Participants spent several hours per day thinking about COVID-19 (M = 4.45). Psychological and social determinants showed stronger associations with anxiety regarding COVID-19 than experiences with the disease. CONCLUSIONS: The current COVID-19 pandemic does cause psychological distress, anxiety, and depression for large proportions of the general population. Strategies such as maintaining a healthy lifestyle and social contacts, acceptance of anxiety and negative emotions, fostering self-efficacy, and information on where to get medical treatment if needed, seem of help, while substance abuse and suppression of anxiety and negative emotions seem to be associated with more psychological burden.

The IMAGEN study: a decade of imaging genetics in adolescents.

Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype 'drug use' to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions.