Stress management and the role of Rhodiola rosea: a review

Objective: Stress describes the physiological reaction to threat or pressure, which manifests as physical symptoms of exhaustion or energy loss and psychological symptoms, including irritability or tension. If untreated, chronic stress or burnout may develop, both are areas of unmet medical need. Evidence-based treatment and prevention measures are needed. Methods: Prevention strategies and existing treatment options for stress-related symptoms were evaluated to establish criteria for an adequate pharmacological approach to stress. The authors reviewed the literature to reach a clinically meaningful strategy for prevention and treatment of persistent stress symptoms and their consequences, including burnout and secondary diseases. Results: Current medication reveals a treatment gap. Most drugs target only psychological or physical stress symptoms. Furthermore, psychotropic medications sometimes prescribed for stress often have unacceptable side effects and bear a risk of overtreatment. Ideally pharmacological therapy should afford comprehensive treatment of all stress symptoms with a favourable safety profile. Conclusions: Rhodiola rosea extract (RRE) fulfils important requirements. It is the main adaptogen approved by the HMPC/EMA for the indication 'stress' and influences the release of stress hormones while boosting energy metabolism as revealed in animal literature. RRE offers comprehensive treatment of stress symptoms and can prevent chronic stress and stress-related complications

A genome-wide association study of the longitudinal course of executive functions

Executive functions are metacognitive capabilities that control and coordinate mental processes. In the transdiagnostic PsyCourse Study, comprising patients of the affective-to-psychotic spectrum and controls, we investigated the genetic basis of the time course of two core executive subfunctions: set-shifting (Trail Making Test, part B (TMT-B)) and updating (Verbal Digit Span backwards) in 1338 genotyped individuals. Time course was assessed with four measurement points, each 6 months apart. Compared to the initial assessment, executive performance improved across diagnostic groups. We performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with performance change over time by testing for SNP-by-time interactions using linear mixed models. We identified nine genome-wide significant SNPs for TMT-B in strong linkage disequilibrium with each other on chromosome 5. These were associated with decreased performance on the continuous TMT-B score across time. Variant rs150547358 had the lowest P value = 7.2 × 10(−10) with effect estimate beta = 1.16 (95% c.i.: 1.11, 1.22). Implementing data of the FOR2107 consortium (1795 individuals), we replicated these findings for the SNP rs150547358 (P value = 0.015), analyzing the difference of the two available measurement points two years apart. In the replication study, rs150547358 exhibited a similar effect estimate beta = 0.85 (95% c.i.: 0.74, 0.97). Our study demonstrates that longitudinally measured phenotypes have the potential to unmask novel associations, adding time as a dimension to the effects of genomics

Genetic association studies in alcohol dependence

Titelblatt und Inhaltsverzeichnis Einleitung - Fragestellung Einleitung - Stand der Literatur Einleitung - Methodik Eigene Arbeiten - Dopaminerges System Eigene Arbeiten - Serotonerges und glutamaterges System bei Alkoholabhängigkeit Diskussion Zusammenfassung Literaturverzeichnis DanksagungAlkoholabhängigkeit als eine multifaktorielle Erkrankung unterliegt unter anderem einem genetischen Einfluss. Verschiedene Neurotransmitter-Systeme wie das dopaminerge, aber auch das serotonerge und glutamaterge System sind daran beteiligt. Allelische Assoziationsstudien bieten die Möglichkeit, Gene geringen bis mittelgradigen Einflusses bei Populationen realistischer Größe zu identifizieren. Bei der Alzheimer-Demenz und der Aufmerksamkeits-Defizit- Störung (ADS) wurden mit diesen Verfahren, die auch als Fall-Kontroll-Studien bekannt sind, Assoziationen gefunden, so zwischen dem Apolipoprotein E-Gen und der Alzheimer-Demenz bzw. zwischen dem DRD4- und DAT1-Gen und der ADS. Bei anderen Erkrankungen jedoch wie der Alkoholabhängigkeit war es hauptsächlich wegen der Heterogenität der Störung, der Unkenntnis der zugrunde liegenden Pathophysiologie und dem Fehlen klarer Linkage-Befunde bislang nicht ohne weiteres möglich, geeignete Kandidatengene zu identifizieren. Die Nachteile von Assoziationsstudien als Fall-Kontroll-Untersuchungen sind zum einen falsch-positive (dann wären Haplotypen-Untersuchungen an Familien informativer), zum anderen falsch-negative Befunde, wenn die Anzahl der untersuchten Personen zu gering ist. Um diese Probleme zu lösen, könnte außer, dass genomweit systematisch nach Assoziationen bei großen Populationen gesucht wird ( high throughput-genetics ) - der zu untersuchende Phänotyp im Sinne eines Endophänotyps genauer definiert werden. Dementsprechend wurden hier zum einen das Erstmanifestationsalter der Alkoholabhängigkeit, zum anderen bestimmte Persönlichkeitsmerkmale bei Alkoholabhängigkeit als Parameter ausgewählt und deren genetische Assoziation mit bekannten Polymorphismen (SNPs) untersucht. In diesem Zusammenhang können stille Mutationen Marker für funktionelle Mutationen, mit denen sie im Kopplungsungleichgewicht stehen, sein. Bei diesen Untersuchungen ergaben sich positive und negative Befunde, die insgesamt den zwar nicht starken, aber wahrscheinlich modulierenden Effekt des DRD2-Gens auf die Entwicklung oder Ausprägung einer Alkoholabhängigkeit nahe legen. Gleichzeitig haben wir anhand eines Provokationstests mit Apomorphin bei entgifteten Alkoholabhängigen versucht, die Funktion des dopaminergen Systems zu überprüfen. Auch hier fanden sich keine eindeutigen Veränderungen des dopaminergen Systems, wenn auch eher unspezifische Parameter wie Cortisol im Serum eine Unterscheidung zwischen Alkoholabhängigen und gesunden Kontrollen ermöglichten. Zusammenfassend kann festgestellt werden, dass Assoziationsstudien als Fall- Kontroll-Studien bezüglich einzelner SNPs nur dann sinnvoll sind, wenn die klinische Zuordnung spezifiziert und die Kontrollbedingungen streng eingehalten werden. Auch dann bleibt jedoch noch ein langer Weg, um von Markern zu involvierten Genen, auf deren Genprodukt und schließlich deren Funktion auf Proteinebene was z.B. mit Provokationstests untersucht werden könnte - zu kommen.Alcohol dependence as a multifactorial disorder is genetically influenced. Different neurotransmitter systems like the dopaminergic, but the serotonergic and glutamatergic are also involved. Allelic association studies give the opportunity to identify genes of low to moderate influence in populations of reasonable size. In Alzheimer´s disease and attention-deficit-hyperactivity- disorder (ADHD) associations were found by this method (known as case-control- studies), namely between the Apolipoprotein E-gene and Alzheimer´s and DRD4- and DAT1-gene and ADHD. In other disorders like alcohol dependence it was much harder to identify candidate genes, because of the heterogenity of the disease, the unknown pathophysiology and the lack of clear linkage-findings. The possible disadvantages of association studies as case-control-studies are false positive findings (then haplotype-studies in families would be better) and false negative findings, if the number of examined individuals is too low. To solve these problems, one could besides the genome wide screening in the sense of high throughput-genetics specify more precisely the phenotype of the studied population. This is what was done in this work, where age of onset of alcohol dependence and several personality traits were chosen as parameters and their possible genetic association with known polymorphisms (SNPs) was investigated. In this context silent mutations could be markers for functional mutations, they are in linkage disequilibrium with. In these studies positive and negative findings occurred, that showed the weak, but still modulating effect of the DRD2-gene in the development or degree of manifestation of alcohol dependence. Simultaneously, we tried by the challenge test with apomorphine in detoxified alcoholics to check the dopaminergic system functionally. Even here, we did not find clear-cut changes in the dopaminergic system, only rather non-specific parameters like serum cortisol made a differentiation between alcoholics and normal controls possible. To sum it up, one might say, that association studies as case- control-studies regarding SNPs are only sensible when a clinical picture is clearly specified and the control conditions are very strict. Even then, there is a long way from markers to involved genes, then to their gene products and finally to their function on protein level, that could be investigated for example by challenge tests

The DGPPN-Cohort : a national collaboration initiative by the German Association for Psychiatry and Psychotherapy (DGPPN) for establishing a large-scale cohort of psychiatric patients

The German Association for Psychiatry and Psychotherapy (DGPPN) has committed itself to establish a prospective national cohort of patients with major psychiatric disorders, the so-called DGPPN-Cohort. This project will enable the scientific exploitation of high-quality data and biomaterial from psychiatric patients for research. It will be set up using harmonised data sets and procedures for sample generation and guided by transparent rules for data access and data sharing regarding the central research database. While the main focus lies on biological research, it will be open to all kinds of scientific investigations, including epidemiological, clinical or health-service research

Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials

To meta-analytically summarize lamotrigine's effectiveness and safety in unipolar and bipolar depression

Facile Electrodeposition-Based Chemosensors Using PANI and C-Hybrid Nanomaterials for the Selective Detection of Ammonia and Nitrogen Dioxide at Room Temperature

Sensor systems for monitoring indoor air quality are vital for the precise quantification of the mechanisms which lead to the deterioration of human health, with a typical person spending an average of 20 h a day in an enclosed space. Thus, a series of layered chemoresistive sensors, obtained by the facile electrodeposition of carbon nanomaterial-enhanced PANI composites, have been tested for the selective detection of two core indoor pollutants: ammonia and nitrogen dioxide. The sensors were tested with respect to sensitivity and selectivity to the target gasses, with performance being assessed based on response linearity and repeatability at room temperature. Of the tested sensors, two have been identified as having an adequate performance on ammonia, with sensitivities of up to 96.99% and resolutions of up to 0.85 ppm being observed, while on nitrogen dioxide, despite the successful sensor having a lower sensitivity, 10.71%, it has shown high resolution, 1.25 ppm, and linearity over a large concentration domain. These high performances highlight the viability of multi-layers chemosensors based on the electrodeposition of nanomaterial-enhanced conductive polymers for the detection of pollutant gasses, with finetuning of the detection layer allowing the accurate monitoring of a wide range of gasses